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1
Q

Clark levels

A

II: Melanoma present but does not fill/expand papillary dermis
III: Fills and expands papillary dermis
IV: Invades reticular dermis
V: Invades subcutis

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2
Q

Melanoma T staging

A

a: no ulceration
b: ulceration
pT1: <0.8 cm (0.8-1.0)
pT2: 1-2.0cm
pT3: 2-4.0 cm
pT4: >4cm

C
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3
Q

Low CSD Melanoma

A

Superficial spreading
Nodular
Nevoid
Lentiginous

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4
Q

High CSD Melanoma

A

Lentigo maligna
Desmoplastic

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5
Q

Melanoma in sun shielded areas or without known UV association

A

Spitz
Acral
Mucosal
Arising in congenital nevus
Arising in blue nevus
Uveal

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6
Q

Merkle cell CA T-staging

A
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7
Q

Merkle cell CA N-staging

A

pN1: clinically undetected met
pN2: in-transit met without LN
pN3: in-transit met with LN

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8
Q

Histopathological features of lichen planus

A

Confluent orthokeratosis without parakeratosis
Wedge shaped hypergranulosis
Epidermal acanthosis with saw-toothed rete ridges
Band-like lymphocytic infiltrate in the superficial dermis
Vacuolar degen of basal keratinocytes with necrotic keratinocytes (Civatte bodies) in the epidermis and papillary dermis (colloid bodies)

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9
Q

4 histopathological variants of lichen planus

A

Bullous lichen planus
Hypertrophic lichen planus
Lichen planopilaris
Atrophic lichen planus

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10
Q

IF findings of lichen planus

A

Colloid bodies stain with IgM, occasionally with IgG, IgA, and C3
Fibrinogen deposits are present in the dermoepidermal junction

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11
Q

Types, timing, and histopathological manifestations of cutaneous GvHD

A

Acute - onset first 3 months posttransplant - vacuolar interface dermatitis
Chronic (lichenoid) - >3 months posttransplant (can follow acute) - lichenoid interface dermatitis
Chronic (sclerodermoid) - up to 18 months posttransplant - morphea-like fibrosing dermatitis

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12
Q

Grading scheme for cutaneous GvHD

A

Grade 1: basal vacuolar change
Grade 2: dyskeratotic keratinocytes
Grade 3: subepidermal cleft and microvesicle formation
Grade 4: Dermoepidermal split +/- epidermal necrosis

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13
Q

Causes of erythema multiforme

A

Variety of triggers:
Infection - HSV, mycoplasma
Drugs - NSAIDs

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14
Q

Histopathological findings in erythema multiforme

A

Early: vacuolar interface dermatitis
More advanced: bullous lesions with subepidermal vasiculation
Severe: resemble toxic epidermal necrolysis with marked epidermal necrosis

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15
Q

Variants and histopathological patterns of lupus skin disease

A

Cutaneous manifestation of active SLE
* - Superficial and deep perivascular dermatitis, vacuolar interface change
* - Subepidermal blister with neutrophils
Subacute cutaneous lupus erythemattosus
* - Superficial perivascular dermatitis, vacuolar interface change
Discoid lupus erythematosus
* - Superficial and deep perivascular dermatitis, vacuolar interface change
Tumid lupus erythematosus
* - Superficial and deep perivascular dermatitis
Lupus profundus
* - Lobular panniculitis

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16
Q

Histochemical stains with utility in diagnosis of cutaneous lupus

A

Stains for increased dermal mucin - AB, Colloida iron
Stains for BM thickening - PAS

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17
Q

Significance and diagnostic value of “lupus band” on DIF

A

Incidence of positivity related to lesion site and duration
Lupus band test has high incidence of positive in systemic SLE in both lesional and nonlesional sun-exposed skin
Lower incidence of + in SLE if nonlesional sun-protected skin sampled
May be falsely pos in chronically sun-exposed skin or normal controls

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18
Q

What to tell a clinician about to sample a pt with bullous disease

A

Lesional skin for routine sections and perilesional skin for DIF
FFPE for routine sample and saline or Miche;’s medium for IF sample
Normal saline if transport time <24h
Michel’s medium if transport time >24h
No formalin contamination for IF specimen or false neg

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19
Q

Conditions requiring lesional over perilesional tissue for DIF

A

Lupus
Vasculitis
Lichen planus

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20
Q

Classification of vesiculobullous diseases

A

Based on 3 features:
- location of split (subepi vs intraepi)
- mechanism of split (intraepi spong, acantholysis, ballooning)
- dermal inflammatory infiltrate

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21
Q

4 disorders characterized by intraepidermal acantholysis, histopath features and IF

A

**Pemphigus vulgaris ** - suprabasal acantholysis with tombstoning, mixed infiltrate, net-like or intercellular IgG +/- C3 on DIF
Hailey-Hailey - Acantholysis in dilapidated brick wall pattern, minimal dyskeratosis. No IF
Darier disease - Acantholysis with prominent dyskeratosis, neg DIF
**Grover disease **- focal acantholysis and variable dyskeratosis, neg DIF

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22
Q

6 disorders character by subepidermal blisters and histopathological findings, IF

A

Epidermolysis bullosa acquista - cell poor blister, linear IgG/C3 staining along basement mebrane zone, immune deposits to dermal side of blister (salt split skin)
Porphyria cutanea tarda - cell poor blister with projection of dermal papillae into cavity, caterpillar bodies in roof. IgG/C3 along BMZ and within thickened pap derm vessels
Bullous pemphigoid - eosinophil-rich blister and dermal infiltrate, sometimes with neuts, eosinophilic spong. DIF linear IgG/C3 along BMZ. Salt split skin to roof
Pemphigoid (herpes) gestationalis - indistinguishable from bullous pemphigoid, occurs in pregnancy
Dermatitis herpetiformis - neutrophil rich blisters and microabscesses at tips of dermal papillae, Granular IgA along BMZ, celiac association
Linear IgG dermatosis - similar to dermatitis herpetiformis, association with IBD, LPDs, drugs

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23
Q

Histopathologic features of leukocytoclasic vasculitis

A
  • Fibrinoid necrosis of small vessel walls with extravasated RBCs
  • Angiocentric neutrophilic infiltrate with nuclear dust
  • DIF: der,al vessel staining with IgG/C3/fibrinogen +/- IgM
  • Secondary changes - necrosis/ulceration or subepidermal blister formation
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24
Q

Possible causes of lekocytoclasic vasculitis

A
  1. Infection - bacterial, rickettsial, fungal, viral
  2. Autoimmunity - immune complex diseeases, ANCA-associated
  3. Drugs
  4. Malignancy
  5. Idiopathic (40%)
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25
Clinical findings and histopathology of Sweet syndrome
**Clinical** * Pts with sudden eruptions of painful plaques and papules on face/extremities, often following infection * fever and leukocytosis * Unknown etiology but assocation with malignancy (esp AML), autoimmunity, infection, drugs **Histopath** * Dense diffuse dermal neutrophilic infiltrate * subepidermal edema * Usually no true vasculitis
26
Histopathological deatures of plaque-type psoriasis
* Regular acanthosis of epidermis with elongated, club-shaped rete ridges and thinned suprapap plates * Prominent dilated capillaries in pap dermis * Confluent dry parakeratosis overlying diminished granular layer * Kogoj microabscess - neut collection in spinous layer * Munro microabscess - mounds of parakeratosis with neuts
27
Patterns of cutaneous granulomatous inflammation with relevant disease associations
**Tuberculoid**: Nodular epithelioid histiocytes with central necrosis and periphera lymphocyte rim - tuberculosis, leprosy, rosacea **Sarcoidal**: naked granulomata without necrosis - sarcoidosis, berylliosis, zirconium granulomas, Crohn's disease **Foreign body**: abdundant irregularly distributed forgei-body giant cells - suture granuloma, keratin, tattoo **Xanthomatous**: foamy histocytes - xanthogranuloma, infections (leprosy, syph) **Suppurative and granulomatous**: aggregations of neuts with interspersed histiocytes - ruptured follicular cyst/unit, deep funal infection, atypical myobacterial infection **Palisading**: geographic pattern with histiocytic rims - granuloma annulare, rheumatoid nodule, necrobiosis lipoidica
28
Clinical and histopathological features of granulama annulare, rheumatoid nodule, necrobiosis lipoidica
**GA**: young adults, acral sites * usually foca involvement of upper anf mid reticular dermis, palisading histiocyters, increased dermal mucin **RN**: bony prominence of forearms, elbows, hands, feet, knees * deep in dermis and/or subcutis * Palisading and sometimes serpiginous granulomas surrounding fibrinoid change, lack of sig dermal mucin **NL**: assocation with diabetes * diffuse dermal involvement and extnding into superficial subcutis * palisaded, interstitial or tiered inflammatory infiltrate with intervening sclerotic collagen (layer cake appearance) * mixed infiltrate of histiocytes lymphs, plasma cells * lack of sig dermal mucin
29
Histopathologic features of erythema nodosum
Predominantly septal panniculitis with some overflow into fat lobules * early phase - predominance of neuts * late phase - predominance of lymphs, eos, multinucleated giant cells * chronic recurrent EM prominant septal fibrosis with inflammation
30
5 conditions associated with erythema nodosum
1. Drug reaction (eg oral contraceptive) 2. Infection 3. Sarcoidosis 4. IBD 5. Malignancy (eg hematolymphoid)
31
5 key causes of lobular panniculitis
1. Infection 2. Nodular vasculitis 3. Lupus profundus 4. alpha-1 antitrypsin deficiency 5. Pancreatic panniculitis
32
Clinical and histopathologic features of fixed drug eruption
Clinical * ovoid or annular erythematous lesions in response to drug exposure and recur in same location upon reexposure * Common sites: lipds, face, hands, genitalia Histopath * vacuolar interface dermatitis with superficial and deep perivascular infiltrate * acute phase resembles EM * pigment incontinece can be observed in quiescent phase
33
Features of pityriasis rosea
* Self limited papulosquamous eruption in children and young adults * starts as salmon-coloured herald path on trunk developing into multiple smaller scaly papules on truck and extremities in Christmas tree pattern * clinically similar to secondary syph * Histopath - subacute spong derm w superficial perivasc lymph infiltrate with overlying mounds of parakeratotic scale
34
What is cornoid lamella and where is it found
Angulated pillar of parakeratosis arising from epidermal invagination with loss of granular layer and localized dyskeratosis Seen in porokeratosis
35
Cinucal and histopathological features of morphea
Clinical * localized/plaque-like, linear, or generalized * Indurated plaques present on trunk and extremities with shiny white centres urrounding by violaceous border Histopath * early - superficial and deep perivasc and interstitial lymphplasmacytic infiltrate * late - thickened dermal collagen resulting in biopsy specimen with square edges, atrophy of adnexal structures with loss of periadnexal fat, diminished inflammation * may be associated lichen sclerosis type changes
36
DDx of "normal appearing skin biopsy"
Dermatophytosis Subtyle pigmentary disorder (eg solar lentigo or vilitigo) Cutaneous amyloidosis Urticaria Icthyosis
37
Clinical and histopathologic features of lichen sclerosus
Clinica * pruritic white plaques with wrinkled appearance most commonly in anogenital area of females Histopath * epidermal atrophy and hyperkeratosis with homogenized superficial dermal collagen and vacuolar degen of basal keratinocytes with associated perivasc lymphocytic infiltrate
38
4 common cysts in skin and their characteristic histopathologival features
1. Epidermal inclusion cyst - lining with squam epi with gran layer, cyst contents laminated keratin 2. Trichilemma cyst - squam epi liming with trichilemmal keratinization without granular layer, cyst contents dense honogenous keratin +/- calcs 3. Steatocystoma - lining squam epi with currogated eosinophilic lining without granular layer * sebaceous lobules within or near cyst wall * cyst appears empty due to loss of sebaceous fluid during processing 4. Hidrocystoma - lining simple cuboidal to columnar +/- decapitation secretion, cyst appears empty
39
Skin conditions with AIDs-association
Psoriasis Seborrheic dermatitis Eosinophilic folliculitis Infections - HSV, molluscum, bacillary angiomatosis, mycobacteria, tc Kaposi sarcoma
40
Histopathologic features of stasis dermatitis
Superficial and deep dermis with neovascularization and lobular prolif of small vessels and mild lymphocytic perivasc infiltrate Adjacent dermis may contain extravasated RBCs and hemosiderin Overlying epidermis may be acanthotic and shows spong and hyperkeratosis
41
Syndromes with cutaneous manifestations
Muir-Torre - sebaceous neoplasms, keratoacanthomas Birt-Hogg-Dube - fibrofolliculomas, acrochordons Cowden - trichilemmomas Tuberous sclerosis - angiofibromas, shagreen patch, ash-leaf macles periungual fibromas
42
Histopath findings of dermatophyte infection
May look normal Neuts in cornified layer Psoriasiform epidermis Vesciular with prominent spong
43
3 common skin infections and histopath findings
HSV/VZV - intraepidermal vesicle, grand glass MMM nuclei HPV - acanthosis, papillomatosis, hyperkeratosis with parakeratosis overlying papillae. Large coarse keratohyalin granules in superficial keratinocytes Molluscum contagiosum (poxvirus) - lobulated and often crateriform lesion, epidermal hyperplasia with henderson-patterson bodies
44
Key variants of cutaneous viral warts and most commonly associated HPV types
Verruca vulgaris - 1, 2, 4 Myrmecial wart - 1 Verruca plana - 3, 5, 10 Condyloma acuminatim - 6, 11, 18 Epidermodysplasia verruciformis - 2, 3, 5, 8
45
Dermatologic conditions associated with significant morbidity/mortality and require urgent recognition
Pancreatic panniculitis SJS/TEN Staph scalded skin syndrome Acute GvHD Calciphylaxis Angioinvasive fungal infection Pemphigus Vasculitis Hematological malignancy
46
Define erythroderma and list possible causes
Generalized redness and scaling of the skin involving >90% of skin surface Causes: * psoriasis * atopic dermatitis * drug reaction * Cutaneous T-cel lymphoma * pityriasis rubra pilaris
47
Conditions affecting the skin in which there are electron micoscopic findings
**Amyloidosis** - randonly arranged, nonbranching 6-10nm diameter filaments **LCH** - birbeck granules **Fabry disease** - lamellar inclusion bodies within endothelial cells, smooth muscle cells, fibroblasts and macrophages 2' lipid deposition in lysosomes **Variants of epidermolysis bullosa** - split at basement membrane zone **Merkle cell CA** - dense core granules within cytoplasm of tumor cells **Melanoma** - melanosomes
48
Clinical findings suggestive for melanoma
**A**symmetry **B**orders - irregular **C**olour variegation **D**iameter > 6mm **E**volution of lesion
49
Staging features of melanoma
Breslow thickness Presence or absence of ulceration Presence or absence of microsatellites
50
How is depth of invasion in melanoma measured
Measure from top of granular layer to the deepst broad base of tumor (avoiding periadnexal extension) If ulcerated epidermis, measure from base of ulcer to base of tumor
51
Definition of ulceration
Full-thickness epidermal defect not due to trauma or previous procedure evidence of reactive changes - fibrin deposition, neutrophils
52
Define cutaneous microsatellite, satellite, in-transit metastasis
Microsatellite mets - microscopically determined, cutaneous and/or subQ tumor deposit adjacent or deep to primary melanoma separated by normal tissue (not fibrotic or inflammed) Satellite met - clinicall evidence cutaneous/subQ tumor deposits within 2cm of primary melanoma In-transit met - clinically evident cutaneous/subQ deposit >2cm from primary melanoma between primary and nearest regional LN
53
Definition of sentinel LN for melanoma
first node to receive lymphatic drainage from primary tumor May be more for some tumors
54
Assessment of sentinel LNs for melanoma
Section at 2-3mm, serial sections cut for H&E and immunostains Single melanoma cell marks it as positive Beware capsular nevus, pigmented melanophages
55
Capsular nevus vs metastatic melanoma in LN
Nevus - location in nodal fibrous tissue, benign cytology, no mits, weak/low HMB45 & Ki67 Melanoma - subcapsular sinus/parenchyma, malignant cytology, mits, strong/high HMB45 & Ki67
56
Features of desmoplastic melanoma
* Occurs in H&N of older patients, flesh coloured nodule * Frequently nonpigmented and looks kike scar * Sometimes associated with subtle junctional prolif of melanocytes * Presence of lymphoid aggregates at periphery of tumor * Frequently has PNI and deep extension * May be associated with elements of "conventional" melanoma * stains with S100/SOX10 but typically negative for other melanocytic markers
57
Gene mutation most frequently associated with melanoma
CDKN2A (p16) BRAF, NRAS, HRAS, CKIT also found in some
58
Histopathological features of CLark nevus/dysplasic nevus
Lentiginous proliferation of melanocytes singly and in nests involving tips and sides of rete ridges with bridging Shouldering Papillary dermal fibrosis Variable cytologic features Perivascular lymphohistiocytic infiltrate
59
Variants of melanoma that may be mistaken for nevi or other lesions
Nevoid melanoma spitzoid melanoma desmoplastic melanoma Blue nevus-like metastatic melanoma
60
Benign melanocytic lesions that may be mistaken for melanoma
Spitz nevus Combined nevus Halo nevus Recurrent/persistent nevus after biopsy/partial resection Irritated/traumatized nevus Nevus in pregnancy with increased mitotic rate Nevi of special sites
61
Histopathologic features of Spitz nevus
Clinical context - usually young patients with a pink dome-shaped papule on the head and neck Microscopically small, symmetrical, and circumscribed proliferation of spindled or epithelioid melanocytes arranged in nests surrounded by clefts at the dermoepidermal junction Junctional, compound, or completely dermal Spindle cells often vertically oriented as "hanging bananas" at tips of acanthotic rete ridges Intraepidermal kamino bodies Minimal pagetoid extension
62
Molecular findings associated with Spitz nevus
HRAS BAP1 loss Deletions in 6p23 Fusion or translocations involving tyrosine kinases (ROS1, ALK, NTRK)
63
Features of Spitzoid nevus with BAP1 loss
Typically dermal, lack epidermal hyperplasia and kamino bodies Typically arise from common nevus showing a biphasic pattern with component of small melanocytes adjacent to spitzoid component. Both components of melanocytes harbour BRAF muitations Only spitzoid component shows BAP1 loss
64
Histopathologic features of blue nevus
**Common blue nevus**: Small, wedge-shaped dermal aggregated of spindled and dendritic melanocytes in a fascicular pattern with admixed melanophages and dermal fibrosis **Cellular blue nevus**: Dermal or subQ fascicles of monomorphous spindle cells without prominent pigmentation
65
Histopathologic features suggestive of congenital nevus
Deep extesion of melanocytes into dermis +/- subQ fat Extension of melanocytes along blood vessels and adnexal structures Splaying of nevus cells between collagen bundles of the reticular dermis
66
Clinical features of SCC that are associated with aggressive clinical course
Immunosuppressed patients Lip, ear, vulva, perineum, penis location Arising in chronic ulcer, scar, sinus
67
Histopathologic variants of SCC associated with aggressive course
Acantholytic Pseudovascular Adenosquamous
68
Benign lesions or conditions that can simulate SCC on histopathology
Pseudoepitheliomatous hyperplasia Prurigo nodularis Hypertrophic cutaneous lupus erythematosus Hypertrophic lichen planus Inverted follicualr keratosis Desmoplasmic trichilemmoma Modified verruca vulgaris Proliferating pilar tumor
69
Histopathologic features of keratoacanthoma
Exophytic and endophytic crateriform epidermal lesion with papillomatosis and abundant keratin in crater Galssy eosinophilic keratinocytes towards center of nests and entrapment of elastic fibres at periphery Exhibits inflammation, usually eos and neutrophilic microabscesses
70
Classic clinical hx of keratoacanthoma
Rapidly growning nodule on sun exposed skin of elderly individuals, often with horn Lesion that usually involutes over several months
71
Factors of oncogenic important in Merkle Cell CA
Risk factors: advanced age, chronic sun exposure, fair skin, immunosuppression Merkel ecll polyomavirus-mediated oncogenesis occurs in 80% UV-mediated oncogenesis in minority of cases
72
IHC for merkel cell CA
Synapto/chromo + CK20/CAM5.2 paranuclear dot-like positivity Dot-like positivity with neurofilament Nuclear pos Merkle cell polyomavirus IHC Neg: TTF1, S100, SOX10, melanoma markers, LCA
73
Basaloid epithelial tumors on the DDx for nodular BCC
Basaloid SCC Merkel cell CA Trichoepithelioma Trichoblastoma Adenoid cystic CA Sebaceous CA
74
Stages of mycosis fungoides
Patch Plaque Tumor
75
Clinical evolution of mycosis fungoides
Chronic scaly patches develop mainly on doubly clothes areas of the body, usually in adults Disease is slowly progressive May evolve into erythroderma LN and other organ involvement can occur
76
Histopathologic features of patch stage mycosis fungoides
* Sparse lymphocytic infiltrate present in superficial dermis and extends into basal epidermis, often single file of cells * Increased lymphocytes within epidermis in absence of significant spong * Pautrier microabscesses - cluters of atypica lymphs in epidermis * Frank atypia uncommon, but cells may be angular with slightly enlarged hyperchromatic nuclei * Papillar dermal collagen has a coarse chiciken-wire pattern
77
Malignant spindle cell lesions of skin
Melanoma SCC AFX/PDS Leiomyosarcoma DFSP MPNST Kaposi sarcoma Angiosarcoma Mets or extension of deep soft tissue tumor
78
IHC for ddx of malignant spindle cell lesion of sun damaged skin
CK5/6, p63, p40 S100, SOX10, MelanA, HMB45 Desmin, actin, calponin ERG, CD31, CD34 D2-40, HHV8 CD10
79
DF vs DFSP
DFSP larger, deep extension, lace-like fat infiltration, uniform cytology with mild atypia DF smaller, poorly circ dermal nodule with collagen trapping, associated epidermal hyperplasia. Heterogeneous cell population with multinucleated, pigmented, foamy cells DFSP CD34+, FXIIIA- DF CD34- FXIIIA+ DFSP COL1A1-PDGFR
80
Differentiate cutaneous sebaceous neoplasms
**Sebaceous hyperplasia** - prominnet sebaceous lobules connected to common central follicular infundibulum **Sebaceous adenoma** - most common sebaceous tumor of MTS. Mature sebocytes with minority of basaloid germinative cells. Circumscribed and lobulated. **Sebaceoma** - Majority of tumor basaloid germinative cells, mature sebocytes are minor. Conspicuous mitoses but no atypica mits, marked pleomorphism etc **Sebaceous CA** - Atypical basaloid cells with large and irregular vesicular nuclei, mild to severe nuclear atypia, mits, necrosis
81
Classic clinical description of a glomus tumor
Painful nodule most commonly on digits, especially subungual Derived from modified smooth muscle cells involved in thermoregulation (Sucquet-Hoyer cells)
82
Painful cutaneous lesions
**A**ngiolipoma **N**euroma **G**lomus tumor **E**ccrine spiradenoma **L**eiomyoma
83
Settings in which patients may develop cutaneous angiosarcoma
* Elderly pts, head and neck, no predisposing condition * chronic lymphedema (stuart-treves syndrome) * Postirradiation
84
2 variants of lipoma seen in skin
**Angiolipoma**: painful nodule, often on forearms, composed of mature adipose tissue with admixed blood vessels containing fibrin thrombi **Spindle cell lipoma**: lesion in cape distribution of older men, composed of mature adipose tissue, CD34+ spindle cells, myxoid matrix, often with thick intervening ropey collagen and mast cells
85
Mammary vs extramammary pagets
Mammary - Mucin+, CK7+, HER2+, often CEA+ Extramammary - less often HER2+ * staining profile similar to associated malignancy
86
Histopathological features of epithelioid sarcoma
Multinodular proliferatio of epithelioid or spindled cells with variable atypia and mits, areas of geographic necrosis may look like palisading Majority pos for vimentin, CK, EMA +/- CD34 Loss of INI1 expression
87
Primary cutaneous lymphoma classification
**Cutaneous T-cell and NK-cell lymphoma** * MF/Sezary syndrome * Adult T-cell leukemia/lymphoma (HTLV-I) * Primary cutaneous CD30+ LPDs **Cutaneous B-cell lymphomas** * MALT * Primary cutaneous follicular centre lymphoma * Primary cutaneous DLBCL, leg type * Intravascular large B-cell lymphoma Other - blastic plasmacytoid dendritic cell neoplasm
88
Inflammatory conditions in which associated lymphoid infiltrate may contain CD30+ lymphocytes
Molluscum contagiosum Persistent arthropod bite reaction Drug eruption Viral warts HSV/VSV

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