Dermatologic neoplasms

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This article deals with dermatologic neoplasms. It includes dermatologic cancer, which can be deadly. Collectively, dermatologic cancers are the most common form of cancer.

An introduction to dermatopathy is found in the dermatopathology article. Non-malignant disease is covered in the non-malignant skin disease article.

The Big Three malignant

Basal cell carcinoma

  • Abbreviated BCC.

General

  • Very common.
  • Sun exposed skin.
  • Hair bearing area; tumour derived from hair follicle - a more appropriate name might be trichoblastic carcinoma.[1]
  • Very rarely metastasizes:
    • Dermatopathologists might see a couple in their career.
    • There are only ~ 300 literature reports of metastatic BCC.[2]

Clinical

  • Telangiectasias.
  • Raised pearly nodule.

As part of a syndrome

Microscopic

Features:[4][5]

  1. Basaloid cells - similar in appearance to basal cells:
    • Moderate blue/grey cytoplasm.
    • Dark ovoid/ellipsoid nucleus with uniform chromatin.
  2. Palisading of cells at the edge of the cell nests.
  3. Artefactual separation of cells (forming the nests) from the underlying stroma - key feature.
  4. Surrounded by blue (myxoid) stroma - key feature.

May be present:[5]

Notes:

  • Palisading = the long axes of the cells are alined and the axes are perpendicular to the interface between the (basaloid cell) nests and stroma.
  • Key elements in a list: Artefactual clefting (of nests), Basaloid cells, Peripheral palisading, Myxoid stroma.
    • Memory device PAM: palisading, artefactual clefts, myxoid stroma.

DDx:

Images:

Basal cell carcinoma subtypes/unique features

  • Many patterns exist.
  • Recurrence higher in morpheaform (sclerosing), infiltrative, micronodular, and superficial patterns.[9]
  • DG says the prognosis is similar for all BCC subtypes, except for sclerosing pattern and infiltrative pattern.[10]

The subtypes:[11]

Pattern Key histologic feature Other histologic features Other
Superficial pattern connected to epidermis
Nodular pattern nodules partial detachment from epidermis subgroup micronodular = nests equal size ~ 0.2 mm dia., >=25% of lesion
Morpheaform (sclerosing) pattern stroma sclerosis often seen with infiltrative pattern
Infiltrative pattern small irregular cell aggregates often also sclerosing or morpheaform
Fibroepitheliomatous pattern cords and columns of basaloid cells fibrous stroma name of pattern comes from fibroepithelioma of Pinkus; DDx: reticulated seborrheic keratosis
Infundibulocystic pattern small keratocysts (keratin cysts) usu. small, often in cords usu. indolent
Adenoidal pattern cribriform / pseudoglandular arch. myxoid stroma, peripheral palisading DDx: adenoid cystic carcinoma

Unique features/differentiation:[11]

Differentiation / unique cell Key histologic feature Other histologic features Other
Pigmented cells any pattern can have pigmentation pigment may be in malignant cell DDx: collision lesion with melanocytic lesion
Squamous differentiation (metatypical BCC) pink cytoplasm, keratinization assoc. with ulceration/tumour recurrence
Eccrine differentiation focal duct formation very rare, DDx: BCC engulfing sweat ducts
Clear cells (Clear cell BCC) clear cytoplasm due to glycogen

IHC

  • CK5/6 +ve.
    • Useful to assess margins... if very close.
  • BerEP4 +ve.
    • SCC usually negative.[12]
  • CD10 +ve.
  • Actin +ve.

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SKIN, SHAVE BIOPSY WITH ELECTRODESICCATION AND CURETTAGE (EDC): 
	- BASAL CELL CARCINOMA, MARGIN STATUS ASSESSED CLINICALLY DURING EDC. 
	- EXTENSIVE SOLAR ELASTOSIS.
SKIN, RIGHT EAR, EXCISION: 
	- BASAL CELL CARCINOMA. 
	- MARGINS NEGATIVE FOR BASAL CELL CARCINOMA. 
	- EXTENSIVE SOLAR ELASTOSIS.

Micro

The sections show hair-bearing skin with nests of basaloid cells in the dermis. The basaloid nests have peripheral palisading of the nuclei, have numerous mitoses, and are surrounded by a myxoid stroma. The nests are well demarcated from the stroma and show focal clefting from the stroma. The margins are negative for basal cell carcinoma.

Squamous cell carcinoma of the skin

  • Abbreviated skin SCC.

General

Precursor:[13]

  • Actinic keratosis (solar keratosis).
    • Clinical: yellow-brown scaly, patches, sandpaper sensation.

Risk factors:[13]

  • Sun exposure.
  • Immune suppression (e.g. organ transplant recipients).

Notes:

  • Keratoacanthoma.
    • Some don't believe this entity exists.
      • These people sign this entity as low grade squamous cell carcinoma, keratoacanthoma type.[14]

Microscopic

High risk features - for SCC of the skin:[15]

  • Primary site is ear or lip.†
  • Clark level IV/V = reticular dermis or deeper.
  • >=2 mm thickness -- measured from granular layer (stratum granulosum) or ulcer base to deepest aspect.
  • Lymphovascular invasion.
  • Perineural invasion.
  • Poorly differentiated.

Note:

  • † The words used are "hair-bearing lip" - but there is considerable confusion about this as the AJCC manual contradicts itself.[16]

DDx:

Bowen disease

Bowen disease is squamous cell carcinoma in situ of the skin.

Histologic DDx of Bowen disease:

Images:

IHC

Bowen's disease panel:

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SKIN, SITE, BIOPSY: 
	- MODERATELY-DIFFERENTIATED INVASIVE SQUAMOUS CELL CARCINOMA, SEE COMMENT. 
	- NEGATIVE FOR LYMPHOVASCULAR INVASION.
	- NEGATIVE FOR PERINEURAL INVASION.

COMMENT: 
The nearest margin (lateral margin) is 1 mm.  The tumour is 9 mm in maximal dimension.
SKIN, SITE, BIOPSY: 
	- INVASIVE SQUAMOUS CELL CARCINOMA, SEE TUMOUR SUMMARY.

TUMOUR SUMMARY:
Histologic type: squamous cell carcinoma, type not otherwise specified.
Histologic grade: moderately differentiated.
Greatest dimension: ___ cm.
Tumour thickness: ___ mm.
Peripheral margin: negative for invasive carcinoma and in situ carcinoma.
Deep margin: negative for invasive carcinoma and in situ carcinoma.
Closest margin: deep margin, ___ mm.
Lymphovascular invasion: not identified.
Perineural invasion: not identified.

Melanoma

General

  • Known as the great mimicker in pathology; it may look like many things.

Microscopic

Features:

  • Classic appearance of melanoma:
    • Loosely cohesive; mix of small nests of cells, single cells.
    • Usu. mixed of spindle and ovoid cell morphology.
    • +/-Occasional large binucleated cells.
    • +/-Cytoplasm: brown pigment (melanin).
    • +/-Prominent (large) red nucleoli (like in serous carcinoma of the ovary).
    • Often marked nuclear pleomorphism - variation in cell size, shape & staining (like in serous carcinoma of the ovary).
    • Nuclear pseudoinclusions (like in papillary thyroid carcinoma).

Less common malignant

Dermatofibrosarcoma protuberans

  • Abbreviated DFSP.

General

  • Dermal location.
  • Destroys adnexal structures.
  • Occasionally transforms to a (more aggressive) fibrosarcoma.[20]

Treatment:[21]

  • Wide excision.
  • May include imatinib (Gleevec).

Gross

Features:[22]

  • Firm plaque, often bosselated, usually on the trunk.
  • +/-Ulceration.

Images:

Microscopic

Features:[21]

  • Dermal spindle cell lesion with storiform pattern.
    • Spokes of the wheel-pattern.
  • Contains adipose tissue within the tumour -- key feature.
    • Described as "honeycomb pattern" and "Swiss cheese pattern".

Notes:

  • Adnexal structure within tumour are preserved -- this is unusual for a malignant tumour -- important.


Main DDx:

  • Dermatofibroma - has entrapment of collagen bundles at the edge of the lesion.

DDx of storiform pattern:

Images:

IHC

Panel:[23]

  • CD34 +ve.
    • Usually negative in dermatofibroma.[24][25]
  • Factor XIIIa -ve.
    • Usually positive in dermatofibroma.[24][25]
  • S100 -ve (screen for melanoma).
  • Caldesmin -ve (screen for muscle differentiation).
  • Beta-catenin. (???)
  • MIB1 (proliferation marker).
    • Should not be confused with MIB-1 a gene that regulates apoptosis.

Molecular

A characteristic translocation is seen:[26] t(17;22)(q22;q15) COLA1/PDGFB.

Cutaneous B-cell lymphoma

  • Abbreviated CBCL.

General

  • CBCL is less common than cutaneous T-cell lymphoma (CTCL).[27]

Microscopic

Features:

  • Dermal lymphoid infiltrate.
  • "Grenz zone" - space between the epidermis and the dermal infiltrate - key feature.

IHC

  • B cell and T cell markers.

Cutaneous T-cell lymphoma

  • Abbreviated CTCL.

General

  • Mycosis fungoides - is a subtype (???).
  • CTCL is more common than cutaneous B-cell lymphoma (CBCL).[28][29]

Stages - like Kaposi sarcoma:

  • Patch.
  • Plaque.
  • Nodular.

Microscopic

  • Atypical lymphocytes:
    • Have folded "cerebriform" nuclei; Sezary-Lutzner cells.[30]
  • Grouping:
    • Nests in the epidermis - known as "Pautrier microabscesses".
    • Single lymphocytes in epidermis; "lymphocyte exocytosis".[31]
    • Short linear arrays of lymphocytes along the basal layer of the epidermis; "epidermotropism".[30]

DDx:

Images:

IHC

Key stain:

Other stains:

  • CD3 +ve.
  • CD8 -ve.
  • CD20 -ve (to r/o significant B cell population).
  • CD30 -ve.
  • CD5 +ve.
  • CD7 -ve (often lost first in T cell lymphomas).
  • Ki-67 high.
  • CD56 -ve.

Merkel cell carcinoma

  • Abbreviated MCC.

General

Features:[33]

  • Rare.
  • Aggressive course/poor prognosis.
  • Neuroendocrine-like.[34]

Etiology:

  • Most caused by Merkel cell polyomavirus.[35][33]
  • Immunocompromised/immunosuppressed (e.g. organ transplant recipients).

Microscopic

Features:[36]

  • Neuroendocrine nuclear features - round nucleus, small nucleoli/no nucleolus, stippled chromatin - key feature.
  • Typically medium size cells ~3x resting lymphocyte.
    • May be small or large.
  • Architecture: nests, sheets or trabeculae.
  • Scant cytoplasm.
  • Abundant mitoses. †
  • +/-Nuclear moulding.
    • Nuclei of adjacent cells conform to one another.
  • +/-Tumour infiltrating lymphocytes. ‡

Notes:

  • † >10 mitoses/HPF = poor prognosis - definition suffers from HPFitis.[37]
  • ‡ May be associated with a worse prognosis.[37]
  • Merkel cell carcinoma lymph node metastases is difficult to diagnose with routine stains; use of IHC stains are advised.[37]
  • Arise from the epidermis - very rarely in situ.[38]

DDx:

Images:

IHC

Features:

  • CK7 -ve.
  • CK20 +ve (perinuclear dot-like).[39]
  • CAM5.2 +ve (dot-like pattern).
  • CD56 +ve.
  • AE1/AE3 +ve.
  • Merkel cell polyomavirus +ve ~85% of cases.[40]

Others:

  • TTF-1 -ve.
  • NSE +ve.[38]

EM

Eccrine carcinoma

General

  • Arises from the proximal sweat duct.

Microscopic

Features:

  • Pleomorphic nuclei with nucleoli.
  • Duct-like structures - key feature.
  • Extends from dermis into epidermis (follows path of a benign sweat duct).

Notes:

Kaposi sarcoma

See Kaposi sarcoma.

Sebaceous carcinoma

General

Notes:

Microscopic

Features:

  • Nuclear atypia.
  • Sebaceous differentiation:
    • Abundant pale fluffy cytoplasm.

Images:

IHC

Microcystic adnexal carcinoma

  • AKA syringomatous carcinoma, AKA sclerosing sweat duct carcinoma.[44]

General

  • Low-grade tumour.
  • Adults.

Microscopic

Features:[45]

  • Small basaloid cells - often forming small cystic spaces - key feature.
  • Fibrotic stroma.

DDx:

Image:

Trichilemmal carcinoma

General

  • Super rare.
  • Not well-described.

Microscopic

Features:[46]

  • Clear (glycogen-rich) cytoplasm in center of lesion.
  • Peripheral palisading at edge of lesion - root sheath differentiation (hair follicle).
  • Contiguous with hair follicle or assoc. with trichilemmoma.

DDx:

Lymphomatoid papulosis

General

  • Rare.
  • Benign behaviour.

Microscopic

Features:

  • Dermal lymphocytosis.
    • No epidermal lymphocytes.
  • Focal nuclear atypia.

DDx:

IHC

Rare malignant

Basosquamous carcinoma

Should not be confused with basaloid squamous cell carcinoma (AKA squamous cell carcinoma, basaloid variant).

General

Microscopic

Features:

Note:

  • Busam notes that there is disagreement about what defines this tumour;[51] however, he goes on the describe it as a collision tumour.[50]

DDx:

Intermediate

Atypical fibroxanthoma

  • Abbreviated AFX.

General

Clinical:

  • Rapid growth.
  • Elderly.
  • Good prognosis.[56]

Microscopic

Features:[57]

  • Dermal lesion - key point.
  • Marked nuclear atypia.
  • Mitoses.
  • Mulitnucleated cells.
  • Foamy cytoplasm - key feature.

DDx:

Notes:

  • No Grenz zone. (???)

Image:

IHC

Features:[57]

  • S100 -ve (done to r/o melanoma).
  • 34betaE12 -ve.
  • p63 -ve (done to exclude SCC)
    • Scant staining not considered +ve.
  • Desmin -ve (done to r/o leiomyosarcoma).

Benign

Syringoma

General

  • Benign sweat duct tumour.
  • Eccrine differentiation.
  • Usually close to lower eyelid.[59]

Microscopic

Features:[60]

  • Proliferation of benign ducts with lined by a bilayer (as in normal sweat ducts) with abnormal architecture:
    • Tadpole like appearing ducts.

DDx:

Images:

Chondroid syringoma

  • Used to be called mixed tumour of skin.[63]

General

  • Mixed apocrine & eccrine tumour of skin, usually in the head & neck[63], especially nose and cheek.[64]
  • May be in major and minor salivary glands.[64]

Microscopic

Features:

  • Mix tumour with:[63]
    1. Epithelial component:
      • Nests of cells with:
        • Moderate dull eosinophilic cytoplasm.
        • Round/ovoid nuclei with nucleoli.
    2. Mesenchymal component - key feature:

Images:

Dermal cylindroma

General

May be familial:[66]

  • Familial cylindromatosis (autosomal dominant).
  • Brook–Spiegler syndrome.

Gross

  • Classically scalp - usually head and neck or face.

Microscopic

Features:[66]

  • Nests of cells that fit together like a jigsaw puzzle - the borders of the nests are opposed and undulate.
    1. Basaloid cells with scant cytoplasm and dark nuclei palisade around the edge of the nests.
    2. Larger cells with moderate eosinophilic cytoplasm and lighter staining nuclei are at the centre of the nests.
  • Cells nests surrounded by a band of hyaline (i.e. glassy, eosinophilic, acellular) material ~ 2X thickness of a basilar cell - key feature.
    • This is basement membrane.

DDx:

Images:

Stains

  • PAS +ve (basement membrane).[66]

Keratoacanthoma

  • Abbreviated KA.

General

Clinical

  • May grow rapidly (weeks or months) then involute.
  • Main DDx is squamous cell carcinoma.
  • Exophytic lesion, well-circumscribed.

Microscopic

Features:[70]

  • Expansion of stratum spinosum - pushing tongue-like downward growth of epidermis into the dermis.
  • Keratin collection ("keratin plug") at the center of lesion-superficial aspect.
  • Cells have glassy pink cytoplasm.
  • Minimal/no nuclear atypia.

Note:

  • Classically described as a "volcano lesion" with pale pink cells.
  • May have features of regression - PMNs, fibrosis (???).

DDx:[71]

Image:

Sebaceous adenoma

General

Notes:

Microscopic

Features:

  • Abnormal sebaceous glands (pale fluffy cytoplasm):
    • Increased basal epithelium.
    • Multiple dilated glands - opening to the surface.

Images:

Trichilemmoma

  • May be spelled tricholemmoma.

General

  • Benign neoplasm with features of the pilosebaceous follicular epithelium.[72]
  • Associated with nevus sebaceous.[73]
  • Muliple trichilemmomas associated with Cowden syndrome.[74]

Microscopic

Features:[74]

  • Superficial dermal lesion contiguous with the epidermis:
    • Core of lesion:
      • Cuboidal cells with round nuclei, eosinophilic-clear cytoplasm.
    • Periphery of lesion:
      • Surrounded by hyaline band.
      • Peripheral palisading.

DDx:

Images:

Eccrine poroma

General

  • Benign tumour arising from the distal sweat duct.
  • Erythematous - gross.

Microscopic

Features:[77]

  • Broad sheets of basaloid cells - attached to the epidermis - containing ductal structures - key feature.
  • Biphasic stroma:
    1. Edematous stroma.
    2. Sclerotic stroma.
  • Moderate nuclear pleomorphism.
  • +/-Occasional mitoses.

Notes:

  • Area above gland appears crusted.

DDx:

Images:

Nodular hidradenoma

General

  • Benign adnexal tumour.[79]

Typical locations:[78]

  • Scalp.
  • Face.
  • Trunk, anterior.

Microscopic

Features:[79]

  • Well-circumscribed dermal lesions with:
    • Back-to-back nests with a whorled appearance.
    • Spaces between cells.
    • Nuclei ovoid and centrally placed in the cell.
      • No nucleolus.
    • Cystic spaces with degenerated cells.

DDx:

IHC

Features:[79]

  • CAM5.2 +ve.
  • AE1/AE3 +ve.
  • EMA +ve.
  • S100 -ve.
  • Desmin -ve.

Trichoblastoma

  • AKA trichoepithelioma.
    • Trichoepithelioma is considered a superficial version of trichoblastoma; WHO lumps the two entities together.[80]

General

  • Benign.
  • May be familial:
    • Multiple familial trichoepithelioma.[81]
    • Brooke-Spiegler syndrome.

Microscopic

Features:[82]

  • Well-circumscribed cell nest in the superficial dermis.
  • Surrounding by a fibrous stroma.
  • Basaloid cells with peripheral palisading.
  • +/-Surround keratin-filled cysts.
  • Fibroblasts-like cell aggregate, similar to a follicular papillae (papillary-mesenchymal body).

Notes:

Variants:

  • Desmoplastic trichoblastoma.

DDx:

Images:

Trichofolliculoma

General

  • Benign.

Microscopic

Features:[85]

  • Irregular hair follicle (basilar nest of cells with an acellular hair shaft) with:
    • Smaller satellites (follicles) consisting of well-circumscribed basilar cells.

Note:

  • Lack artificial clefting between the (basilar) nests and stroma (seen in BCC).
  • Surrounding stroma does not have a basophilic tingle (seen in BCC).

DDx:

Images:

Apocrine carcinoma of the skin

General

  • Rare.[86]
  • Usually very good prognosis.[86]

Microscopic

Features:[86]

  • Nests.
  • Apocrine snouts - "decapitation secretion"

DDx:

Images:

Stains

Features:[86]

  • PAS +ve.
  • PASD +ve.

IHC

  • GCDFP-15 (gross cystic disease fluid protein-15) +ve.[86]

See also

References

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