Clinicopathological analysis of basal cell carcinoma of the anal region and its distinction from basaloid squamous cell carcinoma

Abstract

Basal cell carcinoma of the anal region is rare and morphologically difficult to distinguish from basaloid squamous cell carcinoma, particularly on biopsies. This distinction has therapeutic and prognostic implications. We reviewed morphological features of 9 basal cell carcinomas and 15 basaloid squamous cell carcinomas from the anal region diagnosed during 1993-2011 and determined the utility of Ber-EP4, BCL2, TP63, CK5/6, CDKN2A, and SOX2 as diagnostic tools. Immunostains were scored in a semi-quantitative manner (1 þ -1-10%, 2 þ -11-50%, 3 þ -450%). All basal cell carcinomas were located in the perianal region, while all basaloid squamous cell carcinomas originated in the anal canal/anorectum. Nodular subtype of basal cell carcinoma was the most common subtype. Retraction artifact was the only significant distinguishing histological feature of basal cell carcinoma compared with basaloid squamous cell carcinoma (88% vs 26%; P ¼ 0.04). Atypical mitoses were more common in basaloid squamous cell carcinomas (71% vs 11%; P ¼ 0.05). An in situ component was only present in basaloid squamous cell carcinomas, and was noted in 6/15 cases. Basal cell carcinomas had 2-3 þ Ber-EP4 (basal cell carcinoma 100% vs basaloid squamous cell carcinoma 40%; Po0.001) and BCL2 immunoreactivity (basal cell carcinomas 100% vs basaloid squamous cell carcinoma 33%; Po0.001). Diffuse CDKN2A and SOX2 expression was seen only in basaloid squamous cell carcinomas (basal cell carcinoma 0% vs basaloid squamous cell carcinoma 93%; Po0.001). There was no difference in TP63 and CK5/6 expression. Perianal location, retraction artifact, and lack of atypical mitoses are histological features that help distinguish basal cell carcinoma from basaloid squamous cell carcinoma. An in situ component, when present, supports the diagnosis of basaloid squamous cell carcinoma. Immunostains are extremely helpful as diffuse Ber-EP4 and BCL2 expression is a feature of basal cell carcinoma and basaloid squamous cell carcinoma is typified by diffuse CDKN2A and SOX2 expression. Modern Pathology (2013Pathology ( ) 26, 1382Pathology ( -1389 doi:10.1038/modpathol.2013 published online 19 April 2013 Keywords: Anal; basal cell carcinoma; basaloid squamous cell carcinoma; perianal; SOX2 Anal carcinomas account for nearly 2% of all colorectal malignancies. Squamous cell carcinomas are the most common type of tumors that arise within the anal canal and perianal region, the basaloid variant being the most common phenotype. By contrast, basal cell carcinomas of the anal/ perianal region are extremely rare and comprise 0.2% of all anorectal neoplasms. 1 Basaloid squamous cell carcinoma and basal cell carcinoma show overlapping histological features. Both tumors are composed of nests of oval cells with moderate amount of eosinophilic to basophilic cytoplasm, peripheral nuclear palisading, and variable mitotic activity. Some differences do exist; squamous cell carcinomas arise from a known precursor lesion (anal squamous intraepithelial neoplasia) while basal cell carcinoma...

Basaloid Squamous Cell Carcinoma of the Anus Revisited

“…Where the surface epithelium is not visible, it may be a challenge to distinguish these 2 entities. 8 Our data support the utility of p16 in this differential diagnosis with consistent diffuse expression in neoplastic cells of basaloid SCC. High-risk HPV DNA in situ hybridization was also consistently positive in these cases but this is not surprising as it is well known that basaloid SCC is etiologically linked to high-risk HPV.…”

“…These are useful because the most frequent morphologic pattern of basaloid SCC in our study includes neoplastic cells arranged in trabeculae with a peripheral palisade, which overlaps with basal cell carcinoma. In fact, as Patil et al 8 show and as described in the World Health Organization classification scheme, 6 cases of basaloid SCC may show retraction artifact. Where the surface epithelium is not visible, it may be a challenge to distinguish these 2 entities.…”

“…We performed staining for squamous markers p40 and CK5/6 and p16 to provide affirmative evidence of the diagnosis of basaloid SCC. SOX2 has been reported as a marker of basaloid SCC in a single prior study, 8 and hence we evaluated this marker to validate its usefulness. The specific conditions for each antibody are listed in Table 1.…”

Tumours and inflammatory lesions of the anal canal and perianal skin revisited: an update and practical approach

“…The most frequent site is close to the anal orifice, but very few cases extending into the anal canal have been reported 31 32. BCCs are a rare occurrence in areas of non-sun-exposed skin, and other factors contributing to carcinogenesis in this region have been proposed, such as prior radiotherapy or chronic skin irritation 33 34.…”

“…Histologically, BCCs are most frequently of nodular type and the main differential diagnosis is that of basaloid SCC, which occurs far more frequently in this location, especially when found in the anal canal. Distinguishing between these two entities may be challenging on biopsy material as some features (basaloid morphology with peripheral palisading) may overlap 32 37. The presence of intraepithelial squamous cell neoplasia is useful and strongly favours basaloid SCC as there is no well-defined precursor lesion in BCC.…”