Abstract
Background: Immunotherapy has been used in the management of some cutaneous adnexal neoplasms. There is a paucity of information concerning molecular analysis of adnexal malignancies and its impact on treatment decisions for these rare neoplasms. Case: A 75-year-old female presented with a left cheek lesion; biopsy and surgical excision demonstrated a deeply invasive dermal/subcutaneous carcinoma with sheets and nests of tumor cells with keratin formation, transitioning to cords with ductal differentiation; perineural invasion noted. Immunohistochemical stains revealed positive CK AE1/AE3, focal weak CK7, and CEA in ducts. A diagnosis of squamoid eccrine ductal carcinoma (SEDC) was made. After a total of 4 excisions, clear margins were obtained, followed by 6 weeks of adjuvant radiation and annual surveillance. Three years later she developed biopsy-confirmed recurrent SEDC. Imaging demonstrated a mass centered in the maxillary bone with extension to the maxillary sinus and overlying skin but no evidence of nodal or distant metastasis. Next generation sequencing (Foundation Medicine, Cambridge MA) identified the following: ASXL1 R965*, BRCA1 Q526*, CDKN2A/B loss, HRAS G12S, MTAP loss, NOTCH1 Q1134* and H1735fs*61, SMAD4 Q245*, STK11 A389T, TERT promoter -139_-138CC>TT, TP53 P278L, microsatellite stable, and tumor mutation burden (TMB) high at 64 mutations/Mb. The patient was started on anti-PD1 therapy with pembrolizumab 200mg IV every 3 weeks. After 4 cycles, imaging revealed significant tumor regression consistent with a near-complete response. Given excellent clinical and radiographic response and patient preference for no additional surgery, pembrolizumab was planned for 4 additional cycles. Conclusion: This case, the first report of SEDC managed with anti-PD1 immunotherapy, describes an excellent response to pembrolizumab. This is the first report of mutational analysis of SEDC, providing potential evidence for TMB as a predictor of response to immunotherapy.
Financial Disclosure:
No current or relevant financial relationships exist.
