Dermatopathology Flashcards
DX:
Key histo:
Dx; Spitz nevus
Key histo: Hematoxylin & eosin at low power shows nests of spindled and epithelioid melanocytes at the dermal-epidermal junction and in the dermis.
Dx:
Key feature exemplified by this image:
DDx:
Dx: Spitz nevus
Key feature: Hematoxylin & eosin at medium power shows the characteristic artifactual clefting that occurs between nests of spindled melanocytes and the overlying epidermis
Dx:
Malignant melanoma
Melanocytic nevus
Dx:
Key histo feature
Dx: spitz nevus
Key histo: Kamino bodies - Eosinophilic globules at dermal-epidermal junction
DX:
Key histo features:
DDx:
Dx: Common blue nevus
Histo features:
Elongated, delicate, sometimes branching melanocytes dissect through dermal collagen in reticular dermis
Melanocytes are often periadnexal
Variable numbers of melanophages
Pigment can be so heavy as to obscure melanocytes, although some are amelanotic
May have dermal fibrosis (sclerosing blue nevus)
May have overlying melanocytic or Spitz nevus
DDx:
- Dermatofibroma
- Deep penetrating nevus
- Blue nevus like metastatic melanoma
- Very rare, need h/o previous melanoma
- Melanoma would have atypical melanocytes and mitoses
- melanoma may have inflammatory reaction that blue nevus would not
Which hereditary conditions are a/w BCCs? (5)
Basal cell nevus syndrome
Bazex-Dupre-Christol syndrome
Hereditary infundibulocystic basal cell carcinoma
Xeroderma pigmentosum
Rombo syndrome
Name the more aggressive subtypes of BCC? (4)
micronodular
Infiltrative
Basosquamous
Desmoplastic
What IHC can you use to confirm dx of BCC?
BCC shows greater staining for BCL2, p53, and Ki-67 compared to benign follicular tumors
Picture: STrong and diffuse nuclear staining of Ki67 seen in BCC consistent with elevated proliferative rate of this tumor. This marker is usually low or negative in benign tumors.
Which IHC stain is used to help distinguish BCC from SCC?
BER-EP4
BER-EP4 in BCC shows moderate to strong and diffuse staining of most of the tumor cells. This marker is typically negative in squamous cell carcinoma and most other tumors in the differential diagnosis.
Dx:
Key Histo features:
DDx: (4)
Dx: low magnification nodular BCC
- (low grade malignancy of basal keratinocytes)
Key histo: large, nodular-type BCC with diffuse overlying ulceration/erosion and serum crust
DDx:
- SCC
- Actinic keratosis
- Follicular neoplasm (trichoepithelioma and trichoblastoma)
- Merkel Cell carcinoma
Dx:
Key histo features:
Dx: micronodular BCC
Key histo features: hows a proliferation of small nests of basaloid cells with a prominent retraction artifact in a somewhat sclerotic-appearing stroma.
Common mutation in congenital melanocytic naevus?
NRAS (! not BRAF)
Bx from nail bed of women in 20s.
Pain red-blue lesion.
Dx?
Ancillary testing?
Glomus tumor
Typically solid nests of round cells closely associated with variably sized blood vessels
Characteristic centralized, rounded, uniform nuclei
SMA + Caldesmon +
Desmin, S100, keratin-
Describe the genetic mutation leading to neurofibromas including chromes etc.
Neurofibromas are caused by a biallelic inactivation of the tumor suppressor gene neurofibromatosis type 1 which is located on 17q11.2
Describe how to dx NF1?
Diagnostic criteria of neurofibromatosis type 1 are met if 2 or more of the following are present:
≥ 6 café au lait patches > 0.5 cm in prepubertal individuals or > 1.5 cm in postpubertal individuals
≥ 2 neurofibromas of any type or 1 plexiform neurofibroma
Axillary or inguinal freckling
≥ 2 Lisch nodules
Optic glioma
Sphenoid dysplasia or thinning of long bone cortex with or without pseudoarthrosis
First degree relative diagnosed with neurofibromatosis type 1
How can you differentiate between desmoplastic melanoma and neurofibroma using IHC?
CD34 is rarely positive in desmoplastic melanoma and is often patchy when it is.
Dx:
Key feature?
Dx: Seb K
Key feature: acanthotic, hyperkeratotic, papillomatosis and prominent pseudohorn cysts.
Lesion on face.
Dx & why?
DDx:
IHC:
Solitary circumscribed neuroma.
Most common 5th and 7th decades
Proliferation of axons and nerves. Well-circumscribed. Characteristic clefting at low power. No cytological atypia. Bland spindle cells.
DDx:
Benign nerve sheath tumours
Superficial pilar leiomyoma
Dermatofibroma
IHC:
Strong S100(+)/SOX10(+) in schwann cells and nerve fibres
SMA, desmin, GFAP, melanocytic markers (-)
9 yr F, nodule under left eye.
Gross morph: Nodular, subepidermal.
Dx?
Key histo features?
Pilomatrixoma
Solid nests of basaloid cells undergoing abrupt trichilemmal-type keratinization. Ghost cells, often foreign body reaction, calcification or ossification with extramedullary hematopoiesis
solid pale firm subcutanous nodule removed from face of child
Dx? and why?
Dermoid cyst.
Cyst lined by epidermis with skin appendages. (derived from both ectoderm and mesoderm)
25F dermal nodule, tender
histo features + dx + IHC
Basaloid tumour cells
Biphasic population (peripheral small cells - hyperchromatic; central larger cells - eosinophilic cytoplasm)
lobules a/w a vascularised stroma + haemorrhage
Scattered lymphocytes are present
Focal duct lumen formation
Can be a/w thickened BM (similar to cilindroma)
EMA and CEA highlights ducts
35F head lesion
Dx?
Histo features?
Cylindroma
Non-encapsulated, biphasic population of cells, +/- duct formation, globules of hyaline BM often present in interior of tumour.
35M back
Diagnosis? histo features? IHC?
Hibernoma.
Benign lipomatous tumour composed of a mixture of multivacuolated cells (brown fat) and mature univacuolated adipocytes.
S100+
7M forehead lesion
Dx?
PIlomatrixoma
Diagnosis?
Key histo features
Dermatofibroma
Collagen trapping around periphery, bland spindle cells, sometimes haemosideron macros
70F elbow
Dx? Key histo featuers
rheumatoid nodule.
Nodule in subcutis with central area of necrobiosis and pallisading histiocytes.
60M head nodule lesion excised. Rapidly enlarging.
Dx: and IHC?
DDx:
Merkel cell carcinoma.
proliferation of basaloid cells with high N:C ratio, numerous atypical mitotic figures and nuclear clearing.
IHC: neuroendocrine markers and perinuclear dot-like positivity for CK20 - not seen in BCC
DDx: BCC
60F solitary nodule scalp
Dx?
Key features?
IHC?
DDx?
Adenoid cystic carcinoma
The essential diagnostic feature is the coexistence of true small bilayered ducts and pseudocysts. The true ductal structures are usually sparse, have small round lumina, and are composed of inner epithelial cells with uniform round nuclei (sometimes with small nucleoli) surrounded by an outer layer of basal/myoepithelial cells. Mitoses rare and intraneural invasion rare. Perineural invasion common. Stroma is hyalinised and paucicellular.
Desirable:
Cylindroma-like appearance; Perineural invasion; Coexpression of MYB and CD117; Demonstration of MYB or MYBL1 rearrangements in selected cases.
IHC: epithelial cells (+) for EMA, CEA-M, and CK (Cam5.2, CK7 cytoplasmic).
Peripheral/myoepithelial cells (+): S100, p63, SMA,.MSA
Tumour cells express: MYB and CD117.
DDX: BCC
47M scalp nodule
Dx & description
Warty dyskeratoma
cup shaped keratin filled invagination; acanthotic epidermis with acantholytic dyskeratotic cells; suprabasilar celfting with villi projecting into clefts
59M eyelid nodule ? cancer
description/dx/associated syndromes
sebaceous carcinoma.
Peri- or extra- ocular
A/w Muir torre syndrome (AD w/ mutation in one or more MMR genes)
Well-differentiated: mature multivacuolated sebocytes w/ nuclear indentation relative to basaloid cells. Mild pleo/necrosis/mitoses.
subungal biopsy.
Dx. Key dx features?
Glomus tumor.
Key dx features (3): glomus cells, vascular and sm m cells. Branching capillary sized vessels w collars of glomus cells.
IHC: calponin, SMA, MSA, h-caldesmon. Neg for CK and S100.
NB: glomangioma when prominent vasculature component.
tongue biopsy.
Dx? IHC.
Granular cell Timor.
Soft tissue tumor with neuroectodermal differentiation (S100+, SOX10+, CD68+)
Predilection for tongue.
Eosinophilic cytoplasm + coarse granules. Cells separated by collagenous bands. Mild-mod nuclear atypia. Overlying epithelium can show pseudoepitheliomatous hyperplasia.
4yr old child, lesion right arm
Dx? DDx? distinguishing features
Spitz nevus: spindled - epithelioid melanocytes at the dermal-epidermal junction.
DDx: melanoma. Melanoma lacks maturation, is assymetrical, has more coarse anaplastic nuclear features. More likely if ? 1cm, age greater 10 yrs, ulceration, subcutis involved
4 yr pigmented lesion left dorsal hand
Dx? Features
Blue nevus.
Elongated, delicate, sometimes branching melanocytes dissect through dermal collagen in reticular dermis
Melanocytes are often periadnexal
Variable numbers of melanophages
Pigment can be so heavy as to obscure melanocytes, although some are amelanotic
May have dermal fibrosis (sclerosing blue nevus)
May have overlying melanocytic or Spitz nevus
nodule on neck of 30F
Dx?
Key features?
IHC?
superficial angiomyxoma.
Hypocellular, demral based lesion composed of bland spindled to stellate cells in a myxoid stroma.
Thin-walled plexiform vessels prominent, +/- stromal neutrophils.
IHC: CD34(+), S100(-), SMA(+) 0- 90% -> variable
Blue nevi
Define a blue nevi?
Subtypes and locations?
Blue naevus is a dermal melanocytic tumour composed of dendritic, spindle, and / or ovoid cells associated with melanin pigment and stromal sclerosis; it has a blue tinctorial appearance clinically. Ultraviolet sun light irradiation is not an important etiological factor.
Dendritic blue and cellular blue nevus
DBNs most commonly involve the dorsal distal extremities and face, whereas CBNs typically involve the scalp, back, and buttocks.
Skin.
Dx?
Key features?
Cellular blue nevus
Dumbbell-shaped architecture at low magnification; often extends deeply
Superficial and peripheral desmoplasia with conventional blue nevus cells and melanophages are often conspicuous
Oval and spindle-shaped cells with bland cytology
Lack of mitoses and necrosis***
Cytologic features
Ovoid, pale to clear cells are abundant
Heavily pigmented spindled and dendritic cells alternate with clear cells
lesion on childs head
Dx:
Histo features:
Nevus sebacous/organoid nevus.
Poorly formed pilosebaceous units, lacking hair follicles.
skin lesion
paisely tie/tadpole pattern, DDX?
Syringoma
Microcystic adnexal carcinoma
Desmoplastic trichoepithelioma
Infiltrative/morpheaform BCC
skin lesion. pedunculated papule
Dx?
Features
Poroma
Neoplasm composed of two cellular populations: poroid (smaller and darker) and cuticular (larger and with an eosinophilic cytoplasm) with duct differentiation.
Desirable:
Richly vascular stroma resembling granulation tissue.
skin lesion
Dx?
Features?
Hidradenoma
A well-circumscribed neoplasm, this is composed mainly of clear cells admixed with ductal structures.
skin lesion
What feature of this adnexal tumour is this image demonstrating?
Cells surrounding globules of eosinophilic basement membrane material in a spiradenoma.
scalp lesion.
Dx?
Associated syndrome?
Cylindroma.
Blue basaloid dermal prolifeartion without epidermal connection. At low-power, basaloid cells arranged into geometric micronodules to yeild a “giraffe spot” or jigsaw puzzle” pattern. Dual population of cells (darker cells at periphery, lighter and larger centrally). Sweat ducts present lined by inner pink cuticle.
Brooke-Spiegler syndrome.
bx of small papule on face of adult.
Dx?
Key histo features?
DDx?
syringoma.
Multiple, small sweat ducts aggregated together in dermis. Some have tails (paisely tie). The ducts may contain pink sweat secretions.
B/g dermis is sclerotic.
DDx: MAC, desmoplastic trichoepithelioma, infiltrative/morpheaform BCC
86M white plaque on forearm.
Dx?
Microcystic adnexal carcinoma.
Infiltrative neoplasm with desmoplastic stroma composed of strands and nests of bland cells with variable formation of cysts and ducts and no mitotic activity.
Ulcerated scalp plaque, child:
Dx ?
Key features?
Syringocystadenoma papilliferum
Benign sweat gland tumour. Often arises in pre-existing nevus sebaceous. Epidermal surface is exophyitc (or endophytic) and verrucous. Multiple dilated glandular channels open form skin surface and branch down into the underlying dermis. Papillary islands with central fibrovascular cores float w/i dilated channels. Double layer of bland cuboidal to columnar sweat duct-type epithelium. Plasma cells in FVC.
(This image) endophytic and exophytic components. Superficial aspects sq epi, deep aspects glandular epithelium.
Vulvar lesion
Dx?
Key features?
Hidradenoma papilliferum
circuscribed cystic dermal lesion containing papillae in a maze-like pattern. Papillae lined by a double layer of bland cubodial to columnar cells (similar to SCAP)
head lesion
Dx?
Key features?
Inverted follicular keratosis.
Usually endophytic papillomatous proliferation of epithelium
Numerous squamous eddies are characteristic(Concentric layers of squamous cells with keratin at center) (below)
Basaloid cells at periphery. Can have prominent ortho/paraK -> prominent keratin filled invaginations/cutaneous horns
subcorneal bullous
DDx? (autoimmune vs non-autoimmune)
Auto-immune: pemphigus foliaceus
Non-auto-immune: staphyloccocal scalded skin; bullous impetigo; spongiotic vesicles opening into skin
intraepidermal bulla
DDx? (autoimmune and non-auto-immune)
Autoimmune: pemphigus vulgaris & paraneoplastic pemphigus
Non-autoimmune: spongiotic dermatitis; herpes/pox virus infection; Hailey hailey disease; Darier disease, Transient acantholytic dermatis (Grover disease)
Pemphigus foliaceus and vulgaris have antibodies against which protein?
Desmoglein 1 (PV) and desmoglein 3 (proteins in the desmosome)
Reddish plaques 54M
Dx?
granuloma fasciale
Polymorphous inflammatory infiltrate (often neutrophil predominant) in the upper 2/3s of the dermis, grenz zone and telangiectasia. Extravasated RBCs and haemosideron
Dx?
Key features?
Pyogenic granuloma
Vague lobules of capillary channels arranged around large feeder vessels. Lobules surrounded by fibrous to myxoid CT. Surface epithelium is attenuated and may be ulcerated. Granulation tissue may occur collarette
dysplastic nevi
pathological and clinical size criteria
In general, lesions < 4 mm in diameter on the slides should not be classified as dysplastic naevi unless there is a clinical or gross measurement of > 5 mm
Dysplastic nevi
Nuclear features distinguishing low and high grade dysplasia
Low-grade: 1-1.5 x nucleus size compared to resting basal cell
High-grade: 1.5 x or more
High-grade dysplasia in a dysplastic nevus
Architectural features that indicate high-grade dysplasia even when low-grade cytological features….
Attributes that indicate a diagnosis of high grade (severe) dysplasia even when cytologic atypia is low grade include pagetoid scatter above the basal layer (to a lesser degree than in melanoma, usually not above the middle third, and focal i.e. < 1 HPF), focal continuous basal proliferation, and intraepidermal mitoses (where more than a rare mitosis and/or any dermal mitosis should raise concern for melanoma).
Dysplastic features
Architectural features
Junctional extension (shouldering)
Rete ridge distortion - retal fusion
Asymmetry
Junctional/dermal mitoses
Dermal fibrosis
nests bridging/fusing
solitary painless dermal/subcutaneous nodule.
Dx?
Key features?
IHC?
Myopericytoma.
Commonly, painless, on distal extremities. Dermal or subcutaneous nodule with concentric perivascular growth of bland myoid cells.
IHC: Myopericytoma usually stains for alpha smooth muscle actin, h-caldesmon and occasionally for muscle-specific actin, but desmin immunoreactivity is usually absent or focal
Angioleiomyomas
Histological subtypes (3)
Solid, venous, cavernous - on the basis of their vascular morphologies
Angioleiomyoma
IHC staining
the tumour cells are diffusely positive for SMAs and calponin, and usually strongly positive for h-caldesmon. Desmin expression is variable and may be focal or absent in a minority of tumours { 17270242 }. HMB45 and/or melan-A are negative
Dermal nodule, slow-growing. Knee. Painful
Dx?
Features?
Angioleiomyoma, venous-type
Venous-type angioleiomyoma consists of thick muscle-coated blood vessels with intervascular smooth muscle bundles
Painful nodule lower leg. Dermal
Dx?
Key features?
Angioleiomyoma, solid-type
Solid-type angioleiomyoma is composed of a proliferation of smooth muscle cells with slit-like vascular channels.
Painful nodule, dermal/subcutaneous lesion, distal leg.
Dx?
Key features?
ICH?
Angioleiomyoma, cavernous type
Well-circumscribed tumour composed of cytologically bland smooth muscle cells showing concentric growth around cavernously dilated vascular channels with attenuated walls of smooth muscle cells.
IHC: diffusely positive for SMAs and calponin, and usually strongly positive for h-caldesmon. Desmin expression is variable and may be focal or absent in a minority of tumours.
Short answer:
Discuss the DDx of subepidermal bullae with predominant eosinophils?
Most common.
Also: non-immune: drug reactions and contact dermatitis (will have blisters at other levels)
Short answer:
Discuss the DDx of subepidermal bullae with predominant neutrophils?
short answer
Discuss the DDx of subepidermal bullae with predominant lymphocytes?
short answer
Discuss the DDx of subepidermal bullae cell poor
bullous pemphigoid
Associated with Ig to which protein in the hemidesmisome
Ig to BP230
Phemphigoid gestatianis
Ig to to which protein in the hemidesmisome.
DDx?
BP180
DDX? Puritic, urticarial, papules and plaques of pregnancy. IF (-) and don’t become bulla.
Epidermolysis bullosa acquisita
Ig against which protein?
Associations with which conditions?
Type VII collagen
RA, HCV infection, IBD, thyroiditis and diabetes
Bullous pemphigoid
IF staining pattern?
Linear staining at the DEJ with IgG and C3
(also pemphigoid gestationis and EBA)
Bullous pemphigoid vs EBA
How do you differentiate these entities with IF?
“Salt split”
Remove tissue used for IF put specimen in hypertonic saline for a few days (1 molar) and then partially remove epidermis. Re-do IF. BP IgG/C3 will highlight basal keratinocytes while IgG/C3 in EBA will highlight dermal collagen layer.
Usu you don’t need to do this.
subepidermal bulla with neutrophils
DDx?
Subepidermal bulla with neutrophils
IgG involved in immune mediated DDX
Linear IgA disease
IF pattern staining
Linear staining at the DEJ with IgA and C3
(c.f. BP where you get IgG and C3)
Acute bullous lupus
IF pattern of staining?
Deposition IgG, IgA, IgM C3
In a granular pattern (c.f. linear pattern)
Sweet syndrome also called…?
A/W which malignancy?
demographics
acute febrile neutrophilic dermatosis
AML
Often females
painful cutaneous lesion
DDx?
BLUE ANGEL
Blue rubber bleb nevus
Angioleiomyoma
Neurofibroma or neuroma
Glomus tumor
Eccrine Spiradenoma
Leiomyoma
bilateral, tender painful nodules + fever
skin lesion. Dx?
Key features?
DDx?
Sweet syndrome
Hallmark is intense dermal infiltrate of mononuclear cells (especially neutrophils) often sparing epidermis
Epidermal spongiosis, vesiculation and pustules
Often marked papillary dermal oedema
Leukocytoclasis is common
DDx: abscess
Dermatitis herpetiformis
Presentation
Assocation
Erythematous vesicles on extensor surface.
With gluten-sensitive enteropathy
Dermatitis herpetiformis
Key features?
IF staining?
DDx:
Papillary dermal microabscesses of predominantly neutrophils.
IF: Granular IgA deposits in dermal papillae
DDx: Bullous vasculitis
Subepidermal bulla with lympohcytes
DDx?
subepidermal bulla pauci-cellular
DDx?
Toxic epidermal necrolysis
Dx features?
full thickness epidermal necrosis and subepidermal bullae (late lesions)
Detached and necrotic epidermis, overlying relatively cell-poor dermis a
Non-erythematous vesicle
Dx?
features?
IF staining?
Porphyria cutanea tarda
Subepidermal blist with cell-poor inflammatory infiltrate.
Festooning of dermal papillae
Caterpillar bodies at roof of blister.
IF: Perivascular & BM staining with IgG, C3, fibrinogen, IgA, IgM
Subcorneal, intraepidermal and subepidermal
DDX: immune vs non-immune
Plasma cells are normally found in which anatomical sites?
face, posterior neck, intertriginous sites and pretibial area
Lichen planus
Key features?
IF?
DDx:
Prominent Civatte bodies, band-like inflammatory infiltrate, wedge-shaped hypergranulosis, eosinophilic (PAS-D) colloid bodies are in the papillary dermis. Usu no plasma cells. Hyperkeratosis w/o paraK.
IF: colloid bodies in the papillary dermis, stainng for complement and Ig (esp IgM). An irregular band of fibrin is present along the basal layer (+/- extension into pap dermis) in most cases. (Fibrin usu present in all cases).
DDx: Lupus erythematosus (in contrast to LP, LE mosts often shows epidermal atrophy, persistent vacuolar change of the basilar layer rather than basal keratinocyte loss (with flattening or ‘sawtoothing’ of the epidermal base), BM zone thickening, a deep as well as superficial dermal infiltrate that involves vessels and sweat glands aswell as follicles, and often interstitial dermal mucin deposition.
Other DDx: lichenoid keratosis, lichenoid drug eruptions.
itchy, purpuric, plaque
Dx?
Lichen planus.
Note lymphocyte/histiocyte band-like infiltrate in papillary dermis + eosinophlic colloid bodies and basal cell vacuolation.
What are the major (7) and minor (7) tissue reaction patterns?
Major:
Lichenoid (‘interface dermatitis’)
Psoriasiform
Spongiotic
Vesiculobullous
Granulomatous
Vasculopathic
Combined
Minor:
Epidermolytic hyperkeratosis
Acantholytic dyskeratosis
Cornoid lamellation
Papillomatosis (‘church-spiring’)
Acral angiofibromas
Eosinophilic cellulitis with ‘flame figures’
Transepithelial elimination
Trichilemommas, when common, may be a marker for which syndrome?
Cowden syndrome
What is the genetic mutation in Cowden syndrome?
What does this lead to?
Syndrome with autosomal dominant inheritance caused by mutations in PTEN and sometimes other genes
Causes benign hamartomatous overgrowths of skin, GI tract and thyroid
Also increases risk of malignancy of breast, thyroid, endometrium and colorectum.
Dx?
Key features?
Tricholemmoma
Prominent digitated to bulbous thickening of the follicular infundibulum is seen, with superficial hypergranulosis and hyperkeratosis.
Hair follicle-associated lobules of clear cells with peripheral palisading surrounded by a thick basement membrane.
usually associated with one or more pre-existing hair follicles.
The main bulk of the lesion is composed of lobules of monomorphous epithelial cells with pale, eosinophilic or clear cytoplasm
50M. Painless, slow-growing papule on the right arm
IHC: EMA(+), S100(+), CK(-), SOX10/SMA/p63(-)
Myoepithelioma, cutaneous syncytial.
Syncytial myoepithelioma: sheets of histiocytoid or short spindle cells with pale eosinophilic cytoplasm; positive for EMA and S100 protein.
Atypical fibroxanthoma
Diagnostic criteria.
Variants:
DDx:
IHC:
A circumscribed dermal tumour is present with no involvement of subcutis. Usually pleomorphic (but variable) morphology; strict confinement to the dermis; immunonegativity for at least two epithelial and melanocytic markers, e.g. keratins, P63, S100, HMB45, Melan-A, and SOX10. Necrosis is absent.
Variants: spindle cell, clear cell, granular cell, myxoid, keloidal and sclerotic.
DDx: pleormorphic dermal sarcoma, melanoma, leiomyosarcoma, poorly differentiated SCC.
IHC: S100/SOX10/HMB45, CK, AE1/AE3, MNF116, desmin, caldesom, SMA.
CD10 is usu diffusely positive in AFX (but non-specific as can be seen in melanomas/SCC). SMA is variable but expression with desmin/caldesmon should raise concern for leiomyosarcoma
firm neck lesion 55M
Dx?
Key features?
ICH?
Cutaneous mixed tumour (chondroid syringoma)
Well circumscribed sweat gland neoplasm composed of epithelial, myoepithelial and mesenchymal components. Apocrine subtype more common than eccrine. Numerous variably sized ducts with inner luminal columnar epithelial cells and peripheral cuboidal myoepithelial cells embedded in a myxoid/chondroid/fibrous stroma/mucinous. Follicular/sebaceous differentiation can be present.
IHC: Mixed tumours express SOX10, p63, PS100, calponin, SMA, EMA, c-KIT, CEA, various cytokeratins and PLAG-1, although the eccrine subtype does not express this marker.
Sweat ducts (neoplastic and normal)
IHC used to highlight luminal cells?
EMA and CEA
periorbital lesion bx
Dx:
Key features:
Cutaneous mucinous carcinoma.
Tumour composed of nests and strands of atypical epithelial cells floating in lakes of extracellular mucin.
Associated in situ ductal lesions (ducts with a preserved peripheral basal/myoepithelial cell layer, defining the tumour as primary cutaneous. In the absence of an in situ component, a metastasis should be excluded by clinical investigation.
Dx
Key features
DDx
Trichofolliculoma.
Consists of a central, dilated follicular infundibulum from which several smaller secondary hair follicles radiate into the surrounding dermis.
DDx: Folliculocystic sebaceous hamartoma (has sebaceous glands instead of immature hair follciles budding o fhte central dilated follcile); dilated pore(nothin budding)
Below: foliculocystic sebaceous hamartoma
Dx
Trichoepithelioma/blastoma
dx?
key features
ddx
Pityriasis rosea (caised by reactivation of latent human herpesvirus 6)
Subacute spongiotic dermatitis with perivascular lymphocytic infiltrate.
Mild acanthosis of the epidermis may be present, especially in herald patch
Foci of parakeratosis overlying spongiosis
Granular layer may be diminished or absent under area of parakeratosis.
Erythrocyte extravasates may be focally present in the superficial dermis.
ddx: pityriasis rosea-like drug,
Head papule
Dx?
Key features?
DDx?
90% of cases are located on the head and neck, including the eyelids. Intra-dermal.
Endophytic, crateriform lesion, connected focally to the epidermis/hair follicle, and composed of two layers of cells forming dilated papillary and cystic structures. luminal cells are columnar with rounded or oval nuclei near the basal pole of the cell and abundant eosinophilic cytoplasm with decapitation secretion. Outer layer = basal/myoepithelial cells. Epidermis surrounding SCAP is often papillomatous or wart-like, particularly in cases associated with naevus sebaceus of Jadassohn. The stroma contains numerous plasma cells.
DDx: hidradenoma papilliferum is not connected to the epidermis, lacks plasma cells, and is localized in the vulva
Dx:
Key features?
Verruca vulgaris
The lesions feature hyperkeratosis, acanthosis, and papillomatosis, with prominent, inwardly proliferating rete ridges. Columns of parakeratosis overlie foci of papillomatosis. There is hypergranulosis, with coarse keratohyaline granules. Koilocytes are often present in the superficial epidermis { 22131115 ; 23932731 }. Dilated, tortuous capillaries occupy the papillary dermis. A lichenoid inflammatory infiltrate is sometimes present, and may correlate with regression
small papule
Dx?
What features are demonstrated by this image?
Tricholemomma (infundibular differentation)
Base of lesion showing peripheral palisading and the basement membrane.
45F. Multiple ?cysts on chest wall. PHx breast ca
Dx?
DDx? and how to distinguish.
Atypical vascular proliferation.
Relatively well circumscribed lesion with a somewhat wedge shaped outline, limited to the dermis and not extending into subcutis
2 histologic subtypes with overlapping histologic features:
Lymphatic subtype:
More common subtype
Irregularly shaped, thin walled vascular channels with a branching and anastomosing growth
Lymphatic valve-like structures may be evident
Vessels lined by single layer of endothelial cells without atypia
Hobnailing and nuclear hyperchromasia may be seen
Vascular subtype:
Thin capillary channels lined by flattened to hobnail endothelium, lacking lobular growth pattern
DDX: Angiosarcoma. Large (median size is 7.5 cm) infiltrative lesion with destruction of adnexa and extension into subcutaneous tissues, multilayering of endothelial cells, prominent nucleoli, mitoses, blood lakes and solid areas
Unlike secondary angiosarcomas, atypical vascular lesions lack MYC amplification (by FISH) and MYC overexpression by immunohistochemistry
36M right cheek
Dx?
Key features?
Trichofolliculoma
Folliculocystic tumor that communicates to overlying epidermis
Cystic space filled with keratinous debris and hair shafts
Numerous small, primitive follicles radiate around periphery of tumor and communicate with central cystic space
May have small attached sebaceous glands
Follicles surrounded by perifollicular stromal sheath
Focal granulomatous inflammation secondary to rupture may be present
77M upper lip ? BCC
Dx:
Key features:
IHC:
Pilar sheath acanthoma
Endophytic, lobular proliferation of enlarged, mature squamous cells with prominent acanthosis. Lobules typically surround central dilated follicular structure. Granular layer and foci of infundibular-type keratinization are present. Abortive follicles may be present
Peripheral palisading and thickened basement membrane may be seen (similar to tricholemmoma)
Cells show abundant pale eosinophilic to clear-staining cytoplasm and small nuclei
Clear cells contain glycogen, which can be demonstrated by PAS without diastase digestion
Lesion is usually superficial, well circumscribed, and noninfiltrative
Rare cases may extend deeply into subcutis
Mitotic figures absent to rare, limited to basilar layer
axilla cystic papule female
dx?
Key features
Steatocystoma
Thin-walled, multiloculated cyst located in dermis
Stratified squamous epithelial lining
Undulating, densely eosinophilic cuticle forms inner lining of cyst wall
Absent granular layer
Sebaceous lobules usually identified within cyst wall
Associated primitive follicle and vellus hairs may also be seen
Cystic space is usually empty except for occasional presence of vellus hairs
female purpuric plaque wrist
dx and key histo features
Lichen planus
The “6 Ps”: purple, pruritic, planar (flat), polygonal papules and plaques
Sawtoothed rete ridges, band-like lymphohistiocytic infiltrate at the dermoepidermal junction
Wedge shaped hypergranulosis
Civatte bodies (dyskeratotic keratinocytes)
rapidly growing polypoid lesion
dx
key features
DDx:
Lobular capillary haemangioma
Key features: polypoid, with an epidermal collarette, frequent ulceration, prominent inflammation consisting of neutrophils. Variably dilated capillaries lined by plump endothelial cells are arranged in lobules within oedematous stroma. Mitotic activity is common.. Older lesions show variable fibrosis.
DDx: Nodular Kaposi sarcoma shows a similar architecture but consists of bundles of spindle-shaped cells with clefting, intracytoplasmic eosinophilic globules, and HHV8 positivity. Bacillary angiomatosis (an infectious vascular proliferation caused mainly by Rochalimaea henselae) is histologically similar, but the vascular channels are lined by pale epithelioid endothelial cells and aggregates of neutrophils, and nuclear dust and amorphous basophilic or amphophilic material consisting of Warthin–Starry stain–positive bacteria are identified.
42M right dorsal hand
dx
Key features
Verruciform xanthoma
Papillary architecture, acanthosis, hyperkeratosis and parakeratosis. Loose keratin squames with bright orange-pink color are present on the surface of the papillae as well as within crypts. The epidermal ridges show bulbous expansion and some appear coalesced at their bases. There is marked keratinocyte necrosis associated with a prominent neutrophilic infiltrate. The dermal component of the papillae contains an admixture of foamy or granular xanthoma cells, neutrophils, plasma cells, and lymphocytes in a background of vascular stroma. There is no epithelial atypia and viral inclusions are not present.
face lesion 85F
dx
key features
Microcystic adnexal carcinoma (aka. sclerosing sweat gland carcinoma)
Paisley tie differential
Cords and nests of bland keratinocytes, keratin cysts and ductal differentiation, no mitotic activity
Dense collagenous/desmoplastic stroma
Is invasive, may extend into subcutis or perineural spaces
Resembles syringoma
Rarely is sebaceous differentiation
Desirable:
- Perineural invasion
syringocystadenoma papilliferum
Key features
common sites and age group
DDx:
Key features:
exoendophytic lesion/crateriform
connected focally to the epidermis/hair follicle
2 layers of cells: luminal columnar cells and basal/myoepithelium cells
Papillary and cystic structures
Adjacent epidermis shows verrucous epidermal hyperplasia (papillomatous/wart-like)
Plasma cells in stroma
+/- a/w nevus sebaceous
Common on the head and neck in early childhood
Ddx: hidradenoma papilliferum (usu on vulva, not connected to epidermus and no plasma cells)
Nipple adenoma
hidrocystoma/cystadenoma
Differences:
Key features:
Location:
Ddx:
Mostly occcur on the face/eyelids
Both = cystic lesions
Hidrocystoma = simple cyst
Cystadenoma = complex cyst
Features:
Roudn to oval/solitary /cystic structure; lined by columnar epithelium with decapitation secretion; myoepithelial cells + B.M
Usu abundant mucin in the lumen.
If more complex architecture = cystadenoma
Ddx: lacrimal gland cyst
glans penis erythematous/orange plaque
dx
key features
ddx
Zoon balanitis
Key features:
Epithelium appears thinned and flattened
Sometimes may be partially detached or even absent
Mild spongiosis
Dense lymphocytic lichenoid infiltrate in upper and mid submucosa, with abundant mature plasma cells
Epithelium with diamond- or lozenge-shaped, flattened keratinocytes
ddx: Prim/secondary syphilis - contains more lymphocytes/neutrophils Image: Superficial keratinocytes appear flattened , while keratinocytes in the basal and spinous layers are separated by intercellular edema and adopt the shape of diamonds or lozenges .
65M phimosis
dx
Key features
subtypes (3)
demographic
associations
Balanitis xerotica obliterans
a.k.a: lichen sclerosus et atrophicus
Key features in fully developed lesions:
Epithelial thinning and ulceration
Wide hyalinized band in the upper dermis
Lymphocytic infiltrate below the hyalinized band
Penile intraepidermal neoplasia and/or carcinoma can be associated
Subtypes: (Lymphocytes are the basis for subtyping)
Lichenoid: lymphocytes at the basal layer
Band-like or classic: lymphocyte in deep lamina propria
Lymphocytic depletion: only few lymphocytes present
Middle aged men
A/w PIN (NB: Depletion of lymphocytes is typical of cancer associated lichen sclerosis )
In image: Classic or band-like is the prototype of lichen sclerosus. Sclerotic band replacing the lamina propria is located between the epithelium and a dense and diffuse lymphocytic infiltrate located below.
13F skin lesion
dx
key features
key sites + demographic: usu scalp/forehead in children
Nevus sebaceus
Key features:
Well circumscribed and complex proliferation and alteration of epidermis and adnexal structures/poorly formed pilosebaceous units
primitive hair follicles and markedly decreased terminal hairs (hair follicles are usually vellus) - draining directly onto the skin.
Sebaceous glands can be increased or decreased based on the age
Additional features are variably seen and include:
Increased acanthosis, papillomatosis and basal epidermal melanin pigmentation
Presence of an inflammatory infiltrate
Ectopic apocrine glands (up to half of cases and occasionally dilated)
Anomalous ductal sweat gland structures resembling eccrine hyperplasia
Infants and young children
Only mild acanthosis and mild papillomatosis is present
Immature and abnormally formed pilosebaceous units
After puberty
Enlargement of sebaceous glands, which sit high in dermis
Epidermis is more acanthotic and papillomatous
Hair follicles are vellus
Secondary neoplasms occur, namely trichoblastoma-like tumor, trichilemmoma, syringocystadenoma papilliferum and sebaceous gland neoplasms
eye lid lesion, woman
dx
Key features
IHC
Endocrine mucus producing sweat gland carcinoma
Key features:
Nodular dermal based tumor, solid + cystic areas
Solid areas can show cribriform architecture, pseudorosettes, papillae/pseudopapillae
Some lesions closely resemble hidrocystoma on low power but show multilayering of neoplastic cells and Roman bridges analogous to breast ductal carcinoma in situ
Lesions frequently appear contiguous with benign ducts
Most lesions have an inconspicuous and discontinuous myoepithelial cell layer surrounding them.
IHC: syn/chrom/INSM1
CK7 in lesional cells
SMA/p63/calponin -highlights surrounding myoepithelial cells
CK20/p63 (-)
cheek lesion, 50F
dx
key features
Dx: hidrocystoma
Key features:
Dermal uni/multilocular cyst; often no cyst contents, Cystic spaces lined by 1-2 layers of cuboidal/columnar epithelium; papillary projection; decapitation secretion typically present; PAS-D (+) granules seen in secretory cells.
lower leg painful lesions, 75F CKD
Dx
Key features
Calciphylaxis
Key features:
Calcification of capillary-sized vessels and thrombosis in deep dermis and subcutis that can lead to cutaneous ulceration and necrosis
Necrosis of dermis &/or epidermis
Calcification of soft tissue
Hidradenoma
key features
Well circumscribed but unencapsulated
Dermal nodule usu with no connection to the overlying epidermis
Ducts with eosinophilic cuticles present in solid areas
Shows both solid and cystic components
Fibrovascular, collagenous or hyalinized stroma
Focal apocrine decapitation secretion, squamous differentiation, squamous eddy formation, keratinization, mucinous change or sebaceous differentiation can be seen
plantar surface foot nodule
dx
Poroma
Image showing anastomosing cords and broad columns of basaloid cells with multiple connections to the epidermis
NO peripheral pallisading.
45M ? wart vs SCC posterior ear
dx
Syndromic associaton
Trichilemomma
Differentiates from outer root sheath; pale/eosinophilic cells; hyperkeratosis; peripheral pallisading with reversed polarity; central desmoplasia mimicing SCC; clear cells + distinct BM
Cowden syndrome (mutation in TSG, PTEN)
Image: reverse polarity of the peripheral cells can be seen.
80M head ulcerated nodule
dx:
essential dx criteria
AFX
Essential: usually pleomorphic (but variable) morphology; strict confinement to the dermis; immunonegativity for keratins, S100, and SOX10.
Usually is symmetrical, well-circumscribed with epidermal ulceration/collarette formation. No necrosis/lymphovascular/perineural and subcutaneous invasion
(normally consistently (+) for CD10/vimentin/p53)
Image: Cellular neoplasm composed of atypical spindled, round, polygonal, and pleomorphic tumour cells; numerous mitoses are present.
BCC
Low vs high risk subtypes?
Histological type associated with risk of local recurrence
Lower risk: nodular, superficial, pigmented, infundibulocystic, fibroepithelial
Higher risk: basosquamous, sclerosing / morpheaform, keloidal, infiltrating, BCC with sarcomatoid differentiation and micronodular variants
Skin
Dx?
Dx: Fibroepithelioma of pinkus (fibroepithelial BCC)
Anastomosing strands and cords of basaloid cells connected to the epidermis
Peripheral nuclear palisading with a formation of follicular germ-like structures
Rarely, isthmic differentiation is present
Fibrotic stroma that can differentiate towards follicular papillae in the areas of germ-like structure formation
Image, above: arising from the epidermis is a fenestrated tumor showing both epithelial and stromal components.
Image, below: primitive hair germ formation is evident
Features of Birt Hogg Dube syndrome
Autosomal dominant, multiple folliculomas on head and neck, acrocordons and trichodiscomas; also renal cell carcinoma [various types], renal oncocytoma and oncocytic hybrid tumors, lung cysts and spontaneous pneumothorax
papule biopsy adjacent to nose.
Dx:
Key features:
Fibrofolliculoma
Key features:
shows a central follicular structure with an irregular lumen and thin, radiating epithelial strands attached to both the follicle and the epidermis . The surrounding stroma is composed of loose connective tissue with fine collagen.
A/W: Birth Hogg Dube syndrome multiple folliculomas on head and neck, renal oncocytomas and oncocytic hybrid tumors, lung cysts and spontaneous pneumothorax).
leukocytoclastic vasculitis (aka cutaneous small vessel vasculitis)
Key features?
Hallmark histologic features
Fibrinoid necrosis of blood vessel walls
Endothelial cell swelling
Perivascular neutrophilic infiltrate with occasional lymphocytes, eosinophils, or histiocytes (vasculitis)
Karyorrhexis (leukocytoclasis) of WBCs
RBC extravasation
Postcapillary venules and capillary loops (not arterioles) most often affected
what is bacillary angiomatosis?
Key features?
Aetiology/pathox?
DDx?
Reactive vascular proliferation associated with Bartonella bacterial infection.
Typically nodular to dome-shaped/polypoid, dermal-based vascular proliferation
May have overlying epidermal ulceration and collarette (similar to pyogenic granuloma)
Vessels are arranged in loose lobular configuration
Endothelial cells show mild enlargement and oval to epithelioid shape
Deeper parts of lesion may show greater cellularity and crowding of vessels
No significant cytologic atypia or atypical mitotic activity
Background stroma shows fibrosis, edema, and mixed inflammatory infiltrate
Infiltrate is rich in neutrophils with leukocytoclasia, macrophages, lymphocytes, and may show focal collections of basophilic granular material (clumps of bacteria)
Neutrophils are more plentiful in deeper lesions
Most patients are immunocompromised, especially due to HIV/AIDS
Also associated with organ transplantation, systemic steroids, and leukemia
IHC: Warthin Starry
DDx:
Kaposi sarcoma
pyogenic granuloma
dx
Key features to look for
Low-power view shows eggshells and a scabetic mite burrowed in the cornified layer with a dense, dermal, eosinophilic, inflammatory infiltrate
Below: In this example of nail scabies, eggs and empty egg casings are identified within the nail plate.
55F indurated plaque lower leg
Dx:
Key features:
DDx
Features:
Generally centered in lower dermis
Well-developed lesions show layers of altered collagen (necrobiosis) alternating with layers of inflammation
Inflammatory infiltrate includes giant cells, plasma cells, histiocytes, lymphocytes
Epithelioid granulomas (may predominate in occasional cases) or cholesterol clefts may be present
DDx:
GA:
Areas of altered collagen tend to be encircled by palisading histiocytes
Altered collagen interspersed with mucin
Tends to be centered in dermis
Rheumatoid nodule:
Rheumatoid nodule
Palisades of histiocytes surrounding central fibrin
4M scalp lesion
Dx and key features?
Nevus sebaceus
Varies with age
Infants and young children
Immature and abnormally formed pilosebaceous units
Pilosebaceous units may be reduced in number
Only mild acanthosis and mild papillomatosis
After puberty
Enlargement of sebaceous glands, which sit high in dermis
Hair follicles are vellus
Epidermis is more acanthotic and papillomatous
Dermis is often thickened
Mild lymphoplasmacytic infiltrate
In above image, normal skin with hair follicles on right and NS on left.
SCC, subtypes:
SCC types:
Acantholytic SCC
Clear cell SCC shows abundant clear cytoplasm in at least 25% of tumour cells . While SCC may show focal androgen receptor positivity, sebaceous carcinoma can be excluded because it shows diffuse positivity for AR as well as adipophilin.
Adenosquamous SCC. Metastatic adenosquamous carcinoma from GI, lung and gynecologic origin is excluded with CDX2, TTF-1 and estrogen receptor.
Lymphoepithelioma-like carcinoma (LELC) is an SCC type with islands of syncytial-appearing poorly differentiated epithelial cells infiltrated by lymphocytes and occasional plasma cells Unlike the histologically similar tumour in the nasopharynx, there is no association with Epstein-Barr virus.
Spindle cell SCC, also known as sarcomatoid SCC, shows tumour cells with diffusely spindled morphology with focal or absent keratinization; it is uniformly positive for p63 and/or CK5/6 { 25263756 }.
SCC with sarcomatoid differentiation (carcinosarcoma) is a biphenotypic tumour with both conventional SCC and sarcomatous components, ranging from undifferentiated, chrondroblastic, oseoblastic, rhabdomyosarcomatous, to myoid.
