An Unusual Case of Cutaneous Langerhans Cell Sarcoma Lacking S100 Expression: A Case Report and Review of the Literature.

Langerhans cell sarcoma (LCS) is a rare neoplastic proliferation of Langerhans cell with aggressive clinical behavior and involves multiple organ systems, including the skin. LCS is characterized by marked cytologic atypia, frequent mitoses including atypical ones, and expression of CD1a, S100, and langerin (CD207). CD1a and Langerin-positive but S100- negative LCS is extremely rare in clinical practice. We present a case of a 71-year-old female with a history of melanoma and atypical fibroxanthoma who presented with an erythematous plaque on her left knee. Histopathologic examination revealed a dermal infiltrate comprised of large pleomorphic cells with irregular nuclear contours, prominent longitudinal grooves, and vesicular chromatin, and a high mitotic rate. Notably, there were epidermotropism and a distinctive immunohistochemical profile: S100-, CD1a+, Langerin+, and focal CD68+. Next-generation sequencing identified copy number loss of CDKN2A, CDKN2B, and FOXA1, mutations in TP53, POT1, SH2B3, and SMARCA4, and a high tumor mutational burden. Herein, we discuss the clinical and pathologic features of 38 cases of LCS with cutaneous involvement reported in the literature, including recent advances in understanding molecular characteristics of this disease. This exceptional case may contribute to our understanding of the etiology of this rare neoplasm.