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Flashcards in Dermatopathology Deck (118):
1

Hyperkeratosis

Thickening of the stratum corneum

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Parakeratosis

Flattened, keratinocyte nuclei within the stratum corneum, where nuclei are not normally present

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Orthokeratosis

Hyperkeratosis of anuclear keratinocytes within the stratum corneum

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Acanthosis

Thickened stratum spinosum

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Acantholysis

Loss of cohesion between keratinocytes due to dissolution of intercellular connections

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Dyskeratosis

Abnormally or prematurely cornified (keratinized) keratinocytes in the epidermis that stain pink on H&E

7

What are the layers of the epidermis?

"Cancel labs get some beer"

Stratum Corneum
Stratum Lucidum (thick skin only - palms and soles of feet)
Stratum Granulosum
Stratum Spinosum
Stratum Basale

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Papillomatosis

Irregular undulation of the epidermal surface

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Solar Elastosis

Accumulation of basophilic (grey/blue) matierial in the upper dermis due to sun damage

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Papule

Elevated skin lesion

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Macule

Flat skin discoloration

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Ichthyosis Vulgaris

A disorder of dry, scaly skin due to defective desquamation that leads to build-up into a compacted scale. Often described as “fish scales.”

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What is the inheritance pattern of ichthyosis vulgaris?

Autosomal dominant mutation

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Presents with severe, thick plates of scale that almost resemble reptile scales and present at birth. Mostly affects palms, soles, and flexures.

Lamellar Ichthyosis

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What is the inheritance pattern of lamellar ichthyosis?

Autosomal recessive mutation

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X-linked Ichthyosis

Presents as more brownish and scaly eruption in males, usually in early childhood.

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What is the mutation in X-lined ichthyosis?

Mutation in STS gene leads to defective steroid sulfatase

18

Seborrheic Keratosis

Papillomatosis, acanthosis, and horn cyst formation. Present as stuck on plaques or verrucous lesions

19

Leser-Trelat Sign

Sudden onset of multiple seborrheic keratosis that is indicative of paraneoplastic syndrome and metastatic cancer

20

Acanthosis Nigricans

Lacks acanthosis and horn cyst. Clinically presents as a velvety plaque most common on the back of the neck or axilla.

21

What are fibroepithelial polyps AKA?

- Skin Tag
- Acrochordon

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Common scaly erythematous patch located on sun-damaged skin - Increasingly common with age

Actinic Keratosis

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What is actinic keratosis a precursor for?

SCC

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What is the "flag sign?"

It is seen in actinic keratosis - Basal layer atypia with overlying parakeratosis alternating with orthoparakeratosis.

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What is the most common mutation associated with SCC?

P53 mutations

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Squamous Cell Carcinoma

Squamous cell carcinomas are generally erythematous, scaly papules or plaques with ill-defined borders, and they may be confused with large, hypertrophic AKs.

27

Clinical Presentation of SCC

SCCs usually present as firm, skin-colored to pink, papules or plaques, commonly found on the head and neck region of elderly individuals.

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What is seen on histology of SCC?

- Keratin pearls
- Mitotic figures
- Cells have a glassy eosinophilic cytoplasm, with large nuclei

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Bowen's Disesase (SCC in-situ)

Full thickness atypia, basal layer sparing and may show skip areas but involves follicles with no invasion into the dermis in contrast to SCC

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Bowenoid Papulosis

Similar appearance to Bowen's disease:

- HPV-induced, located on the genitals
- Frequently multiple papules
- May spontaneous regress or progress

31

What is the appearance of basal cell carcinoma on the skin?

Pearly, pink papule with overlying telangiectasia

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What is the most common invasive skin cancer?

Basal Cell Carcinoma

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What demographic is more often affected by BCC?

Older population

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What are the 2 mutations most often seen in BCC?

- p53
- PTCH

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What is the most frequent location of BCC?

Sun-exposed areas

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Initially presents as a small, translucent, pearly papule with telangiectasias on its surface. As the lesion progresses, the center may become ulcerated and the borders become indurated, rolled and pearly.

Nodular BCC

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Where are nodular BCCs most often found?

This variant is frequently found on the face.

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It appears as a pink, scaly plaque with a slight elevation pearly border. Crusting and ulceration may sometimes be present.

Superficial BCC

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Where are superficial BCCs most often found?

The superficial BCC is commonly located on the thorax and limbs.

40

Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome)

Autosomal dominant disease - multiple BCCs seen before age 20 and seen with PCTH mutation

41

An 65 year old, Caucasian male patient present to dermatology clinic for an annual skin check. He has an occupational history as a banking executive. He splits his time between your suburban city (were they reportedly have high chlorine levels in the water system) and his near by lake home. He was very active until a chronic lower leg ulcer secondary to his severe diabetes has been affecting him the last couple of years and he reports a recent 20 pound weight gain since. His risk factors for squamous cell carcinoma include:
A) Occupational exposure, age, gender, and chronic leg ulcer.
B) Age, gender, exposure to UVB rays, chronic cutaneous wound
C) Choline exposure, diabetes, activity levels
D) Age,gender,diabetes,activitylevel,andobesity.

B) Age, gender, exposure to UVB rays, chronic cutaneous wound

42

Recently your Aunt has been diagnosed with cutaneous SCC. She comes to you (the family doctor) to ask what is the likely cause and outcome of her diagnosis? Which of the following is the best statement about SCC of the skin?

A) It is hereditary and it often metastases. She will require sentinel node biopsy and if positive chemotherapy.
B) Many things cause SCC but her chances are great with local radiation at the site
C) SCC is directly associated with sun exposure. The treatment is local excision. Less than 5% metastasize.
D) SCCismostcommonlycausebyoccupational exposure to carcinogen. She needs to consider suing her previous employers. She will need an excision to prevent metastasis.

C) SCC is directly associated with sun exposure. The treatment is local excision. Less than 5% metastasize.

43

A 13 year old patient present with 2 separate nodules that you biopsy and the path report demonstrates a proliferation of basaloid cells extending from the lowest level of the epidermis into the dermis. This patient’s tumor likely has which of the following genetic mutations:
A. A sporadic mutations in TP53
B. Familial mutation in either PATCH or TP53 genes
C. Familial mutation in CDKN2A
D. None of the above; these tumor have no known genetic mutations.

B. Familial mutation in either PATCH or TP53 genes

44

Freckle (Ephelis)

Small, tan-red to light brown macules on sun-exposed areas. Most common lesion of childhood.

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Lentigo

Small, oval tan-brown. Mucous membranes and any age.

Melanocytic hyperplasia along the basal layer.

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Melanocytic Nevi

Tan to brown macules and papules.

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What are the common types of melanocytic nevi and where they are generally found?

Junctional - epidermis at the DEJ
Compound - between the epidermis and dermis with some nest present in the dermis
Intradermal - nests are exclusively within the dermis

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Melanoma

Nests and single malignant melanocytes which are the clearish cells in the basal layer.

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Dysplastic Nevi

They are a subgroup of nevi which have an irregular outline, variable pigmentation, indistinct borders, and can be larger than 5 mm in diameter.

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Does dysplastic nevi progress to melanoma?

No. It has never been proven and most are stable but they do indicate a risk factor for melanoma.

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Dysplastic Nevus Syndrome

Tendency to develop multiple dysplastic nevi and melanoma - 50% have early melanoma by age 60

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What is the inheritance pattern of dysplastic nevus syndrome?

Autosomal dominant, CDKN2A gene on chromosome 9

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Sentinel Lymph Node Biopsy

Done for prognosic indication - positive is poor prognostic indicator for melanoma

54

What are the characteristics of skin melanoma?

- Asymmetrical
- Irregular border
- Uneven color
- Growth in diameter
- Evolving changes

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What are the most important predisposing factors in the development of melanoma?

Two most important predisposing factors are inherited genes and sun exposure

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What is the main mutation seen in familial melanoma?

CDKN2A

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What is the treatment for melanoma and what are the limitations?

Vemurfenib can create disease free state but does not change overall survival

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Radial Growth Phase of Melanoma

Superficial spreading that highly involves the epidermis

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Vertical Growth Phase of Melanoma

Nodular or progression of radial growth phase melanoma that implies metastatic potential

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What types of melanoma can progress to vertical growth phase?

ALL types

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What is Stage III melanoma indicative of?

Nodal involvement beyond the skin

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The prognostic features of melanoma include:
A) Type, location, age of patient, and quantity of sun exposure
B) Age, location, nodular or superficial spreading type, and ulceration
C) Type, mitotic figures, Clarks level, clinical measurement of size
D) Ulceration, depth of invasion, and mitotic count.

D) Ulceration, depth of invasion, and mitotic count.

63

The biopsy is taken from a pigmented lesion on the upper back of a 48 year old female patient. The histology shows an intradermal and dermal proliferation of nested and single melanocytes. The epidermal population of melanocytes extends well past the dermal population. There is an increase in the number of single melanocytes normally seen in the rete and many of the nests are touching forming bridges. Many of the melanocytes appear slightly larger and demonstrate mild atypia. The best diagnosis is:
A) Malignant melanoma
B) Melanoma in situ
C) Common Compound Nevus
D) Compound Dysplastic Nevus

D) Compound Dysplastic Nevus

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Trichilemmoma

A proliferation of the outer root sheath, with small solitary lobules or groups of lobules connected to the epidermis with vertical growth.

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Cowden's Disease

Multiple trichilemmomas, sclerotic fibromas, acral keratosis, oral fibromas. Also has an increased risk of breast/endometrial/thyroid cancer.

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What is the inheritance pattern of Cowden's disease and what is the mutation?

Autosomal dominant pattern of inheritance, caused by a mutation in the PTEN gene.

67

Dermatofibroma

Pink papule common on the extremities

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What are the histological signs of dermatofibroma?

- Hyperpigmented basal layer that “tables”
- Scattered boomerrang shaped cells

69

Dermatofibrosarcoma Protuberans

Most commonly seen on youngish patients on the trunk. Presents as papules or nodules - has high morbidity due to the aggressiveness of the invasion

70

What are the histological features of dermatofibrosarcoma protuberans?

- Monomorphic spindle cells arranged in a “storiform” or “cartwheel” pattern
- CD 34 positive

71

Keloid Scar

Nodular fibroblastic proliferation and the presence of hypocellular, glassy, eosinophilic, hyalinized and disordered collagen fibers in dermis.

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Cylindroma

Thought to be apocrine in origin, will see histopathologically multiple puzzle-like basaloid lobules in a mosaic or puzzle pattern. Clinically appears as a “turban” around the head or forehead.

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Sebaceous Adenoma

Clinical: papule or small nodule that are an overgrowth of a sebaceous gland. Yellowish. May be part of Lynch Syndrome / Muir Torre syndrome

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Leiyomyoma

Small fascicles of bland, eosinophilic spindle cells in mid dermis that are tumors of the pilar muscles

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What are the histological features of leiyomyoma?

Bubbles and cigar cells

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Polyarteritis Nodosum

- Rare, inflammatory disease of small and medium sized muscular arteries
- Multiple organs; also cutaneous only variant involving small-med art. of subcutis

77

Erythema Nodosum

- Most common on front of legs
- May be associated with drugs
- Macular "bruised" look

78

Lichenoid Dermatitis

Lichenoid infiltrate with acanthoisis - saw toothing on histology

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Erythema Multiforme

Self resolving caused by infections most common HSV - lichenoid dermatitis with civatte bodies

80

What kind of rash will be seen with erythema multiforme?

Annular Targetoid Rash

81

What are the characteristics of Stevens Johnson Syndrome and Toxic Epidermal Necrolysis?

Defined by mucosal involvement and body surface involvement

82

Epidermal atrophy w/interface, superficial and deep perivascular & periadnexal infiltrate of lymphocytes with plasma cells.

Discoid Lupus Erythematosus

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What will be seen in the dermis of a DLE patient?

Mucin

84

Histologic findings similar to LE, but often milder with epidermal atrophy and less inflam infiltrates, no deep or periadnexal infiltrates, less mucin.

Dermatomyositis

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Atrophy and papillary dermal edema with collagen sclerosis, follicular plugging.

Lichen Sclerosus Et Atrophicus

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Where is lichen sclerosis et atrophicus often found?

On the vulva as a white patch.

87

Psoriasiform Dermatitis

Acanthosis that is even throughout

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What gene is psoriasis associated with?

HLA-C

89

- Well demarcated plaques with adherent silver / white scale
- Nail discoloration or pitting

Psoriasis

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Auspitz Sign

Seen in psoriasis where thinning of the suprapapillary plates with dilated papillary vessels can lead to micro-bleeds with peeling off of the scale

91

What diseases will see a loss of the stratum granulosum?

- Psoriasis
- Ichtyosis Vulgaris

92

What is edema between the keratinocytes indicative of?

Spongiotic Dermatitis

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Allergic Contact Dermatitis

Inflammatorydisorder initiated by contact with an allergen to which to person has been previously sensitized - erythematous papules

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Bullous Dermatitis

Separation of the dermis from the epidermis with the formation of bulla or vesicles

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What is used for the diagnosis of bullous dermatitis?

Direct immunofluorescence for auto-Ab

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Bullous Pemphigoid

Tense bulla often in the inner aspects of thighs, flexor
surfaces of forearms, axillae,
groin, and lower abdomen

97

Subepidermal blister with eosinophils....

Bullous Pemphigoid

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What does DF show for bullous pemphigoid?

Linear IgG deposition at the DEJ

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Pemphigus Vulgaris

Superficial vesicles and bullae that rupture easily, leaving shallow, crusted erosions - tombstoning

100

What does DF show for pemphigus vulgaris?

Net-like IgG and C3 on direct immunofluorescence

101

Dermatitis Herpetiformis

Pruritic papules / vesicles on erythematous base. Associated w/ celiac disease, both the vesicular dermatitis and the enteropathy respond to a gluten-free diet.

102

What will DF show for dermatitis herpetiformis?

Granular IgA deposits

103

What is a disease that can have granulomatous dermatitis?

Sarcoidosis

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Variant of leukoclastic vasculitits that is accompanied by arthritis, abdominal pain, and or hematuria

Henoch-Schonlein Purpura

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What is the most common cutaneous lymphoma?

Mycosis Fungoides

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Lymphocytes line up on the DEJ - epidermotrophism

Mycosis Fungoides

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Verruca Vulgaris

HPV driven infection with hyperkeratosis and hypergranulosis.

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What are koilocytes and when are they present?

Koilocytes: vacuolated keratinocytes with raisin like nuclei - verruca vulgaris

109

Molluscum Contagiosum

Small papules - can look umbilicated with a
hole in the center

110

Multinucleated, marginated chromatin seen in tissue or Tzanck Smear

Herpes Simplex Virus Infection

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Oral Herpes Cause

HSV 1

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Genital Herpes Cause

HSV 2

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Shingles

Reactivation of VZV infection - HZV
- Focal unilateral / dermatomal distribution unless disseminated
- Painful/pruritic vesicle most common on trunk

114

Hutchinson's Sign

HZV involvement of the nose alerts the physician to the possibility of ocular involvement which can result in vision impairment if not treated promptly.

115

Bullous Impetigo

Common in children due to S. aureus infection - presents as flaccid blisters that collapse easy resulting in honey colored crust

116

Onychomycosis

Dermatophyte infection of the nail

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Broad based budding yeast forms present in tissue.

Blastomycosis

118

Large, intracellular or free yeast-like organisms, mucin stains thick capsule.

Cryptoccocus

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