Always search for perineural space invasion (neurotropism) because of the implied need for local adjuvant radiation to cover for the fact that wide to extra-wide margins may not be surgically possible.

[(1) IHC DDX table.....(2) old IHC outline (some markers we don't have)]

• Malignant melanoma (MM): (info at the link).
• Small-cell (basaloid) poorly differentiated malignancies (always think of Merkle cell):
  • lymphoma: LCA positive
  • carcinoma (excluding ordinary BCC...CD10 positive²):
    1. neuroendocrine: H&E nuclei with dispersed chromatin; NET-positive IHC markers; Merkle cell is TTF1 negative and metastatic small cell of lung is TTF1 positive.
    2. non-neuroendocrine: H&E nuclei with nucleoli & vesicular chromatin & may have comedonecrosis (skin met from breast cancer may show comedonecrosis).
    • trichoblastic carcinoma³ (de-differentiated trichoblastoma with only slight clues to trichoid features, comedonecrosis, and high mitotic rate) [S07-3368].
    • basaloid ductal eccrine carcinoma¹: CD10² & K903 negative & can have some NSE positive & some S100 pos.; may have comedonecrosis & high mitotic rate. Intracytoplasmic lumen, by d-PAS, EMA, or CEA positivity may be a positive tip-off to DX.
    • basaloid SCC⁴: comedonecrosis, high mitotic rate, no adnexal features, K903 positive, not purely CD10 positive² & can have some weak NSE positive.
  • sarcoma:
    1. melanoma: melanoma IHC markers positive.
    2. non-melanoma: look for H&E and IHC features of the various sarcomas.
• Squamous cell carcinoma (SCC) (including Bowen's disease): K903 positive; CEA neg.¹; squamous "look", attachment to epidermis which has a dysplastic background...including dysplastic parakeratosis, & negative for peripheral palisading; and, can almost always see cell areas in which desmosomes easily seen [S-04-11211]. SCC cells CD10² neg. but desmoplasia may be pos.
  • acantholytic ("adenoid") SCC: usually face or neck & 19% of deeply invasive metastasize¹; pseudoglandular spaces; CEA & S100 neg. and HMWK pos.¹.
  • clear cell SCC: usually face and neck; those with significant pleomorphism locally recurr & can met.¹.
  • Pagetoid Bowen's disease: can mistake it as mammary or extra-mammary Paget's.
  • spindled or sarcomatoid SCC: is K903 positive...watch out for desmoplastic melanoma [L04-19] (NSE & S100 pos.) and MFH (both DM & MFH K903 negative).
• Basal cell carcinoma (BCC)⁴: BCC cells are EMA & CEA negative (all other skin epithelial malig. can be EMA pos.)¹; CD10² pos. 86% of cases; have peripheral palisading, mitotic, cell necrosis, BCC-stromal clefts⁴.
  • clinical growth patterns:
  1. nodular/ulcerative
  2. diffuse (infiltrative & morpheaform)
  3. superficial (multifocal)
  4. pigmented
  5. fibroepithelioma of Pinkus
  • histological subtypes:
  1. nodulocystic BCCs: basaloid cells with at least focal epidermal attachment (point of origin) plus tendency of cells to palisade at tumor periphery and to have artifactual clefts at tumor-stromal interface.
  2. superficial BCCs: tip off is the fibroinflammatory papillary dermal thickening which, if you see it & clinician had concern for BCC, stepcut until you find it.
  3. adenoid BCCs¹: as compressed "glands" or a microcystic pattern [S-05-6750].
  4. micronodular BCCs: tend to be great numbers of tiny interconnected nests & peripheral palisading hard to see & retraction spaces absent.
  5. desmoplastic/infiltrative variety/morpheaform: these are the most likely to recur and can be problematic as to margins...some feel that a clear margin is one that is clear by 1-2 mm, at least; &, depending on the lesion site and patient compliance factors, other experienced dermatologists are comfortable just curetting and following these. Can mistake a desmoplastic trichoepithelioma (no mitotic activity, no apoptotic cells, often has micro-calcification, and on the face of women) as this variant of BCC. Almost always find that a BCC attaches to epidermis.
  6. keratotic BCC or metatypical (basosquamous...pilar) ca.: a BCC begins to change/differentiate into an SCC morphology; tip-off may be the relative lack of any real squamous dysplasia in the associated epidermis plus at least a vague focal retaining of a "look" of BCC-type peripheral palisading; and BCCs that have keratinized almost always have some epidermal defect, excoriation, or ulceration;typically have an infiltrative growth pattern [S-04-955; S-04-11112].
  7. metaplastic BCC (carsinosarcoma): any type of skin epithelial carcinoma pattern PLUS a malignant sarcomatous component.
  8. pigmented BCCs: only significant in that clinically could have been melanoma.
  9. pleomorphic BCCs: extreme pleomorphism.
  10. BCC with glandular...with sebaceous differentiation: same as a basosebaceous epithelioma or basosebaceous BCC & found on sun exposed scalp & forehead [S07-6774].
  11. BCCs with glandular differentiation...in form of true lumens, vs.:
      • eccrine epithelioma: which behaves as ordinary BCC¹.
      • apocrine epithelioma: which behaves as ordinary BCC¹.
  12. signet ring BCC: many signet ring cells; behaves as ordinary BCC¹.
  13. clear cell BCC: rare.
  14. granular BCCs: rare.
  15. BCCs with follicular...with shadow-cell or more subtle matrical differentiation (shadow cell BCC vs. pilomatrixoma); with trichoepitheliomatous features [S-04-12465] of small infundibular cysts (infundibulocystic BCC); with mixed features [S-07-6151].
  16. keloidal BCCs: may be mistaken clinically as keloids.
  17. BCCs with thickened basement membranes: vs. cylindroma.
  18. BCCs with schwannomatous nuclear palisading.
  19. mimic BCC: immature trichoepithelioma (benign) [LMC-04-5901].
• Adnexal carcinomas (adenocarcinomas): (info at the link).
• Neuroendocrine (Merkel cell) cancer.
• Mesenchymal tumors: (info at the link).
• Extramammary Paget's disease: (info at the link).
• Spindle cell skin lesions: (info at the link).
• Other: (info at the link).

References:

1. Cutaneous Adnexal Tumors..., Wick MR & Swanson PE, 1991, 238 pages (BWD's office).
2. Am. J. Dermatopath. 26(4):463-71, Dec. 2004.
3. Modern Pathology 13(6):673-678, June 2000.
4. McKee, Calonje, & Granter, Pathology of The Skin... Two volumes, 3rd Ed. 2005.

(posted 9 February 2002; latest update 30 May 2007)