basal cell carcinoma

Images

 Superficial crust on the sole of foot : BCC

• https://twitter.com/JAADjournals/status/876864956611907588

Digital cases

 UI:1828 : cutaneous basal cell carcinoma.
 UI:1276 : cutaneous basal cell carcinoma.
 JRC:10423 : Adenoid basal cell carcinoma.
 JRC:10424 : Basal cell carcinoma (Pseudo-Brooke).
 JRC:10425 : Adenoid basal cell carcinoma.
 JRC:10427 : Basal cell carcinoma ("Fibroepithelioma").
 JRC:10431 : Multicentric basal cell carcinoma.

Microscopy

Basal cell carcinomas are composed of islands or nests of basaloid cells, with palisading of the cells at the periphery and a haphazard arrangement of those in the centers of the islands. The tumor cells have a hyperchromatic nucleus with relatively little, poorly defined cytoplasm. The intercellular bridges are invisible on routine light microscopy.

There are numerous mitotic figures, sometimes atypical and a correspondingly high number of apoptotic tumor cells. This high rate of cell death accounts for the paradoxically slow growth of basal cell carcinomas which possess numerous mitoses.

The vast majority of cases show some attachment to the undersurface of the epidermis.

Ulceration is not infrequent in larger lesions.

Lesions of long standing and aggressive tumors usually extend into the lower dermis.

Deep extension occurs either diffusely or within the paths of the cutaneous adnexae. Involvement of the subcutis or of the underlying cartilage in lesions of the nose and ear is quite uncommon. Perineural invasion is present in nearly I % of cases, although the incidence is higher in aggressive variants.

Islands of tumor cells are surrounded by a stroma, which is newly formed and different from the adjacent dermis.

Amyloid, which is formed by the tumor cells, is present in the stroma in up to 50% of cases. It is less common in aggressive variants.

The adjacent dermis shows solar elastosis in over 90% of cases, although its degree is sometimes mild. The overlying epidermis may show the changes of a solar keratosis, although this is only rarely the precursor of a basal cell carcinoma.

A variable inflammatory cell infiltrate is usually present, although there is a paucity of cells in some recurrences. The presence of plasma cells in the infiltrate correlates with ulceration. The infiltrate is usually composed mainly of T cells, the majority of which are CD4. Natural killer cells, mast cells and Langerhans cells are also present.

Past regression can be recognized by finding areas of eosinophilic new collagen within a tumor, associated with absence of tumor nests, an increase in small blood vessels, loss of appendages and a variable inflammatory cell infiltrate.

Prominent central regression with the formation of scar tissue is a feature of the so‑called ’field fire’ type of basal cell carcinoma.

Calcification may be present in the center of the keratin cysts that form in several of the histological subtypes. Ossification is an exceedingly rare event.

Another rare finding is the presence of transepidermal elimination of tumor nests.

Also rare is the development of pseudoepitheliomatous hyperplasia or keratoacanthoma‑like changes in the epidermis following irradiation or excision of a basal cell carcinoma: this is known as pseudorecidivism.

Basal cell carcinomas or closely related changes may overlie a dermato­fibroma.

Basal cell carcinomas have also been reported in association with seborrheic keratoses, intra­dermal nevi, porokeratosis, Darier’s disease, lupus vulgaris, keratoacanthoma, desmoplastic tricholemmoma, neurofibromas and, as already mentioned, organoid nevi.

Sometimes no tumor can be found in a biopsy specimen despite a strong clinical suspicion that basal cell carcinoma is present.

This is particularly so with the multifocal superficial basal cell carcinoma where nests can be widely spaced or undergo regression.

It is good practice to order, routinely, three levels of all punch and shave biopsies to prevent sampling errors.

Clues in an initial non‑diagnostic slide that suggest that deeper sections may yield basal cell carcinoma include focal basal atypia, stromal or superficial fibrosis, empty dermal spaces, equivocal adnexae and microcalcifications.

Immunochemistry

The tumor cells in basal cell carcinoma resemble epidermal basal cells, both in their glycoconjugate pattern, their keratin expression and the presence of bcl‑2. Clinically aggressive basal cell carcinomas have low labeling with bcl‑2.

However, the cells also express cytokeratins, which are found only in follicular epithelium.

Tumor cells stain with the murine monoclonal antibody VM‑1; they usually do not stain for involucrin, epithelial membrane antigen or CD44, as occurs in squamous cell carcinomas, although CD44has been found in infiltrative tumor strands.

However they do stain diffusely for Ber EP4, unlike squamous cell carcinomas, which are always negative; basaloid carcinoma of the anus is also negative.

A band‑like peritumorous reaction with peanut agglutinin has been reported in most basal cell carcinomas but not in trichoepitheliomas.

Other features that can be used to distinguish these two tumors are the staining pattern for bcl‑2 (expressed in virtually all cells in most basal cell carcinomas, but only weakly in some aggressive variants, and only in the basal layer of trichoepitheliomas) and CD34 (found in the peritumoral fibroblasts around trichoepitheliomas but not in those around sclerosing basal cell carcinomas), in contrast, stromelysin‑3 is expressed by the fibroblastic cells of nearly 70% of morpheic basal cell carcinomas, but not by fibroblasts in desmoplastic trichoepithelioma.

Light microscopy is still the most reliable method of distinguishing these two tumors, although the diffuse staining of basal cell carcinomas with bcl‑2 is of some value.

Subtypes

There is considerable variability in the morphology of basal cell carcinomas, and as a consequence a number of histopathological subtypes have been defined. Certain features are shared by more than one of these subtypes, and these will be considered first.

Various morphological subtypes have been defined. These include solid (nodular), micronodular, cystic, multifocal superficial (superficial multifocal), pigmented, adenoid, infiltrating, sclerosing, keratotic, infundibulocystic, metatypical, basosquamous and fibroepitheliomatous. Mixed patterns are quite common.

Several other rare variants have also been described. It should be remembered that punch and shave biopsy techniques provide approximately 80% accuracy in the diagnosis of the various subtypes of basal cell carcinoma.

 superficial basal cell carcinoma
 nodular basal cell carcinoma
 infiltrative basal cell carcinoma

• infiltrative trabecular basal cell carcinoma
• infiltrative micronodular basal cell carcinoma

 sclerodermiform basal cell carcinoma or morpheaform basal cell carcinoma
 adenoid basal cell carcinoma
 infundibulocytic basal cell carcinoma
 clear cell basal cell carcinoma
 metatypical basal cell carcinoma
 basal cell carcinoma with monster cells

Miscellaneous variants

Appendageal differentiation is sometimes present in basal cell carcinomas, with ollicular (pilar) variants.

Matrical and tricholemmal differentiation may also occur: basal cell carcinomas that show this feature require differentiation from matrical carcinomas.

Sebaceous differentiation is sometimes seen in areas of an otherwise typical basal cell carcinoma: such lesions require differentiation from other sebaceous tumors.

A rare variant with histochemical and ultra­ structural features of apocrine differentiation has been reported.

Tumors with eccrine differentiation also occur, and these shade into lesions best classified with eccrine carcinomas.

Other variants include the exceedingly rare granular cell, clear cell and ’signet‑ring’ cell (hyaline inclusion) types.

Lesions with giant tumor cells and large nuclei have been variously reported as ’basal cell epithelioma with giant tumor cells, ’basal cell carcinoma with monster‑­cells’ and ’pleomorphic basal cell carcinoma’. The giant cells do not appear to represent a senescent change. There is a ­report of this variant in which there were stromal giant cells as well.

Adamantinoid, schwannoid and neuroendocrine differentiation are further variants.

It has been suggested that the tumor reported as a basal cell carcinoma with thickened basement membrane was really a trichilemmal carcinoma.

The rare lesion showing myoepithelial differentiation needs to be distinguished from a carcinosarcoma.

Links

 http://www.med.muni.cz/biomedjournal/pdf/2006/05/261_270.pdf
 http://www.epathologies.com/pcoll/derm/p_ref/ca_baso_wee.htm

Differential diagnosis

 cutaneous basaloid cell tumors

 nodular variant

• trichoepithelioma
• trichoblastoma
• nodular hidradenoma
• eccrine spiradenoma

 superficial variant

• actinic keratosis
• seborrheic keratosis

 infiltrative-morpheaform variants

• desmoplastic trichoepithelioma
• microcystic adnexal carcinoma

 adenoid variant

• adenoid cystic carcinoma
• malignant mixed tumor of the skin

 infundibulocystic variant

• trichoepithelioma
• reticulated seborrheic keratosis
• basaloid follicular hamartoma

 clear cell variant

• sebaceous adenoma
• tricholemmoma
• clear cell hidradenoma
• clear cell acanthoma
• ballon cell nevus
• balloon cell melanoma

 metatypical variant

• squamous cell carcinoma

Cytogenetics

 tumoral trisomy 6

LOH

 9q21-q31 LOH (93%) (16204023)

• 9q21-q31 uniparental disomy (38%) (16204023)

 6q23-q27 LOH (36%) (16204023)

Genic inactivation by somatic mutations

 PTCH1 (69%) (16204023)
 PTCH2
 SMOH

See also

 epidermal tumors

References

 Teh MT, Blaydon D, Chaplin T, Foot NJ, Skoulakis S, Raghavan M, Harwood CA, Proby CM, Philpott MP, Young BD, Kelsell DP. Genomewide single nucleotide polymorphism microarray mapping in basal cell carcinomas unveils uniparental disomy as a key somatic event. Cancer Res. 2005 Oct 1;65(19):8597-603. PMID: 16204023

 Rubin AI, Chen EH, Ratner D. Basal-cell carcinoma.
N Engl J Med. 2005 Nov 24;353(21):2262-9. PMID: 16306523

 Bale AE, Yu KP. The hedgehog pathway and basal cell carcinomas. Hum Mol Genet. 2001 Apr;10(7):757-62. PMID: 11257109