BACKGROUND: Histiocytic sarcoma (HS) is a rare and aggressive hematopoietic malignancy characterized by histiocytic cell proliferation. Its rarity and nonspecific presentation create significant diagnostic and therapeutic challenges, particularly in HIV-positive patients.

CASE REPORT: An HIV-positive man in his late 20s from a rural area and low-income background, referred from a district hospital, presented with asymptomatic nodular and crateriform lesions on the face, thorax, and back, characterized by central keratosis, crust, and erythematous-violaceous infiltrated edges. Histopathological and immunohistochemical analysis confirmed the diagnosis of histiocytic sarcoma, with tumor cells positive for CD68. Considering the patient’s multisystem involvement, 6 to 8 cycles of CHOP chemotherapy were recommended. However, the patient declined systemic therapy and opted for a watch-and-wait approach. No invasive procedures such as bone marrow biopsy were performed, as the patient exhibited no constitutional symptoms or cytopenias. Clinical follow-up over 6 months revealed significant improvement in tumor size and overall condition. This favorable outcome may have been partially influenced by immune reconstitution associated with ongoing antiretroviral therapy (ART), although a direct causal relationship cannot be established. Management of histiocytic sarcoma remains controversial due to the lack of established guidelines and variability in natural history. For this patient, a non-aggressive, observational approach yielded favorable outcomes, challenging the conventional use of systemic chemotherapy in all cases of multisystem involvement. Regular clinical follow-up has been integral to monitoring disease progression.

CONCLUSIONS: This report underscores the diagnostic and therapeutic challenges associated with histiocytic sarcoma and highlights the importance of a multidisciplinary team approach involving infectious disease specialists and hematology-oncology experts in achieving optimal clinical outcomes. Despite declining systemic treatment, the patient had a favorable clinical outcome.

Keywords: Histiocytic Sarcoma, HIV Infections, Immunohistochemistry, Hematology, Sarcoma, Histiocytic, Skin Neoplasms, Watchful Waiting, Case Reports, CHOP Protocol