Dermpath theory Flashcards
Name 4 features of mycosis fungoides
Pautrier microabcesses Papillary dermal fibroplasia Epidermotropism of lymphocytes Predominance of CD4+ over CD8
What is the IF pattern seen in pemphigus vulgaris?
net or lacelike
Name 4 features of Lichen planus
Wedge-shaped hypergranulosis Band-like lymphocytic infiltrate Apoptotic keratinocytes Colloid bodies
Name 4 features important in T staging of melanom
- Breslow thickness - Mitotic count - Ulceration - Invasive vs in-situ
Name 3 stains positive in Merkel cell carcinoma
- Cam 5.2, synaptophysin, CK20
Name 4 features of tuberous sclerosis
- Cortical tubers - angiofibromas - shagreen patch - cardiac rhabdomyomas
Name 4 features considered high-risk in SCC
- Perineural invasion - depth of invasion - ear lesions - histologic grade
What is the antigen in pemphigus vulgaris?
- Desmoglein 3
Which of the following vesicobullous lesions has caterpillar bodies in the cavity?
- Porphyria cutanea tarda
Name 4 features associated with SLE
- Photosensitivity - Serositis - Renal failure - Malar rash
What cutaneous malignancy is associated with Muir-Torre?
- Sebaceous carcinoma
Name 4 lesions that may show granulomatous inflammation in the skin
- Sarcoidosis - Drug reaction - Granuloma annulare - tuberculosis
Name 4 features of Gorlin syndrome
- Autosomal dominant - multiple basal cell carcinomas - may have skeletal abnormalities (bifid ribs) - Odontogenic keratocyts are associated
List the histologic features of lichen planus
- Confluent orthokeratosis without parakeratosis - Wedge-shaped hypergranulosis - Epidermal acanthosis with saw-tooth rete ridges - Band-like lymphocytic infiltrate in superficial dermis - Vacuolar degeneration of basal kertinocytes with civatte bodies (necrotic keratinocytes in epidermis) and dermis (colloid bodies)
What features in a biopsy, resembling lichen planus, would suggest an alternate diagnosis
- Significant inflammatory cells other than lymphocytes (plasma cells, eosinophils) - Inflammation extending to deep dermis - Parakeratosis
Name some variants of lichen planus
- Oral lichen planus - Hypertrophic lichen planus - Lichen planopilaris - Atrophic lichen planus
What are the immunofluorescence findings of lichen planus?
- Colloid bodies stain with IgM, occasionally IgG, IgA, C3 - Fibrinogen deposits apparent at DEJ
What features are helpful in distinguishing lichenoid drug reactions from lichen planus?
- Drug reactions have more parakeratosis, eosinophils, dermal melanin incontinence, less dense infiltrate of lymphocytes - Usually apoptotic keratinocytes in lower level of dermis
Cutaneous GVHD: What is the basic histologic pattern in the skin?
- Lichenoid with prominent basal vacuolar damage
How is acute GVHD graded?
- Grade 1: basal vacuolar change - Grade 2: dyskeratotic keratinocytes with satellite necrosis - Grade 3: subepidermal cleft formation and microvesicle formation - Grade 4: dermal-epidermal split
What are the histologic findings in chronic GVHD?
- first type looks like LP with hyperkeratosis, hypergranulosis, lichenoid dermal infiltrate and apoptotic keratinocytes - second type looks like morphea
Erythema multiforme: Name 2 etiologies
- infection (HSV, mycoplasma) - drugs (NSAIDS)
What are the histologic findings in erythema multiforme?
- Early: lichenoid pattern, obscuring DEJ with vacuolar degeneration and necrotic keratinocytes along basal epidermis and extending into upper epidermis - Well developed: bullous lesions with subepidermal edema progressing to dermal-epidermal split - Severe: looks like TEN with epidermal necrosis
What are three types of cutaneous lupus?
- Systemic lupus erythematosus - Subacute cutaneous lupus - Discoid lupus
What are the main histologic features of lupus?
- Lichenoid inflammation with vacuolar changes, with or without keratinocyte necrosis, dermal mucin and variable epidermal changes - DLE: above + hyperkeratosis and follicular plugging, with periadnexal inflammation and BM thickening - Systemic: subtle, with mild perivascular infiltrate - Subacute: moderate perivascular infiltrate, lichenoid changes including apoptotic keratinocytes
What are the IF findings in SLE that differ from subacute and discoid lupus?
- Lupus band test POSITIVE in non-lesional skin
List clinical features that are important in diagnosis of systemic lupus
- LUpus nephritis - Arthritis - Serositis - Photosensitivity - SKin: malar rash
What gross appearance characterizes skin lesions of subacute and discoid lupus?
- subacute: annular plaques/psoriasiform lesions - discoid: plaques, atrophy, scarring, pigment
What histochemical stains may be useful in the diagnosis of lupus?
- Mucin (colloidal iron) - PAS for basement membrane thickening
What are some features of hidradenitis suppurativa?
- Bacterial infection of apocrine glands - usually in axilla, anearobic - follicles plugged by keratin, neutrophilic infiltration of apocrine gland with abcess and fistula formation - tends to scar/chronicity
Mycobacterial infections in skin: list some possible presentations of myobacterium (other than leprosy)
Cutaenous tuberculosis:
a. lupus vulgaris: reactivation type of TB. Red patches with small firm nodules. Caseating/non-caseating granulomas in dermis. Use culture/PCR
b. papulonecrotic tuberculoid: dermal necrosis, poorly formed granuloma, vasculitis, edema. Usually devoid of organisms.
c. erythema induratum: recurrent tender subcutaneous nodules on calves of women with tuberculin sensitivity.
- atypical mycobacteria: ulceration, abcesses, granulomas, panniculitis, rheumatoid-like nodules. Culprits are M. kansasii, M. marinum, M. ulcerans
Leprosy: what is a key feature and what are 2 types
Leprosy: granulomas with lymphocytic infiltrate centered around cutaneous nerves and /or destroying erector pili muscle
Types:
Lepromatous: has Virchow cells (foamy histiocytes) filled with acid-fast bacilli
tuberculoid & intemediate: bacilli are scanty
Cutaneous lesions of syphilis. What are some features?
- Maculopapular rash, ddx drug eruption, lichen planus, psoriasis and other dermatoses
- early lesions may be non-specific
- late lesions: dense perivascular or diffuse plasmacytic infiltrate +/- non-caseating granulomas, endothelial swelling +/- proliferation
- Special studies: IHC for Treponema pallidum, PCR
What is a quick ddx of granulomas in skin?
- Infections (TB, atypical mycobacterium, syphilis)
- Fungal infections (blastomycosis)
- Sarcoid
- Foreign material (berylium, aluminum, talc, silica, lipids, zirconium)
- arthropod bites
What are some features of erythema nodosum? List 3 septal panniculitides
EN: painful red subcutaenous lesions, anterior surface of legs
- often antecedant streptococcal infection, sarcoid, or tuberculoid
- junction of dermis/subcutis is inflammed, with inflammation spreading down fibrous septae
- composition of infiltrate depends on age of lesions, may have giant cells/non-caseating granulomas, may have non-necrotizing vasculitis
- characteristic early lesion: cluster of small histiocytes, radially arranged around central cleft
- other septal panniculitides: nodular vasculitis, subacute nodular migratory panniculitis
Name some conditions presenting with a lobular panniculitis
- Weber-Christian (subacute pannicuitis with necrosis of fat cells)
- -a1-antitrypsin deficiency
- chronic pancreatitis
- pancreatic endocrine tumors
- cytophagic histiocytic panniculitis (a form of cutaneous t-ell lyphoma)
Cutaneous lupus: list 2 forms and their features
Chronic discoid lupus: delineated, erythematous hyperkeratotic or atrophic patches on face, neck scalp, trunk. May be exacerbated by sun. Predominantly follicular hyperkeratosis, epidermal atrophy with liquefactive degeneration of basal layer, patchy periadnexal lymphocytic infiltrate. Will shows IgG/IgM + MAC complements at involved sites only.
SLE: immune mediated disease w/abs to DNA. Systemic sx. Fibrinoid necrosis at DEJ with atrophy/liquefactive degeneration of epidermis. Coalescing clumps of IgG, IgM, C5b, C6-9 at DEJ in involved AND uninvolved areas.
Scleroderma: list some features
- Can be localized (morphea) or systemic involving heart, esophagus, lungs
- Dominant change is an increase in normal (types 1 & 3) collagene in the dermis, leading to homogenization and eosinophilic chage
- Predominantly affects papillary dermis, with secondary atrophy of epidermis +/- non-specific lymphocytic inflammation
- direct IF is negative
Name skin lesions seen in patients with HIV
- maculopapular eruptions
- pauplar pruritic eruptions (superficial perivascular ymphocytic infiltrates)
- vasculitis (leukocytocastic-CMV)
- follicultisi syringitis
- seborrheic dermatitis
- psoriasis
7 drug rxn
- infection: parasites (scabies), fungal, bacterial, viral esp. herpes simplex, varicella zoster, CMV, molluscum
- papular neutrophilic xanthoma
In SCC of skin, what are some predisposing factors other than actinic keratoses?
- Xeroderma pigmentosum (defect in UV-induced DNA damage repair)
- Scars seondary to burns x-rays, chronic osteomyolitic sinues, necrobiosis lipoidica
- chemical exposure: arsenic, coal, soot
- immunocompromised invididuals (organ translplant ,HIV)
- PUVA_treated psoriasis pts
- ichthyosis, epidermal nevus, porokeratosis, congenital lympahdema
What are some IHC differences between SCC and BCC?
SCC: will stain with HMWCK, EMA, CEA, Ulex europeaus
BCC: neg for Ulex europeaus, EMA, CEA
stains with LMWCK, BerEP4, CD10
Discuss mammary pagets and extramammary pagets
- Mammary:
- location is mammary skin, with a proliferation of malignant cells percolating through epidermis
- neoplastic cells larger than keratiniocytes
- stain for CK7, CEA, Her2 neg for melanocytic markers and CK20
- associated with underlying breast CA
- extramammary:
- in genital/perianal skin, looks like mammary pagets
- may occur in isolation or with underlying visceral malignancies, or cutaenous adnexal adenocarcinomas
- mucin +, other stains variable depending on underlying condition
Describe 2 variants of lipoma in skin
angiolipoma: painful nodule, often on forearms, composed of mature adipose tissue with admixed blood vessels with fibrin thrombi
spindle cell lipoma: lesion of neck/shoulder of older men, variable proportons of CD34+ spindle cells, myxoid matrix with thick intervening collagen and mast cells
What is bowenoid papulosis?
- Verrucous genital plaques in young adults
- associated with HR-HPV
- full thickeness keratinocytic atypia
- usually resolves spontaenously
What are settings in which cutaneous angiosarcomas can develop?
- elderly: Head and neck. No predisposing
- chronic lymphadema
- radiation
List painful cutaenous lesions
ANGEL
- angiolipoma
- neuroma
- glomus tumor
- eccrine spiradenoma
- leiyomyoma
What is the classic clinical description of a glomus tumor?
- painful nodule on digits
- derived from modified smooth muscle cells involved in thermoregulation
How do you approach the diagnosis of a small round blue cell tumor in skin?
- Most common ones include Merkel cell carcinoma, melanoma and hematolymphoid but PNET can occur
- mets (esp. neuroblastoma in children) and epithelial/lung primaries in adults
- clinical history + IHC
How can you differentiate dermatofibroma from DFSP?
- DFSP is larger, deep extension into dermis and subcutis with wrapping of tumor around fat cells “perls”
- DFSP shows more collagen wrapping
- DFSP shows more storiform formation, fewer foamy cells
- IHC: DFSP is CD34+ and neg. for factor XIIIa
- DFSP shows t (17:22) COLA1/PDGFRA
Provide a DDX for spindle cell lesions in the skin
Benign:
- spindle-cell (neurotized) nevus
- dermatofibroma
- neurofibroma
- hemangioma
- leiyomyoma
- mastocytosis
- scar
malignant:
- melanoma
- SCC
- malignant adnexal neoplasm
- atypical fibroxanthoma
- DFSP
- malignant mesenchymal (MPNST, leiyomyosarc, angiosarcoma)
- met
Provide a basic IHC panel for spindle cell lesions in skin
Initial:
- cytokeratins (CK 5/6 and p63)- SCC
- S100 - melanoma, nerve sheath
- desmin -leiyomyosarcoma
- CD10-AFX
- Factor XIIIa-DF
- CD34-DFSP
What are the stages of MF? List the histologic features of patch stage
Stages: patch, plaque, tumor
Histologic features of patch: sparse lymphocytic infiltrate in superficial dermis and extending to basal epidermis, often single file of cells along basal layer
increased # of lymphocytes within epidermis in ABSENCE of spongiosis
pautrier microabcesses: clusters of atypial lymphocytes in epidermis
minimal atypia, but cerebriform cells; enlarged with cerebriform folding of nucleus and perinuclear halos
What is the clinical presentation of MF, and what are some useful ancillary studies?
Irregular scaly patche on trunk, usually adults
Slowly progressive disease, pts die of other causes
Poorer prognosis if progression to erythematous plaques and later nodules/tumors that ulcerate; lymph node involvement can occur
Ancillary tests: IHC: T cell (usually CD4), some loss of T cell markers including CD7, CD5
- CD30 neg
- clonal T cell rearrangement
List the histologic features of BCC
- Neoplastic proliferation of basal-type of follicular type cells
- histologic architecture can be nodular, superficial/multifocal, morpheaform
- Islands/nests of basaloid cells with peripheral palisading, usually attached to overlying epidermis
- mitoses/apoptoses in nests
- clefts between nests and surrounding stroma
- possible calcification or pigmentation
What is nevoid basal cell carcinoma syndrome?
- AD, Ghorlin syndrome, caused by mutatio in PTCH on chromosome 9
- cutaneous findings: multiple BCCs, even in kids, palmar/plantar pits
- others: odontogenic keratocyts, rib anomalies, intracranial calcs
What is the etiology of Merkel cell carcinoma, and what are some IHC stains that can be used?
- Is a primary malignancy of skin neuroendocrine cells
- Polyomavirus is implicated
- IHC: synaptophysin, chromogranin, dot-like CK20/cam 5.2. TTF-1 to rule out small cell Ca from lung.
- also an IHC stain for the polyoma virus:
Keratoacanthoma: what is the clinical history and histologic features
History: rapidly growing nodule on sun exposed skin of elderly ppl, often with cutaneous horm. Often involutes over months-years
Histo: exo-endophytic craterifrom leseion with cupping of peripheral epidermis over lesion. POssible overyling hyper/parakeratotic horn. Glassy eosinophilic keratinocytes showing abrupt maturation towards center of nests. Well demaracated periphery of nests with minimal cytologic atypia and mitoses. Inflammation, usually with some eos.
What are some “high-risk” features of SCC skin?
perineural invasion
primary site: ear or non-hair-bearing lip
>2mm breslow thickness
poorly differentiated/undiff histology
What is the AJCC staging system for SCC skin?
T1 <2cm, with fewer than 2 HR features
T2 >2cm +/- HR feature, or any size with >2 HR features
T3: invasoin of maxilla, mandilble, orbit or temporal bone
t4: tumor with direct/indirect perineural invasion of skull base/axial skeleton
What features suggest a congenital nevus
- Deep extension of melanocytes into dermis
- extension of melanocytes along adnexal structures
- single file extension of melanocytes between collagen bundles
List the histologic features of a blue nevus
- Common blue nevus: dermal spindled melanocytes in an interstitial pattern in dermis with admixed melanophages and dermal fibrosis
- Cellular: islands/nests of plump epithelioid cells without prominent pigment, with possible invasion into subcutis. Mitotic rate is low.
What are some features of a Spitz nevus?
- Usually young pts with a pink, dome shaped papule
- Symmetrical, circumscribed proliferation of psindled/epithelioid melanocytes with amphophilic cytoplasm arranged in nests
- spindle cells often vertically oriented as hanging bananas at tipos of acanthotic rete ridges
- Kamino bodies (eosinophilic collections of basement membrane material)
- Minimal pagetoid extension, few mitoses, maturation with extension into dermis
- Epidermis often acanthotic, hypergranulotic and hyperkeratotic
List the histologic features of a dysplastic nevus
- Lentiginous proliferation of melanocytes singly and in nests involving the tips and sides of rete ridges with bridging between adjacent rete ridges
- papillary dermal fibrosis
- variable cytologic atypia
- shouldering with extension of epidermal component beyond dermal component
What are the features of familial atypical mole melanoma syndrome?
- Syndrome associated with mutations in CDKN2A
- Pts have multiple atypical nevi and increased risk of melanoma
- pts need full-body dermatologic screening including mucosal surfaces and scalp beginning at a young age
Name the gene whose mutation is most frequently associated with melanoma
CDKN2A-encodes p16 (chromosome 9)
- BRAF, NRAS, HRAS and CKIT also found
How should a bx for bullous disease be handled?
- take separate samples for H&E/formalin and for IF
- for IF, bx of perilesional skin is most informative
- bx for IF should go in Michel transport media, bx for H&E in formalin as usual
- give appropriate clinical history on requisition!
How are vesiculobullous diseases classified?
- Based on 3 features: location of split (subepidermal, suprabasal)
- Mechanism of split (spongiosis, BM destruction)
- Intensity/composition of infiltrate in dermis
(also by IF)
Pemphigus foliaceus: What is the split level? What are the IF findings?
- Subcorneal
- Histology shows loss of corneal layer
- Dyskeratotic cells in superficial epidermis
- intercellular staining for IgG
- antigen: desmoglein1
Name 6 causes of subepidermal blisters and their IF findings
- Epidermolysis bullosa: group of diseases, one inherited AD, one acquired. Cell-poor blisters with IgG and C3 along BM (Ig localize to blister floor in salt-split)
- Porphyria cutanea tarda: cell-poor subepidermal blisters with festooning of dermal papillae into blister cavity, caterpillar (PAS+ hyaline) bodies in blister roof. IgG along BM and withint dermal blood vessels.
- Bullous pemphigoid: dermal infiltrate of eosinophils, blisters cell poor. IgG and C3 along DEJ. Salt split deposits on blister roof.
- Pemphigoid gestationalis: Pruritic vesicles beginning on periumiblical region during pregnancy. Looks like bullous pemphigoid. C3 and IgG along BM.
- Dermatitis herpetiformis: Neutrophil-rich subepidermal blisters, associated with celiac. Granular IgA at DEJ concentrated above dermal papillae.
- Linear IgA bullous dermatitis: looks like dermatitis herpetiformis. Linear IgA at DEJ.
What are clinical associations with dermatitis herpetiformis?
- Gluten sensitive enteropathy
- HLA B8, DR3, DQ8
What are the histologic and IF findings in pemphigus vulgaris?
- Suprabasal acantholysis with tomb stoning of basal keratinocytes and scattered acantholytic cells in blister cavity
- acantholysis over long stretches of epidermis, involving follicular epithelium
- mild, mixed mononuclear infiltrate
- DIF: lacelike/intercellular IgG, sometimes with IgM, IgA and C3
- antigen: desmoglein 3
What are the target genes in bullous pemphigoid?
- BPAG1
- BPAG2
List the ddx of intraepidermal blisters/acantholysis
- Pemphigus vulgaris
- Hailey-Hailey
- Darier disease
- grover disease
- warty dyskeratoma
What are some features of Hailey-Hailey, Darier, Grover and warty dyskeratoma?
Hailey-Hailey: genodermatosis, mutation of ATP2C1. Acantholysis in a collapsed brick pattern. Minimal dyskeratosis.
Darier; genodermatosis, mutation in ATP2A2. Suprabasilar acantholysis and prominent dyskeratosis with formation of corps ronds and grains.
Grover: transient eruption with focal acantholysis and focal dyskeratosis. 4 variants including pemphigus-like, Hailey-Hailey like, Darier-like, spongiotic
Warty dyskeratoma: solitary crateriform lesion with suprabasilar acantholysis and dyskeratosis
What are the histologic features of leukocytoclastic vasculitis?
- Fibrinoid necrosis of small vessel walls with extravasated red blood cells
- neutrophils in vessel walls and dermis with nuclear dust (karryorexis)
- mixed inflammation
- possible necrosis/ulceration of epidermis or subepidermal blister formation
What are possible underlying causes of leukocytoclastic vasculitis?
- Infection (bacterial, ricksettial, fungal, viral)
- Immune complex associated
- Autoimmune diseases
- Drugs
- Paraneoplastic/malignancy associated
- ANCA associated
- idiopathic
What are the clinical findings and histology of Sweet syndrome?
- Clinical; pts have sudden eruption of painful plaques and papules on face/extremities, often following an infections. Fever and leukocytosis. ? etiology, but associated with malignancies, drugs, infection and autoimmune.
- Histology: dense perivascular and dermal interstitial neutrophilic infiltrate, often with subepidermal edema
- Neutrophils surround vessels, but usually not a primary vasculitic process
HSP: what are the IF findings?
- IgA in vessel walls (both involved and uninvolved by apparent vasculitis)
What are the histologic features of psoriasis?
- Regular acanthosis of epidermis with elongated, thin pencil-shaped rete ridges and thinned suprapapillary plates
- prominent dilated capillaries in the papillary dermis
- confluent parakeratosis overlying an attenuated granular layer
- increased numbers of mitotic figures
- spongiform pustules: loose aggregates of neutrophils in the superficial epidermis
- munro microabcesses: mounds of parakeratosis with neutrophils
Give a ddx for a bx with psoriasiform epidermal hyperplasia
- Psoriasis (including variants)
- chronic ezcematous dermatitis/subacute dermatitis
- seborrheic dermatitis
- pityriasis rubra pilaris
- lichen simplex chronicus
- mycosis fungoides
- dermatophyte infection
Give a ddx of granulomatous inflammation in the skin
- Infection (tb, leprosy, leishmaniasis, fungi)
- sarcoid
- foreign body rxn
- necrobiotic granulomas (granuloma annulare, necrobiosis lipoidica, rheumatoid nodule)
- xanthogranulomas
- granulomatous drug rxns
What are the clinical, histologic and histochemical stain findings in granuloma annulare?
- Clinical: single or multiple papules, sometimes arranged in an annular fashion, often on extremities
- unknown etiology, usual suspects implicated (drugs infection)
- Histology: histiocytes and lymphocytes dermally located and palisading, surround necrobiotic centers containing mucin.
- Beware of interstitial pattern, characteriszed by interstial lymphocytes/histiocytes with increased dermal mucin
- Occasionally can have sarcoid-like appearance
- Histochemistry: mucin stains, hales colloidal iron
Give some clinical and histologic features of necrobiosis lipoidica
- Clinical: atrophic yellow plaques on lower legs. Frequent in those with DM.
- Histo: necrobiosis alternates with histiocytes, sometimes other admixed inflammatory cells involving dermis and subcutis, in a ladder-like arrangement.
Differentiate granuloma annulare from necrobiosis lipoidica
- GA: focal lesion, palisading histiocytes surrounding necrobiosis, increased mucin deposition
- NL: more diffusely involved in bx, more layered, horizontal ararngement of histocytes, no increased mucin
What are histologic features of rheumatoid nodules?
- Necrobiotic granuloma with palisading histiocytes and lymphocytes
- degenerated collagen in necrobiotic centre
- possibly deeply located in dermis/subcutis
What do you need to do for gout specimens?
- Specimen fixed in alcohol, rather than formalin, to preserve crystals
List histologic features of erythema nodosum
- Septal panniculitis
- Multinucleate giant cells, lymphocytes, eosinophils and neutrophils in subcutaneous septae
- possible lobular spillage but primarily a septal panniculisit
List 5 causes of erythema nodosum
- drug rxn (OCPs
- infection
- sarcoid
- IBD
- malignancies (lymhomas)
List 4 causes of lobular panniculitis
- Erythema induratum
- Subcutaneous fat necrosis of newborn
- Alpha-1-antitrypsin
- Pancreatitis
What are the classical clinical and histologic findings in fixed drug eruptions?
- Clinical: ovoid/annular erythematous lesions developping in response to exposure to a drug, resolves with hyperpigmentation but recurs when exposed to same drug again (in same location)
- common sites include lips, face, hands, genitalia
Histo: lichenoid inflammatory infiltrate extends to deeper dermis with vacuolar degeneration in the basal layer and apoptotic keratinocytes above the basal layer
- pigment incontinence is present
- resembles erythema multiforme
Describe pityriasis rosea
- Self-limited eruption occuring in kids/young aduls
- characteristic progression: salmon coloured, scaly “herald patch” on trunk ,develops into multiple smaller papules on trunk/extremities in a Christmas tree pattern
- histology: spongiosis with vesicles, undulating epidermis, variable mounds of parakeratosis
Whats a cornoid lamella? what dermatosis is it found in
- column of parakeratosis overlying an epidermis with attenuated granular cell layer and dyskeratosis
- characteristic feature of porokeratosis
What are the clinical and histologic features of morphea?
- Clinical: localized/plaque form, linear and generalized
- INudrated plaques present on trunk and extremities, often with shiny white centers
- Histo: squared edge biopsies, extensive collagen deposition in dermis with replacement of dermal fat and atrophy of adnexal structures
- Perivascular lymphocytic infiltrate with admixed histocytes and plasma cells
- thickening of dermal blood vessels
What does CREST stand for?
- Refers to features of a limited systemic form of scleroderma.
C-calcinosis, R-raynaud, E-esophageal dysfunction, S-sclerodactyly, T-telangiectasia
Elderly woman with pruritic white genital lesions, thined skin. Dx?
- Lichen sclerosus et atrophicus
- Histo: epidermal atrophy with homogenized subepidermal collagen and vacuolar degeneration of basal keratinocytes, with associated perivascular lymphocytic infiltrate
Name 3 common skin cysts and their histology
- Epidermal inclusion cyst (stratified squamous epithelium, granular cell layer and basket-weave keratin)
- Trichilemmal cyst (stratified squamous epithelium, non granular layer, abrupt keratinization, homogenous compact keratin +/- calcs)
- Steatocystoma: stratified squamous epithelium, no granular layer, corrugated surface with sebaceous lobules
Name cutaneous lesions occuring in AIDS patients
- psoriasis
- seborrheic dermatitis
- infections
- kaposi sarcoma
What are the histologic features of stasis dermatitis?
- superficial and deep dermis with neovascularization, lobular pattern of vessels and mild perivascular lymphocytic infiltrate
- adjacent dermis may contain extravasated RBCs, hemosiderin
- overlying epidermis may be acanthotic, show spongiosis/hyperkeratosis
List syndromes with cutaneous manifestations
- Muir-Torre: AD mutations of mismatch-repair genes. Visceral tumors (colon, endometrium). Sebaceous neoplasms, keratocanthomas, epidermal cysts
- Birth-Hogg-Dube: AD, folliculin gene. Renal tumors, pulmonary cysts. Fibrofolliculomas, trichodiscomas, achrocordons
- Cowden: AD PTEN mutation, hamartomatous lesions in multiple systems. Benign/malignant lesions of breast, thyroid. Trichilemommas palmar pits
- Tuberous sclerosus: AD mutations of TSC1/2 (hamartin, tuberin). Cortical tubers, angiomylopomas, lymphangioleiyomyomatosis. Angiofibromas, shagreen patch, ash-leaf macules, periungal fibromas
What are some histologic findings in dermatophyte infections?
- Bx can look norma
- compact orthokeratosis, alternating ortho/parkaratosis, neutrophils in corneal layer
- epidermis can be psoriasiform/spongiotic
- PAS stain highlights fungi
Name 3 viral infections of skin and their histologic findings
- HSV: ground glass nuclei, chromatin margination, multinucleation, molding. eosinophilic nuclear inclusions. Intraepidermal vesicle formation.
- HPV: acanthosis, papillomatosis, hyperkeratosis with parakeratosis. Dilated blood vessels in dermal papillae. Large, coarse keratohyaline granules in superficial keratinocytes +/- koilocytes.
- Molluscum contagiosum: epidermal hyperplasia, cup shaped, eosinophilic molluscum bodies in keratinocyte cytoplasm
Give the current staging for melanoma
T1: 1mm or less (T1a=no ulceration, mitoses less than 1/mm2, while b is ulceration or mitoses)
T2: 1-2 mm a/b depending on ulceraion
T3: 2-4mm a/b depending on ulceration
T4: >4mm, a/b depending on ulceration
In melanoma, what are most important prognostic factors affecting staging?
- Breslow thickness
- Presence/absence of ulceration
- presence/absence of satellites
- mitotic count
What are some histologic features to include in report for melanoma?
- histologic subtype
- presence of microsatellites (nodular tumor >0.05 mm in diameter, separate from main mass)
- vascular invasion
- PNI
- clark level
- tumor regression
- tumor infiltrating lymphocytes
- overall tumor size
- margins
4 histologic subtypes of melanoma
- lentio maligna melanoma
- superficial spreading
- nevoid
- nodular
- acral lentiginous
How do you measure depth of invasion in melanoma?
- from top of granular cell layer to deepest tumor
- don’t include follicular extension
- if epidermis ulcerated, measure from base of ulcer
What are Clark levels and significance
Clark levels refer to level of invasion in dermis
1-intraepidermal
2- invades papillary dermis
3-expands/fills papillary dermis
4-invades reticular dermis
5-invades subcutis
No longer included in melanoma staging, but may be part of treatment decisions; some believe important in areas with less subcutaneous tissue
What clinical findings are suggestive of melanoma, and what are basic treatment strategies?
- ABCD (assymetry, borders, colour variegation, diameter greater than 6mm + changes in a lesion
- Tx: wide local exicison, sentinel ymph node bx. Adjuvant therapies including inteferon, BRAF therapy, some immunomodulating therapies
List 3 locations other than skin, where melanoma ca be primary
- Mucosal (anywhere along GI tract/GU)
- Eye
- Meningeal
What are some important features of desmoplastic melanoma?
- Spindle cell lesion, may look monotonous
- frequently shows perineural invasion and deep extension
- stains with S100 negative for melan-A and HMB45
List IHC stains useful in melanoma dx
- Melanocyte markers (S100, Melan-A, HMB45) to indicate lineage
Deep dermal HMB45 not typical of benign lesions (except blue nevus)
Desmoplastic melanomas are neg for all but S100
Sox10 is a nuclear transciption factor needed for normal neural crest development
MiTF nuclear stain, can assess confuence of intraepidermal component
Ki67-proliferation rate
p16, WT1skin-most will be +, however dysplastic nevi too
