Langerhans cell sarcoma (LCS) is a high-grade neoplasm with overtly malignant cytological features and a Langerhans cell phenotype. The underlying genetic features are poorly understood, and only a few alterations, such as those of the MARK pathway-related genes, CDKN2A and TP53 have been reported. Here we present a 70-year-old male with LCS on the scalp and pulmonary metastasis. The multinodular tumor, 3.0 cm in diameter, consisted of diffusely proliferated pleomorphic cells with numerous mitoses (53/10 HPFs). Immunohistochemically, the tumor cells were positive for CD1a, Langerin and PD-L1, and the Ki-67 labeling index was 50%. These pathological features were consistent with LCS, and were also observed in the metastatic tumor. Whole-exome sequencing revealed that both the primary and metastatic tumors harbored a large number of mutations (>20 mutations/megabase), with deletion of CDKN2A and TP53 mutation, and highlighted that the mutational signature was predominantly characteristic of ultraviolet (UV) exposure (W = 0.828). Our results suggest, for the first time, that DNA damage by UV could accumulate in Langerhans cells and play a role in the pathogenesis of LCS. The high mutational burden and PD-L1 expression in the tumor would provide a rationale for the use of immune checkpoint inhibitors for treatment of unresectable LCS.
Keywords: CDKN2A; Langerhans cell histiocytosis; Langerhans cell sarcoma; MAPK pathway; PD‐L1; TP53; ultraviolet; whole‐exome sequencing.
© 2020 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.