Systemic Path - Exam 3

Question 1

What type of glands make up the endocrine system?

Answer 1

Ductless glands

Question 2

Where are hormones from the endocrine system secreted?

Answer 2

Bloodstream

Question 3

This organ has both exocrine and endocrine function.

Answer 3

Pancreas

Question 4

What are mixed function organs?

Answer 4

Has both exocrine and endocrine function.

Question 5

What are diffuse endocrine systems?

Answer 5

Comprised of scattered cells within organs acting locally on adjacent cells without entry into blood stream.

Question 6

Which type hormones are biologically active?

Answer 6

Free hormones

Question 7

Purpose of hormones bound to plasma proteins

Answer 7

Serve as a reserve for acute changes (e.g. thyroid and steroid)

Question 8

General characteristics of hormones.

Answer 8

• Have a specific rate and pattern of secretion.
• Feedback systems: to maintain an optimal internal environment
• Affect only cells with appropriate receptors
• Excreted by one organ and deactivated by another (e.g. excreted by the kidney, deactivated by the liver or other mechanisms)

Question 9

Functions of endocrine system.

Answer 9

• Response to stress and injury
• Growth and development
• Reproduction
• Homeostasis
• Energy metabolism

Question 10

How does the feedback loop mechanism work?

Answer 10

• When biological sensor detects that a hormone level is low, it will cause processes that increase the hormone level.
• When the hormone level is too high, the sensors will cause a decreased in hormonal production.

Analogous to a thermostat and furnace.

Question 11

Classification of diseases.

Answer 11

1. Hyperfunction - overproduction of secretion
2. Hypofunction - underproduction
3. Mass effects (tumors)

Question 12

The parathyroid is a derivative of…

Answer 12

Third and forth branchial pouches

Question 13

How many parathyroid glands does the typical person have?

Answer 13

Most have four glands, but may vary 1-12.

Question 14

Ectopic locations of the parathyroid

Answer 14

• intrathyroid
• intrathymic
• anterior mediastinum

Question 15

Location of the parathyroid.

Answer 15

Normally on the posterior thyroid surface.

Question 16

What cells make up the parathyroid?

Answer 16

• Chief cells
• Oxyphil cells
• Stromal fat

Question 17

What do chief cells secrete?

Answer 17

parathyroid hormone (PTH)

Question 18

What controls the activity of the parathyroid gland?

Answer 18

Free (ionized) calcium, not trophic hormones

Question 19

Where does PTH act?

Answer 19

Bones, kidneys, and intestines

Question 20

Describe PTH and regulation of systemic calcium homeostasis

Answer 20

• PTH increases bone resorption in bone –> increases plasma Ca++
• PTH decreases PO4 reabsorption, but increases Ca++ reabsorption in the kidney –> increases plasma Ca++
• After hydroxylation in the liver and kidney, active form of vitamin D3 (1,25-dihydroxy-vitamin D3) increases calcium reabsorption in the intestine –> increases plasma Ca++

As plasma calcium increases, this is sensed by the parathyroid glands as negative feedback –> less PTH will be produced, and this is how calcium homeostasis is maintained

Question 21

What is normal PTH level?

Answer 21

10 to 65 nanomoles/L

Question 22

What are the causes of hypercalcemia?

Answer 22

1) Due to raised PTH –> hyperparathyroidism (increased production of PTH)

2) Due to decreased PTH:
• Hypercalcemia of malignancy
• Vitamin D toxicity
• Immobilization
• Thiazide diuretics
• Granulomatous disease (sarcoidosis)

Question 23

What is hyperparathyroidism?

Answer 23

• Increased production of parathyroid hormone

* Serum calcium may be decreased, increased or normal, depending upon renal function

Question 24

What is primary hyperparathyroidism?

Answer 24

Excess of parathyroid hormone from adenoma (85 to 95%), hyperplasia (5 to 10%) or carcinoma (1%)

Note: >95% of cases, primary hyperparathyroidism is caused by a sporadic adenoma or sporadic hyperplasia

Scribe note: PTH normal or increased, calcium increased

Question 25

What is secondary hyperparathyroidism?

Answer 25

Adaptive increase in parathyroid hormone secondary to hypocalcemia and hyperphosphatemia of chronic renal failure Scribe note: PTH increased, calcium normal or decreased

Question 26

What is tertiary hyperparathyroidism?

Answer 26

autonomous parathyroid hyperfunction in patients with secondary hyperparathyroidism Scribe note: Both PTH and calcium are increased since it is autonomous

Question 27

Signs and symptoms of hyperparathyroidism

Answer 27

* Asymptomatic | * “Bones, stones, abdominal groans, psychic moans”

Question 28

Effects/symptoms of the main cause of hyperparathyroidism, parathyroid adenoma:

Answer 28

BONE. Excess PTH acts on bone, causing calcium to leech out and cause osteoporosis (prone to fractures) and osteitis fibrosa cystica (radiolucent areas, called brown tumor, due to hemorrhage). RENAL. Patient may develop kidney stones, frequent urination, and nephrocalcinosis (increased calcium reabsorption in renal tubules causes calcifications). GI TRACT. Patient may develop peptic ulcer, gallstones, and acute pancreatitis BRAIN. Hyperparathyroidism can cause depression or seizures BLOOD. Hypercalcemia, hypophosphatemia

Question 29

Brown tumor

Answer 29

Osteitis fibrosa cystica

Question 30

What's parathyroid adenoma?

Answer 30

* Benign neoplasm * Involve a single gland, rarely two or more (<1%) * Major cause of primary hyperparathyroidism * Any age, F:M 3:1 * Excellent prognosis after excision

Question 31

Major cause of hyperparathyroidism

Answer 31

Parathyroid adenoma

Question 32

Appearance of parathyroid adenoma

Answer 32

- Sharply demarcated from the adjacent rim of normal parathyroid - Predominantly chief cells in sheets or tubules - Adipose tissue inconspicuous

Question 33

What's parathyroid hyperplasia?

Answer 33

* Classically all four parathyroid involved (frequently asymmetrical) * Sporadic or as a component of MEN syndrome * 75% of patients – sporadic * 15% of patients – part of MEN 2A (not MEN 2B) * 15% of hyperparathyroidism cases Note: diagnosis of adenoma versus hyperplasia may depend on the size of the other glands

Question 34

Appearance of parathyroid hyperplasia

Answer 34

* Enlarged parathyroids * Stromal fat inconspicuous * Usually chief cell hyperplasia, diffuse or nodular * Variable oncocytes * Cystic change in markedly enlarged glands

Question 35

What's parathyroid carcinoma?

Answer 35

* Palpable neck mass (75%) * Excessive PTH secretion, high serum calcium > 14 mg/dl * Non-functioning tumors are rare * Diagnosis based on local invasion and metastases (clinical criteria, NOT microscopic criteria) * 1/3 recur locally, 1/3 have distant metastases

Question 36

Appearance of parathyroid carcinoma

Answer 36

* Capsular invasion * Densely adherent to surrounding soft tissue * Thick fibrous bands * Predominantly chief cells arranged in solid or trabecular pattern * Macronucleoli, more than five mitoses per 50 high-power fields, and necrosis associated with aggressive behavior * Cytological detail, unreliable for the diagnosis of carcinoma * Vascular invasion and metastasis (ABSOLUTE CRITERIA) * Local recurrence (1/3 of cases), distant metastasis (in another 1/3)

Question 37

What is hypoparathyroidism?

Answer 37

* Disorder in which insufficient parathyroid hormone (PTH) is secreted from the parathyroid glands, resulting in abnormally low levels of calcium in the blood * Far less common

Question 38

Causes of hypoparathyroidism

Answer 38

* Damage to the gland or its vessels during thyroid surgery | * Idiopathic, autoimmune disease, congenital

Question 39

Clinical features of hypoparathyroidism

Answer 39

* Tetany * Convulsion * Neuromuscular irritability * Cardiac arrhythmias * Increased intracranial pressure * Seizures

Question 40

MEN stands for?

Answer 40

Multiple Endocrine Neoplasia

Question 41

What's MEN I?

Answer 41

* AKA Wermer syndrome | * Neoplasia of: pituitary, parathyroids, pancreas and carcinoids, parathyroid hyperplasia

Question 42

What's MEN IIA?

Answer 42

* AKA Sipple's Syndrome | * Medullary throid carcinoma (c-cell), parathyroid hyperplasia, pheochromocytomas (tumor of adrenal medullary)

Question 43

What's MEN IIB?

Answer 43

* Neuromas of the eye, buccal mucosa, and GI mucosa | * There may be medullary thyroid carcinoma and pheochromocytomas

Question 44

What's the largest endocrine organ?

Answer 44

Thyroid

Question 45

What are the thyroid hormones?

Answer 45

• Thyroid hormones (TH): - Thyroxine (T4) - Triiodothyronine (T3) - Calcitonin

Question 46

Layers of skin

Answer 46

• Epidermis - top most layer, contains melanocytes (makes pigment) and Langerhans cells (immune cells) • Dermis - located beneath the epidermis, contains dendritic cells (immune cells) and appendages - appendages include: hair follicles, sweat glands, Pacinian corpuscles (pressure receptors). - Red tissue you see when you skin your knee and the epidermis has been removed • Subcutaneous fat

Question 47

Where are melanocytes derived from?

Answer 47

* Neural crest derived cells * Present in epidermal basal layer * Synthesize melanin

Question 48

Synthesis of melanin

Answer 48

* Synthesized in melanosomes * Catalyzed by tyrosine * Tyrosine -> DOPA --> melanin * Dendritic processes extend between keratinocytes * Melanin is transferred from melanocytes to neighboring keratinocytes in melanosomes

Question 49

Innate immune response: what is it, physical barriers, soluble factors, cells involved?

Answer 49

* Immediate defense; short lived; no memory * Physical barriers include skin and mucosal epithelia * Soluble factors include complement, antimicrobial peptides, chemokines, and cytokines * Cells include monocytes/macrophages, dendritic cells, natural killer cells, and neutrophils

Question 50

Adaptive immune response

Answer 50

* Has memory; has specificity; long lasting * Initiated by dendritic antigen-presenting cells * Langerhan cells in the epidermis * Dermal dendritic cells in the dermis * Executed by T cells and antibodies produced by B cells and plasma cells

Question 51

Which dendritic antigen presenting cell is present in the epidermis?

Answer 51

Langerhans cells

Question 52

Which dendritic antigen presenting cell is present in the dermis?

Answer 52

Dendritic cells

Question 53

What are keratinocytes?

Answer 53

* Present in melanosomes | * Secrete cytokines, chemokines, arachidonic acid metabolites, complement components, and antimicrobial peptides

Question 54

What are Langerhans cells?

Answer 54

* Antigen presenting cells in the epidermis * Phagocytose antigens * Migrate via lymphatics to regional lymph nodes * Expresses protein on its surface to T lymphocytes then undergo clonal proliferation

Question 55

What do Langerhans cells do, and how do they travel?

Answer 55

* Phagocytose antigens * Migrate via lymphatics to regional lymph nodes * Express antigen protein on their surface and present to T lymphocytes, then undergo clonal proliferation

Question 56

Plays a similar role to Langerhans cells in the dermis...

Answer 56

Dermal dendritiic cells

Question 57

What are natural killer (NK) cells?

Answer 57

* Survey the body looking for transformed or infected cells | * Kill cells directly or indirectly via the secretion of cytokines

Question 58

What are macrophages?

Answer 58

* Cutaneous immune surveillance in the dermis | * Phagocytic function (also neutrophils): take up pathogens, recognize them, and destroy them

Question 59

What is a macule?

Answer 59

* Circumscribed FLAT lesion | * 5mm or smaller in diameter

Question 60

What is a patch?

Answer 60

* Flat circumscibed lesion | * > 5mm

Question 61

What is a papule?

Answer 61

* ELEVATED dome-shaped or flat-topped lesion | * 5mm or less across

Question 62

What is a nodule?

Answer 62

Greater than 5mm

Question 63

What is a pustule?

Answer 63

Discrete, pus-filled, raised lesion

Question 64

What is a plaque?

Answer 64

* Elevated flat-topped lesion | * Greater than 5mm across

Question 65

What is a petechiae?

Answer 65

* Small (1-2mm) red or purple macules due to minor hemorrahage * Do not blanch with pressure

Question 66

What is a purpura?

Answer 66

* Large hemorrhagic lesion * 0.3 - 1cm red or purple macules and patches * Do not blanch with pressure

Question 67

These two skin lesions do not blanch with pressure...

Answer 67

Purpura and petechiae

Question 68

What is a vesicle?

Answer 68

* Fluid-filled raised lesion | * 5mm or less across

Question 69

What is a bulla?

Answer 69

* Fluid-filled raised lesion | * Greater than 5mm

Question 70

What is a wheal?

Answer 70

* Itchy, transient, elevated lesion, +/- erythema | * Dermal edema

Question 71

What is a scale?

Answer 71

* Dry, horny, plate like excrescence | * Imperfect cornification

Question 72

What is lichenification?

Answer 72

• Caused by repeated rubbing/scratching • Thickened and rough skin, prominent skin markings ** Looks like lichen

Question 73

What is ulceration?

Answer 73

Complete loss of the epidermis, revealing dermis or subcutis.

Question 74

What is eschar?

Answer 74

When tissue dies, turns black, and sloughs.

Question 75

What is onycholysis?

Answer 75

Nail separates from nail bed.

Question 76

Microscopic terms used to describe skin findings

Answer 76

* Hyperkeratosis: thickening of the stratum corneum * Basket weave hyperkeratosis: most normal healthy skin on our body is keratinized in this fashion * Compact hyperkeratosis: the soles of feet and palms of hands are thicker * Parakeratosis: keratinization with retained nuclei in the stratum corneum * Hypergranulosis: hyperplasia of the stratum granulosum * Spongiosis: intercellular edema of the epidermis * Hydropic swelling (ballooning): intracellular edema of keratinocytes * Acanthosis: diffuse epidermal hyperplasia wih thickening of the malphigian layer * Acantholysis: loss of intercellular cohesion between keratinocytes * Dysplasia: premalignant proliferation; disorderly, pleomorphic, lacks maturation * Dyskeratosis: premature keratinization of cells below the stratum granulosum

Question 77

What is hyperkeratosis?

Answer 77

Thickening of the stratum corneum. • Basket weave hyperkeratosis: most normal healthy skin on our body is keratinized in this fashion • Compact hyperkeratosis: the soles of feet and palms of hands are thicker

Question 78

What is parakeratosis?

Answer 78

Keratinization with retained nuclei in the stratum corneum.

Question 79

What is hypergranulosis?

Answer 79

Hyperplasia of the stratum granulosum.

Question 80

What is spongiosis?

Answer 80

Intercellular edema of the epidermis.

Question 81

What is hydropic swelling (ballooning)?

Answer 81

Intracellular edema of keratinocytes.

Question 82

What is acanthosis?

Answer 82

Diffuse epidermal hyperplasia with thickening of the malphigian layer.

Question 83

What is acantholysis?

Answer 83

Loss on intercellular cohesion between keratinocytes

Question 84

What is dysplasia?

Answer 84

* Premalignant proliferation | * Disorderly, pleomorphic, lacks maturation

Question 85

What is dyskeratosis?

Answer 85

• Premature keratinization of cells below the stratum granulosum.

Question 86

Histologic pattern of inflammatory skin disease --> perivascular dermatitis

Answer 86

Can be superficial and deep

Question 87

Histologic pattern of inflammatory skin disease --> vasculitis

Answer 87

* Injury to blood vessels, causing blood cells to leak out | * Grossly we see petechiae and purpura

Question 88

Histologic pattern of inflammatory skin disease --> vesicular dermatitis

Answer 88

Blistering diseases like pemphigoid

Question 89

Histologic pattern of inflammatory skin disease --> diffuse dermatitis

Answer 89

Example: sarcoidosis

Question 90

Histologic pattern of inflammatory skin disease --> panniculitis

Answer 90

Subcutaneous fat is inflamed.

Question 91

Group of disorders of differing etiologies that share similar morphologic and histological features spongiotic dermatitis. Skin rash

Answer 91

Eczematous dermatitis

Question 92

Acute appearance of eczematous dermatitis

Answer 92

* Erythema * Aggregates of tiny pruritic vesicles (1mm) * Itchy, excude clear fluid, and become encrusted

Question 93

Chronic appearance of eczematous dermatitis

Answer 93

* Scaly and thickened (lichenification) from continued scratching * Acanthosis: spongiosum layer gets thickened due to causes like rubbing or psoriasis * Hyperkeratosis: thickening of the stratum corneum * Dermal scarring

Question 94

A generic term applied to acute or chronic inflammatory reactions to substances that come in contact with the skin.

Answer 94

Contact dermatitis

Question 95

Two variants of contact dermatitis

Answer 95

* Allergic contact | * Irritant contact

Question 96

What is allergic contact dermatitis?

Answer 96

* Idiosyncratic immunological reaction to an environmental allergen * Cell-mediated, delayed (type IV) hypersensitivity reaction mediated by Langerhans cells and t-cells. * Ex: poison ivy; nickel; chromates; synthetic rubber; primula; topical creams

Question 97

What is irritant contact dermatitis?

Answer 97

* Follows exposure to physical or chemical substances capable of direct damage to the skin. * Mechanisms include keratin denaturation, removal of surface lipids and water, damage to cell membranes, and direct cytotoxic effects * Ex: Soaps, detergents, acids and alkalis, industrial solvents

Question 98

What is atopic dermatitis?

Answer 98

* Chronic, relapsing eczematous rash. * Any age, but often begins in infancy * In infants it often affects: head, face, neck, diaper area, and extensor aspects * In childhood it involves flexural aspects (e.g. back and knees). * Pruritus is intense - scratching leads to lichenification * Risk of secondary bacterial, dermatophyte and viral infections * Disease improves during childhood, with >50% clearing by teen years.

Question 99

Etiology of atopic dermatitis

Answer 99

``` Multifactorial: • Genetic susceptibility • Abnormal skin barrier function • Abnormal immune system activity • Environmental factors ``` Personal or family history of asthma or allergies: • 75% have a family history of atopy (genetic disposition to develop an allergic reaction) • 50% have associated asthma or hay fever Associated with dry skin (xerosis): worsens in the winter months

Question 100

A very common chronic dermatosis characterized by redness and scaling where the sebaceous glands are most active: face, scalp, presternal area, body folds

Answer 100

Seborrheic dermatitis * Presents in infants; second peak in adults * Male predominance; often a family history

Question 101

Skin findings of seborrheic dermatitis

Answer 101

Erythematous or yellowish patches, covered by a greasy scale

Question 102

Pathogenesis of seborrheic dermatitis

Answer 102

Pathogenesis is unknown. • Linked with the yeast Malessezia, immunologic abnormalities, sebaceous activity, stress, neurological disorders, and AIDS

Question 103

Course of seborrheic dermatitis

Answer 103

* Self-limited with a good prognosis in infants | * Chronic and relapsing in adults

Question 104

Delayed hypersensitivity type 4 reaction to photo product of topical or systemic medications and chemicals

Answer 104

Photoallergic reactions • An allergic reaction to something on skin or in blood, as a result of photochemical reaction

Question 105

Skin lesions observed in photoallergic reactions

Answer 105

* Eczematous papular, vesicular, scaling, and crusted | * Can persist for months or years

Question 106

What are phototoxic reactions?

Answer 106

UV radiation associated with use of medications causes formation of toxic photoproducts such as free radicals • Damages DNA or cell membranes

Question 107

Skin findings of phototoxic reactions

Answer 107

* Occurs on sun-exposed skin * Occurs minutes to hours after sun exposure * Mimics severe sunburn: erythema, edema, and blistering desquamation and post inflammatory hyperpigmentation

Question 108

An acute self-limited, usually mild, often relapsing mucocutaneous syndrome characterized by presence of target-shaped plaques with or without central blisters, predominantly on face and extremeties.

Answer 108

Erythema multiforme • Any age, peaks in 20-40s; children

Question 109

What is erythema multiforme minor?

Answer 109

No mucosal involvement

Question 110

What is erythema multiforme major?

Answer 110

Mucosal involvement

Question 111

Pathogenesis of erythema multiforme

Answer 111

Epithelial cells are killed by skin-homing CD8+ cytotoxic T lymphocytes • Immunologic response, most often, to a recurrent herpes simplex virus • Can also be stimulated by M. peumoniae, drugs, neoplasia • Begins a week after a recurrence of herpes In other words: caused by CD8+ T-cells that kill epithelial cells. This is stimulated by herpes simplex cirus, which makes us attach our own skin.

Question 112

TARGET LESIONS, macules, papules, vesicles, bullae are associated with which inflammatory skin disease?

Answer 112

Erythema multiforme Additional skin findings: • symmetric, extremities, arms, legs, hands, feet, anywhere • Half have oral or vermillion border lesions

Question 113

Microscopic appearance of erythema multiforme

Answer 113

* interface dermatitis because vacuolar change and cleft formation occur at the dermal-epidermal junction * Necrotic basal keratinocytes * Lymphocytic infiltrates of interface and superficial perivascular zones.

Question 114

What is Stevens-Johnson Syndrome, aka Toxic Epidermal Necrolysis?

Answer 114

* Acute, life-threatening skin and mucous membrane reaction characterized by extensive necrosis and detachment of the epidermis. * Previously considered severe variants of erythema multiforme, but now considered a separate entity. * An epidermal emergency

Question 115

Stevens-Johnson-Syndrome and Toxic Epidermal Necrolysis are the same process, but vary in the % of involved surface area...

Answer 115

* SJS if involved area < 10% of body surface * SJS/TEN overlap if 10-30% * Toxic epidermal necrolysis if > 30%

Question 116

Risk factors for SJS and TEN

Answer 116

* Rare * Any age, but risk increases with age * 2F:1M predilection * Increased risk: HIV, collagen vascular disease and cancer

Question 117

Mortality SJS vs TEN

Answer 117

SJS: 5-12% TEN: > 30%

Question 118

Skin findings on SJS/TEN

Answer 118

* Confluent, erythematous, purpuric and target-like macules evolve into flaccid blisters and epidermal detachment * Mostly trunk, extremities, and mucous membranes

Question 119

Pathogenesis of SJS/TEN

Answer 119

Cell-mediated cytotoxic reaction against keratinocytes leads to massive apoptosis.

Question 120

Common (1%), pruritic (itchy), symmetrical, papulosquamous dermatosis

Answer 120

Lichen planus Add'l info: • Often presents in fourth to sixth decades; uncommon in childhood • Slight female predominance • Familial cases reported. Associated with specific HLA types • Usually self-limiting-lesions clear from weeks to 1 or 2 years. Sometimes protracted.

Question 121

Skin findings for lichen planus

Answer 121

* Four P's: polygonal, pruritic, purple papule; few millimeters to 1 cm * Wickham's striae - white streaks

Question 122

Inflammatory skin disease where Wickham's striae (white streaks) are observed

Answer 122

Lichen Planus

Question 123

Sites affected by Lichen Planus

Answer 123

* Flexor aspect of the wrists, the forearms, the extensor aspect of the hands and ankles, lumbar area, nails, glans penis and generalized * Oral involvement common: may involve pharynx, larynx, esophagus, nose, anus, and genitalia; ocular rare

Question 124

Microscopic appearance of Lichen Planus

Answer 124

* Interface dermatitis * Dense, band like lymphocytic infiltrate along the D-E junction * Vacuolar degeneration of the basal layer * Hypergranulosis, hyperkeratosis and sawtoothing of epidermis * Necrotic keratinocytes - "Civatte bodies"

Question 125

Civatte bodies, which are necrotic keratinocytes, are observed in which inflammatory skin disease?

Answer 125

Lichen Planus

Question 126

Pathogenesis of Lichen Planus

Answer 126

* Possibly expression of altered external antigen stimulus elicits a cell-mediated cytotoxic T-cell immune response at the level of the dermoepidermal junction * Assoociated with viral infections, metals, and drugs. * Body mistakes own antigens for external antigens

Question 127

Course of Lichen planus

Answer 127

* Unpredictable disease * Typically persists for 1-2 years, but may follow a chronic, relapsing course over many years * Rx: Topical and systemic glucocorticoids, cyclosporine * NAILS may be affected: longitudinal ridging, thinning, and distal splitting of the nail plate

Question 128

Common chronic inflammatory dermatosis characterized by erythmatous scaly plaques of the elbows, knees, scalp, lumbosacral areas and other sites

Answer 128

Psoriasis

Question 129

Which inflammatory skin disease is this: * Associated with arthritis, myopathy, enteropathy, joint disease, AIDS. * Polygenic trait

Answer 129

Psoriasis Additional info: • Any age, bimodal • Often presents in the teens and in early adult life (type I). • Second peak in sixth decade (type II). More on polygenic trait: one parent has psoriasis 8% of kids get psoriasis. Both parents have psoriasis, 41% of kids get psoriasis.

Question 130

Acute form of psoriasis

Answer 130

Eruptive, guttate psoriasis; multiple small lesions; greater tendency toward spontaneous resolution; 2%

Question 131

Chronic stable plaque psoriasis

Answer 131

* Majority of patients | * Chronic indolent lesions present for months and years

Question 132

Pathogenesis of psoriasis

Answer 132

* Multifactorial, both genetic and environmental factors * Interactions between CD4+ T-cells, CD8+ T-cells, dendritic cells, and keratinocytes causing bassal keratinocytes to hyperproliferate * Strong association with HLA-Cw6; only 10% develop psoriasis * Systemic glucocorticoids, oral lithium, antimalarial drugs, interferon, adrenergic blockers and alcohol can cause flares

Question 133

Which inflammatory skin disease has a strong association with HLA-Cw6?

Answer 133

Psoriasis

Question 134

Skin findings for psoriasis

Answer 134

* Begin as papules, coalesce to form raised, sharply demarcated plaques, silvery scale surface, erythematous base * Elbows, knees, scalp, lumbosacral areas, intergluteal cleft, and glans penis * Nail pitting and onycholysis * Auspitz's sign: small droplets of blood when removing scales

Question 135

What is Auspitz's sign, and in which inflammatory skin disease is it observed?

Answer 135

* Auspitz's sign is small droplets of blood when removing scales * Psoriasis

Question 136

Destruction of the interphalangeal joints resulting in telescoping fingers.

Answer 136

Psoriatic arthritis

Question 137

Microscopic appearance of psoriasis

Answer 137

* Acanthosis * Elongation of the rete ridges, suprapapillary thinning, parakeratotic scale, spongiosis and superficial perivascular inflammation * Munro's microabscesses - neutrophils aggregates within the parakeratotic stratum corneum * Spongiform pustules - neutrophils form small aggregates within epidermis

Question 138

In which inflammatory skin disease are Munro's microabscesses and spongiform pustules are observed?

Answer 138

Psoriasis * Munro's microabscesses: neutrophils aggregates within the parakeratotic stratum corneum * Spongiform pustules: neutrophils form small aggregates within epidermis

Question 139

Inflammatory skin diseases include _______ disorders and _______

Answer 139

Blistering disorders; adverse cutaneous drug reactions

Question 140

Infectious skin diseases can be _____, _____, or _____

Answer 140

Viral, fungal, or infestations

Question 141

Pemphigus Vulgaris, Bullous Phemphigoid, Dermatitis Herpetiformis

Answer 141

Blistering Disorders

Question 142

Exanthematous drug eruption, Acute exanthematous pustulosis, Acneiform eruptions, Urticarial eruptions, Fixed drug eruption

Answer 142

Adverse cutaneous drug reactions

Question 143

Verruca vulgaris, Mulluscum contagiosum, Herpes simplex, Varicella zoster (chickenpox and shingles)

Answer 143

Viral diseases

Question 144

Dermatophyte infections, pityriasis versicolor, candida infection

Answer 144

Fungal disease

Question 145

Pediculosis

Answer 145

Infestations

Question 146

What is pemphigus?

Answer 146

* A serious autoimmune mucocutaeous blistering disorder caused by IgG autoantibodies against desmogleins (proteins involved in cell to cell attachment) causing acantholysis and intraepidermal bullae. * Disease associated with specific HLA haplotypes. * Majority fourth to sixth decades; M = F

Question 147

Net-like pericellular IgG deposit for immunofluorescence indicates this...

Answer 147

Pemphigus

Question 148

Skin findings for pemphigus vulgaris..

Answer 148

* Superficial vesicles and FLACCID bullae which rupture leaving shallow crusted erosions. * Commonly involves scalp, face, axilla, groin, trunk, and pressure points. * Oral ulcers may persist for months before onset of skin involvement. * Extracutaneous sites include the nasopharynx, larynx, esophagus, ear, eye, urethra, anal, and colonic mucosa. * Nikolsky sign positive, dislodge epidermis by lateral pressure near lesions.

Question 149

Which blistering disorder involves positive Nikolsky sign and dislodge epidermis by lateral pressure near lesions?

Answer 149

Pemphigus vulgaris

Question 150

Treatment for Pemphigus vulgaris

Answer 150

• Systemic corticosteroids, immunosuppressive agents. Manage fluids and infections

Question 151

Course of Pemphigus vulgaris

Answer 151

* Systemic glucocorticoids and use of immunosuppressive therapy have dramatically improved the prognosis; still significant mortality because patients have trouble maintaining fluid dynamics (ooze causes loss of water) and high risk of infection. * Before glucocorticoid therapy, almost invariably fatal.

Question 152

Microscopic appearance of pemphigus vularis

Answer 152

* Acantholysis: the lysis, of the desmosomes connecting squamous cells leads to a suprabasal vesicle. * Superficial dermal infiltration by lymphocytes, histiocytes, and eosinophils.

Question 153

What is bullous pemphigoid?

Answer 153

* A bullous autoimmune disease usually in elderly patients. | * Most cases sporadic. Few associated with UV light and medications.

Question 154

Pathogenesis of bullous pemphigoid

Answer 154

* Auto-antibodies react with basal cell -- basement membrane hemidesmosomes involved in dermoepidermal bonding. * Two forms of antigen recognized: BPAG1 and BPAG2 (collagen type XVIII). * Causes complement activation, recruitment of neutrophils & eosinophils and injury.

Question 155

What antigens are recognized in Bullous Pemphigoid?

Answer 155

BPAG1 and BPAG2 (collagen type XVIII).

Question 156

Skin findings of Bullous Pemphigoid

Answer 156

* TENSE bullae, filled with clear fluid, on normal or erythematous skin usually up to 2 cm or greater in diameter * Nikolsky sign negative * Affects any area; lower abdomen, thighs, forearms, axillae, and groin most common * Oral lesions in 10% to 15%; usually appear after skin lesions

Question 157

Treatment for bullae pemphigoid

Answer 157

Systemic prednisone alone or combined with azathioprine

Question 158

Course of bullae pemphigoid

Answer 158

* Patients often go into a permanent remission after therapy. * Some go into spontaneous remission without therapy.

Question 159

Microscopic appearance of bullous pemphigoid

Answer 159

* SUBEPIDERMAL BLISTERS containing eosinophils, lymphocytes, and occasional neutrophils. * Dermal edema, perivascular lymphocytes and eosinophils.

Question 160

When doing immunoflorescence a linear deposition of IgG and complement in the basement membrane zone...

Answer 160

Bullous pemphigoid

Question 161

What is dermatitis herpetiformis?

Answer 161

* A rare, chronic, intensely burning, pruritic papulovesicular eruption associated with GLUTIN SENSITIVE ENTEROPATHY AND IgA DEPOSITS in upper dermis. * all ages, but 20-40 years most common * Male to female ratio is 2:1 * Caucasians mainly affected; rare in Asians and blacks * Familial involvement; up to 10% of cases * Relatives of patients with DH have increased risk for celiac disease.

Question 162

Relatives of patients with dermatitis herpetiformis have increased risk for this...

Answer 162

celiac disease

Question 163

Skin findings for dermatitis herpetiformis

Answer 163

* Pruritic papulovesicular and urticarial rash * Often symmetrical, posterior scalp, shoulders, back, buttocks, and extensor aspects of the limbs; excoriation and/or lichenification * Occasionally, larger blisters. Oral involvement is rare.

Question 164

Pathogenesis of dermatitis herpetiformis

Answer 164

* Genetically predisposed patients develop IgA antibodies to gluten in diet * Antibodies cross-react with reticulin, a component of the fibrils that anchor the epidermal basement membrane to the dermis. * Asymptomatic patients can develop GI lesions with large gluten intake. Some people with DH and GSE respond to a gluten free diet. * Increased incidence of thyroid disease, insulin-dependent diabetes mellitus, and connective tissue diseases.

Question 165

Immunofluorescence reveals discontinuous, granular deposits of IgA localized to the tips of ermal papillae in normal appearing skin.

Answer 165

Dermatitis Herpetiformis

Question 166

Treatment for dermatitis herpetiformis

Answer 166

Sulfones; gluten free diet

Question 167

Microscopic findings for dermatitis herpetiformis

Answer 167

* Papillary dermal neutrophilic microabscesses within the tips of the dermal papillae. * Coalesce to multilocular subepidermal vesicles. * Dermal mixed inflammatory infiltrate of lymphocytes, histiocytes, and abundant neutrophils.

Question 168

What are adverse cutaneous drug reactions?

Answer 168

* Mimic virtually all skin rashes. * First consideration in the DDx (differential diagnosis?) of a suddenly appearing eruption. * Occur in both systemic or topical administration of a drug. * Most are mild, pruritic, and resolve after drug discontinued. * Severe, life-threatening ACDRs do occur.

Question 169

What causes adverse cutaneous drug reactions?

Answer 169

* Caused by immunologic and nonimmunologic mechanisms. * The majority are immunologic hypersensitivity reactions and may be of types I, II, III, or IV. * Nonimmunologic mechanisms include idiosyncratic, irritant toxicity photosensativity reaction, accumulation of drug, atrophy secondary to drug effect.

Question 170

What is exanthematous drug eruption?

Answer 170

* Exanthem = breaking out in mouth * Moribiliform = measles-like * Hypersensitivity reaction to an ingested or parenterally administered drug * Symmetric; almost always on trunk and extremities * Intertriginous areas

Question 171

What are pustular eruptions?

Answer 171

* Acute generalized exanthematous pustulosis * Acute febrile eruption; often leukocytosis * Drug or virus can trigger the eruption

Question 172

Skin findings for pustular eruptions

Answer 172

* Nonfollicular sterile pustules on a diffuse, edematous erythema * Usually starting in the folds and/or the face * Resolves spontaneously in two weeks

Question 173

Acneform eruptions (mimics acne) may appear in atypical areas, such as on the arms and legs, in this adverse cutaneous drug reaction...

Answer 173

Pustular eruptions

Question 174

What are urticarial eruptions?

Answer 174

* Pruritic red WHEALS, generally last for < 24 hours; new lesions can develop * Pruritus, cutaneous flushing, nausea, vomiting, diarrhea, abdominal pain, rhinorrhea, laryngeal edema, bronchospasm, hypotension * Angiodema - deep dermal and subcutaneous tissues swollen, nonpruritic; lasts for 1-2 hours, up to 2-5 days * Can be IgE-mediated or non-IgE-mediated * IgE mediated: immediate hypersensitivity reaction: penicillin; ABs * Non IgE mediated: direct stimulation of mast cells: NSAIDs, ACE-inhibitors and opioids

Question 175

What are fixed drug eruptions?

Answer 175

* Solitary, erythematous,dusky macules or plaques; May blister * 30 min to 8-16 hours after ingestion * ** On rechallenge, lesions recur in same spot; often with new lesions * Commonly genitalia and perianal area; anywhere * +/- burning fever, malaise, and abdominal symptoms * Acute phase lasts days to weeks; residual hyperpigmentation * Hundreds of drugs can cause fixed eruption

Question 176

Which adverse cutaneous drug reaction on rechallenge, lesions recur in the same spot?

Answer 176

Fixed drug eruptions

Question 177

What is verruca vulgaris?

Answer 177

* Common wart | * Human papillomavirus (HPV) infection

Question 178

Common warts (verruca vulgaris) are caused by HPV types...

Answer 178

1, 2, 4, 7, and 26-29

Question 179

Skin findings for verruca vulgaris

Answer 179

* Firm, flesh colored, keratotic papules 1-10mm * Anywhere, any age * Most common location: backs of the hands, fingers and knees * Persist for months up to years and often regress spontaneously

Question 180

Microscopic finding for verruca vulgaris

Answer 180

* Acanthosis * Hyperkeratosis * Papillomatosis * Hypergranulosis * Inward folding of rete

Question 181

Treatment for verruca vulgaris

Answer 181

* Topical salicylic acid preparations, liquid nitrogen, and very light electrocautery for initial therapy. * Burn or freeze warts off

Question 182

HPV types that cause plantar warts

Answer 182

* Plantar surface of feet can get warts | * Caused by HPV 1, 2, 4, 63

Question 183

HPV types that cause planar warts

Answer 183

HPV 3, 10, 27, 38, 41, 49, 75, 76

Question 184

HPV types that cause condyloma accuminatum

Answer 184

* Fleshy moist warts on genitalia, can look like syphilis | * HPV 6, 11, 30, 43, 43, 44, 45, 51, 54, 55, 70

Question 185

HPV types that cause epidermodysplasia verruciformis

Answer 185

* A genetic disease, patient is highly predisposed to HPV infection * HPV 5

Question 186

What is mulluscum contagiosum?

Answer 186

Viral skin infection from DNA pox virus

Question 187

Transmission of mulluscum contagiosum

Answer 187

Direct cutaneous contact; fomites; sexual contact in young adults

Question 188

Skin findings for mulluscum contagiosum

Answer 188

* Clusters of small 1 to 6 mm white, pink or brown papules with CENTRAL PIT (umbilicated) * Can be much larger in HIV patients * Face, trunk, and limbs • COURSE: may persist for months or occasionally years and remit

Question 189

Microscopic appearance of Mulluscum Contagiosum

Answer 189

* Proliferation of epidermis in PEAR shaped lobules | * Maturing epidermal cells contain mulluscum bodies, eosinophilic inclusions compressing the nucleus

Question 190

Which viral skin disease is associated with pear-shaped lobules of epidermal proliferation with pink bodies (mulluscum bodies) that rise into the umbilication?

Answer 190

Mulluscum contagiosum

Question 191

Are HSV-1 and HSV-2 DNA or RNA viruses?

Answer 191

DNA

Question 192

HSV-1 usually causes...

Answer 192

• Herpes labialis

Question 193

HSV-2 usually causes...

Answer 193

• Herpes genitalis

Question 194

How is HSV transmitted?

Answer 194

* Transmitted through mucosal surfaces or break in skin by contact or exposure to secretions. * First-episode often with fever and malaise

Question 195

What is herpetic whitlow?

Answer 195

• HSV infection, involvement of a finger or hand; often healthcare workers, dental practitioners

Question 196

How to diagnose this is a herpes virus?

Answer 196

* Tzank smear * Unroof a vesicle and scrape the base onto a slide * Viral cytopathy present in cells

Question 197

Skin findings for herpes simplex

Answer 197

* Small grouped vesicles * +/- erythematous base * Evolve into pustules, rupture and form a crusted ulcer * Mucosal lesions ulcerate early

Question 198

Microscopic findings for herpes simplex

Answer 198

* Ballooning degeneration coalesce to intraepidermal vesicle * Multinucleation * Intranuclear inclusions * Nuclei have a ground-glass look because millions of live virus inside * Dense red inclusion is a degeneration byproduct * Nuclear molding * Margination * Almost looks like vasculitis, because so much dermal inflammation

Question 199

Course of herpes simplex

Answer 199

* Primary episode resolve completely in around 15 days * Virus persists, become latent within the ganglia of the corresponding sensory nerve * Recurrent HSV lesions are usually less florid than the first infection without general symptoms * Secondary outbreaks are precipitated by sunlight, fever, menstruation, pregnancy, HIV infection, emotional stress, or local trauma

Question 200

Treatment ofr herpes simplex

Answer 200

Acyclovir tropical and oral

Question 201

What is varicella zoster?

Answer 201

* Herpes varicella zoster virus infection * Chickenpox * Worldwide, all races, gender and age * Largely a childhood disease < 10 years of age * Incubation period 2-3 weeks * ** Remains in anterior horn cells and be reactivated as herpes zoster infection (shingles)

Question 202

Mode of transmission of varicella zoster?

Answer 202

* Highly contagious * Inhaled fomite droplets * Direct contact with the fluid from the open sores

Question 203

Used to diagnosis chickenpox/varicella zoster

Answer 203

Tzank smear

Question 204

Skin findings for chickenpox

Answer 204

* Pruritic red papules & vesicles to crusted ulcer * Commonly affected areas include trunk, back, face * Spreads distally (lesions usually start centrally - near bellybutton - then grow out peripherally) * Can involve palms soles and mouth * Remain infectious for 4-5 days until vesicles crusted

Question 205

What are varicella zoster - shingles?

Answer 205

• Reactivation of varicella virus infection manifests as a painful outbreak of papules and vesicle in a dermatome distribution

Question 206

Shingles, increasing incidence with...

Answer 206

* Age: average 55 y/o * Immunosuppression * Malignancy, especially from lymphoproliferative disorders and chemotherapy/radiotherapy * HIV/AIDS: eightfold increased incidence of HZ * Most cases triggering factors are not known

Question 207

What is prodrome?

Answer 207

``` Shingles may have a prodrome, meaning certain symptoms occur before specific symptoms of shingle occur: • pain in dermatome distribution • fever and headache • lymph nodes enlarged and tender • 1-3 day prior to rash ```

Question 208

Skin findings for varicella zoster-shingles

Answer 208

* Crops of red papules, progress to vesicles in a dermatome pattern * Thoracic, lumbar, facial * Lesions very painful Even after rash resolves you can have post-herpetic neuralgia: • Pain may persist for months or years

Question 209

Treatment for varicella zoster

Answer 209

* Acyclovir | * Prevention through vaccination

Question 210

What is impetigo?

Answer 210

* Superficial staph aureus skin infection; strep pyogenes may also be the culprit * Can occur at any age, but most common in children

Question 211

How is impetigo spread?

Answer 211

* Contagious | * Spread by close contact through primary breaks in skin or secondary involvement of rash or preexisting lesion

Question 212

Clinical presentation of impetigo

Answer 212

* Bullous (less common): * caused by an epidermolytic toxin produced at the site of intefection (bacteria produces toxin that causes epidermal cells to lyse) * causes intraepidermal cleavage below or within the stratum granulosum * Nonbullous

Question 213

Skin findings for impetigo

Answer 213

* Pustules and oozing patches * Golden yellow honey crusts or blisters (bullous impetigo) * Most often exposed areas such as the hands and face, or in skin folds (axilla)

Question 214

Golden yellow honey crusts or blisters observed in ...

Answer 214

Impetigo

Question 215

Microscopic appearance of impetigo...

Answer 215

Neutrophil filled subcorneal vesicle

Question 216

What is cellulitis?

Answer 216

* Bacterial infection of skin and subcutis | * Usually caused by strep pyogenes (2/3), and staph aureus (1/3)

Question 217

Skin findings for cellulitis

Answer 217

* Expanding area of redness, swelling, warmth, tenderness, blistering abscess, ulteration * Often fever and leukocytosis * Can ascend up lymphatics = lymphangitis * Infection involves lymphatics * Red line originates from the cellulitis leading to draining lymph nodes * Minor trauma to the skin is common cause * Seen commonly in peripheral vascular disease, diabetes, lymphedema, and alcohol predispose

Question 218

Treatment for cellulitis

Answer 218

Antibiotics

Question 219

What is scarlet fever?

Answer 219

• Streptococcus pharyngitis with erythrogenic toxic strains (a streptococcus infection - a toxin causes redness in affected person)

Question 220

Clinical findings of scarlet fever

Answer 220

* Fever * Sore throat * Lymphadenopathy * Headache * Vomiting * Strawberry tongue * Abdominal pain * Aches * Malaise

Question 221

Manifestation of strawberry tongue

Answer 221

Scarlet fever

Question 222

What are sand paper rash

Answer 222

* Rashes for scarlet fever | * Begins as scarlet blotches, progresses to look like sunburn with goose pimples

Question 223

Treatment for scarlet fever

Answer 223

Systemic antibiotic

Question 224

What's dermatophyte infections?

Answer 224

* Superficial fungal infection of the keratin of the stratum corneum, hair or nail * Three species: Microsporum, Trichophyton, and Epidermophyton * Spread is by contact, animals, or soil * Favors moist and warm conditions

Question 225

Skin findings for dermatophyte infections

Answer 225

* Expanding, erythematous, scaly, annular lesions with central clearing (ringworm) * Less common vesicles, bullae, pustules

Question 226

Treatment for dermatophyte infections

Answer 226

* Topical antifungals | * Systemic for severe or refractory cases

Question 227

Microscopic findings for dermatophyte infections

Answer 227

PAS stain will reveal fungal hyphae in the stratum corneum

Question 228

KOH (potassium hydroxide) prep

Answer 228

* Another test that can be done for dermatophyte infections * A scraping of the lesion placed on a slide in a drop of KOH * Visualization of fungal hyphae is a positive test

Question 229

What's Wood's lamp?

Answer 229

* A backlight, which will cause infected lesion to fluoresce * Pertains to dermatophyte infections * Can be used for differential diagnosis against psoriasis

Question 230

Clinical name for dermatophyte infection

Answer 230

• Tinea Buffet of tinea infections: • Tinea corporis - when fungal infection involves body • Tinea capitis - involves scalp • Tinea pedis - aka athlete's foot • Onychomycosis - fungal infection of nails. Less treatable when involves nails

Question 231

What is pityriasis versicolor?

Answer 231

* Superficial fungal infection by Malassezia furfur * Often young adults 20-40 * F:M, 2:1 * More common in warm climate * Children more common in tropics

Question 232

Skin findings for pityriasis versicolor

Answer 232

* Multiple, oval, well demarcated, hypo- or hyperpigmented macular lesions * Become confluent and extensive * Trunk and shoulders most common

Question 233

Microscopic findings for pityriasis versicolor

Answer 233

Yeast and short septate hyphae, spaghetti and meatballs

Question 234

Spaghetti and meatballs

Answer 234

Pityriasis versicolor

Question 235

Treatment for pityriasis versicolor

Answer 235

Tropical antifungals

Question 236

What is a candida infection?

Answer 236

* Persistent/recurrent infections of the skin, nails, and oropharynx * Fungal organisms with yeast and pseudohyphal forms * Candida albicans most common

Question 237

Predisposing factors for candida infection

Answer 237

* Immunosuppression * Diabetes * Cushings disease * Pregnancy * Malnutrition * HIV * Systemic steroid and antibiotics * Predelection for moist, occluded skin * Intertrigo (seen below the breast), occlusive dressings, diaper dermatitis

Question 238

Skin findings for candida infection

Answer 238

* Erythematous, pruritic, tender, painful rash | * In neonates, curd like pseudomembrane on an erythematous base

Question 239

Mucosal candiasis

Answer 239

* Oral thrush - white patches inside mouth * Angular chelitis - inflammation at corners of mouth * Vulvovaginal trush

Question 240

Chronic forms of candida infection frequently associated with...

Answer 240

Endocrinopathies

Question 241

What are scabies?

Answer 241

* Infestation by mite | * Sarcoptes scabiei

Question 242

Skin findings for scabies

Answer 242

* Papules and burrows between fingers or along the sides of the fingers, soles, and sides of the feet with excoriations and eczematous dermatitis * Also affects elbows, axillae, scrotum, penis, labia

Question 243

Transmission of scabies

Answer 243

Close personal contact and sexually transmitted

Question 244

What is pediculosis?

Answer 244

• An infestation of sucking lice that lay their eggs on hair shafts or in seams of clothing

Question 245

Species that infest humans to cause pediculosis...

Answer 245

* Pediculus humanus: capitus (headlice) and humanus (bodylice) * Pthirius pubis: public lice

Question 246

Transmission of pediculosis

Answer 246

direct contact

Question 247

Skin lesions associated with pediculosis

Answer 247

* Vary with immune sensitivity * From subclinical to papules, urticaria and pruritus * May become secondarily infected

Question 248

Treatment for pediculosis

Answer 248

* Topical insecticides: malathion, permethrin * Environment vacuumed, bedding, clothing * Combs and brushes cleaned

Question 249

What's actinic lentigo?

Answer 249

* Benign, irregular, pigmented macular lesions that involves sun-damaged skin of the middle aged and elderly * Fair skin Caucasians most at risk * 0.1 to > 1.0 cm * Not precancerous, needs no Rx

Question 250

Mimics lentigo maligna

Answer 250

Actinic lentigo

Question 251

What's vitiligo?

Answer 251

* Common acquired loss of pigment due to autoimmune destruction of melanocytes by cytotoxic T-cells * Peak incidence 10 and 30 years * More common in dark skin * 15-30% associated autoimmune disease

Question 252

Skin presentation of vitiligo.

Answer 252

Hyperpigmented macules enlarge and become confluent

Question 253

Microscopic presentation of vitiligo

Answer 253

Loss of melanocytes and melanin pigment. Perivascular lymphocytic infiltrate.

Question 254

What is melanocytic nevus?

Answer 254

* "nevus" = "birthmark" * Benign melanocytic neoplasm; acquired or congenital * Acquired - present in childhood and adolescence * Skin, nails, mucosa, conjunctiva, uveal tract * More common in pale skinned with light colored eyes * Caucasians average 15-40 nevi * Related to sun exposure (intermittent intense sunlight) during the first two decades of life. People who burn. * Rare cases develop melanoma

Question 255

In what type of people are melanocytic nevus more common in?

Answer 255

* Pale skinned with light colored eyes | * Caucasians average 15-40 nevi

Question 256

What's a junctional nevus?

Answer 256

* Ovoid to round, well circumscribed; light to dark brown, macular or slightly raised, up to 0.5 cm, regular border * Micro --> proliferaion begins in nests at the dermo-epidermal junction

Question 257

What's a compound nevus?

Answer 257

* Raised, often warty, often deeply pigmented; circumscribed with a regular border * Micro --> Nevus cells, still proliferating at the D-E junction, descent into the dermis and form nests

Question 258

What's an intradermal nevus?

Answer 258

* Raised * +/- pigment * May be dome shaped nodule, papillomatous, or pedunculated * Micro --> melanocytes are only found in nests in the dermis. Cells "mature" as they descend deeper into the dermis

Question 259

Congental Nevus

Answer 259

Risk of malignancy (if large) and can be covered with hair

Question 260

Blue nevus

Answer 260

* Collections of spindled dermal melanocytes | * Tyndall effect: blue light is scattered more passing through the dermis

Question 261

Halo nevus

Answer 261

A zone of HYPOpigmentation represents immunologic regression seen microscopically as an intense lymphocytic dermal infiltrate

Question 262

What's a dysplastic nevi?

Answer 262

* Melanocytic nevi with dysplastic melanocytic proliferation * Isolated solitary lesions of familial autosomal dominant syndrome * May progress to melanoma * Most remain clinically stable and never progress * In 36% of melanomas we find adjacent dysplastic nevi.

Question 263

Skin findings for dysplastic nevi

Answer 263

* Large (>6mm) * Irregular shaped * Ill-defined border * Variable shades of browns, tans, and pink * May be erythematous surround * Not all clinically atypical nevi are dysplastic

Question 264

What's dysplastic nevus syndrome?

Answer 264

``` • Inherited autosomal dominant syndrome • Normal at birth, develop large numbers of nevi in early childhood • Few to > hundred • Acquire atypical clinical features around puberty. Predilection for trunk, face, and arms; also buttocks, genitalia, breasts, scalp. • Histology show dysplastic features. • Increased incidence of melanoma; 50% by age 60. • Five dysplastic nevi – relative risk for melanoma increases to 46%. ```

Question 265

What's malignant melanoma?

Answer 265

Malignant transformation of melanocytes.

Question 266

Highest incidence of malignant melanoma occurs in...

Answer 266

* Fair skinned caucasians - highest incidence. * The incidence increasing. * 1 in 50 born in the US in 2010. * 1 in 1500 in 1935. * Mean age 52 years; 35% < 45 years of age.

Question 267

Prognosis of malignant melanoma

Answer 267

* Early detection of melanoma - high cure rates after excision. * Prognosis directly related to size and depth of invasion.

Question 268

Etiology and pathogenesis of malignant melanoma

Answer 268

* Sun exposure; Genetic predisposition. | * Germline mutations in the chromosome 9p21 tumor suppressor gene, account for 40% of hereditary melanoma cases.

Question 269

Risk Factors for Development of Melanoma

Answer 269

* Genetic markers (CDKN2a mutation) * Skin type I/II (light skin) * Family history of dysplastic nevi or melanoma * Personal history of melanoma * Ultraviolet irradiation; childhood sunburns, intermittent burning exposures * Number (>50) and size (>5 mm) of melanocytic nevi * Congenital nevi * Number of dysplastic nevi (>5) * Dysplastic melanocytic nevus syndrome

Question 270

Melanoma signs, ABCDE rule

Answer 270

* Asymmetry: 1/2 unlike the other * Border: irregular, poorly defined edges * Color: not uniform; all shades of brown, black, pink * Diameter: greater than 6.0 mm * Elevation & enlargement: change in size or shape

Question 271

Growth phases of melanoma

Answer 271

Most melanomas show an initial radial growth phase followed by a subsequent vertical phase. * Radial growth: cells are running up and down rete, with upward invasion into epidermis; cells spread out laterally * Vertical growth phase: loose E-cadherin and express N-cadherin

Question 272

What is superficial spreading melanoma?

Answer 272

* 70% of melanomas * Any site, lower extremities, trunk * Radial growth phase - Months to 2 years

Question 273

Microscopic appearance of superficial spreading melanoma

Answer 273

* Neoplastic melanocytes proliferate along D-E junction * Pagetoid invasion of epidermis * Severe atypia. Inflammation * Gas not invaded dermis, so this is called melanoma in situ

Question 274

What's Nodular melanoma?

Answer 274

* 15% of melanomas * Any site, trunk, head, neck * Arises rapido; NO RADIAL GROWTH PHASE * Brown, black, or pink, nodule

Question 275

What's lentigo maliga melanoma?

Answer 275

* Occurs in older patients with heavily sundamaged skin; mean age 65 * Flat, irregular variably pigmented macule or patch * Face, neck, dorsa of hand * 5% of melanomas * Radial growth phase - very long; years

Question 276

What's Acral Lentiginous melanoma?

Answer 276

* 5-10% of melanomas * Asians, Africans, and African Americans most common * 50-70% of the melanomas found in these populations * Palms, soles, subungual (nails?) * Radial growth phase - months to years

Question 277

What is mucosal melanoma?

Answer 277

* Can be seen in the mouth | * Biopsy patient if present

Question 278

What's Amelanotic melanoma?

Answer 278

• Little to no pigment - bizarre giant cells with prominent nucleoli.

Question 279

Which type of melanoma is most common?

Answer 279

Superficial spreading melanoma (70% of melanomas)

Question 280

Which type of melanoma is most commonly observed in palms, soles, subungual (nails)?

Answer 280

Acral lentiginous melanoma

Question 281

Which type of melanoma is most commonly observed on the face, neck, dorsa of hand?

Answer 281

Lentigo maligna melanoma

Question 282

Which type of melanoma affects any site, but more commonly the trunk, head, neck?

Answer 282

Nodular melanoma

Question 283

Which type of melanoma affects any site, but more commonly the lower extremities, trunk?

Answer 283

Superficial spreading melanoma

Question 284

Compare and contrast the radial growth phases of the different types of melanoma

Answer 284

* Superficial spreading melanoma --> radial growth phase: months to 2 years * Nodular melanoma --> arises rapidly, no radial growth phase * Lentigo maligna melanoma --> radial growth phase: very long; years * Acral lentiginous melanoma --> growth phase: months to years

Question 285

What is staging?

Answer 285

* T Staging is based on tumor thickness and +/- ulceration. * T1: < 1.0mm * T2: 0.1-2.0mm * T3: 2.01-4.0mm * T4: >4.0mm

Question 286

Treatment for melanoma

Answer 286

* Surgical excision with 1.0 cm. Margin * Sentinel node biopsy in lesions > 1.0mm thickness * Complete lymph node dissection for metastatic disease * Chemotherapy, immunotherapy for higher stage disease

Question 287

Survival rates for melanoma (general idea)

Answer 287

* Lymph node involvement and metastasis indicates very poor prognosis. * Presence of any mitosis (?) means only 10% survival.

Question 288

What is seborrheic keratoses?

Answer 288

* Most common BENIGN epithelial tumor seen in middle-aged or older * Trunk most common, also extremities, head, and neck

Question 289

Skin findings for seborrheic keratoses

Answer 289

* Sharply delineated * Round or oval * Brown-black or flesh-colored warty plaques * Millimeters to several centimeters

Question 290

Activitating mutations in which growth factor is though to drive the growth of the tumor in seborrheic keratoses?

Answer 290

Fibroblast growth factor receptor-3

Question 291

Seborrheic keratoses occur explosively in large numbers associated with gastric adenocarcinoma...

Answer 291

Leser-Trelat sign

Question 292

Microscopic appearance of seborrheic keratoses

Answer 292

* Exophytic and sharply demarcated proliferation of small basal like keratinocytes * Hyperkeratotic with horn cysts

Question 293

What is dermatoheliosis?

Answer 293

* Means chronic photodamage * Involves epidermis, vascular system, and dermal connective tissue * Severity depends on duration, intensity, skin color, tanning capacity

Question 294

What is Fitzpatrick's skin phototypes?

Answer 294

• Lists different skin types and how they tan/damage

Question 295

Which type in Fitzpatrick's skin phototypes is most susceptible to chronic photodamage (dermatoheliosis)?

Answer 295

* Type 1 will get the worst * Pale skin, blue/hazel eyes, blond/red hair * Always burns, does not tan * Photodamage occurs mostly in types 1-3, and also 4 with heavy exposure * SPT I and II make up 25% of the white population in the US

Question 296

Which is the most damaging UV radiation?

Answer 296

UVB

Question 297

Pathogenesis of chronic photodamage/dermatoheliosis

Answer 297

UVB is the most damaging UV radiation

Question 298

Skin findings for chronic photodamage/dermatoheliosis

Answer 298

* Epidermal atrophy * Wrinkles * Telangiectasia * Hypo/hyperpigmentation * Solar lentigines

Question 299

Microscopic appearance of chronic photodamage/dermatoheliosis

Answer 299

* Acanthosis hyperkeratosis | * Elastosis

Question 300

Treatment for chronic photodamage/dermatoheliosis

Answer 300

* Protective sunblocks * Change of behavior * Topical sun-protective lotions * SPT I and II persons should avoid the peak hours of sun 10-2:00

Question 301

What is actinic keratosis?

Answer 301

* Sun induced dysplasia of the epidermis. * Excessive exposure to UV radiation, particularly UVB. * Males > females * Middle aged or elderly * Fair complexions that burn rather than tan * 2-5% of cases develop an invasive squamous cell carcinoma. Numerous lesions for many years have higher risk. * Predictor of risk for melanoma and other skin cancers.

Question 302

2-5% of cases of Actinic keratosis develop this...

Answer 302

* Invasive squamous cell carcinoma * Numerous lesions for many years have higher risk * Predictor of risk for melanoma and other skin cancers

Question 303

Appearance of actinic keratosis

Answer 303

* Erythematous or yellow-brown, flat, rough, scaly papules * 2 mm to > cm * Sun exposed surfaces: face and neck, dorsal hands and forearms * Sun damaged of surrounding skin

Question 304

Microscopic appearance of actinic keratosis

Answer 304

Epithelial dysplasia with alternating parakeratosis and orthokeratosis

Question 305

Etiology for squamous cell carcinoma in situ

Answer 305

* Ultraviolet radiation * Chronic arsenicism * Immunosuppression * Ionizing radiation, HPV, PUVA Rx * 3-5% progress to invasive carcinoma

Question 306

Treatment for squamous cell carcinoma in situ

Answer 306

* Excision * Mohs micrographic surgery * Histopathologic evaluation to exclude invasive SCC

Question 307

What's invasive squamous cell carcinoma?

Answer 307

* Malignant tumor of keratinocytes, arising in the epidermis * Usually arises in epidermal precancerous lesions * M>F, except legs * Age of onset - >55 in the US * 20s & 30s in Florida, Southwest, Southern California, Australia, New Zealand * Incidence varies with sun exposure * Continental US: 7-12/100,000 * Hawaii: 62/100,000 whites

Question 308

Aggressiveness of invasive squamous cell carcinoma

Answer 308

* Aggressiveness varies with etiology and differentiation * Sun induced lesions low rate of metastasis * Immunosuppressed --> more aggressive more often metastasizes

Question 309

Skin findings for invasive squamous cell carcinoma

Answer 309

* Indurated erythematous, yellowish or skin tone papule, plaque or nodule * Keratotic scale * Eroded or ulcerated, firm elevated margin

Question 310

Etiology of invasive squamous cell carcinoma

Answer 310

* Ultraviolet radiation * HPV * Immunosuppression * Chronic inflammatory and scarring conditions * Industrial carcinogens * Inorganic arsenic

Question 311

Cellular process in the development of invasive squamous cell carcinoma

Answer 311

* Multistep process that involves: * p53 * cyclin D1 * human telomerase reverse transcriptase * p16 * thrombospondin * Dysregulation of p53 and other apoptotic regulatory proteins

Question 312

Factors for high risk of invasive squamous cell carcinoma

Answer 312

* diameter > 2cm * depth > 4mm * bone, muscle, nerve involvement * location on ear, lip * tumor arising in scar * high grade * immunosuppression * absence of inflammation

Question 313

Treatment for invasive squamous cell carcinoma

Answer 313

* Conventional surgical excision * Mohs micrographic surgery * Radiation therapy

Question 314

What's the most common invasive cancer in humans?

Answer 314

Basal cell carcinoma

Question 315

What is Basal cell carcinoma?

Answer 315

* Most common invasive cancer in humans; 1 million per yer in US * Slow growing, locally invasive, and destructive; METASTASIS rare * Tendency to sun-exposed sites and in lightly pigmented people * Males > females, usually > 40 years * Increased and younger in immunosuppression and inherited defects in DNA repair (xeroderma pigmentosum)

Question 316

Pathogenesis for basal cell carcinoma

Answer 316

* Derived from an undifferentiated pluripotent epithelial germ cell * Exposure to UVL, particularly UVB induces mutations in tumor suppressor genes * Also arise in scars, stasis ulcers, surgical, burn, and post vaccination, and healed infectious diseases such as leuishmania and chickenpox

Question 317

Clinical types of basal cell carcinoma

Answer 317

* Nodular * Ulcerating * Pigmented variant * Superficial variant * Sclerosing variant

Question 318

Treatment for basal cell carcinoma

Answer 318

* Surgical excision * Mohs micrographic surgery * Electrodesiccaiton * Curettage

Question 319

Microscopic appearance of basal cell carcinoma

Answer 319

* Proliferating monotonous hyperchromatic, basaloid cells attached to epidermis * Peripheral palisading * Infrequent mitoses

Question 320

Pheripheral palisading is important in the diagnosis for...

Answer 320

Basal cell carcinoma

Question 321

What is Kaposi's sarcoma?

Answer 321

• Multifocal tumor of endothelial origin development linked to Human herpesvirus (HHV)-8 infection

Question 322

Compare the clinical variants of Kaposi's sarcoma

Answer 322

* Classical KS - extremities of old mediterranean male, slow growing * Endemic African KS - Central African countries; rapidly progressive lymphadenopathic variant, extracutaneous sites * AIDS-related KS - rapidly progressive form with early involvement of extracutaneous sites * KS associated with immunosuppressive therapy - organ transplant recipients. Course varies from slow or rapid

Question 323

Treatment for Kaposi's sarcoma

Answer 323

Chemotherapy and radiation therapy

Question 324

Small, reddish-blue macules or flat plaques, often multiple, gradually enlarge. May become nodular, pigmented, coalesce or fungate.

Answer 324

Kaposi's sarcoma

Question 325

Microscopic appearance of kaposi's sarcoma

Answer 325

Spindle cell proliferation with blood percolating between slits

Question 326

What is Langerhans Cell Histiocytosis?

Answer 326

* Group of idiopathic disorders characterizes by infiltration of tissues by Langerhans cells. * Varies from localized self-healing forms to generalized and fatal

Question 327

Pathogenesis of Langerhans cell Histiocytosis

Answer 327

* Unclear * Debate whether LCH is a neoplasm, a reactive disorder, or immune dysfunction * Viral involvement?

Question 328

Clinical syndromes of Langerhans Cell Histiocytosis

Answer 328

* Eosinophilic granuloma: unifocal skin, mucous membranes, bone, or soft tissue lesions; childhood and young adult * Hand-Schuller-Christian: chronic, progressive multifocal form of LCH; childhood and adult * Letterer-Siwe Disease: the most aggressive multifocal LCH form, with skin and internal organ involvement. Infant and child

Question 329

Which of the Langerhans Cell Histiocytosis syndromes is the most aggressive?

Answer 329

* Letterer-Siwe-Disease * Mutlifocal * Skin and internal organ involvement * Infant and child

Question 330

Single system disease of Langerhans Cell Histiocytosis

Answer 330

* Eosinophilic granuloma: unifocal | * Hand-Schuller-Christian disease: multifocal

Question 331

Multisystem disease of Langerhans Cell Histiocytosis

Answer 331

* Letterer-Siwe Disease * And more extensive presentations of Hand-Schuller-Christian disease ** Can be low risk (involve skin, bone, lymph node, pituitary) or high risk (involve hematopoietic system, lungs, liver, spleen)

Question 332

Skin findings range from soft tissue swelling, to dermatitis to papules, pustules, erosions, and shallow punched out ulcers

Answer 332

Langerhans cell histiocytosis

Question 333

How many bones comprise the skeletal system?

Answer 333

206 bones connect by joints

Question 334

Inorganic mineral of skeletal system consists mainly of...

Answer 334

Calcium hydroxyapatite

Question 335

Organic portion of the skeletal system includes...

Answer 335

The bone cells and osteoid

Question 336

What are osteoprogenitor cells

Answer 336

* Pluripotent mesenchymal stem cells found in the vicinity of all bony surfaces * When appropriately stimulated by growth factors they produce offspring that differentiate into osteoblasts

Question 337

What are osteoblasts

Answer 337

• Synthesize, transport, and arrange the many proteins of matrix and initiate the process of mineralization

Question 338

What are osteoclasts?

Answer 338

Responsible for bone resorption

Question 339

What are osteocytes?

Answer 339

* Help to control calcium and phosphate levels in the microenvironment (responsible for homeostasis) * Detech mechanical forces and translate them into biologic activity

Question 340

What factors regulate bone remodeling?

Answer 340

* RANK * RANK Ligand (RANKL) * Osteoprotegerin

Question 341

What is RANK?

Answer 341

* Receptor activator for nuclear factor kB * Member of the TNF family * Expressed on cell membranes of preosteoclasts and mature osteoclasts * Stimulated by RANKL

Question 342

What is RANK Ligand (RANKL)?

Answer 342

* Expressed by osteoblasts and marrow stromal cells | * Stimulates RANK which leads to activation of NF-kB which in turn stimulates osteoclasts

Question 343

What is osteoprotegerin?

Answer 343

Blocks the actions of RANKL

Question 344

RANK and RANKL relation to bone resorption

Answer 344

* RANKL present on osteoblasts * RANK present on osteoclasts and preosteoclasts * Increase in RANK and RANKL = increase in bone resorption

Question 345

What is osteogenesis imperfecta?

Answer 345

* AKA brittle bone disease * a phenotypically diverse disorder caused by deficiencies in the synthesis of type 1 collagen * Principally affects bone, but also impacts other tissues rich in type 1 collagen (joints, eyes, ears, skin, and teeth) * Usually results from autosomal dominant mutations in the genes that encode the alpha1 and alpha2 chains of type 1 collagen.

Question 346

Caused by deficiencies in the synthesis of type 1 collagen

Answer 346

Osteogenesis imperfecta

Question 347

Most common inherited disorder of connective tissue.

Answer 347

Osteogenesis imperfecta

Question 348

Usually results from autosomal dominant mutations in the genes that encode the alpha 1 and alpha 2 chains of type 1 collagen.

Answer 348

Osteogenesis imperfecta

Question 349

Subtypes of osteogenesis imperfecta

Answer 349

* Type I, or mild OI, is the most common form. Persons with this type can live a normal lifespan. * Type II is a severe form that usually leads to death in the first year of life. * Type III is also called severe OI. Persons with this type have many fractures starting very early in life and can have severe bone deformities. Many become wheelchair bound and usually have a somewhat shortened life expectancy. * Type IV, or moderately severe OI, is similar to type I, although persons with type IV often need braces or crutches to walk. Life expectancy is normal or near normal.

Question 350

What's the most common form of osteogenesis imperfecta?

Answer 350

* Type I. | * Persons with this type can live a normal lifespan.

Question 351

What's the most severe form of osteogenesis imperfecta?

Answer 351

* Type III (severe OI) * Persons with this type have many fractures starting very early in life and can have severe bone deformities * Many become wheelchair bound and usually have a somewhat shortened life expectancy.

Question 352

The fundamental abnormality in osteogenesis imperfecta is...

Answer 352

* Too little bone. | * Body is not laying down enough matrix to form proper bone.

Question 353

Classic gross finding of blue sclera is a flag for...

Answer 353

osteogenesis imperfecta

Question 354

Most common disease of the growth plate.

Answer 354

Achondroplasia

Question 355

Most common form of dwarfism.

Answer 355

Achondroplasia

Question 356

What is Achondroplasia?

Answer 356

* Most common form of dwarfism; affects all bones which undergo endochondral ossification * Autosomal dominant; almost 80% are new mutations and most of these are paternally derived * Caused by an activating point mutation in fibroblast frowth factor receptor 3 (FGFR3)

Question 357

What is Thanatophoric dwarfism?

Answer 357

* Lethal variant of dwarfism * Affects 1 in every 20,000 live births * Caused by missense or point mutations in FGFR3 * Has extreme shortening of limbs, frontal bossing of the skull, extremely small thorax

Question 358

What is osteopetrosis?

Answer 358

* AKA marble bone disease and Albers-Schonberg disease * A group of rare genetic diseases that are characterized by abnormal osteoclast function * The term osteopetrosis reflects the stonelike quality of the bones, but the bones are abnormally brittle and fracture easily, like a piece of chalk. They lack a medullary canal and Ehrlenmeyer flask deformity is common. * The autosomal recessive severe type and the autosomal dominant mild type are the most common variants.

Question 359

In which congenital disorder of bone and cartilage lacks a medullary canal and has a Ehrlenmeyer flask deformity?

Answer 359

Osteopetrosis

Question 360

Other effects of osteopetrosis includes..

Answer 360

* cranial nerve palsies (due to compression of nerves within cranial foramina) * infections (due to reduced marrow size and activity) * hepatosplenomegaly (due to extramedullary hematopoiesis)

Question 361

What is osteoporosis?

Answer 361

* Characterized by porous bones and decreased bone mass * Postmenopausal women are most commonly affected, and Caucasian women more than African-American women * In postmenopausal women, bones with high surface area, such as vertebral bodies, become thinned and the trabeculae are fine. * Kyphosis (curving of the spine) and rib fractures are common.

Question 362

Treatment for osteoporosis.

Answer 362

* Exercise * Appropriate calcium and vitamin D intake * Pharmacologic agents, most commonly bisphosphonates

Question 363

What happens in menopause that increases risk for osteoporosis?

Answer 363

* Decreased serum estrogen * Increased IL-1, IL-6, TNF levels * Increased expression of RANK, RANKL * Increased osteoclast activity

Question 364

Aging and osteoporosis

Answer 364

* Decreased replicative activity of osteoprogenitor cells * Decreased synthetic activity of osteoblasts * Decreased biologic activity of matrix-bound growth factors * Reduced physical activity

Question 365

Honeycomb pattern

Answer 365

• Osteoporosis, much, much more porous than normal bone matrix.

Question 366

Thin trabeculae (thin bony spaces with lots of fat and marrow in between), unfilled spaces cause porous appearance in this...

Answer 366

Osteoporosis

Question 367

What is Paget disease of bone?

Answer 367

* Also known as osteitis deformans. * Separated into three phases: an initial osteolytic stage, followed by a mixed osteolytic/osteoblastic phase, and ending in a quiescent osteosclerotic stage. * Common in whites in England, France, Austria, regions of Gernamny, Australia, New Zealand, and the United States.

Question 368

What is the hallmark of Paget's disease?

Answer 368

• Mosaic pattern of lamellar bone, which is linked to a jigsaw puzzle and is produced by prominent cement lines that anneal haphazardly oriented units of lamellar bone.

Question 369

Most common cause of rickets and osteomalacia?

Answer 369

• Malabsorption of vitamin D

Question 370

What is rickets?

Answer 370

Rickets occurs in children and results in derangement of bone growth.

Question 371

What is osteomalacia?

Answer 371

Osteomalacia occurs in adults and results in remodeled bone which is poorly mineralized. Osteopenia and insufficiency fractures result.

Question 372

In children with rickets you can experience...

Answer 372

1. Genu varum - bow leggedness 2. Windswept deformity 3. Genu valgum - knock knees

Question 373

Histological appearance of rickets and osteomalacia

Answer 373

* Normal bone has slight areas of remodeling | * In osteomalacia and rickets, there are large areas of poor mineralization, which can lead to fracture.

Question 374

What is hyperparathyroidism?

Answer 374

* Increased PTH concentrations are detected by receptors on osteoblasts, which release factors that stimulate osteoclast activity. * Skeletal manifestations of hyperparathyroidism are caused by unabated osteoclastic bone resorption. * The entire skeleton can be affected. * The bone loss leads to microfractures and secondary hemorrhages that elicit an influx of macrophages and an ingrowth of reparative fibrous tissue, creating a mass of reactive tissue, known as a brown tumor.

Question 375

PTH concentrations are detected by receptors on ...

Answer 375

Osteoblasts

Question 376

Increased bone cell activity + peritrabecular fibrosis + cystic brown tumors =

Answer 376

Generalized osteitis fibrosa cystica (von Recklinghausen disease of bone)

Question 377

What is a pathologic fracture?

Answer 377

If the break occurs in bone altered by a disease process.

Question 378

What is a stress fracture?

Answer 378

A slowly developing fracture that follows a period of increased physical activity in which the bone is subjected to new repetitive loads.

Question 379

Classification of fractures

Answer 379

* Complete or incomplete * Closed (simple) when the overlying tissue is intact * Compound, when the fracture site communicates with the skin surface * Comminuted when the bone is splintered * Displaced when the ends of the bone at the fracture site are not aligned

Question 380

Process of fractures and healing...

Answer 380

* When you fracture a bone, you create a hematoma. * Pooling blood around ends of fracture allows bone building proteins to gather. * Osteoprogenitor cells are activated to make osteoblasts. * First lay down cartilage in long bones (endochondral ossification) or fibrous tissue (intramembranous ossification). * Cartilage lets bone fill in to create a fracture callous (bony callous).

Question 381

Nonunion of fractures

Answer 381

Displaced (ends of bones at fracture site not aligned) and comminuted (bone is splinteered) fractures frequently result in some deformity, and inadequate immobilization permits constant movement at the fracture site, so that the normal constituents of callus do not form, resulting in delayed union and nonunion.

Question 382

What is pseudoarthrosis?

Answer 382

* False joint * If a nonunion allows too much motion along fracture gap, the central portion of the callus undergoes cystic degeneration, and the luminal surface can actually become lined by synovial-like cells, creating a false joint. * Scribe: [...] no proper callous formation/healing... these cases often need repeat surgery... ends of the bone do not join and you get what is called a false joint.

Question 383

What is avascular necrosis?

Answer 383

* Osteonecrosis * Infarct of bone or marrow which occurs in the medullary cavity * Fracture, corticosteroid use, and idiopathic causes are most common * Geographic in appearance * Eventually results in collapse of the bone with possible distortion and fracture of the bone and sloughing of the articular cartilage.

Question 384

A wedge shape infarct is commonly observed in...

Answer 384

• Avascular necrosis (osteonecrosis)

Question 385

Histology of osteonecrosis

Answer 385

* Dead bone with empty lacunae * Fat necrosis * Insoluble calcium soaps

Question 386

What is osteomyelitis?

Answer 386

* Bone infection. * Most common infectious agent is S. aureus. * Common infectious agent seen in sickle cell-disease is Salmonella. * Acute, subacute, and chronic * Acute is almost always caused by bacteria, which reach the bone via 3 routes - hematogenous, direct extension, and trauma.

Question 387

How to distinguish between tumor and osteomyelitis?

Answer 387

We know it is not a tumor if, upon inserting a needle, pus sprays everywhere.

Question 388

What are bone tumors?

Answer 388

* Very diverse and rare group of diseases * Accurate diagnosis is essential for survival and also to maintain optimal function * Correlation with radiological images is of utmost importance * Classification is based on cell of origin, connective tissue matrix they produce and differentiate

Question 389

Clinical findings for bone forming tumors

Answer 389

* Common lesions are most often asymptomatic and are detected as incidental findings. * Some tumors produce pain and are slow growing - but pain does not always indicate malignancy.

Question 390

What may be the first evidence of a bone tumor?

Answer 390

Pathologic gracture

Question 391

Multidisciplinary team required to diagnose and treat patients with bone tumors...

Answer 391

* Oncologist * Radiologist * Pathologist to read biopsy * Orthopedic surgeon

Question 392

Tumors occur at different places depending on age...

Answer 392

* Younger patient --> more likely to be primary tumor | * Older patient --> more likely from metastasis

Question 393

Osseous lesions must be __-__% destructive before they can be seen on plain films

Answer 393

40-50%

Question 394

Purpose of x-rays

Answer 394

• to localize and assist in the biopsy of a lesion

Question 395

Purpose of computed tomography (CT) scans

Answer 395

• Good evaluation of bone, but not soft tissue

Question 396

Purpose of magnetic resonance imaging (MRI)

Answer 396

• Good evaluation of soft tissue but not bone

Question 397

What is osteoma?

Answer 397

* Bosselated, round to oval sessile tumors that project from the surface of the cortex * M:F ratio approximately 2:1 * Usually solitary, detected in middle age * Most often arise on or inside the skull and facial bones * Multiple osteomas are seen in the setting of Gardner syndrome * Of little clinical significance unless a vital structure is impinged upon

Question 398

Xray findings for osteoma

Answer 398

• dense radioopaque circumscribed mass

Question 399

What is osteoid osteoma?

Answer 399

* Classic lesion * 75% occur between 5 and 25 years old * M:F ratio 2:1 to 3:1 * Any bone; commonly long tubular bones, diaphyseal, cortical * Histologically, the nidus is surrounded by osteoblasts which are variably mineralized

Question 400

Bone forming tumor characterized by painful lesion (relieved by aspirin), and pain most common at night.

Answer 400

Osteoid osteoma

Question 401

X-ray finding for osteoid osteoma

Answer 401

Central lucent nidus surrounded by dense sclerosis

Question 402

Treatment for osteoid osteoma

Answer 402

Excision of nidus is curative

Question 403

What is osteoblastoma?

Answer 403

* Same thing as osteoid osteoma, except it's larger than 2 cm. * Occurs between 10 and 35 years. * Axial skeleton - spine common. * Pain is NOT relieved by aspirin * X-ray is not specific - mimics other lesions * Complete excision is curative-rare local aggressiveness. * Again, size >2cm - histologically identical to osteoid osteoma

Question 404

Histologically identical to osteoid osteoma, except size > 2cm

Answer 404

Osteoblastoma

Question 405

Most common primary malignant tumor of bone.

Answer 405

Osteosarcoma

Question 406

Skip lesions are prognostically grave for this disease...

Answer 406

Osteosarcoma

Question 407

What is osteosarcoma?

Answer 407

* Most common primary malignant tumor of bone * Bimodal age distribution - second and fifth decades * Site of predilection is proportional to the rate of skeletal growth (distal femur and proximal tibia are the commonest sites) * Often present clinically as pain present for several months. * Radiographic presentation can vary greatly (lytic or sclerotic or mixed). * Accompanying soft tissue mass is common.

Question 408

Site of predilection is proportional to the rate of skeletal growth (distal femur and proximal tibia are commonest sites)

Answer 408

Osteosarcoma

Question 409

Thin lace like woven osteoid/bone is hallmark of this...

Answer 409

Osteosarcoma

Question 410

Most common treatment modality for osteosarcoma

Answer 410

* Chemotherapy followed by a limb sparing resection and post operative chemotherapy * Aggressive and highly lethal neoplasm

Question 411

Common sites of metastasis include the lungs (most common), liver, and skeletal system for ...

Answer 411

osteosarcoma

Question 412

Most common primary benign bone tumor

Answer 412

Osteochondroma (Exostosis)

Question 413

What is osteochondroma?

Answer 413

* Cartilaginous lesions * Most common primary benign bone tumor * 85% are solitary; the remainder are part of the multiple hereditary exostosis syndrome, an autosomal dominant syndrome * Inactivation of EXT1 and EXT2 is seen in syndromic and hereditary osteochondromas * Develop only in bones with enchondral ossification * Present more commonly in the syndrome because of bony deformity

Question 414

Treatment for osteochondroma

Answer 414

Excision is curative

Question 415

Histologic appearance of osteochondroma

Answer 415

* Pedunculated or sessile * Range in size from 1-20 cm * Cap is constructed of hyaline cartilage * Cartilage undergoes endochondral ossification, resulting in the bone in the center of the lesion

Question 416

Neoplasm consisting of mature hyaline cartilage

Answer 416

Enchondroma

Question 417

Enchondromas can appear as part of syndromes involving...

Answer 417

* Multiple enchondromas - Ollier's Disease | * Enchondromas and soft tissue hemangiomas - Mafucci's syndrome

Question 418

X-ray appearance --> radiolucent lesions with ring like calcification

Answer 418

Enchondroma

Question 419

Histologic appearance of enchondroma

Answer 419

Mature hyaline cartilage (grey-blue) with calcifications

Question 420

Enchondroma is most commonly found on...

Answer 420

* Encondromas-metaphyseal ends of tubular bones | * Common in hands and feet

Question 421

What is chondrosarcoma?

Answer 421

* Malignant tumor of cartilage * Second most common primary malignant tumor of bone * Adults - 40 and older. Males more common * Location: pelvis, ribs, shoulder, long bones * Dull aching pain waking the patient at night * Classification - Location: intramedullary and juxtacortical * Survival and tumor progression are based on grade.

Question 422

Histology: conventional, clear cell, mesenchymal, and dedifferentiated

Answer 422

Chondrosarcoma

Question 423

Hypercellular lesion containing numerous malignant chondrocytes in a pale grey cartilaginous background is observed in this disease...

Answer 423

Chondrosarcoma

Question 424

Chondrosarcoma may appear in these two locations...

Answer 424

1. Intramedullary (center) | 2. Juxtacortical (edge)

Question 425

What is a benign lesion of bone made up of fibro-osseous tissue proliferating in an irregular manner; some think of as localized developmental arrest...

Answer 425

Fibrous dysplasia • It is a fibro-osseous lesion

Question 426

What are the two forms of fibrous dysplasia?

Answer 426

• Monostotic - Single bone, 70% of all cases) • Polyostotic - Multiple bones, 27% of all cases

Question 427

What is McCune-Albright syndrome?

Answer 427

• 3% of cases of fibrous dysplasia is part of McCune-Albright syndrome Characterized by: • Polyostotic fibrous dysplasia • Precocious puberty • Cafe-au-lait spots Due to a somatic mutation of guanine-nucleotide binding protein (G-protein), encoded by the GNAS gene. This has a female predominance.

Question 428

Which gender is more likely to get Albright's syndrome?

Answer 428

Female

Question 429

Fibrous dysplasia affects which gender more?

Answer 429

* Males more than females | * Young adults

Question 430

Which bones are involved in fibrous dysplasia?

Answer 430

• Any bone can be involved

Question 431

X-ray appearance of fibrous dysplasia

Answer 431

X-ray lucent lesion with "ground glass" appearance

Question 432

How frequently does fibrous dysplasia transform to sarcoma?

Answer 432

RARE

Question 433

Fibrous stroma containing osteoid and woven bone - "Chinese letters" associated with which disease?

Answer 433

Fibrous dysplasia Note: we almost never see mitotic figures in the background, as it is generally benign

Question 434

Malignant small blue cell tumor

Answer 434

Ewing sarcoma

Question 435

Promiscuous gene (EWS), characterized by unique chromosomal translocation t(11;22)(q24;q12)(EWS-FLI-1)

Answer 435

Ewing sarcoma

Question 436

Most common chromosomal translocation for Ewing sarcoma

Answer 436

t(11;22) Result is a fusion of EWS gene to FLI1 gene. EWS is a promiscuuous gene because it has a lot of partners.

Question 437

Treatment for Ewing sarcoma

Answer 437

* Radiation and chemotherapy | * 5 year survival about 70%

Question 438

Commonly affected areas of the skeleton for Ewing sarcoma

Answer 438

Axial and appendicular skeleton

Question 439

Permeative with "onion-skin" periosteal reaction observed in which disease...

Answer 439

Ewing Sarcoma

Question 440

Histological appearance of Ewing Sarcoma

Answer 440

* Sheets of small round blue cells, not much larger than lymphocytes make up the lesion. * Scant cytoplasm with white halos due to glycogen production * Necrosis may be prominent

Question 441

Most common joint disorder

Answer 441

Osteoarthritis

Question 442

In what age range is osteoarthritis most commonly seen?

Answer 442

* Most commonly seen in patients over 65 | * Most commonly appears with advancing age and without cause (primary OA)

Question 443

Which joint disorder is primarily a degenerative disorder of articular cartilage?

Answer 443

Osteoarthritis • Chondroid matrix is broken down

Question 444

What is eburnation?

Answer 444

Eburnation is identified as holes in the articular surface

Question 445

Histologic appearance of osteoarthritis

Answer 445

* The surface cartilage appears chewed, compatible with the gross finding of eburnation * Eburnation: holes in the articular surface

Question 446

Which joint disorder is a systemic, chronic inflammatory autoimmune disease which principally attacks the joints?

Answer 446

Rheumatoid Arthritis

Question 447

When extraarticular involvement develops in this joint disorder, it may resemble lupus or scleroderma.

Answer 447

Rheumatoid arthritis

Question 448

What happens in rheumatoid arthritis

Answer 448

Causes a nonsuppurative proliferative synovitis that frequently progresses to destroy articular cartilage and underlying bone with resulting disabling arthritis.

Question 449

Incidence of rheumatoid arthritis

Answer 449

* Relatively common condition, with a prevalence of approximately 1% * Three to five times more common in women than in men * Peak incidence is in the second to fourth decades of life

Question 450

Pathologic changes in rheumatoid arthritis are caused mainly by...

Answer 450

Cytokine-mediated inflammation, with CD4+ T cells being the principal source of the cytokines

Question 451

Risk factors for rheumatoid arthritis

Answer 451

* Estimated that 50% of the risk of developing RA is related to genetic factors * Susceptibility to RA is linked to the HLA-DRB1 locus * Inflammatory and environmental insults such as smoking and infections may induce the citrullination of some self proteins, creating new epitopes that trigger autoimmune reactions.

Question 452

Histologic appearance of rheumatoid arthritis

Answer 452

* On histologic examination, the affected joints show chronic papillary synovitis * The classic appearance is that of a pannus, formed by proliferating synovial lining cells admixed with inflammatory cells, granulation tissue, and fibrous connective tissue

Question 453

Incidence of gout

Answer 453

Affects about 1% of the population, and shows a predilection for males.

Question 454

What causes gout?

Answer 454

* Caused by excessive amounts of uric acid, an end product of purine metabolism, within tissues and body fluids * Monosodium urate crystals precipitate from supersaturated body fluids and induce an acute inflammatory reaction * Recurrent episodes of acute arthritis, sometimes accompanied by the formation of large crystalline aggregates called tophi, and eventual permanent joint deformity (joint deformity can occur if not treated)

Question 455

T/F: Although an elevated level of uric acid is an essential component of gout, not all such persons develop gout, and genetic and environmental factors also contribute to pathogenesis

Answer 455

True

Question 456

What increases urate level? (Related to gout)

Answer 456

Increase in urate level due to: • Dietary purine load • Endogenous purine synthesis Excretion: • Renal excretion • Gut In gout: • Urate supersaturation and crystallization

Question 457

Histologic appearance of gout...

Answer 457

* Aggregations of urate crystals surrounded by an intense inflammatory reaction of lymphocytes, macrophages, and foreign-body giant cells, attempting to engulf the masses of crystals * Under polarized light, the crystals are needle shaped and demonstrate negative birefringence

Question 458

Which joint disorder is also known as chondrocalcinosis and calcium pyrophosphate crystal deposition disease?

Answer 458

Pseudogout

Question 459

This joint disorder most commonly occurs in people over 50, with no race or gender predilection..

Answer 459

Pseudogout

Question 460

What happens in pseudogout?

Answer 460

* Crystals first appear in structures composed of cartilage. | * When the deposits enlarge enough they may rupture, resulting in inflammation.

Question 461

Histologic appearance of pseudogout

Answer 461

* Numerous foci of calcification are identified in the cartilage * The crystals are rhomboid in shape and demonstrate positive birefringence under polarized light

Question 462

What are soft tissue tumors?

Answer 462

* Proliferations occuring in the extraskeletal, nonepithelial tissues of the body * Classified according to the normal tissues they recapitulate (muscle, fat, etc) * Some of these have no normal histologic counterpart * Benign outnumber malignant 100:1

Question 463

Location of soft tissue tumors

Answer 463

* Lower extremity: 40% * Upper extremity: 20% * Trunk and retroperitoneum: 30% * Head and neck: 10%

Question 464

Most common tissue tumor of adulthood

Answer 464

Lipoma

Question 465

Treatment for lipoma

Answer 465

Simple excision is curative

Question 466

Conventional lipomas show genetic rearrangements in which chromosomes?

Answer 466

Chromosome 12q13-15

Question 467

Incidence of lipoma more common in which gender?

Answer 467

Male preponderance most striking in spindle cell variant (9:1 M:F ratio)

Question 468

One of the most common sarcomas of adulthood

Answer 468

Liposarcoma

Question 469

Age range that liposarcoma most commonly appears in...

Answer 469

40s-60s

Question 470

Where does liposarcoma usually arise?

Answer 470

Usually arise in the deep soft tissues of the proximal extremities and retroperitoneum

Question 471

Well differentiated liposarcoma contains mutations in which gene and chromosome?

Answer 471

Well differentiated liposarcoma contains mutations in MDM2 gene on 12q14-q15.

Question 472

Well documented translocation, t(12;16)(q13;p11) occurs in what type of liposarcomas?

Answer 472

Myxoid and round cell liposarcomas

Question 473

Histologic hallmark: lipoblasts - mimic fetal fat cells is observed in which adipose tissue tumor?

Answer 473

Liposarcoma

Question 474

Most common of the reactive pseudosarcomas

Answer 474

Modular fasciitis

Question 475

Most common location of nodular fasciitis

Answer 475

Most often occurs in adults on the forearm, chest, and back

Question 476

Histologic appearance of nodular fasciitis

Answer 476

* Cellular lesion with plump myofibroblasts in an often myxoid stroma * Stroma contains lymphocytes and extravasated blood cells

Question 477

Variants of superficial fibromatoses include...

Answer 477

* Palmar (Dupuytren contracture) * Plantar * Penile (Peyronie disease) fibromatoses

Question 478

Characteristic of superficial fibromatoses

Answer 478

• All variants are characterized by nodular thickenings of the affected area

Question 479

Which variant of superficial fibromatoses is bilateral in 1/2 of cases?

Answer 479

Palmar variant

Question 480

Which gender does superficial fibromatoses occur more in?

Answer 480

All variants affect males more than female

Question 481

T/F: For superficial fibromatoses, some recur after excision, particularly the palmar variant

Answer 481

True

Question 482

Also known as desmoid tumors

Answer 482

Deep fibromatoses

Question 483

Which fibrous tumor presents as large infiltrative masses, most commonly abdominal, and recur after excision, but the cells appear benign

Answer 483

Deep fibromatoses

Question 484

Gender predilection of deep fibromatoses

Answer 484

* Extraabdoominal variants affect men and women equally | * The abdominal variant is most commonly seen in women after pregnancy

Question 485

The intra-abdominal variant of deep fibromatoses occurs most frequently in..

Answer 485

* Mesentery and pelvic walls | * Associated with Gardner syndrome

Question 486

What mutation is observed in deep fibromatoses?

Answer 486

Mutatioons in beta-catenin are seen in these lesions regardless of the presence of Gardner syndrome.

Question 487

Gross appearance of deep fibromatoses

Answer 487

* Tumorss appear as grey/white, firm, poorly demarcated masses * Very rubbery when cut

Question 488

Histologic appearance of deep fibromatoses

Answer 488

* Composed of plump benign fibroblasts arranged in broad fascicles that invade the surrounding tissue * Mitoses may be frequent

Question 489

Where does fibrosarcoma occur in the body?

Answer 489

Occur anywhere in the body; most common in the deep soft tissues of the extremities

Question 490

Which fibrous rumor appears most often unencapsulated, infiltrative, soft fleshy masses demonstrating areas of hemorrhage and necrosis?

Answer 490

Fibrosarcoma

Question 491

Spindle cells grow in a herringbone fashion in this tumor...

Answer 491

fibrosarcoma

Question 492

Benign fibrous histiocytoma usually occurs in...

Answer 492

* Skin and subcutis | * Lesion is often pigmented

Question 493

Incidence of benign fibrous histiocytoma

Answer 493

* Relatively common | * Presents in mid-adult life as firm small nodule (usually < 1cm)

Question 494

Gross appearance of benign fibrous histiocytoma.

Answer 494

* firm small nodule (usually <1 cm) * Lesion is often pigmented * Overlying hyperpigmented squamous mucosa is also evident

Question 495

Microscopic appearance of benign fibrous histiocytoma

Answer 495

Composed of crossing spindle cells in a background of sclerotic collagen

Question 496

What are the different types of pleomorphic undifferentiated sarcoma?

Answer 496

* Inflammatory * Myxoid * Angiomatoid * Giant cell * Storiform-pleomorphic

Question 497

What appears as a grey/white fleshy tumor with infiltrative margins, unencapulated, hemorrhage/mecrosis may be present

Answer 497

Pleomorphic undifferentiated sarcoma (formerly malignant fibrous histiocytoma)

Question 498

Histologic appearance of pleomorphic spindle cell tumor with necrosis and numerous mitoses is found in this...

Answer 498

Pleomorphic undifferentiated sarcoma

Question 499

Most common soft tissue sarcoma of childhood and adolescence (usually presents before 20 years of age)

Answer 499

Rhabdomyosarcoma

Question 500

In which location does rhabdomyosarcoma occur?

Answer 500

* May arise in any location * Most occur in the head, neck, or genitourinary tract * Only appear in relation to skeletal muscle in the extremities

Question 501

Treatment for rhabdomyosarcoma

Answer 501

Usually treated with surgery and chemotherapy with or without radiation

Question 502

Types of rhabdomyosarcma

Answer 502

1. Embryonal rhabdomyosarcoma 2. Alveolar rhabdomyosarcoma 3. Pleomorphic rhabdomyosarcoma All contain rhabdomyoblasts in variable quantities

Question 503

Most common type of rhabdomyosarcoma

Answer 503

* Embryonal rhabdomyosarcoma | * Accounts for 60%

Question 504

Subtypes of embryonal rhabdomyosarcoma

Answer 504

* Sarcoma botryoides * Spindle cell * Anaplastic

Question 505

Present as soft grey, infiltrative masses...

Answer 505

Embryonal rhabdomyosarcoma

Question 506

Age range for embryonal rhabdomyosarcoma..

Answer 506

•Typically arises in children <10 years old in head and neck, prostate, and paratesticular areas

Question 507

Round and spindled cells may be present in this type of rhabdomyosarcoma...

Answer 507

Embryonal rhabdomyosarcoma

Question 508

Accounts for 20% of rhabdomyosarcomas

Answer 508

Alveolar rhabdomyosarcoma

Question 509

This rhabdomyosarcoma tends to develop in early to middle adolescence and commonly arises in the deep muscle of the extremities...

Answer 509

Alveolar rhabdomyosarcoma

Question 510

Translocations that are diagnostic for alveolar rhabdomyosarcoma

Answer 510

* t(2;13)(q35;q14) | * t(1;13)(p36;q14)

Question 511

Rhabdomyosarcoma that is seen more often in adults than children

Answer 511

Pleomorphic rhabdomyosarcoma

Question 512

Rhabdomyosarcoma that can resemble pleomorphic undifferentiated sarcoma

Answer 512

Pleomorphic rhabdomyosarcoma

Question 513

Characterized by numerous large, sometimes multinucleated bizarre eosinophilic tumor cells

Answer 513

Pleomorphic rhabdomysarcoma

Question 514

What is Leiomyoma?

Answer 514

* Benign smooth muscle tumors * Most commonly seen in the uterus * May also arise from erector pili muscles of the skin, nipples, scrotum, and labia * Also occur in the deep soft tissues and wall of the GI tract

Question 515

Multiple cutaneous leiomyomas in some individuals are associated with ...

Answer 515

* Renal cell carcinomas * Hereditary leiomyomatosis and renal cell carcinoma syndrome transmitted as autosomal dominant * Associated with chromosome 1q42.3

Question 516

Histologic appearance of leiomyoma

Answer 516

Composed of fascicles of spindle cells that tend to intersect each other at right angles

Question 517

Histologically consist of cigar shaped nuclei arranged in interweaving fascicles...

Answer 517

Leiomyosarcoma

Question 518

Gender predilection of leiomyosarcoma

Answer 518

Afflict women more frequently than men

Question 519

Where does leiomyosarcoma most commonly occur?

Answer 519

Vast majority occur in the skin and deep soft tissues of the extremities and retroperitoneum

Question 520

A special subgroup of leiomyosarcoma exists in what type of patients?

Answer 520

* HIV positive patients | * Occurs in unusual sites such as the liver

Question 521

Represent 10-20% of soft tissue sarcomas

Answer 521

Leiomyosarcoma

Question 522

Characteristic translocation for synovial sarcoma

Answer 522

t(X,18)(p11.2;q11.2)

Question 523

Treatment for synovial sarcoma

Answer 523

Treated with preoperative chemotherapy followed by wide resection

Question 524

Histologic appearance of synovial sarcoma

Answer 524

* Monophasic: consist of only spindle cells (could also be only epithelioid cells) * Biphasic: contains both spindle and epithelioid cells * Stain with epithelial and mesenchymal markers

Question 525

Where does synovial sarcoma occur?

Answer 525

* Majority arise in the deep soft tissues, and 60-70% occur in the thigh * Less than 10% are extra articular

Question 526

Thyroid physiology

Answer 526

* Hypothalmus releases TRH which acts on the pituitary, which then releases TSH to stimulate the thyroid to make hormones * Free hormones act to inhibit the pituitary from releasing TSH to stimulate the thyroid * Thyroid binding proteins come from the liver to bind to T4 or T3, this plays a role in equilibrium of free hormones and bound hormones

Question 527

Most common site of heterotopic thyroid

Answer 527

* Most frequent --> base of tongue (lingual thyroid) * Total migration failure * 75% of patients with lingual thyroid have no other thyroid tissue

Question 528

Other sites of heterotopic thyroid

Answer 528

* Anterior tongue * Larynx * Trachea * Mediastinum - if it descends too far * Heart

Question 529

Embryology of thyroid

Answer 529

* Foramen cecum is located at the midline between the anterior 2/3 and posterior 1/3 of the tongue * This is where the thyroid tissue starts developing * Thyroglossal duct forms and descends down to its normal position in front of the larynx * In other words: foramen cecum to suprasternal notch

Question 530

Thyroglossal duct cyst

Answer 530

* Occurs when the thyroglossal duct does not obliterate * Occurs in the midline of neck (looks like Adam's apple) * Asymptomatic unless infected * Moves when swallowing * Squamous or respiratory epithelium lining cyst

Question 531

What is hypothyroidism?

Answer 531

* Underactive thyroid | * High TSH, but low T3 and T4

Question 532

Hypothyroidism in infants cause...

Answer 532

Cretinism: • Poor growth • Results in short stature, delayed development of permanent teeth, delayed puberty, poor mental development

Question 533

Hypothyroidism in adults results in...

Answer 533

Myxedema: | • Periorbital and pretibial edema due to mucopolysaccharide deposition underneath skin

Question 534

Treatment for hypothyroidism

Answer 534

Synthetic thyroid hormone

Question 535

Cause of primary hypothyroidism

Answer 535

Loss of thyroid tissue due to surgery or radiation therapy

Question 536

Most common cause of hypothyroidism in the USA

Answer 536

Hashimoto's thyroiditis, an autoimmune disease

Question 537

Most common cause of hypothyroidism worldwide...

Answer 537

Iodine deficiency, specially in endemic areas

Question 538

Cause of secondary hypothyroidism

Answer 538

* Pituitary or hypothalamic failure | * Causes no hormone to be secreted

Question 539

Most common cause of goiter in the United States | Goiter --> swelling of the neck due to enlarged thyroid gland

Answer 539

Hashimoto thyroiditis

Question 540

Histologic diagnostic triad for Hashimoto thyroiditis (Stuma Lymphomatosa)

Answer 540

* Lymphocytic infiltrate * Lymphoid follicles with germinal centers * Hurthle cell metaplasia of follicular epithelium

Question 541

Patients with Hashimoto thyroiditis are high risk for...

Answer 541

* B-cell lymphoma * Papillary carcinoma * Hurthle cell neoplasm

Question 542

What presents as a painless enlargement, believed to represent a disease of autoimmune origin, has variable functional status, diffuse nontender rubbery thyroid enlargement, with flashy cut surface?

Answer 542

Hashimoto thyroiditis (Stuma lymphomatosa) • Variable functional status: euthyroid, hyperthyroid (Hashitoxicosis), or hypothyroid

Question 543

What's believed to be the cause of subacute thyroiditis (granulomatous thyroiditis or De Quervain thyroiditis)?

Answer 543

• Viral infection

Question 544

Clinical course of subacute thyroiditis (granulomatous thyroiditis or De Quervain thyroiditis)...

Answer 544

* Onset often acute, with fever and malaise | * Triphasic clinical course of hyperthyroidism, hypothyroidism, and return to normal thyroid function (within 6-8 weeks)

Question 545

Most common cause of painful thyroid

Answer 545

Subacute thyroiditis (granulomatous thyroiditis or De Quervain thyroiditis)

Question 546

Histologic appearance of subacute thyroiditis

Answer 546

* Disruption of follicles with inflammation * Granulomatous reaction to colloid * Multinucleated giant cells

Question 547

Stony, hard, painless thyroid gland observed in...

Answer 547

Riedel's thyroiditis

Question 548

Thyroiditis that clinically resembles carcinoma, compress trachea...

Answer 548

Riedel's thyroiditis

Question 549

Obliterating phlebitis, where vein is obliterated by infiltrate and surrounded by dense collagen, is observed in which thyroiditis?

Answer 549

Riedel's thyroiditis

Question 550

Gross appearance of Riedel's thyroiditis (Riedel's struma, fibrous thyroiditis)

Answer 550

* Extensive fibrosis involving thyroid and contiguous neck structures * Broad brands of fibrosis with keloid like fibers

Question 551

Microscopic appearance of Riedel's thyroiditis (Riedel's struma, fibrous thyroiditis)

Answer 551

* Follicles are obliteraed | * Patchy lymphocytes, plasma cells, and eosinophils

Question 552

Incidence of Riedel's thyroiditis

Answer 552

Rare, suggest autoimmune etiology

Question 553

What is thyrotoxicosis?

Answer 553

Hypermetabolic state caused by increased T4 and T3

Question 554

What is primary thyrotoxicosis?

Answer 554

Grave's disease

Question 555

What is secondary thyrotoxicosis?

Answer 555

TSH secreting pituitary adenoma

Question 556

Clinical picture of thyrotoxicosis

Answer 556

* Heat intolerance, sweating, warm skin, malabsorption * Cardiac: palpitation, tachycardia, CHF * Menstrual disturbances * Neuromuscular: Tremor, muscle weakness * Ocular: thyroid ophthalmopathy

Question 557

Lab findings for Graves' Disease (diffuse goiter)

Answer 557

* Increased T4 * Increased T3 * Decreased TSH

Question 558

Radioactive findings for Graves' Disease (Diffuse goiter)

Answer 558

Diffuse uptake of radioactive iodine

Question 559

What Is Graves' disease (diffuse goiter)?

Answer 559

* Thyrotoxicosis with smooth symmetrical enlargement of thyroid * Infiltrative ophthalmopathy with exophthalmus in 40% of patients

Question 560

Most common cause of endogenous hyperthyroidism

Answer 560

Diffuse goiter (Graves' disease)

Question 561

Triad of clinical findings for Graves' disease (Diffuse goiter)

Answer 561

* diffuse enlargement of thyroid * infiltrative ophthalmopathy (exophthalmos) * infiltrative dermatopathy (periorbital myxedema)

Question 562

Histologic appearance of diffuse goiter (Graves' disease)

Answer 562

* Diffuse hyperplasia of thyroid follicular cells * Papillary hyperplasia * Scalloped appearance of the edges of the colloid * Lymphoid follicles • Scribe: We do not see round follicles lined by epithelial cells. Instead we see papillary projections in the lumen.

Question 563

Which type of nodule in the thyroid is more likely to be neoplastic?

Answer 563

* Solitary nodule is more likely to be neoplastic than multiple * Nodules in younger patients are more likely to be neoplastic * Nodules in males are more likely to be neoplastic

Question 564

Which nodules in the thyroid are more likely to be benign?

Answer 564

* Hot nodules are more likely to be benign * Up to 10% of cold nodules prove to be malignant * History of previous radiation to the neck is associated with increased risk of malignancy

Question 565

Incidence of multinodular goiter

Answer 565

Incidence 3-5%, and 50% in autopsy cases

Question 566

Location and effect of multinodular goiter

Answer 566

* Sometimes extends in the mediastinum * Pressure effect on trachea * Can arise sporadically or endemic (iodine deficiency)

Question 567

Histological appearance of multinodular goiter

Answer 567

* Distended follicles of various sizes, filled with colloid, flat follicular epithelium * Focal hyperplasia, scalloping * Calcification * Fibrosis * Hemorrhage

Question 568

Most common endocrine malignancy

Answer 568

Thyroid neoplasm • Less than 2% of all human cancers

Question 569

Gender predilection of thyroid neoplasm

Answer 569

Generally more common in women

Question 570

Benign to malignant ratio of thyroid neoplasm

Answer 570

10:1

Question 571

Neoplasm associated with radiation exposure and endemic goiters

Answer 571

Thyroid neoplasm

Question 572

Clinical manifestations include: • Most patients are euthyroid and present with thyroid nodule • Symptoms such as dysphagia, dyspnea, and hoarseness usually indicate advanced disease • Ipsilateral cervical lymph nodes may be present

Answer 572

Thyroid neoplasm

Question 573

Definitive diagnosis for thyroid neoplasm

Answer 573

Fine needle aspiration biopsy

Question 574

Subcategories of thyroid neoplasms

Answer 574

* Follicle derived | * C-cell derived

Question 575

Most common thyroid neoplasm

Answer 575

Follicular adenoma

Question 576

Thyroid neoplasm that is almost always solitary, well capsulated, has uniform follicles within the lesion, compress adjacent normal thyroid tissue, no vascular or capsular invasion...

Answer 576

Follicular adenoma

Question 577

Make up 10-15% of thyroid cancer

Answer 577

Follicular carcinoma

Question 578

Thyroid neoplasm that usually shows as "cold" on radionuclide scan

Answer 578

Follicular carcinoma

Question 579

``` Thyroid neoplasm that is: • more aggressive • hematologic spread • architectural patterns, follicular, or solid • Capsular invasion • Vascular invasion beyond the capsule ```

Answer 579

follicular carcinoma

Question 580

Prognosis for follicular carcinoma

Answer 580

60% 10 year survival

Question 581

Most common malignant thyroid tumor (75%)

Answer 581

Papillarry carcinoma

Question 582

How papillary carcinoma spreads...

Answer 582

Spread via lymphatics - propensity for lymph node metastasis

Question 583

Thyroid neoplasm that's associated with prior radiation...

Answer 583

Papillary carcinoma

Question 584

Which thyroid neoplasm has this histologic finding: • Branching papillae with fibrovascular core, lined by cuboidal to columnar epithelial cells and psammoma bodies • Optically clear nuclei (Orphan Annie)

Answer 584

Papillary carcinoma

Question 585

Prognosis for papillary carcinoma depends on SAGES...

Answer 585

* Sex: women better prognosis * Age: children better prognosis * Grade: dedifferentiation, poor prognosis * Extent: extrathyroid extension, poor prognosis * Size: large lesions, poor prognosis

Question 586

Thyroid neoplasm that's a neuroendocrine neoplasm...

Answer 586

Medullary carcinoma

Question 587

Thyroid neoplasm that originate from the calcitonin producing parafollicular C-cells

Answer 587

Medullary carcinoma

Question 588

``` Thyroid neoplasm that: • solitary or multiple lessons • 5-10% of all thyroid cancers • 80% Sporadic • 20% occurs in the setting of MEN syndrome 2A or 2B or as familial tumors ```

Answer 588

Medullary carcinoma

Question 589

Thyroid neoplasm that is congo red positive (acellular amyloid deposits) and tumor cells positive to Calcitonin immunostain

Answer 589

Medullary carcinoma

Question 590

Thyroid neoplasm that has polygonal to spindle-shaped cells, and form nests, trabeculae or follicles

Answer 590

Medullary carcinoma

Question 591

Which thyroid neoplasm grows rapidly, spreads locally, invades trachea, esophagus, mediastinum b local invasion?

Answer 591

Anaplastic carcinoma

Question 592

Which thyroid neoplasm originates from follicular cells?

Answer 592

Differentiated: • Papillary (75%) • Follicular (10%) • Hurthle cell (5%) Undifferentiated: • Anaplastic (5%)

Question 593

Which thyroid neoplasm is highly fatal, most patients die within one year?

Answer 593

Anaplastic carcinoma

Question 594

Gross presentation of anaplastic carcinoma (thyroid neoplasm).

Answer 594

Large solid tumor with necrosis and hemorrhage.

Question 595

Incidence of anaplastic carcinoma

Answer 595

* Constitutes 5-10% of all thyroid carcinomas | * Peak incidence - 7th decade

Question 596

Different histological morphologies of anaplastic carcinoma.

Answer 596

* Multinucleated osteoclast - type giant cells * Spindle cell sarcoma-like morphology * Squamoid morphology

Question 597

Compare and contrast the prognosis of the various thyroid carcinomas.

Answer 597

* Papillary - excellent * Follicular - good * Anaplastic - poor * Medullary - varies

Question 598

Compare and contrast the method of spread for each thyroid carcinoma.

Answer 598

* Papillary - lymph * Follicular - blood vessel * Anaplastic - local (grows so fast it has no time to spread) * Medullary - all

Question 599

Compare and contrast the age incidence for each thyroid carcinoma.

Answer 599

* Papillary - young < 45 years (75% of all thyroid carcinomas) * Follicular - middle age (15%) * Anaplastic - Elderly (5%) * Medullary - Elderly, familial (5%)

Question 600

Structure and location of pituitary gland.

Answer 600

* Present in the sphenoid bone, inside a cup-shaped space in the bone called the sella turcica. * Weighs about 0.5 g. * Connected to the hypothalamus with stalk. * Composed of: * Anterior - adenohypophysis (80%) * Posterior - neurohypophysis

Question 601

Function of the neurohypophysis?

Answer 601

• Small posterior lobe of pituitary • Stores hormones secreted by the hypothalamus: 1. Oxytocin 2. Anti-diuretic hormone (ADH)

Question 602

Function of adenohypophysis

Answer 602

``` • Large anterior lobe • Releases hormone: - Follicle stimulating hormone (FSH) - Melanocyte stimulating hormone (MSH) - Lutenizing hormone (LH) - Growth hormone (GH) - Adenocorticotropic hormone (ACTH) - Thyroid stimulating hormone (TSH) - Prolactin (PRL) ```

Question 603

Pituitary disease pertaining to TSH

Answer 603

* Hypersecretion = hyperthyroidism | * Hyposecretion = hypothyroidism

Question 604

Pituitary diseases pertaining to ACTH

Answer 604

* Hypersecretion = Cushing's disease | * Hyposecretion = Addison's disease

Question 605

Pituitary diseases pertaining to FSH

Answer 605

``` • Hyposecretion - M = poor sperm production - F = low estrogen, amenorrhea • Hypersecretion - F = menopause ```

Question 606

Pituitary diseases pertaining to LH

Answer 606

• Hyposecretion - F = no ovulation - M = low testosterone

Question 607

Pituitary diseases pertaining to MSH

Answer 607

• Hypersecretion = excess pigment

Question 608

Pituitary diseases pertaining to GH

Answer 608

• Hypersecretion - during growth = gigantism - after growth = acromegaly • Hyposecretion = dwarfism

Question 609

Pituitary disease pertaining to PRL

Answer 609

* Hypersecretion = galactorrhea (excess milk production), infertility * Hyposecretion = poor milk production

Question 610

Pituitary disease pertaining to ADH

Answer 610

• Hypersecretion = SIADH - Syndrome of inappropriate ADH secretion • Hyposecretion = diabetes insipidus

Question 611

Histology of anterior pituitary

Answer 611

• Pink acidophils secrete: growth hormone (GH) and prolactin • Dark purple basophils secrete: - corticotrophin (ACTH) - thyroid stimulating hormone (TSH) - gonadotrophins - follicle stimulating hormone (FSH) - luteinizing hormone (LH) • Pale staining chromophobes have few cytoplasmic granules, but may have secretory activity

Question 612

Acidophils of the anterior pituitary secrete...

Answer 612

* Growth hormone | * Prolactin

Question 613

Basophils of the anterior pituitary secrete...

Answer 613

* Follicle stimulating hormone (FSH) * Corticotrophin (ACTH) * Thyroid stimulating hormone (TSH) * Luteinizing hormone (LH)

Question 614

Chromophobes of the anterior pituitary secrete...

Answer 614

* Have few cytoplasmic granules | * May have secretory activity

Question 615

General diseases of the pituitary

Answer 615

* Hyperpituitarism: excessive secretion of tropic hormones; most often secondary to a benign tumor (adenoma) arising in the anterior lobe --> called anterior pituitary adenomas * Hypopituitary: deficiency of tropic hormones because pituitary gland is destroyed by destructive process such as injury, inflammation, surgery or radiation * Local mass effect: tumors compress adjacent structures - such as the optic chiasm - causing headache, loss of vision, and hydrocephalus

Question 616

Hyperpituitarism, in most cases, excess is due to __________ arising in the __________ lobe.

Answer 616

adenoma; anterior

Question 617

Benign (pituitary) adenomas have symptoms that fall into 2 main categories:

Answer 617

• Pressure symptoms from glandular enlargement - Headache, seizures, drowsiness, visual defects • Hormonal effects - Usually stimulatory if functional tumor - May be inhibitory (non-functional with pressure necrosis)

Question 618

Most common hormonally active adenomas

Answer 618

Prolactinoma

Question 619

Features common to all pituitary adenomas

Answer 619

* 10% of all intracranial neoplasms & 25% incidental findings * Usually benign and sporadic * 3% occur with MEN syndrome * May or may not be functional * Functional - the clinical effects are secondary to the hormone produced * Non-functional - large size, hypopituitarism (destroy adjacent ant. pituitary), visual field abnormalities

Question 620

Hormones most commonly over-produced by adenomas...

Answer 620

Prolactin and GH

Question 621

Sizes of pituitary adenoma

Answer 621

* Microadenoma, < 10mm, may cause focal bulging | * Macroadenoma, > 10mm, cause problem related to mass effect

Question 622

How to diagnose pituitary adenoma

Answer 622

* Imaging: MRI brain with and without IV contrast * Labs: check the levels of different hormones to determine which type of tumor it is * Visual fields: to be performed by ophthalmologist, to see if tumor is causing visual symptoms

Question 623

Gross appearance of pituitary adenomas are usually...

Answer 623

* Well circumscribed, invasive in up to 30% * Size 1cm or more, specially in nonfunctioning tumor * Hemorrhage & necrosis seen in large tumors

Question 624

Uniform cells, one cell type (monomorphic/monomorphism), absent reticulin network, rare or absent mitosis are histologic characteristic of...

Answer 624

Pituitary adenomas

Question 625

Most common pituitary adenoma...

Answer 625

PRL secreting adenoma

Question 626

Type of immunostain that can be done for GH

Answer 626

* Immunoperoxidase * Hormone will light up Note: this stain is not necessary, since GH can be detected in serum

Question 627

Growth hormone producing adenoma

Answer 627

Can result in: • Gigantism: if hypersecretion occurs before puberty • Acromegaly: if hypersecretion occurs after puberty

Question 628

Name condition: • High linear growth due to excessive action of insulin-like growth factor I (IGF-I) while the epiphyseal growth plates are open during childhood • Very tall, very long legs, and arms

Answer 628

Acromegaly/Gigantism (growth hormone producing adenoma) • Other symptoms include: diabetes, hypertension, heart failure, increased blood pressure, arthritis, osteoporosis, large jaw & hands, etc.

Question 629

Excessive action of insulin growth factor - I (IGF-I) is related to...

Answer 629

Acromegaly or gigantism

Question 630

Physical features of acromegaly

Answer 630

* Enlarged hands, feet, tongue * Enlarged liver, heart, kidney, spleen, and other organs * Coarsened, enlarged facial features * Increased chest size (barrel chest) * Impaired vision * Headaches * Menstrual cycle irregularities in women * Erectile dysfunction in men

Question 631

What are non-functioning adenomas (null cell adenoma)?

Answer 631

* Do not function and so do not secrete hormone (25-30% of patients) * May grow to a large size before they are detected (mass effect) * Patient can experience: visual deficits, hormone deficiency

Question 632

Hypopituitarism symptoms occur only when there is a loss of greater than __% of ________ pituitary

Answer 632

75%, anterior pituitary

Question 633

Acquired causes of hypopituitary

Answer 633

1. Nonsecretory pituitary adenoma 2. Ischemic necrosis, e.g. postpartum 3. Iatrogenic by radiation or surgery 4. Autoimmune (lymphocytic) hypophysitis 5. Inflammatory e.g. sarcoidosis or TB...

Question 634

T/F: Hypopituitarism can be congenital or acquired

Answer 634

True

Question 635

Symptoms of _______ include dwarfism & effect of individual hormone deficiencies. Ex: Loss of MSH ---> decreased pigmentation

Answer 635

Hypopituitarism

Question 636

Medical condition in which the pituitary gland does not produce enough growth hormones

Answer 636

Pituitary dwarfism

Question 637

Height of the affected individuals who have pituitary dwarfism

Answer 637

2'8" to 4'8"

Question 638

Histologic appearance of posterior pituitary

Answer 638

Modified glial cells (pituicytes) and axonal process

Question 639

Posterior pituitary syndromes include...

Answer 639

* Abnormal oxytocin secretion * ADH deficiency * ADH hypersecretion

Question 640

Effects of abnormal oxytocin secretion...

Answer 640

Abnormalities of synthesis & release have NOT been associated with an significant abnormality

Question 641

ADH deficiency causes...

Answer 641

Diabetes insipidus: | • excessive urination, dilute urine, due to inability to reabsorb water from the collecting tubules

Question 642

Secretion of inappropriately high level of ADH secretion (SIADH-syndrome of inappropriate ADH) causes...

Answer 642

Excessive resorption of water --> hyponatremia: | • So much water in the blood results in a low sodium concentration

Question 643

Which lobe of the pituitary is most commonly affected in metastic tumors...

Answer 643

* Posterior lobe mostly affected * Anterior lobe rarely affected • Metastic tumor comes from breast, lung, GI tract

Question 644

What is a benign, slow growing tumor, that is derived from remnants of Rathke's pouch? It can be suprasellar or intrasella, often presenting with cystic calcification.

Answer 644

Craniopharyngioma

Question 645

Age range of patients most commonly affected by craniopharyngioma, and the symptoms they experience.

Answer 645

* Children or adolescents most affected | * Symptoms of hypofunction or hyperfunction of pituitary and/or visual disturbances, diabetes insipidus.

Question 646

Stellate reticulum and wet keratin are prominent features

Answer 646

Craniopharyngioma

Question 647

Gross appearance: low grade circumscribed epithelial tumor, partly cystic and calcified mass.

Answer 647

Craniopharyngioma

Question 648

Histological appearance showing squamoid and columnar epithelium lining cystic spaces filled with oily fluid...

Answer 648

Craniopharyngioma

Question 649

Most common cause of hyperpituitarism is...

Answer 649

An anterior lobe pituitary adenoma

Question 650

Two distinctive morphologic features of most (pituitary) adenomas are...

Answer 650

* Absence of reticulin network | * Cellular monomorphism

Question 651

Function and location of adrenal glands.

Answer 651

* Pair of endocrine glands just above the kidney | * They secrete steroids from cortex and catecholamines from medulla.

Question 652

Layers of the adrenal cortex

Answer 652

1. Zona glomerulosa --> mineralcorticoids (aldosterone) -- SALT 2. Zona fasiculata --> glucocorticoids (cortisol) -- SUGAR 3. Zona reticularis --> estrogens & androgens -- SEX

Question 653

What does the zona glomerulosa secrete?

Answer 653

• Mineralocorticoids (aldosterone) --> SALT

Question 654

What does the zona fasiculata secrete?

Answer 654

• Glucocorticoids (cortisol) -- SUGAR

Question 655

What does the zona reticularis secrete?

Answer 655

• Estrogens and androgens -- SEX

Question 656

Syndromes associated with adrenal cortical hyperfunction:

Answer 656

1. Cushing's syndrome (excess of cortisol) 2. Hyperaldosteronism 3. Adrenogenital or virilizing syndrome (excess of androgen)

Question 657

Elevation of cortisol level

Answer 657

Cushing's syndrome Recall: zona fasiculata --> glucocorticoids (cortisol) --> sugar

Question 658

Most common exogenous cause of hypercortisolism (elevation of cortisol level, aka Cushing' Syndrome)

Answer 658

Steroid therapy

Question 659

Most common endogenous cause of hypercortisolism (elevation of cortisol level -- Cushing' Syndrome)

Answer 659

Pituitary Cushing Syndrome - hypersecretion of ACTH (70%) Other endogenous causes include: • Ectopic secretion of ACTH by non-pituitary neoplasm (10%) • Primary adrenocortical neoplasm and rarely hyperplasia (15-20%)

Question 660

What's Pituitary Cushing Syndrome?

Answer 660

* Tumor in anterior pituitary secretes too much ACTH | * Causes cortex to thicken (hyperplasia) and results in excess cortisol secretion

Question 661

What's Adrenal Cushing Syndrome?

Answer 661

Adenocortical adenoma or hyperplasia increases cortisol level.

Question 662

What is Paraneoplastic Cushing Syndrome?

Answer 662

* Neuroendocrine carcinoma of lung (or other nonendrocrine cancer) can secrete ACTH * Results in hyperplasia and excess cortisol * Most common site of these paraneoplasms is lung

Question 663

What is Iatrogenic Cushing Syndrome?

Answer 663

Taking a lot of steroids causes adrenal ATROPHY and elevated cortisol.

Question 664

Clinical features of Cushing Syndrome

Answer 664

* Central obesity (85-90%) * Moon face (85%) * Weakness and fatigability (85%) * Hirsutism (abnormal hair growth, esp. in women) (75%) * Hypertension (75%) * Glucose intolerance/diabetes (75%) * Osteoporosis (75%) * Menstrual abnormalities (70%) * Cutaneous striae (50%)

Question 665

What happens in hyperaldosteronism?

Answer 665

Increase in aldosterone causes sodium retention and potassium excretion, increased blood pressure, hypokalemia

Question 666

What is primary hyperaldosteronism?

Answer 666

* Adrenal gland hypersecretes aldosterone | * distinguished by decreased plasma renin

Question 667

Potential causes for primary hyperaldosteronism?

Answer 667

* Nodular hyperplasia (60%) * Neoplasm (35%) * Rarely familial

Question 668

What is secondary hyperaldosteronism?

Answer 668

* Hypersecretion is caused by something outside the adrenal gland * Distinguished by increased plasma renin

Question 669

Potential causes of secondary hyperaldosteronism

Answer 669

* Decreased renal perfusion * Arterial hypovolemia and edema * Pregnancy

Question 670

What is virilizing syndromes?

Answer 670

* Overproduction of sex hormones in the zona reticularis, the innermost layer * Virilization, precocious puberty, ambiguous genitalia * Neoplasms can occur at any age, frequently malignant

Question 671

Patients who have this syndrome have increased risk for acute adrenocortical insufficiency

Answer 671

Virilizing syndromes

Question 672

Causes of virilizing syndromes

Answer 672

* Primary gonadal disorders * Adrenocortical neoplasms * Congenital adrenal hyperplasia

Question 673

Gross appearance of adrenal cortical tumors.

Answer 673

``` • Encapsulated, solitary, usually yellow • Size variable • Can be nonfunctioning or functioning • Can be benign or malignant: - Malignant tumors with necrosis, hemorrhage (>= 300 g) ```

Question 674

How to tell if an adrenal cortical tumor is malignant or benign...

Answer 674

Local invasion, & the presence of metastases differentiate benign from malignant tumors

Question 675

Histology of this type of tumor shows: • Capsulated tumor with uniform or slightly pleomorphic cells, may be eosinophilic or clear cell type • Spironolactone bodies [DIAGNOSTIC]

Answer 675

Adrenal cortical adenoma • If tumor is mineralocorticoid, you will see spironolactone bodies (in hyperaldosteronism)

Question 676

How does an adrenal cortical carcinoma differ from an adenoma?

Answer 676

* Larger than adenoma | * Non-capsulated with nuclear pleomorphism, mitoses, and necrosis

Question 677

When acute adrenocortical insufficiency is caused by infection it is called...

Answer 677

Waterhouse-Frederickson syndrome

Question 678

Causes of acute adrenocortical insufficiency

Answer 678

1. Massive adrenal hemorrhage as in anticoagulant therapy, DIC, sepsis by N. meningitidis, pseudomonas 2. Sudden withdrawal of steroid therapy 3. Stress in a patient with underlying chronic insufficiency

Question 679

Causes of chronic (Addison's disease) adrenocortical insufficiency

Answer 679

1. Autoimmune disorder: 75-90%, may be sporadic 2. Infections, e.g. Tuberculosis, fungi (AIDS) 3. Metastatic tumors destroying adrenal, e.g. lung, breast, ... others

Question 680

What is chronic adrenocortical insufficiency (Addison's disease)?

Answer 680

Progressive destruction of the adrenal

Question 681

What cells make up the adrenal medulla, and what does it secrete?

Answer 681

Composed of Chromaffin cells secreting catecholamines.

Question 682

Adrenal medulla are derived from...

Answer 682

* Neural crest | * Part of sympathetic system

Question 683

Diseases of the adrenal medulla...

Answer 683

Mainly tumors: • Pheochromocytoma • Neuroblastoma

Question 684

Neuroendocrine tumor of the medulla of the adrenal glands, secretes excessive amounts of adrenaline and noradrenaline

Answer 684

Pheochromocytoma

Question 685

Diagnosis of pheochromocytoma...

Answer 685

Increased urinary excretion of free catecholamine and their metabolites (VMA and metanephrins)

Question 686

Three familial syndromes that predisposes to catecholamine secreting tumors like Pheochromocytoma...

Answer 686

* MEN2 * Neurofibromatosis type 1 (NF1) * von Hippel-Lindau syndrome (VHL)

Question 687

Where does Pheochromocytoma originate...

Answer 687

Originates from the chromaffin cells along the paravertebral SYMPATHETIC CHAIN extending from pelvis to base of skull... • >95% are abdominal • >90% in adrenal medulla

Question 688

Pheochromocytoma "rule of 10"

Answer 688

* 10% extra-adrenal (closer to 15%) * 10% occur in children * 10% familial (closer to 20%) * 10% bilateral or multiple (more if familial) * 10% recur (more if extra-adrenal) * 10% malignant * 10% discovered incidentally

Question 689

Pheochromocytoma, signs & symptoms, the five P's

Answer 689

* Pressure (HTN) 9% * Pain (headache) 80% * Perspiration 71% * Palpitation 64% * Pallor 42% * Paroxysms (the sixth P!): symptoms come and go

Question 690

Classical triad for pheochromocytoma

Answer 690

* Pain (headache), perspiration, palpitations | * Lack of all 3 virtually excluded diagnosis of pheo in a series of > 21,000 patients

Question 691

Zellballen (small nests or alveolar pattern), trabecular or solid patterns of polygonal/spindle shaped cells in rich vascular network is the histologic appearance of...

Answer 691

Pheochromocytoma (adrenal medulla tumor)

Question 692

Benign vs malignant pheochromocytoma

Answer 692

* May have mitoses and marked pleomorphism * Capsular and vascular invasion common in benign behaving tumor * Definitive Dx of malignancy - presence of metastasis

Question 693

Second most common solid childhood neoplasm, after CNS tumors...

Answer 693

Neuroblastoma

Question 694

Treatment for neuroblastoma...

Answer 694

* Surgery * Radiation therapy * Chemotherapy

Question 695

Adrenal medulla tumor associated with the deletion of short arm of chromosome 1...

Answer 695

Neuroblastoma

Question 696

Some differentiate into ganglioneuroblastoma and spontaneously regress...

Answer 696

Neuroblastoma

Question 697

What helps in the diagnosis of neuroblastoma?

Answer 697

VMA excreted in 24 hr. urine helpful in diagnosis

Question 698

Small round blue cell tumor with rosettes indicates...

Answer 698

Neuroblastoma Add'l info: • Large mass with necrosis • Areas of necrosis and calcification

Question 699

What is MEN Syndrome?

Answer 699

* Multiple Endocrine Neoplasia Syndrome * Inherited diseases resulting in hyperplasia, adenomas, and carcinomas * Younger age * Multiple endocrine involvement (synchronous or metachronous) * Asymptomatic stage of endocrine hyperplasia * More aggressive and recur

Question 700

Which organ secretes insulin?

Answer 700

Pancreas

Question 701

This hormone reduces the level of sugar (glucose) in the blood...

Answer 701

* Insulin | * Secreted by the pancreas

Question 702

Parts of the pancreas...

Answer 702

Head, neck, body and tail

Question 703

Location of the pancreas

Answer 703

* Retroperitoneum, 2nd lumbar vertebral level | * Extends in an oblique, transverse position

Question 704

Gland with both exocrine and endocrine function

Answer 704

Pancreas

Question 705

Blood sugar and health...

Answer 705

* Sugar (glucose) is an important source of energy * What is eaten is absorbed into the blood * Insulin is produced by the pancreas when blood sugar is high * Insulin keeps blood sugar level within the normal range for health

Question 706

Different cells within the islets of Langerhans of the pancreas

Answer 706

* beta cells --> insulin * alpha cells --> glucagon * delta cells --> somatostatin * pancreatic polypeptide (PP) --> VIP

Question 707

Which hormone does the alpha cells of the islets of Langerhans of the pancreas secrete?

Answer 707

* Glucagon | * Effect: glucose synthesis & glycogen breakdown in the liver --> increases blood glucose concentration

Question 708

Which hormone do beta cells of the pancreas secrete?

Answer 708

* Insulin | * Effect: stimulation of lipids & glycogen storage & formation --> decreases blood glucose concentration

Question 709

Which hormone do delta cells of the pancreas secrete?

Answer 709

* Somatostatin | * Effect: inhibits secretion of insulin & glucagon

Question 710

Islet cell diseases include..

Answer 710

* Diabetes | * Islet cell tumors

Question 711

Normal blood glucose level

Answer 711

Homeostasis --> about 90 mg/100 mL

Question 712

How insulin and glucagon function...

Answer 712

Stimulus: rising blood glucose level (e.g. after eating a carbohydrate rich meal) --> high blood glucose level --> beta cells of the pancreas stimulated to release insulin into the blood --> • liver takes up glucose and stores it as glycogen • body cells take up more glucose --> blood glucose level decline to a set point; stimulus for insulin release diminishes Stimulus: declining blood glucose level (e.g. after skipping a meal) --> alpha cells of pancreas stimulated to release glucagon into the blood --> liver breaks down glycogen and releases glucose to the blood --> blood glucose level rise to set point; stimulus for glucagon release diminishes

Question 713

Where is glycogen stored?

Answer 713

* Glycogen = store of glucose | * Stored in the liver

Question 714

Leading cause of end stage liver disease, adult-onset blindness, and non-traumatic lower extremity amputation in the US.

Answer 714

Diabetes Mellitus

Question 715

What is diabetes mellitus?

Answer 715

* Metabolic disorders * Hyperglycemia * Defects in insulin secretion, insulin action, or most commonly, both * Affects multiple organ systems: kidneys, eyes, nerves, blood vessels * Affects over 20 million in adults and children

Question 716

Diabetes classification

Answer 716

• Causes could be primary in the pancreas, or secondary to other disease conditions • Primary diabetes is classified into: A- Type 1 (approximately 10%) B- Type 2 (approximately 90%) C- Genetic & miscellaneous causes • Whatever the type, complications are the same.

Question 717

Type 1 Diabetes

Answer 717

* Develops in childhood * Autoimmune destruction of islet cells * Heavy lymphocytic (CD4, CD8) infiltrates appear in and around islets (insulitis) * The islets of Langerhans are destroyed (>90% of beta cells lost before metabolic changes appear) * 3P's: polyuria (excessive urination), polydipsia (excessive thirst), polyphagia (excess hunger) * Metabolic acidosis, weight loss, dehydration, and electrolyte imbalance

Question 718

In which type of diabetes is ketoacidosis common?

Answer 718

* Ketoacidosis is common in type 1 | * In type 2 ketoacidosis is rare

Question 719

Which type of diabetes develops in childhood and involves the autoimmune destruction of islet cells?

Answer 719

Type 1

Question 720

Type 2 diabetes

Answer 720

* Age > 30 years, often present incidentally * Sedentary life style and overwight * Insulin resistance & beta cells dysfunction, resulting in relative insulin deficiency * Fibrosis and deposition of amylin polypeptide within islets * 3 P's +/- symptoms of complications * Rare ketoacidosis

Question 721

Which type of diabetes involves insulin resistance & beta cells dysfunction, resulting in relative insulin deficiency...

Answer 721

Type 2

Question 722

Secondary miscellaneous causes of diabetes...

Answer 722

* Diseases of exocrine pancreas (e.g. chronic pancreatitis) * Endocrinopathies (e.g. Cushing's Syndrome, Acromegaly) * Infections (e.g. CMV) * Drugs (e.g. glucocorticoids) * Gestational diabetes

Question 723

Common differences between type 1 and type 2 diabetes

Answer 723

Type 1 • Often diagnosed in childhood • Not associated with excess body weight • Often associated with higher than normal ketone levels at diagnosis • Treated with insulin injections or insulin pump • Cannot be controlled without taking insulin Type 2 • Usually diagnosed in over 30 year olds • Often associated with excess body weight • Often associated with high blood pressure and/or cholesterol levels at diagnosis • Is usually treated initially without medication or with tablets • Sometimes possible to come off diabetes medication

Question 724

Laboratory diagnosis for diabetes

Answer 724

* Random glucose >/= 200 g/dL + symptoms * Fasting glucose >/= 126 g/dL on more than one occasion * Abnormal oral glucose tolerance test when glucose level is more than 200 g/dL 2 hours after standard glucose load of 75g.

Question 725

What is glycosylated hemoglobin, HbA1c?

Answer 725

* Blood test that measures the amount of glucose that has been incorporated into the hemoglobin protein of the red blood cell (RBC). * HbA1c levels remain more stable than sugar levels. * Not affected by short-term fluctuations in sugar * Normal is 4-6% * Evaluated periodically (1-2 per year)

Question 726

Normal HbA1c

Answer 726

4-6% is normal

Question 727

A1C% of 6.5 or above corresponds with...

Answer 727

* Diabetes * Fasting glucose 126 mg/dL or above * Oral glucose tolerance test 200 mg/dL or above

Question 728

A1C% of 5.7 to 6.4 corresponds with...

Answer 728

* Prediabetes * Fasting plasma glucose of 100 to 125 mg/dL * Oral tolerance test of 144-199 mg/dL

Question 729

A1C% of about 5 corresponds with...

Answer 729

* Normal (not diabetes) * Fasting glucose of 99 mg/dL or below * Oral glucose tolerance test 139 mg/dL or below

Question 730

Renal complications associate with diabetes

Answer 730

* Both nodular (Kimmelstiel - Wilson lesion) and diffuse glomerulosclerosis * Chronic renal failure * Infections - pyelonephritis (bacterial and fungal infections)

Question 731

Ocular complications associated with diabetes

Answer 731

* diabetic retinopathy (one of the leading causes for irreversible blindness) in the United States * cataract * glaucoma * blindness

Question 732

What is one of the leading causes for irreversible blindness in the US?

Answer 732

Diabetic retinopathy

Question 733

What is cataracts?

Answer 733

* Complication from diabetes | * Protein deposits cloud the lens

Question 734

What is retinopathy?

Answer 734

* Complication of diabetes | * Exudate from blood vessels on retina

Question 735

What is glaucoma?

Answer 735

* Complication of diabetes | * Increased intraocular pressure, which can lead to blindness

Question 736

What's a vascular complication of diabetes?

Answer 736

Atherosclerosis: • Early and accelerated atherosclerosis • Hypertension • Heart disease, cerebrovascular disease, and renal disease • The most common cause of death - myocardial infarction • Peripheral vascular disease • Diabetic neuropathy, leading to propensity for injury

Question 737

What's the most common cause of death?

Answer 737

Myocardial infarction

Question 738

Treatment for diabetes mellitus type 1

Answer 738

Insulin administration

Question 739

Treatment for diabetes type 2

Answer 739

* Diet and exercise * Oral hypoglycemics * Insulin

Question 740

What are pancreatic neuroendocrine tumors (PanNETs)?

Answer 740

* AKA islet cell tumors * 2% of all pancreatic neoplasms * Common in adults, and in the body/tail of the pancreas where there are more islet cells * Single or multifocal * Functional (excessive hormone production) and nonfunctional (without hormone production) larger * Slow growing, metastases to nodes, liver, bone * 80% occur in MEN1 patients

Question 741

Most common type of pancreatic neuroendocrine tumor

Answer 741

Insulinomas are the most common, followed by gastrinomas

Question 742

Types of islet cell tumors

Answer 742

* Insulinoma - beta cells * Gastrinoma - delta cells * Somasostatinoma - delta cells * Glucagonoma - alpha cells * VIPoma - delta cells * Nonfunctional

Question 743

Which type of islet tumor cells affects beta cells?

Answer 743

Insulinoma

Question 744

Which type of islet cell tumor affects delta cells?

Answer 744

* Gastrinoma * VIPoma * Somasostatinoma

Question 745

Which type of islet cell tumor affects alpha cells?

Answer 745

Glucagonoma

Question 746

Islet cell tumor histology

Answer 746

* Solid, gyriform, trabecular and grandular patterns * Nests of polygonal cells with moderate to abundant eosinophilic cytoplasm * Amyloid is produced by insulin-secreting tumors (from amylin or somatostatin)

Question 747

Important neuroendocrine markers for islet tumor cells

Answer 747

* Synaptophysin * Chromogranin Electron microscopy reveals dense core granules

Question 748

WHO grading system

Answer 748

• Low grade (G1): if 20 mitoses

Question 749

Treatment for insulinoma

Answer 749

90% cured by resection

Question 750

Symptoms of insulinoma...

Answer 750

* Hypoglycemia

Question 751

Lab findings for insulinoma...

Answer 751

* Decreased serum glucose | * Increased serum insulin

Question 752

Are insulinomas mostly benign or malignant?

Answer 752

* Majority are benign, 10% can be malignant | * Most tumors solitary (< 2cm), can be multiple.

Question 753

Which islet cell tumor is "histologically bland"?

Answer 753

Gastrinoma

Question 754

Are gastrinomas mostly benign or malignant?

Answer 754

2/3 of cases malignant

Question 755

Lab findings for gastrinoma...

Answer 755

Marked elevation of serum gastrin (>1000 pg/ml)

Question 756

Which islet cell tumor presents with Zollinger-Ellison syndrome?

Answer 756

* Gastrinoma * Triad: hypersecretion of gastric acid, severe peptic ulceration, presence of non-beta cell tumor of the pancreas or duodenum * May also be associated with MEN1

Question 757

Treatment for gastrinoma...

Answer 757

Medical therapy for control of the acid hypersecretion

Question 758

Nonfunctional islet cell tumors

Answer 758

* 25% of islet cell tumors * 90% malignant * Age 50 year, female predominance * Compression related symptoms * Treatment - surgery

Question 759

Layers of our head, from the outside to inside...

Answer 759

1. Skin 2. Bone a. Epidural space (potential space if pathology occurs) 3. Dura mater (attached to bone) a. Subdural space 4. Arachnoid mater a. Subarachnoid space 5. Pia mater 6. Brain (with specialized blood vessels that prevent many substances from entering brain)

Question 760

Which cells of the CNS are derived from neuroectoderm?

Answer 760

* Oligodendrocytes * Neurons (nerve cells) * Ependymal cells * Astrocytes

Question 761

Which cells of the CNS are derived from mesoderm?

Answer 761

* Microglial cells | * Endothelial cells

Question 762

What makes up the meninges?

Answer 762

* Dura * Arachnoid * Pia mater

Question 763

What are the longest cells of the body?

Answer 763

Motor neurons

Question 764

Which neurons are most susceptible to hypoxia?

Answer 764

* Most susceptible: pyramidal neurons of Sommer's Sector (CA1) of hippocampus * Also highly susceptible: Purkinje cells of cerebellum * Also susceptible: pyramidal neurons in middle layers (III, IV, V) of cerebral cortex, neurons in basal ganglia

Question 765

Which neurons are relatively resistant to hypoxia?

Answer 765

Neurons in brainstem and cerebellum.

Question 766

What do oligodendrocytes produce?

Answer 766

* Myelin | * Help transmit electrical impulses and supports axons.

Question 767

Shape of microglial cells.

Answer 767

* Rod-shaped cells | * Enlarge in a disease state

Question 768

Purpose of Ricinus communis agglutinin 1 (RCA-1)

Answer 768

Highlights microglial cells that are at rest

Question 769

What are microglial nodules?

Answer 769

Clusters that form in viral diseases as a defense mechanism. This is a hallmark of viral infections of the CNS.

Question 770

Hallmark of viral infections in the CNS.

Answer 770

Microglial nodules

Question 771

Two components of the blood brain barrier, separated by a basement membrane...

Answer 771

* Capillary endothelial cells | * Foot processes of astrocytes

Question 772

Disruption of the blood brain barrier causes...

Answer 772

Vasogenic edema

Question 773

Appearance of endothelial cells...

Answer 773

* Specialized * Reduced numbers of pinocytotic vesicles * Many mitochondria * Tight junctions

Question 774

How do tumors cause edema in the brain?

Answer 774

* They produce their own blood vessels | * New vasculature does not have a normal blood brain barrier --> edema --> headache or even seizure

Question 775

What is glioblastoma?

Answer 775

* An aggressive tumor with dark area of hemorrhage and necrosis. * Edema around tumor causes a midline shift (impinges onto opposite hemisphere).