Histiocytic sarcoma (HS) is an exceptionally rare and aggressive hematopoietic malignancy, representing less than 1% of hematologic neoplasms [1]. No standardized therapeutic regimen exists; patients are often treated with lymphoma-like regimens such as CHOP or ICE, with limited efficacy and median survival of approximately six months [2,1]. Recent advances in molecular pathology have revealed recurrent BRAF^V600E mutations, ALK rearrangements, and PD-L1 expression, providing new diagnostic and therapeutic implications [3]. Case-based evidence suggests that PD-1 inhibitors may induce durable responses in select patients with PD-L1–positive HS [4,5].

A 28-year-old male presented with abdominal pain and swelling. Imaging demonstrated a large intra-abdominal mass with peritoneal implants. Histopathology confirmed HS, positive for CD45, CD163, and CD14, with a Ki-67 index of 80%. Bone marrow biopsy was normocellular. Molecular analysis excluded BRAF and ALK alterations but demonstrated PD-L1 expression with a tumor proportion score (TPS) of 1–49% and a combined positive score (CPS) of 35%. The patient was started on ICE chemotherapy (ifosfamide, carboplatin, etoposide). Following biomarker analysis, nivolumab was introduced beginning with the second cycle. The treatment was well tolerated, and subsequent PET-CT demonstrated marked metabolic regression with clinical improvement. Follow-up abdominal imaging confirmed complete radiological response, with disappearance of the initially described mesenteric mass.

Discussion HS poses a therapeutic challenge because of its aggressive course and lack of standardized therapy [2,1]. Conventional chemotherapy regimens have limited durability, and reported responses are often transient. The presence of PD-L1 expression provided a rationale for incorporating a PD-1 inhibitor, even at moderate expression levels, consistent with emerging literature [4]. Previous case reports have demonstrated clinical benefit from pembrolizumab and nivolumab in PD-L1–positive HS, including durable complete responses [5]. In this patient, radiological assessment corroborated complete remission after combined ICE and nivolumab, supporting the potential role of checkpoint inhibition in improving depth of response. This case represents one of the few documented examples of combining intensive chemotherapy with checkpoint blockade in HS, highlighting the potential synergistic role of immunotherapy.Conclusion This case illustrates the rarity and therapeutic complexity of HS. The addition of nivolumab to ICE chemotherapy, guided by PD-L1 expression, resulted in meaningful clinical response in a young patient with advanced disease. These findings underscore the importance of integrated histopathological and molecular assessment in guiding personalized management for HS.Keywords: Histiocytic sarcoma; Nivolumab; ICE protocol; PD-L1; ImmunotherapyReferences1.Takimoto, T., et al. (2023). Histiocytic sarcoma: A clinicopathologic analysis of 50 cases. American Journal of Surgical Pathology, 47(1), 1–12. 2. Emile, J. F., et al. (2022). Histiocytic and dendritic cell neoplasms: Update of the 2022 WHO classification. Blood, 140(11), 1200–1218. 3. Go, H., et al. (2019). Frequent detection of BRAF V600E mutations in histiocytic and dendritic cell neoplasms. Histopathology, 74(3), 389–400. 4. Bossard, C., et al. (2021). PD-1/PD-L1 blockade in rare hematologic malignancies: Case reports and literature review. Hematological Oncology, 39(3), 327–334. 5.Yoon, D. H., et al. (2022). Efficacy of pembrolizumab in histiocytic sarcoma with high PD-L1 expression: Case report and review. Annals of Hematology, 101(7), 1525–1530.