Derm Flashcards

Question

Answer 1

INCONTINENTIA PIGMENTI (IP), VESICULAR STAGE * X-linked dominant * male lethal * rarely occur in males with Klinefelter (XXY) or somatic mosaicism * mutations in the NEMO/IKK -gamma gene, chromosome Xq28, regulatory subunit of the inhibitor kappa kinase (IKK) complex and is required for the activation of the transcription factor NF-kappaB (NF-kB). NF-kB is central to many immune, inflammatory, and apoptotic pathways. * neurocutaneous syndrome with cutaneous, neurologic, ophthalmologic, and dental manifestations (ectoderm and neuroectoderm ) * early, vesicular and/or verrucous stages of incontinentia pigmenti are present at birth or develop in the first few weeks of life i * Eosinophilic spongiosis w/dyskeratotc keratinocytes DDx: * eczematous derm * erythema toxicum neonatorum (no dyskeratosis)

Answer 2

NEUTROPHILIC SPONGIOSIS Found in: * pustular psoriasis * subcorneal pustulosis (Sneddon Wilkinson) * acute generalized exanthematous pustulosis (AGEP) * dermatophytosis * bacterial infections * Reiter’s syndrome

Answer 3

PSORIASIS * Common chronic inflammatory dermatosis * most frequently affects the elbows, knees, scalp, lumbosacral areas, intergluteal cleft, and glans penis * Well-demarcated, pink to salmon-colored plaque covered by loosely adherent scales that are silver-white in color * nail changes in 30% of cases

Answer 4

Histpathology of psoriasis Regular acanthosis, hypogranulosis, wafer-like parakeratosis with neutrophils, increased pap dermal capillaries (thinning of supra-papillary plates) • Guttate and early psoriasis exhibit less acanthosis and more spongiosis • DDx: clear cell acanthoma (discrete pale zones), chronic spongiotic dermatitis, PRP, LSC, MF

Answer 5

CHRONIC SPONGIOTIC DERMATITIS * Irregular or uneven hyperplasia, w/parakeratosis * spongiosis may be minimal * no loss of the granular layer * Any spongiotic dermatitis in chronic phase, including tinea!

Answer 6

LICHEN SIMPLEX CHRONICUS (LSC) AND PRURIGO NODULARIS * hyperkeratosis * irregular acanthosis * hypergranulosis * papillary dermal fibrosis * chronic inflam (+/- eos)

Answer 7

MYCOSIS FUNGOIDES, PLAQUE STAGE * Psoriasiform lichenoid pattern * look for cytologic atypia, epidermotropism, Pautrier’s

Answer 8

NECROLYTIC MIGRATORY ERYTHEMA (NME) * a/w glucagonoma syndrome * glucagon-secreting tumor * diabetes mellitus * hypoaminoacidemia * cheilosis * anemia * venous thrombosis * weight loss * neuropsychiatric features * genital, anal, buttocks, groin, lower legs * Histology * Pale keratinocytes * superficial necrosis * neutrophilic crust DDx: * zinc (acrodermatitis enteropathica) or niacin (pellagra) deficiency * psoriasis

Answer 9

Vesiculobullous Reaction Pattern * Vesicles or bullae at any level of epidermis * DIF VERY helpful * Diagnosis depends on assessment of three features: * Anatomic level of Split * Underlying mechanism responsible for split * Nature of inflammatory infiltrate

Answer 10

BULLOUS PEMPHIGOID (BP) * Clin: common, typically older pts. with itchy, tense vesicles/ bullae on flexor surfaces * Lots of eosinophils in papillary dermis and along DE jn * DIF: linear basement membrane deposition of IgG, C3

Answer 11

DERMATITIS HERPETIFORMIS * Clin: young adult pts, h/o celiac disease; grouped vesicles on extensor surfaces * Neutrophils ± eos in dermal papillae, ± subepi split * DIF: papillary dermal deposition of IgA • * DDx: linear IgA (need DIF to distinguish)

Answer 12

EPIDERMOLYSIS BULLOSA ACQUISITA (EBA) Clin: adults, a/w/autoimmune diseases; noninflammatory bullae, extensor surfaces Histo: pauci-inflammatory blister with few lymphs; rare inflam bullae with neuts, few eos DIF: thick band of IgG, and to a lesser extent C3, deposited linearly at the basement membrane, +/- IgM or IgA

Answer 13

PORPHYRIA CUTANEA TARDA (PCT) * Acral site * cell-poor blister shows “festooning” (dermal papillae preserved) * caterpillar bodies adherent to epidermis * roof of blister has eosinophilic, PAS-D+linear globules * DIF: * IgG; to lesser extent IgM, fibrinogen and C3, outline donut–shaped blood vessels in the papillary dermis * Immunoreactivity also at the dermo-epidermal junction and within basement membrane region of eccrine sweat glands and duct

Answer 14

PEMPHIGUS VULGARIS (PV) * Flacid, easily ruptured blisters. Oral involvement. * Suprabasilar acantholysis with “tombstoning” of remaining basal keratinocytes * Direct immunofluorescence (DIF): intercellular IgG and C3 (fishnet stockings) * DDx: Darier’s, Grover’s disease, fixation artifact in oral mucosa

Answer 15

PEMPHIGUS FOLIACEUS (PF) * Superficial bullae usually start on the trunk * Cleavage at granular layer: beware of the missing stratum corneum * DIF: mainly IgG4 directed against a cell adhesion molecule, desmoglein 1 (160 kd), expressed mainly in the granular layer of the epidermis. * DDx: Staph scalded skin syndrome

Answer 16

DARIER’S DISEASE * Clin: autosomal dominant disease, greasy papules on head and neck * Acanthosis, suprabasal acantholytic dyskeratosis with “corps ronds” (dyskeratotic cells) and grains (parakeratotic cells) * Mutations in the gene ATP2A2, located on 12q23-24.1, encodes the sarcoplasmic/endoplasmic reticulum Ca2+ -ATP isoform 2 protein (SERCA2) * This pump maintains a low cytoplasmic Ca2+ level by actively transporting calcium ions from the cytosol into the lumen of the endoplasmic reticulum. * Miglustat: orphan drug, α-glucosidase inhibitor, restores mature adherens junctions and desmosomes and increases adhesion strength

Answer 17

TRANSIENT ACANTHOLYTIC DERMATOSIS (GROVER’S) * Usually trunk of older males, itchy lesions * 3 patterns may be apparent: * Spongiotic * PV or Darier’s-like suprabasilar acantholysis * Hailey-Hailey-like full thickness acantholysis * DDX: PV, Darier’s and HHD (clin history), focal acantholytic dyskeratosis (incidental or a/w/underlying lesion, e.g., nevus, scar, etc.)

Answer 18

HAILEY-HAILEY DISEASE (BENIGN FAMILIAL PEMPHIGUS) * Vesicles and erythematous plaques with overlying crusts typically occur in the genital area, as well as the chest, neck, and axillary * “dilapidated brick wall” with full-thickness and suprabasilar acantholysis * Defect in a calcium pump protein, ATP2C1 which encodes the secretory pathway Ca2+/Mn2 ATPase (hSPCA1). * loss of sensitivity to Ca2+ and Mn2+ion binding and transport * low levels of Ca2+ within Golgi bodies impair protein processing * DIF is negative

Answer 19

Granulomatous Reaction Pattern * Presence of chronic granulomatous inflammation * Five types * Sarcoidal * Tuberculoid * Necrobiotic (collagenolytic) granulomas * Suppurative * Foreign body

Answer 20

GRANULOMA ANNULARE (GA) * Dermal papules and annular plaques, young females * Histology * Palisaded histiocytes surrounding foci of necrobiosis (degenerative collagen) * few neuts or eos may be seen * mucin present * deep and interstitial forms described * DDx: NLD (broad, parallel layers of necrobiosis), epithelioid sarcoma (necrosis, atypical cells)

Answer 21

NECROBIOSIS LIPOIDICA DIABETICORUM (NLD) * Broad, palisaded layers (“lasagna-like”) of necrobiosis * Not as discrete as GA, lacks mucin * All of the dermis all of the time

Answer 22

RHEUMATOID NODULE * Deep dermal or SQ nodule * palisaded histiocytes w/ fibrin in center * lymphs and plasma cells * Difficult to tell from deep GA (mucin helpful)

Answer 23

SARCOIDOSIS * “Naked” granulomas with scattered lymphocytes, lack necrosis, may see asteroid or Schaumann bodies * Clinical essential to rule out sarcoid, always mention sarcoidosis in differential diagnos

Answer 24

TUBERCULOSIS & ATYPICAL MYCOBACTERIAL INFECTIONS * numerous lymphocytes surrounding granulomas * abundant histiocytes * may have neutrophils, esp. early lesions * often central necrosis * AFB, Fite stains, cultures required

Answer 25

FOREIGN BODY REACTION * Look for “holy” pattern (paraffin, silicone) or ruptured hair follicle/cyst material

Answer 26

Leukocytoclastic Vasculitis

Answer 27

Urticaria * dermal edema * dilated lymphovascular spaces

Answer 28

NEUTROPHILIC DERMATOSIS (SWEET’S SYNDROME) * sudden onset of fever * elevated white blood cell count * tender, red, well-demarcated papules and plaques * dense dermal neutrophilic infiltrate * NO leukocytoclastic vasculitis

Answer 29

Overview of classification of inflammatory skin diseases * A. Lichenoid dermatitis * B. Spongiotic dermatitis * C. Psoriasiform dermatitis * D. Vesiculobullous dermatitis * E. Granulomatous dermatitis * F. Vasculopathic dermatitis * G. Infectious Disease * H. Panniculitis * I. Alopecia

Answer 30

Lichenoid Dermatitis 1. LICHEN PLANUS (LP) 2. ERYTHEMA MULTIFORME (EM) & TOXIC EPIDERMAL NECROLYSIS (TEN) 3. ACUTE GRAFT-VERSUS-HOST DISEASE (GVHD) 4. LUPUS ERYTHEMATOSUS (LE) 5. DERMATOMYOSITIS (DM) 6. LICHEN NITIDUS 7. LICHEN SCLEROSUS ET ATROPICUS (LS&A) 8. PITYRIASIS LICHENOIDES ET VARIOLIFORMIS ACUTA (PLEVA) AND CHRONICA (PLC) 9. MYCOSIS FUNGOIDES

Answer 31

Spongiotic Dermatitis 1. SPONGIOTIC DERMATITIS +/- EOSINOPHILS 2. DERMATOPHYTOSIS (TINEA) 3. PITYRIASIS ROSEA (PR) 4. INCONTINENTIA PIGMENTI (IP), VESICULAR STAGE 5. NEUTROPHILIC SPONGIOSIS

Answer 32

Psoriasiform Dermatitis 1. PSORIASIS 2. CHRONIC SPONGIOTIC DERMATITIS 3. LICHEN SIMPLEX CHRONICUS (LSC) AND PRURIGO NODULARIS 4. MYCOSIS FUNGOIDES, PLAQUE STAGE 5. NECROLYTIC MIGRATORY ERYTHEMA (NME)

Answer 33

Vesiculo- Bullous Dermatitis SUBEPIDERMAL 1. BULLOUS PEMPHIGOID (BP) 2. DERMATITIS HERPETIFORMIS 3. EPIDERMOLYSIS BULLOSA ACQUISITA (EBA) 4. PORPHYRIA CUTANEA TARDA (PCT) INTRAEPIDERMAL 1. PEMPHIGUS VULGARIS (PV) 2. PEMPHIGUS FOLIACEUS (PF) ACANTHOLYTIC DYSKERATOSIS 1. DARIER’S DISEASE 2. TRANSIENT ACANTHOLYTIC DERMATOSIS (GROVER’S) 3. HAILEY-HAILEY DISEASE (BENIGN FAMILIAL PEMPHIGUS)

Answer 34

Granulomatous Dermatitis 1. GRANULOMA ANNULARE (GA) 2. NECROBIOSIS LIPOIDICA DIABETICORUM (NLD) 3. RHEUMATOID NODULE 4. SARCOIDOSIS 5. TUBERCULOSIS & ATYPICAL MYCOBACTERIAL INFECTIONS 6. FOREIGN BODY REACTION

Answer 35

Vasculopathic Dermatitis 1. Leukocytoclastic Vasculitis 2. Urticaria 3. NEUTROPHILIC DERMATOSIS (SWEET’S SYNDROME)

Answer 36

INFECTIOUS DISEASES 1. STAPH. SCALDED SKIN SYNDROME 2. HSV/VZV 3. MOLLUSCUM CONTAGIOSUM 4. VERRUCA VULGARIS (VV) 5. DERMATOPHYTOSIS 6. TINEA VERSICOLAR 7. CANDIDIASIS 8. CHROMOBLASTOMYCOSIS (A.K.A., CHROMOMYCOSIS) 9. CRYPTOCOCCUS NEOFORMANS 10. HISTOPLASMA CAPSULATUM 11. LEISHMANIASIS 12. SCABIES 13. Bullous Impetigo

Answer 37

STAPH. SCALDED SKIN SYNDROME * Cell-poor bullae (no organisms) * very superficial cleavage within or just below granular layer (like pemphigus foliaceus)

Answer 38

HSV/VZV * Ballooned and multinucleated keratinocytes with peripheral margination of chromatin * “steel gray” nucleus * often epidermal ± follicular necrosis

Answer 39

MOLLUSCUM CONTAGIOSUM * Molluscum bodies (eosinophilic intracytoplasmic inclusions) * caused by poxvirus

Answer 40

VERRUCA VULGARIS (VV) * Verrucous epidermal hyperplasia * HK and PK * stratum corneum hemorrhage * prominent keratohyaline granules * HPV cytopathic changes? * DDx: verrucous SK, atypical squamous proliferation, verrucous SCC

Answer 41

DERMATOPHYTOSIS (TINEA) * Spongiosis +/- eosinophils * Parakeratosis containing neutrophilic dust * “Sandwich sign”: hyphae sandwiched between basketweave orthokeratosis above and compact hyperkeratosis or parakeratosis below

Answer 42

TINEA VERSICOLOR * Tinea versicolor presents as macules and patches of hypo/hyperpigmentation on trunk. * Hyphae and yeast forms can be seen on H&E

Answer 43

CANDIDIASIS * Yeast and septate pseudohyphae (no branching) * mucosal surfaces and intertriginous zones

Answer 44

CHROMOBLASTOMYCOSIS (A.K.A., CHROMOMYCOSIS) * Medlar bodies * pigmented yeast forms * resemble “copper pennies”

Answer 45

CRYPTOCOCCUS NEOFORMANS * Large, intracellular or free yeast-like organisms * mucin stains thick capsule

Answer 46

HISTOPLASMA CAPSULATUM * Small intracytoplasmic organisms with surrounding clear halo * PAS & GMS+ * DDx: leishmaniasis (kinetoplast, Giemsa+)

Answer 47

LEISHMANIASIS * Tiny intracytoplasmic organisms * eccentrically located basophilic kinetoplast * lack capsule * Giemsa+

Answer 48

SCABIES * Spong derm with prominent dermal eosinophils * may see intracorneal burrow with mite

Answer 49

Bullous Impetigo * Honey Colored Crusts * Subcorneal blister with neutrophils and bacteria present * Microbiology Correlation: Gram stain of the blister contents shows gram positive cocci in clusters

Answer 50

PANNICULITIS In practice, biopsy of panniculitis is often not diagnostic may only be able to classify as to lobular or septal panniculitis, and give DDx

Answer 51

ERYTHEMA NODOSUM (EN) * Septal pattern of panniculitis * Miescher’s radial granulomas * essentially normal epidermis and dermis * Most common on front of legs * May be associated with * drugs (sulfa or NSAID or OCPs) * infections (TB) * idiopathic

Answer 52

ERYTHEMA INDURATUM- NODULAR VASCULITIS * Classified as a lobular panniculitis * 30-80% have mycobacterial DNA by PCR * Histology: * Septo-lobular panniculitis * granulomatous inflammation * vasculitis * focal necrosis * DDx: polyarteritis nodosa (more localized)

Answer 53

PANCREATIC FAT NECROSIS * Clinical hx important * Lobular necrosis with abundant neutrophils, presence of calcification

Answer 54

LIPODERMATOSCLEROSIS (SCLEROSING PANNICULITIS) * septal and lobular * lipomembranous fat necrosis * cystic degeneration * seen w/stasis dermatitis

Answer 55

DDX FOR NEEDLE-SHAPED CLEFTS IN THE FAT * Sclerema neonatorum (lipocytes, min inflammation) * Subcutaneous fat necrosis of the newborn (lipocytes and giant cells/ inflammation) * Post-steroid panniculitis (clinical hx)

Answer 56

Lupus profundus

Answer 57

DDX FOR SUBQ LYMPHOID INFILTRATES * Lupus profundus * Reactive lymphoid hyperplasia/B-cell “pseudolymphoma” * Chronic insect bite * drug reaction * Marginal zone B- cell lymphoma * Follicle center lymphoma * Subcutaneous panniculitis like T cell lymphoma

Answer 58

ALOPECIA AREATA * “Swarm of bees”: lymphocytes surrounding anagen hair bulbs * May only be present in acute/subacute phase

Answer 59

TRICHOTILLOMANIA * Trichomalacia (damaged or distorted follicles) * may see follicular hemorrhage, pigment casts

Answer 60

LICHEN PLANOPILARIS (LPP) * Alopecia secondary to inflammatory destruction of follicles * may see characteristic LP changes * interface inflammation with dyskeratotic cells * usually superficial portions of follicles * Diff dx: * Lupus-associated alopecia: superficial and deep perivascular and periadnexal infiltrate, ↑’d dermal mucin, BM thickening, DIF+

Answer 61

SCARRING ALOPECIA * Often nonspecific, end-stage finding in many different (including inflammatory) causes of alopecia * Specific entities include: * central centrifugal scarring alopecia (pseudopelade folliculitis decalvans) * dissecting cellulitis * acne keloidalis * chronic traction

Answer 62

Dermatofibrosarcoma Protuberans * slow-growing dermal spindle cell tumor of intermediate malignancy * typically occurs on the trunk and proximal extremities of young and middle-aged adults * solitary lesion or multiple polypoid nodules arising in an indurated plaque * Local recurrence is common, occurring in one third of all cases. * immunohistochemical and ultrastructural evidence indicates a fibroblastic origin * t(17;22) translocation in \> 90% --\> pathogenic COL1A1-PDGFB fusion gene * most helpful diagnostic marker is CD34, which stains 50% to 100% of the cells * CD34 is negative or focally positive in dermatofibromas * PCR may be used to identify the COL1A1-PDGFB fusion gene DDx: Giant cell fibroblastoma * considered a variant of dermatofibrosarcoma protuberans that often manifests in childhood * may exhibit the same immunogenetic and cytogenetic profile as DFSP Fibrosarcomatous change in DFSP * characterized by a fascicular or herringbone growth pattern, represents malignant transformation * fibrosarcomatous areas express CD34 in less than 50% of cases

Answer 63

Langerhans Cell Histiocytosis * Langerhans cell histiocytosis previously was divided into multiple clinical subtypes, but there is much overlap. The different forms of Langerhans cell histiocytosis have similar pathology in that there is a proliferation of Langerhans cells, which can be identified by the distinctive reniform, or kidney-shaped, nuclei. * Langerhans cells stain positively with S-100 protein and CD1a immunohistochemical stains. Langerhans cells do not stain with CD68. * With electron microscopy, characteristic Birbeck granules are seen within Langerhans cells. The Birbeck granules resemble a tennis racquet. * BRAF V600Emutation Letterer-Siwe disease * acute disseminated form of Langerhans cell histiocytosis * usually seen in infants and has many systemic manifestations * skin lesions are characterized by hyperpigmented scaly patches, which can coalesce and form a seborrheic dermatitis–like eruption * unresponsive dermatitis in the diaper area * hyperpigmented papules with associated hemorrhage at the periphery of the dermatitis area Hand-Schüller-Christian disease * a form of Langerhans cell histiocytosis that is characterized by the triad of bone lesions, exophthalmos, and diabetes insipidus Eosinophilic granuloma * a form of Langerhans cell histiocytosis that usually consists of either a few lesions or one lesion and most commonly affects the bone * skin and oral mucosa occasionally can be involved. Congenital self-healing reticulohistiocytosis * also known as Hashimoto-Pritzker disease * a variant of Langerhans cell histiocytosis with a very good prognosis * lesions are often present at birth but can manifest within the first few weeks of life as well * most commonly, there are scattered papules and nodules over the skin * occasionally, only a single lesion is present

Answer 64

Tuberous sclerosis cutaneous lesions * hypomelanic macules (ash-leaf) * facial angiofibromas * periungal or subungal fibromas * shagreen patches * fibrous hamartomas Two different genes are associated with tuberous sclerosis: * TSC1 gene: hamartin, 9q34 * TSC2 gene: tuberin, 16p13.3

Answer 65

Lichen Amyloidosis * Amyloidosis refers to a group of disorders characterized by abnormal extracellular deposition of β-pleated amyloid protein, either systemically or localized to a specific organ. There are approximately 25 distinct forms of amyloid fibril proteins. * Primary localized cutaneous amyloidosis is associated with the deposition of amyloid in the skin without associated deposits in internal organs. The most common variants are macular amyloidosis and lichen amyloidosis. * The amyloid in macular amyloidosis and lichen amyloidosis is believed to be keratinocyte-derived. This belief has been supported by ultrastructural studies demonstrating transitional forms between viable keratinocytes and amyloid and by positive reactions with monoclonal antibodies directed against keratin. * Lichen amyloidosis usually manifests as persistent, pruritic plaques on the shins or other extensor surfaces of the extremities, particularly the anterior thighs or forearms. Macular amyloidosis manifests as pruritic, hyperpigmented macules that form a rippled pattern, most commonly on the upper back. * On histopathologic examination, macular amyloidosis and lichen amyloidosis demonstrate amorphous, eosinophilic deposits of amyloid limited to the papillary dermis. Pigment incontinence within melanophages and a sparse perivascular lymphohistiocytic infiltrate are often seen. In lichen amyloidosis, the deposits may expand the papillae and displace the elongated rete ridges laterally. The overlying epidermis is acanthotic and hyperkeratotic. * Congo red stains amyloid protein a brick-red color, and amyloid exhibits positive “apple-green” birefringence under polarized light. Other histochemical stains that can be used to detect amyloid deposits include crystal violet, methyl violet, PAS, Sirius red, pagoda red, and thioflavine T.

Answer 66

Pernio * aka chilblains * inflammatory skin condition * pruritic, painful, or pruritic and painful violaceous papules and nodules that occur on acral surfaces, most commonly the dorsum of the fingers and toes, but the nose, ears, and thighs also can be affected * A clue to the diagnosis is the anatomic distribution and cyclic nature of the lesions * develops in patients exposed to nonfreezing cold in damp conditions * lesions develop with a change of weather going into winter and resolve during spring and summer * most commonly, occurs in young women * Histology * superficial and deep perivascular land periadnexal ymphocytic dermal inflammatory infiltrates t * perieccrine accentuation of the infiltrate is characteristic * varying amount of interface change can be seen * Pernio and chilblains lupus erythematosus have overlapping clinical and histologic features, evaluate for SLE * should not be confused with lupus pernio, which refers to a form of cutaneous sarcoidosis

Answer 67

Dermatofibrosarcoma protuberans * young adults * male predominance * trunk and the proximal extremities * early lesions have a plaquelike appearance and late lesions are multinodular with skin ulceration * low-grade sarcoma with a high propensity for local recurrence if incompletely excised * complete excision requires wide margins because of infiltration beyond the grossly visible margins * recurrence rate of 20% within 2 years of surgery * Mohs surgery significantly reduces the rate of recurrence ( * Gross: the lesion is firm and fibrous and varies from a small dermis based plaquelike area or nodule to a large multinodular lesion that ulcerates the overlying skin and deeply involves the underlying adipose tissue * occasionally may be purely subcutaneous * Histology: * proliferation of uniform, mildly atypical spindle cells, arranged in a tight, repetitive storiform pattern * infiltrates the dermis surrounding the epidermal appendages and infiltrates the fat in a checkerboard or beaded pattern * lesional cells are uniformly CD34 positive * may contain fascicular areas that are indistinguishable from fibrosarcoma * composed of intersecting fascicles of spindle cells with increased atypia and mitotic activity (\>10 mitoses per 10 HPFs) * to be considered fibrosarcomatous, must represent \> 5% of the entire lesion * DFSP with fibrosarcomatous transformation has a small but definite metastatic potential 5% to 10% * lung is the most common site of dissemination * t(17;22) *COL1A1-PDGFB*

Answer 68

Reparative Granuloma (Formerly Giant Cell Reparative Granuloma) * benign, reactive lesion of bone of unknown cause * 10 to 25 years * predilection for facial bones such as the mandible and maxilla * second most common site is the bones of the hands and feet * local swelling secondary to the expansion of the contour of the underlying bone * Xray: * round or oval lucency with fine trabeculations and well-defined margins * may expand the contours of the bone and cause cortical thinning * usually no cortical destruction or periosteal new bone formation * surgical curettage is the treatment of choice * recurrence rate is high (33% to 50%) in the lesions of the hands and feet * in these locations, reparative granulomas that show destructive behavior are best treated by amputation or ray resection

Answer 69

Pemphigus Vulgaris autoimmune blistering disorder autoantibodies directed against desmoglein 3 and desmoglein 1, desmosomal proteins that are part of the cadherin family flaccid blisters can develop both in the oral mucosa and on the skin lesions tend to appear in the oral cavity and proceed to involve the skin blisters commonly break and leave erosions on the skin Histology: * intraepidermal blister, acantholysis and “tombstone” pattern of basal layer keratinocytes Direct immunofluorescence testing * perilesional skin adjacent to a blister, distinct pattern of intercellular deposition of IgG and C3 (vulgar fishnet stockings) Indirect immunofluorescence * testing a patient’s serum on monkey esophagus, pemphigus vulgaris has a distinct pattern of intercellular deposition of IgG. ELISA testing can be employed as an additional technique to evaluate a patient’s serum for the presence of antibodies to desmoglein 3 and desmoglein 1. The presence of antibodies to desmoglein 3 is correlated with oral involvement, and the presence of antibodies to desmoglein 1 is correlated with skin involvement. • The disease activity of pemphigus vulgaris correlates with antibody titers.

Answer 70

Porokeratosis (Disseminated Superficial Actinic Type) * **The key histopathologic feature is a cornoid lamella, which is a column of parakeratotic cells beneath which there is absence or diminution of the granular layer as well as dyskeratotic or vacuolated keratinocytes.** * **The linear type of porokeratosis has the greatest risk of malignant transformation to squamous cell carcinoma.** * genetic condition with many clinical forms * solitary or multiple * Porokeratosis of Mibelli is characterized by one or more round plaques with an atrophic center and a thin, elevated, keratotic border. * Disseminated superficial actinic porokeratosis manifests as multiple, annular lesions with a hyperkeratotic, threadlike border on sun-exposed areas. * Other variants include linear porokeratosis and punctate porokeratosis. * The cornoid lamella corresponds clinically to the raised, keratotic or threadlike rim that is seen in lesions of porokeratosis. * • Two cornoid lamellae may be present, often in disseminated superficial actinic porokeratosis type, and the intervening epidermis is often atrophic and hyperkeratotic. The dermis may demonstrate a bandlike, lichenoid inflammatory infiltrate, mimicking a lichenoid keratosis. Solar elastosis may be present. * Multiple cornoid lamellae may be present in the linear and reticulated forms as well as in porokeratosis ptychotropica. Porokeratosis ptychotropica is a rare variant that manifests as verrucous papules in the perianal area.

Answer 71

Mastocytosis A diagnosis of systemic mastocytosis requires the major criterion: * presence of multifocal compact mast cell clusters that exceed 15 cells in either bone marrow or any extracutaneous organs 4 minor criteria of which 3 must be fulfilled for a diagnosis of systemic mastocytosis. * Spindled morphology in 25% or more of mast cells * Aberrant CD2 and/or CD25 expression in mast cells * A persistently elevated serum tryptase level of 20ng/mL or higher * The presence of a KIT mutation involving codon 816.

Answer 72

Reactive Perforating Collagenosis * Reactive perforating collagenosis is a rare perforating disorder characterized by transepidermal elimination of altered collagen. * Classic reactive perforating collagenosis is a genodermatosis inherited in an autosomal dominant or recessive manner, in which lesions are precipitated by trauma. The adult-onset, acquired type of reactive perforating collagenosis is associated with diabetes mellitus and chronic renal failure, especially in patients on dialysis, and is considered a type of acquired perforating dermatosis. * Reactive perforating collagenosis is clinically characterized by papulonodules that have a central keratotic dell and resemble lesions of molluscum contagiosum or prurigo nodularis. The histologic combination of a saucer-shaped invagination containing neutrophilic debris and vertically oriented strands of collagen that have perforated through the epidermis is characteristic. * Masson trichrome stain can be performed to confirm that the perforating fibers represent collagen. The collagen stains blue-green. * Other forms of perforating disorders in the differential diagnosis of reactive perforating collagenosis include Kyrle disease, perforating folliculitis, and elastosis perforans serpiginosa. Kyrle diseases results in a cornified plug within an invaginated epidermis without follicular involvement. Perforating folliculitis shows a hyperkeratotic plug with basophilic debris associated with a follicular unit. Elastosis perforans serpiginosa demonstrates perforation of van Gieson-positive elastic fibers through the epidermis.

Answer 73

Langerhan’s Cell Histiocytosis * aka histiocytosis X, eosinophilic granuloma, Hand-Schuller-Christian disease, Letterer-Siwe disease * clinically diverse and can have local or generalized symptoms * Histology * proliferation of Langerhan-type histiocytes accompanied by a mixed inflammatory component * Approximately 85% of cases occur before age 30 and 60% occur before age 10 * Prognosis is excellent for single-focus disease * Common sites include skin, bone, liver, and lung

Answer 74

Leprosy * Histopathologically, tuberculoid leprosy is characterized by epithelioid cell granulomas with Langhans giant cells surrounded by lymphocytes and plasma cells. Eosinophils are not characteristic. Granulomas develop in and around cutaneous nerves and are often elongated rather than round, which is a helpful feature to distinguish them from sarcoidosis. * With the worldwide implementation of supervised multidrug therapy, there has been a significant reduction in the case detection rate of leprosy. * M. leprae and Mycobacterium lepromatosis are the two causative agents of leprosy. M. lepromatosis was discovered more recently and has been implicated in cases of diffuse lepromatous leprosy. * In tuberculoid leprosy, M. leprae bacilli are few and require patient examination of Fite-Faraco–stained sections. The organisms stain only weakly (or not at all) with standard acid-fast stains, such as Ziehl-Neelsen. By contrast, the lepromatous form of leprosy is characterized by numerous bacilli that are easily identifiable in the foamy histiocytes characteristic of this entity. * Worldwide, the number of new cases of leprosy has decreased approximately 44% in the past 6 years. In the United States, the prevalence rate of leprosy is less than 1 case per 10,000, and leprosy occurs mainly in the southern states. It was reported in a heart transplant patient in 2003.

Answer 75

BASAL CELL CARCINOMA (BCC) * Subtypes * Superficial * nodular * micronodular * infiltrative * sclerosing/morpheaform * basosquamous * fibroepithelioma of Pinkus * Basaloid cells with peripheral palisading, mucinous stroma, clefting around nests * Mitoses and apoptotic figures are abundant

Answer 76

BASAL CELL CARCINOMA * Most common invasive cancer in humans * elderly, sun exposed sites, XRT, immunosuppressed, DNA mismatch repair syndromes (xeroderma pigmentosa) * PTCH gene mutations (regulateds Hedgehog pathway signaling) in 30% * single allele in sporadic BCC * P53 mutations in 40-60% * Nevoid Basal Cell Carcinoma Syndrome / Gorlin Syndrome * Genetics * Autosomal dominant * PTCH gene on chromsome 9q22.3 * “2 hit” hypothesis * Skin: * multiple BCC before age 20 * palmar and plantar pits * Nervous system: * medulloblastoma * Others: * odontogenic keratocysts * ovarian fibroma * skeletal abnormalities

Answer 77

GORLIN SYNDROME - NEVOID BCC SYNDROME * Genetics * Autosomal dominant * PTCH gene on chromsome 9q22.3 (regulateds Hedgehog pathway signaling) * “2 hit” hypothesis * Skin: * multiple BCC before age 20 * palmar and plantar pits * Nervous system: * medulloblastoma * Others: * odontogenic keratocysts * ovarian fibroma * skeletal abnormalities

Answer 78

BCC Poor Prognostic Features * Histologic subtypes: infiltrative, morpheaform, micronodular, basosquamous * Dense fibrous stroma and loss of peripheral palisading * Reduced expression of syndecan-1 and BCL2 * Greater expression of p53 and aneuploidy * Perineurial invasion * Positive margins

Answer 79

BCC sclerosing/morpheaform

Answer 80

Micronodular BCC

Answer 81

Infiltrative BCC

Answer 82

Fibroepithelioma of Pinkus * long, thin, branching and anastomosing strands of basal cell carcinoma * loose fibrovascular stroma * many strands show a connection with the epidermis * basaloid strands show 2 distinct-appearing cells * lighter staining cell comprises the bulk of the strand * scattered, small groups of darker cells are seen tapering off the main trunk in a palisading arrangement like buds on a branch

Answer 83

Actinic Keratosis * Scaly, “gritty,” erythematous thin non-indurated papule on sun damaged skin * Atypia of the lower levels of the epidermis * Atypia spares the follicles * Alternating ortho and parakeratosis * Solar Elastosis

Answer 84

SCC IN SITU (BOWEN’S DISEASE) * bulbous rete ridges, full thickness atypia, basal layer sparing (“eyeliner sign”) * may show skip areas but involves follicles (in contrast to AKs)

Answer 85

Squamous Cell Carcinoma * 2nd most common skin tumor * Sun-exposed sites, older individuals, males \> females * Causes * UV light exposure is most common * Genetics * TP53 mutations most common and are seen often at pyrimidine dimers * Activating mutations in HRAS * Loss of function mutations in Notch receptors * Xeroderma pigmentosum * Immunosuppression, HPV 5 and 8 * Other: industrial, chronic wounds, burn scars, arsenic, ionizing radiation * Less than 5% metastasize

Answer 86

KERATOACANTHOMA (KA) (PUTATIVE SCC) * Low-grade tumor, rapid growth and spontaneous regression in most cases * Histology: * cup-shaped, symmetric keratin-filled lesion * enlarged, glassy-appearing keratinocytes with squamous whorls * acute inflammation * infiltrative borders * Controversial whether truly SCC or not, but may be aggressive in immunosuppressed pts.

Answer 87

SEBORRHEIC KERATOSIS (SK) * acanthosis with pseudohorn cysts * papillations, +/- verrucoid * clonal * +/- irritated/inverted (inverted follicular keratosis) or pigmented

Answer 88

EPIDERMAL NEVUS * Clinical: usually children, head and neck, upper extremities * Histology: variable, usually hyperkeratosis, acanthosis, papillomatosis * may resemble SK or acanthosis nigricans

Answer 89

CLEAR CELL ACANTHOMA * acanthosis * psoriasiform hyperplasia * pale-staining keratinocytes (glycogen → PAS+/D-) * mild spongiosis and neutrophils

Answer 90

PILAR CYST (A.K.A., ISTHMUS-CATAGEN, TRICHOLEMMAL CYST) * Clinical: usually scalp * Histo: compact eosinophilic cyst contents w/trichilemmal (abrupt) keratinization, minimal/absent granular layer, calcification

Answer 91

STEATOCYSTOMA MULTIPLEX * undulating squamoid epithelium with corrugated eosinophilic lining * lacks keratin debris * often a/w sebaceous glands or follicular structures

Answer 92

HIDROCYSTOMA * Head and neck, solitary lesions, most are apocrine (few “eccrine”) * Flattened to columnar 1-2 cell lining, often with snouting and decapitation secretion

Answer 93

ADNEXAL NEOPLASMS - DUCTAL/GLANDULAR NEOPLASMS 1. SYRINGOMA 2. CUTANEOUS MIXED TUMOR (CHONDROID SYRINGOMA) 3. POROMA 4. HIDRADENOMA 5. SPIRADENOMA (“ECCRINE SPIRADENOMA”) 6. CYLINDROMA 7. HIDRADENOMA PAPILLIFERUM 8. MICROCYSTIC ADNEXAL CARCINOMA (MAC) 9. EXTRAMAMMARY PAGET’S DISEASE 10. SEBACEOUS ADENOMA 11. SEBACEOMA (“SEBACEOUS EPITHELIOMA”) 12. SEBACEOUS CARCINOMA 13. TRICHOEPITHELIOMA/TRICHOBLASTOMA 14. PILOMATRIXOMA

Answer 94

SYRINGOMA * Clinical: multiple small flesh-colored papules on the face of a woman, Asians * Histo: bland ductal structures with occasional cords and tadpole-shapes in a fibrotic stroma * DDx: desmoplastic trichoepithelioma (follicular diff, calcs), MAC (follicular cysts, deep and perineural invasion)

Answer 95

POROMA * anastomosing strands of bland adnexal keratinocytes * originates from epidermis, extends into dermis * focal duct formation (closely related to hidradenoma and dermal duct tumor)

Answer 96

HIDRADENOMA * dermal nodule * well-circumscribed * eosinophilic or clear-staining cells, with apocrine & variable ductal differentiation

Answer 97

SPIRADENOMA (“ECCRINE SPIRADENOMA”) * Lobules and nests of adnexal cells * 2 epithelial cell types * smaller outer dark cells * larger inner pale cells * Often eosinophilic hyaline droplets, or cylindar formation, cystic spaces, prominent vessels, hemorrhage * Likely apocrine

Answer 98

CYLINDROMA * “Jigsaw puzzle” pattern of irregularly-shaped, well-circumscribed nests separated by thickened basement membrane * Occasional ducts (much less than spiradenoma), may also see hyaline droplets * likely apocrine

Answer 99

HIDRADENOMA PAPILLIFERUM * Clinical: perineal region of women * Histo: dermal-based nodule of tubular and cystic structures with apocrine differentiation

Answer 100

MICROCYSTIC ADNEXAL CARCINOMA (MAC) * Clin: depressed plaque on face, esp. lip, young adults * Histo: * Superficial bland follicular cysts * deeply infiltrative epithelial strands with follicular and sweat duct formation * often perineural invasion DDx: * Sclerosing BCC: lacks superficial follicular cysts and ductal diff’nt, rare perineural invas, hi Ki-67 * Desmoplastic trichoepithelioma: lacks deep invasion or perineural invasion, has calcifications, follicular but no ductal diff’nt; neg CK7, EMA

Answer 101

EXTRAMAMMARY PAGET’S DISEASE * Clinical: eroded plaque, usually genital or perineal area, but also axilla and eyelid * Histo: pagetoid intraepidermal spread of large, cytologically atypical, pale to foamy-appearing cells, occasional signet ring or gland formation * mucin and PASD+ * IHC: CEA+, GCDFP+, CAM5.2+, EMA+, CK7+; CK20-, S100-

Answer 102

SEBACEOUS ADENOMA * Papule/nodule on face/scalp * +/- Muir Torre syndrome * especially if multiple or cystic lesions * HNPCC * MLH1, MSH2, MSH6 * Histo: * well-circumscribed growth * \> 50% well-differentiated sebocytes * no atypia

Answer 103

Sebaceous hyperplasia * most common sebaceous gland lesion * elderly, umbilicated yellowish papules on nose or cheeks * Histology: * expansion of normal lobular sebaceous gland architecture * no thickening of peripheral germinative layer of seboblasts

Answer 104

SEBACEOMA (“SEBACEOUS EPITHELIOMA”) * +/- Muir Torre syndrome * especially if multiple or cystic lesions * HNPCC * MLH1, MSH2, MSH6 * Histo: * circumscribed growth * \< 50% well-differentiated sebocytes * \> 50% basaloid cells

Answer 105

SEBACEOUS CARCINOMA * Clinical: * eyelids \> head and neck * aggressive tumor * Histology: * infiltrative growth pattern, +/- pagetoid spread * should find vacuolated cells * marked atypia, +/- squamous or basaloid differentiation * IHC: Adipophilin+, CK7+, CAM5.2+, Androgen R+, EMA± (lost in poorly diff’nt); GCDFGP-, CEA- * high p53 & Ki-67 (low in adenoma/sebaceoma)

Answer 106

FOLLICULAR NEOPLASMS: TRICHOEPITHELIOMA/TRICHOBLASTOMA * Familial cases * 9q21, mutation in tumor suppressor gene * PTCH, 9q22.3 (BCC) also involved * CYLD (cylindromatosis oncogene), 16q12-q13 * Brooke-Spiegler syndrome * familial cylindromatosis * multiple familial trichoepithelioma * Clinical: * head and neck, young to aging adults * hereditary form may be younger * Histology: * basaloid nodules with palisading * keratinous microcysts (often calcified) * papillary mesenchymal bodies (hair papillae-like structures) * fibrotic stroma, lacks mucin * Desmoplastic TE shows more infiltrative features * DDx: BCC (mucin, clefting, increased mitoses and apoptoses), MAC (deeper, perineural invasion)

Answer 107

FOLLICULAR NEOPLASMS: PILOMATRIXOMA * Clinical: * slowly growing, solid nodule on head and neck * children/young adults * Histology: * biphasic population of dark basaloid cells merging with palely eosinophil “ghost cells” * calcifications common, even bone formation

Answer 108

SPITZ NEVUS * Symmetric, well-circum, usually compound proliferation w/ epidermal hyperplasia * Spindled and epithelioid cells, vertically oriented junctional nests w/streaming (“raining down” appearance) * Clefting and Kamino bodies (eosin globules)

Answer 109

REED’S/PIGMENTED SPINDLE CELL NEVUS

Answer 110

PALISADED ENCAPSULATED NEUROMA (PEN) * Clinical: small papule on the face * Histo: upper dermis, circumscribed proliferation of fascicles; stroma less myxoid than neurofibroma; no Verocay bodies