Misclassification of Aggressive Basal Cell Carcinoma Subtypes and Implications for Management

Abstract

BACKGROUND Management of basal cell carcinoma (BCC) varies by histopathologic subtype; however, biopsies may inadequately characterize them as nonaggressive, risking potential suboptimal treatment. OBJECTIVE To characterize the rate of undetected aggressive BCC subtypes by size, location, and histopathology type. MATERIALS AND METHODS Retrospective cohort study of 928 BCCs treated with Mohs Micrographic Surgery (MMS) at a tertiary academic institution from 2015 to 2017, comparing patient and tumor characteristics and histopathologic subtype on biopsy versus Mohs. RESULTS Among the 825 BCCs with known subtypes on biopsy, 68% (561/825) were classified as nonaggressive, 28% (159/561) of which were subsequently found to have aggressive subtypes on MMS. Aggressive features were more often underrepresented in biopsy samples taken from Area H compared with Area M/L (odd ratio [OR] 2.65, 95% confidence interval [CI] 1.73-4.08, p , .001) or those with nodular subtypes (OR 2.19, CI 1.08-4.45, p 5 .03). Of concern, these unsuspected aggressive BCCs required more Mohs stages for clearance (mean 2.37, SD 0.72, p , .001) compared with BCCs that remained nonaggressive on both biopsy and Mohs (mean 1.50, SD 0.75). CONCLUSION Given the high percentage of BCCs with unsuspected aggressive subtypes, higher clinical suspicion for undiagnosed high-risk BCCs should be given to nodular BCCs and to BCCs on Area H.

Basal cell carcinoma in situ of the skin revisited: case reports of the superficial type and fibroepithelioma type of this in situ cutaneous neoplasm

“…If a cutaneous neoplasm is a basal cell carcinoma with mixed histology and a very superficial biopsy specimen-that only extends into the papillary dermis-is obtained using the shave technique, only the in situ subtype portion of the basal cell carcinoma may be present for microscopic evaluation and the deeper-potentially aggressive-subtype may not be diagnosed. Therefore, when a skin cancer is clinically suspected, the clinician should consider the morphology and location of the lesion when determining whether to use a shave technique, or a punch tool, or a scalpel excision to perform the biopsy [49][50][51][52][53][54].…”

Immunohistochemical expression of p53, Ki67, α-SMA, CD44 and CD31 in different histological subtypes of basal cell carcinoma

“…Indolent subtypes, including superficial and nodular BCC, are described as well demarcated nodules, either small or large, with peripheral palisading. Aggressive subtypes, including morpheaform, micronodular and metatypical, are less demarcated and have mitotic activity, increased cell necrosis and deeper growth [ 13 , 14 , 15 , 16 , 17 , 18 ]. Because of its contribution in maintaining genetic integrity, p53 is known as the “guardian of the genome”.…”

Immunohistochemical Analysis of Single-Stranded DNA Binding Protein 2 in Non-Melanoma Skin Cancers

“…All tissue slides used at diagnosis were reviewed to determine pathological characteristics, including histological subtypes of BCC, histological grade of SCC, level of invasion, and perineural invasion. Micronodular, infiltrating, sclerosing/morphoeic, and basosquamous patterns were classified as histopathologically aggressive BCC subtypes [20,21]. The histological grade of SCC was divided using a three-level grading system according to several morphologic features of differentiation (nuclear pleomorphism, degree of keratinization) [22].…”