Comment on “Pagetoid Spread in Basal Cell Carcinoma: Potential for Misdiagnosis”

To the Editor: We read with great interest the article by Khurana et al,1 “Pagetoid Spread in Basal Cell Carcinoma: Potential for Misdiagnosis” (Am J Dermatopathol. 2023;45:254–258). This insightful case series highlights a diagnostically challenging variant of basal cell carcinoma (BCC), characterized by pagetoid intraepidermal spread that may closely mimic other malignant or premalignant intraepidermal neoplasms. The authors' analysis expands the histopathologic spectrum of BCC and underscores the importance of awareness of this rare pattern among dermatopathologists, particularly in the evaluation of small, superficial, or fragmented biopsies. In our daily practice, we encountered a case that closely mirrors the phenomenon described in the aforementioned study. We wish to share our findings to further substantiate the existence and the clinical relevance of this entity. A 47-year-old woman presented with 2 contiguous erythematous macules on her left arm, clinically suspicious for epithelioma. An excisional biopsy was performed, and sent for histological evaluation. Microscopically, the epidermis displayed multiple and confluent intraepidermal nests composed of round basaloid cells with moderate nuclear atypia and scant cytoplasm. These nests varied in size associated with pagetoid intraepidermal spread of single cells. Remarkably, despite several sections at different levels have been performed, no dermal component was identified, and classic features such as peripheral palisading, stromal retraction, and dermal basaloid nests were absent. The lesion appeared entirely intraepidermal, raising concern for a melanocytic neoplasm, matching the nested variant of superficial spreading melanoma. Given the ambiguous morphology, an extended immunohistochemical panel was performed. Scattered SOX10 and Melan-A–positive cells highlight melanocytic hyperplasia, while most tumor cells were negative ruling out a melanocytic origin. p16 was completely lost. CK7 was also negative, excluding extramammary Paget disease, pagetoid Bowen disease, and sebaceous carcinomas. Tumor cells were diffusely and strongly positive for BerEP4, prompting the diagnosis of superficial BCC with pagetoid intraepidermal spread Figure 1. While Khurana et al described cases of pagetoid BCC associated with typical underlying components (e.g., nodular, micronodular, or basosquamous areas), our case is notable for the complete absence of any dermal component, thus mimicking an in situ neoplasm1. To the best of our knowledge, this may represent one of the first reported instances of BCC presenting purely as an intraepidermal neoplasm with pagetoid features. FIGURE 1.: Multiple variable size and confluent intraepidermal nests composed of round basaloid cells; no dermal component was identified. Note scattered pagetoid cells (arrows, A). Tumor cells were diffusely and strongly positive for BerEP4 (B).The main differential diagnosis includes the nested variant of melanoma in situ. As our case demonstrates, the immunophenotypic profile, in particular the correct interpretation of immunohistochemical melanocytic markers as melanocytic hyperplasia and the strong and diffuse BerEP4 expression, is critical to avoid misdiagnosis and inappropriate management. We agreed with Khurana et al that pagetoid intraepidermal spread in BCC may be underrecognized and a correct diagnosis can be particularly challenging in the absence of classic BCC features. We endorse the authors' recommendation to approach superficial and fragmented biopsies with heightened suspicion and to use comprehensive immunohistochemical panels when appropriate. We thank the authors for bringing attention to this underappreciated histologic variant and believe our case will contribute to increasing awareness in the dermatopathology community.