Derm Flashcards
Clark levels
II: Melanoma present but does not fill/expand papillary dermis
III: Fills and expands papillary dermis
IV: Invades reticular dermis
V: Invades subcutis
Melanoma T staging
a: no ulceration
b: ulceration
pT1: <0.8 cm (0.8-1.0)
pT2: 1-2.0cm
pT3: 2-4.0 cm
pT4: >4cm
Low CSD Melanoma
Superficial spreading
Nodular
Nevoid
Lentiginous
High CSD Melanoma
Lentigo maligna
Desmoplastic
Melanoma in sun shielded areas or without known UV association
Spitz
Acral
Mucosal
Arising in congenital nevus
Arising in blue nevus
Uveal
Merkle cell CA T-staging
Merkle cell CA N-staging
pN1: clinically undetected met
pN2: in-transit met without LN
pN3: in-transit met with LN
Histopathological features of lichen planus
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)
4 histopathological variants of lichen planus
Bullous lichen planus
Hypertrophic lichen planus
Lichen planopilaris
Atrophic lichen planus
IF findings of lichen planus
Colloid bodies stain with IgM, occasionally with IgG, IgA, and C3
Fibrinogen deposits are present in the dermoepidermal junction
Types, timing, and histopathological manifestations of cutaneous GvHD
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
Grading scheme for cutaneous GvHD
Grade 1: basal vacuolar change
Grade 2: dyskeratotic keratinocytes
Grade 3: subepidermal cleft and microvesicle formation
Grade 4: Dermoepidermal split +/- epidermal necrosis
Causes of erythema multiforme
Variety of triggers:
Infection - HSV, mycoplasma
Drugs - NSAIDs
Histopathological findings in erythema multiforme
Early: vacuolar interface dermatitis
More advanced: bullous lesions with subepidermal vasiculation
Severe: resemble toxic epidermal necrolysis with marked epidermal necrosis
Variants and histopathological patterns of lupus skin disease
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
Histochemical stains with utility in diagnosis of cutaneous lupus
Stains for increased dermal mucin - AB, Colloida iron
Stains for BM thickening - PAS
Significance and diagnostic value of “lupus band” on DIF
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
What to tell a clinician about to sample a pt with bullous disease
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
Conditions requiring lesional over perilesional tissue for DIF
Lupus
Vasculitis
Lichen planus
Classification of vesiculobullous diseases
Based on 3 features:
- location of split (subepi vs intraepi)
- mechanism of split (intraepi spong, acantholysis, ballooning)
- dermal inflammatory infiltrate
4 disorders characterized by intraepidermal acantholysis, histopath features and IF
**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
6 disorders character by subepidermal blisters and histopathological findings, IF
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
Histopathologic features of leukocytoclasic vasculitis
- 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
Possible causes of lekocytoclasic vasculitis
- Infection - bacterial, rickettsial, fungal, viral
- Autoimmunity - immune complex diseeases, ANCA-associated
- Drugs
- Malignancy
- Idiopathic (40%)
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
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
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
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
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
5 conditions associated with erythema nodosum
- Drug reaction (eg oral contraceptive)
- Infection
- Sarcoidosis
- IBD
- Malignancy (eg hematolymphoid)
5 key causes of lobular panniculitis
- Infection
- Nodular vasculitis
- Lupus profundus
- alpha-1 antitrypsin deficiency
- Pancreatic panniculitis
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
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
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
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
DDx of “normal appearing skin biopsy”
Dermatophytosis
Subtyle pigmentary disorder (eg solar lentigo or vilitigo)
Cutaneous amyloidosis
Urticaria
Icthyosis
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
4 common cysts in skin and their characteristic histopathologival features
- Epidermal inclusion cyst - lining with squam epi with gran layer, cyst contents laminated keratin
- Trichilemma cyst - squam epi liming with trichilemmal keratinization without granular layer, cyst contents dense honogenous keratin +/- calcs
- 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 - Hidrocystoma - lining simple cuboidal to columnar +/- decapitation secretion, cyst appears empty
Skin conditions with AIDs-association
Psoriasis
Seborrheic dermatitis
Eosinophilic folliculitis
Infections - HSV, molluscum, bacillary angiomatosis, mycobacteria, tc
Kaposi sarcoma
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
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
Histopath findings of dermatophyte infection
May look normal
Neuts in cornified layer
Psoriasiform epidermis
Vesciular with prominent spong
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
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
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
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
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
Clinical findings suggestive for melanoma
Asymmetry
Borders - irregular
Colour variegation
Diameter > 6mm
Evolution of lesion
Staging features of melanoma
Breslow thickness
Presence or absence of ulceration
Presence or absence of microsatellites
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
Definition of ulceration
Full-thickness epidermal defect not due to trauma or previous procedure
evidence of reactive changes - fibrin deposition, neutrophils
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
Definition of sentinel LN for melanoma
first node to receive lymphatic drainage from primary tumor
May be more for some tumors
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
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
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
Gene mutation most frequently associated with melanoma
CDKN2A (p16)
BRAF, NRAS, HRAS, CKIT also found in some
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
Variants of melanoma that may be mistaken for nevi or other lesions
Nevoid melanoma
spitzoid melanoma
desmoplastic melanoma
Blue nevus-like metastatic melanoma
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
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
Molecular findings associated with Spitz nevus
HRAS
BAP1 loss
Deletions in 6p23
Fusion or translocations involving tyrosine kinases (ROS1, ALK, NTRK)
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
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
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
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
Histopathologic variants of SCC associated with aggressive course
Acantholytic
Pseudovascular
Adenosquamous
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
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
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
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
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
Basaloid epithelial tumors on the DDx for nodular BCC
Basaloid SCC
Merkel cell CA
Trichoepithelioma
Trichoblastoma
Adenoid cystic CA
Sebaceous CA
Stages of mycosis fungoides
Patch
Plaque
Tumor
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
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
Malignant spindle cell lesions of skin
Melanoma
SCC
AFX/PDS
Leiomyosarcoma
DFSP
MPNST
Kaposi sarcoma
Angiosarcoma
Mets or extension of deep soft tissue tumor
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
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
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
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)
Painful cutaneous lesions
Angiolipoma
Neuroma
Glomus tumor
Eccrine spiradenoma
Leiomyoma
Settings in which patients may develop cutaneous angiosarcoma
- Elderly pts, head and neck, no predisposing condition
- chronic lymphedema (stuart-treves syndrome)
- Postirradiation
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
Mammary vs extramammary pagets
Mammary - Mucin+, CK7+, HER2+, often CEA+
Extramammary - less often HER2+
* staining profile similar to associated malignancy
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
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
Inflammatory conditions in which associated lymphoid infiltrate may contain CD30+ lymphocytes
Molluscum contagiosum
Persistent arthropod bite reaction
Drug eruption
Viral warts
HSV/VSV
