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Skin - Nonmelanocytic tumors

Carcinoma (non-adnexal)

Basal cell carcinoma

Reviewer: Christopher Hale, M.D. (see Reviewers page)
Revised: 19 September 2012, last major update June 2012
Copyright: (c) 2001-2012, PathologyOutlines.com, Inc.

Clinical features

● Most frequent form of skin cancer
● Usually sun exposed skin (not mucosal surfaces), in proportion to number of pilosebaceous units present
● Rosai claims these tumors attempt to differentiate toward pilosebaceous units, but often this is not readily apparent
● Often multiple tumors
● Usually older adults
● Slow and indolent, untreated cases may invade subcutis, skeletal muscle and bone
● Facial tumors may invade skull, nares, orbit or temporal bone
● Only 100 metastatic cases described, often associated with basal cell nevus syndrome or basosquamous histology, on sunlight-protected skin
● Metastases are rare
● 60% to regional lymph nodes, also lung, liver, bone

Risk factors:
● Fair skin, blue eyes, immunosuppression (higher incidence, more aggressive tumors), xeroderma pigmentosum
● Also associated with nevus sebaceus of Jadassohn, chronic venous stasis of lower leg, arsenic, X-rays, skin injury, chickenpox scars, tattoos, hair transplant scars, immunosuppression
● Less common in children or young adults, sunlight-protected skin
● Rarely coexists with benign nevus

Poor prognostic factors:
● Dense fibrous stroma and loss of peripheral palisading
● Reduced expression of syndecan-1 and bcl2
● Greater expression of p53 and aneuploidy
● Basosquamous histology
● Perineurial invasion
● Positive margins

Basal cell nevus syndrome

● Also called Gorlin’s syndrome
● Due to mutations in PTC (patched) gene on 9q22.3
● Autosomal dominant, young patients with multiple basal cell carcinomas (with more varied histologic types than normal, often superficial and multicentric, often with osteoid), palmar pits (in situ basal cell carcinomas), dural calcification, keratinous cysts of jaws, skeletal abnormalities, occasional abnormalities of CNS, mesentery and endocrine organs
Case Report: 68 year old man with multiple brown macules and plaques on face and body (Case of Week #251)


Basosquamous (metatypical) carcinoma:
● Basal cell carcinoma plus atypical squamous cells
● More aggressive than classic basal cell carcinoma
● May metastasize

Clear cell basal cell carcinoma:
● Tumor cells with prominent cytoplasmic vacuoles or signet ring morphology

Fibroepithelial tumor:
● Also called Pinkus’ tumor, fibroepithelioma
● Polypoid variant, often on back, with abundant stroma

Granular basal cell carcinoma:
● Contains tumor cells resembling those in granular cell tumor
● No clinical significance

Infundibulocystic basal cell carcinoma:
● Has hair follicle differentiation

Superficial (multicentric) basal cell carcinoma:
● Arises in skin of trunk and other sites with sparse fine hairs and thin epidermis
● Primarily grows laterally, has high recurrence rate, tumors may also regress
● Has multiple small tumor nests attached to undersurface of epidermis with associated stromal proliferation

Case reports

● Malignant basomelanocytic tumor with subsequent metastatic melanoma (Am J Surg Pathol 2004;28:1393)


● Excision with frozen section evaluation of margins, curettage, desiccation, radiation therapy
● 1/3 with positive margins will recur

Clinical images

Various images

Gross description

● Nodular, ulcerative, superficial, erythematous or sclerosing (morphea-like)
● Often with telangiectasia (prominent, subepidermal vessels)

Micro description

● Patterns are solid, cystic, adenoid, keratotic (resembles squamous cell carcinoma, but has apopototic keratinocytes, no atypia, abundant stroma), pigmented, infiltrating, sclerosing (morphea-like, with slender, deeply infiltrating nests and abundant reactive stroma)
● Almost always epidermal attachment
● Nests or lobules of hyperchromatic but uniform basaloid cells with peripheral palisading, surrounded by loose stroma, often with myofibroblasts and mucinous changes
● Also cleft-like retraction spaces (due to stromal mucin)
● May appear pigmented due to dermal melanophages
● Variable Langerhans cells
● Occasional amyloid
● Rare spindled tumor cells, mitotic activity, atypical mitotic figures, bizarre tumor giant cells, atypical stromal cells, osseous metaplasia, collagen crystal-like structures, eccrine differentiation, thickened basement membrane or perineurial invasion

Micro images

Superficial tumor - contributed by Dr. Amy Lynn, Toledo, Ohio

Various images

Positive stains

● Keratin, BerEP4, p53, bcl2

Negative stains

● EMA, CEA, involucrin


● +18, +9, +20, +7, +5
● Also loss of heterozygosity at 9q22.3 and trisomy 6

Differential diagnosis

● Basaloid proliferations associated with dermatofibromas
● Actinic keratosis or Bowen’s disease
● Trichoepithelioma: also basaloid but with follicle-like structures and no clefts

End of Skin - Nonmelanocytic tumors > Carcinoma (non-adnexal) > Basal cell carcinoma

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