Basal-cell carcinoma

Author: Mikael Häggström

Nodular basal-cell carcinoma.

Basal-cell carcinoma (BCC):

Fixation

Generally 10% neutral buffered formalin.

  See also: General notes on fixation

Gross processing

Gross examination

Note:

• Color
• Well-defined or diffuse border
• Size
• Any elevation

Tissue selection

Tissue selection from suspected malignant skin lesions, by lesion size:

<4 mm	4 - 8 mm	9 - 15 mm

In table above, each top image shows recommended lines for cutting out slices to be submitted for further processing. Bottom image shows which side of the slice that should be put to microtomy. Dashed lines here mean that either side could be used. Further information: Gross processing of skin excisions

Microscopic evaluation

Broadly consists of determining the following:

• Whether it is basal-cell carcinoma or a differential diagnosis.
• Aggressiveness pattern
• Radicality

Optionally, further subtyping of basal-cell carcinoma can be made.

Characteristics

• 

  Nests of cells appearing similar to epidermal basal cells, and are usually well differentiated.

• 

  Palisading is a typical feature.

• 

  Cleft formation is fairly specific, but may not be seen in smaller nests.

Basal-cell carcinomas may be pigmented as shown (but consider the possibility of melanoma in such cases).

In uncertain cases, immunohistochemistry using BerEP4 can be used, having a high sensitivity and specificity in detecting only BCC cells.

Differential diagnoses

Main histological differential diagnoses of basal cell carcinoma:

Hair follicles

• 

  Hair follicles: Peripheral sections may look like nests, but do not display atypia, and nuclei are smaller.

• 

  Also, hair follicles generally display more distinct features when looking at adjacent levels.

• 

  Hair follicle tissue may be superficial, resembling a superficial basal-cell carcinoma.

The edges of hair follicle cells may resemble palisades, but are less pronounced, and are generally more diffusely delineated compared to surroundings.

Squamous-cell carcinoma

Squamous-cell carcinoma of the skin is generally distinguishable by for example relatively more cytoplasm, horn cyst formation and absence of palisading and cleft formations.

Yet, a high prevalence means a relatively high incidence of borderline cases. In such cases, look particularly at the surface and attempt to classify as either of the following:

• 

  Basal-cell carcinoma with squamous cell metaplasia or metatypical (squamoid) basal-cell carcinoma. It is basal-cell carcinoma with subepidermal (but no intraepidermal) areas resembling squamous-cell carcinoma.

• 

  Basaloid squamous-cell carcinoma, in this case showing a biplastic pattern with basaloid elements associated with both conventional dysplastic squamous surface (arrow heads) and conventional squamous cell carcinoma (arrow).

In unclear cases, the most useful immunohistochemistry marker appears to be MOC-31, which essentially always stains metatypical basal-cell carcinomas but not basaloid squamous-cell carcinomas. UEA-1 appears to be the second most useful marker, staining almost all basaloid squamous-cell carcinomas but only a few metatypical basal-cell carcinomas.

Others

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  Trichoblastoma: Absence of cleft, rudimentary hair germs, papillary mesenchymal bodies.

• 

  Adenoid cystic carcinoma: Lack of basaloid cells disposed in peripheral palisades; adenoid-cystic lesion without connection to the epidermis; absence of artefactual clefts

• 

  Microcystic adnexal carcinoma: Bland keratinocytes, keratin cysts, ductal differentiation. BerEp4- (in 60% of cases), CEA+, EMA+

• 

  Trichoepithelioma: Rims of collagen bundles, calcification, follicular/sebaceous/infundibular differentiation and cut artefacts. Cytokeratin (CK)20+, p75+, Pleckstrin homology-like domain family A member 1 + (PHLDA1+), common acute lymphoblastic leukemiaantigen + (CD10+) in tumor stroma, CK 6-, Ki-67- and Androgen Rceptor- (AR-)

• 

  Merkel cell carcinoma: Cells arranged in a diffuse, trabecular and/or nested pattern, involving also the subcutis. Mouse Anti-Cytokeratin (CAM) 5.2+, CK20+, S100-, human leukocyte common antigen- ( LCA-), thyroid transcription factor 1- (TTF1-)

Aggressiveness

Aggressiveness can be classified as low-level aggressive, moderately aggressive and highly aggressive, based mainly the cohesion of cancer cells, but also upon other histopathologic subtypes:

Low-level aggressive patterns

• 

  Nodular. Also known as "classic basal-cell carcinoma". It accounts for 50% of all BCC. It typically has relatively cohesive aggregates of basaloid cells with well-defined borders, showing palisading and one or more clefts. Central necrosis with eosinophilic, granular features may be also present, as well as mucin. The heavy aggregates of mucin determine a cystic structure. Calcification may be also present, especially in long-standing lesions. Mitotic activity is usually not so evident, but a high mitotic rate may be present in more aggressive lesions.

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  Superficial

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  Fibroepitheliomatous pattern: anastomosing basaloid epithelial strands enclosing round islands of fibrous stroma

Moderately aggressive pattern

• 

  Moderate cohesion

Highly aggressive patterns

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  Cicatricial or morphoeic pattern: Narrow strands and nests of basaloid cells, typically with sharp edges, surrounded by dense sclerotic stroma.

• 

  Micronodular pattern: Small and closely spaced nests.

Radicality

Determine if there are basal-cell formations continuous with resection margins, or if they are closer or farther than 1 mm from the closest edge. If closer, measure the distance.

If uncertain, immunohistochemistry with BerEP4 helps in distinguishing the BCC cells.

Comparison H&E stain (left) with BerEP4 immunohistochemistry staining (right) on a pathological section having BCC with squamous cell metaplasia. Only BCC cells are stained with BerEP4.

Further information: Evaluation of tumors

Reporting

• Aggressiveness pattern, at least if highly aggressive.
• Radicality, mainly into either of the following:

• >1 mm (as per Radicality above): "Clear margins" (or: "Clear margins at over __ mm")((or the exact distance thereof)).))
• <1 mm but not continuous with edge: "Close margins at __ mm at (location). [[Locations are mainly the deep edge, or the (superior/inferior/medial/lateral) radial edge.]]." Numbers are generally given at an exactness of 0.1 mm.
• Continuous with margin: "Not radically excised at (location)."

Optionally, subtype of basal-cell carcinoma

Example:

(Skin excision with stratified squamous keratinized epithelium, where the dermis contains) moderately aggressive basal-cell carcinoma, not radically excised at the right margin.

  See also: General notes on reporting

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