Page 278 - Haematologica Vol. 107 - September 2022

CASE REPORT
Figure 1. Core biopsy of mesenteric mass involved by Langerhans cell sarcoma characterized by large pleomorphic cells (arrows) with expression of CD1a (partial) and Langerin. PD-L1 immunostain demonstrates membranous positivity in 95% of the tumor cells. H&E: hematoxylin and eosin; magnification x200.
therapy and demonstrated an ongoing reduction in the size and FDG avidity of the of the dominant mesenteric mass (Figure 2D). At 1-year follow-up, her PET-CT demon- strated a significant reduction in size of the mesenteric mass from 9.0 cm x 8.6 cm (SUVmax 18.0) to 2.7 cm x 2.4 cm (SUVmax 3.2) and resolution of FDG uptake all other sites of disease (Figure 2E). Approximately 18 months into the pembrolizumab therapy, the patient developed grade 2 diarrhea and grade 1 transaminitis that prompted symp- tomatic treatment and dose reduction to 300 mg i.v. every 6 weeks. At the time of last follow-up, after 36 months of initiation of pembrolizumab, she continued to be in a sus- tained near complete remission.
Treatment options for multisystem LCS are not well- defined and the use of lymphoma-based chemotherapy regimens have limited success. Therefore, novel ap- proaches are needed in the treatment of these aggressive malignancies. Malignant histiocytic neoplasms demon-
strate occasional presence of mutations in MAPK pathway (like the presence of a NRAS mutation in our patient), but limited data currently exist on the role of targeted therapy in these patients. A recent report demonstrated a durable (>2 year) complete response with trametinib in a patient with histiocytic sarcoma (HS) that was noted to have an activating MAP2K1F53L mutation.5 Similarly, an excellent in- itial response with vemurafenib was noted in a BRAFV600E primary central nervous system HS, but the disease prog- ressed quickly after only 4 months of treatment.6
PD-L1 immunohistochemistry and TMB have been used as predictive markers in selecting patients for treatment with ICI in various malignancies (e.g., lung cancer, esophageal cancer, triple negative breast cancer among others).7,8 However, limited information exists for PD-L1 staining and TMB in histiocytic neoplasms. A prior study of histiocytic and dendritic cell neoplasms included 14 patients with HS, of which seven were noted to be PD-L1 positive, but
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