Kaposi sarcoma (KS) is a rare vascular tumor strongly associated with human herpesvirus 8 (HHV-8) and typically seen in immunocompromised states such as HIV/AIDS or post-transplant settings. However, with the increasing use of immunomodulatory therapies in hematologic malignancies, KS has also been reported in patients receiving Janus kinase (JAK) inhibitors. We present a case of HHV-8-positive cutaneous Kaposi sarcoma developing in a patient with primary myelofibrosis under ruxolitinib treatment.

A 72-year-old female with a 2-year history of intermediate-2 risk primary myelofibrosis, positive for the JAK2 V617F mutation, was being followed in our hematology department. She had been on ruxolitinib (2 × 10 mg/day) for symptom control, which provided initial improvement in systemic complaints and splenomegaly. However, after 14 months of treatment, she developed painless violaceous plaques and nodules on her lower extremities, raising suspicion for Kaposi sarcoma. Dermatologic examination confirmed the presence of multiple dark purple nodules predominantly on the left lower leg. A punch biopsy was performed, and histopathological examination revealed spindle-cell proliferation consistent with Kaposi sarcoma. Immunohistochemical staining was strongly positive for HHV-8.

Laboratory evaluation revealed hemoglobin of 9.2 g/dL, white blood cell count of 13,000/mm³, and platelet count of 120,000/mm³. Peripheral smear showed typical findings of myelofibrosis, including teardrop-shaped erythrocytes. HIV, HBV, and HCV tests were all negative. Abdominal ultrasonography confirmed stable splenomegaly (19 cm). The ruxolitinib treatment was discontinued, and hydroxyurea was initiated as an alternative. Given that the Kaposi lesions were localized and the patient remained asymptomatic, systemic chemotherapy was not started. The patient is being followed with close dermatological and hematological monitoring.

This case highlights a rare but clinically significant complication of ruxolitinib therapy in a patient with primary myelofibrosis. JAK inhibition may lead to immune dysregulation, impaired antiviral T-cell responses, and viral reactivation—particularly HHV-8 in susceptible individuals. Although KS is commonly associated with HIV, this patient had no underlying immunodeficiency other than the JAK inhibitor–mediated suppression. The temporal relationship between ruxolitinib exposure and KS onset, combined with HHV-8 positivity and regression of symptoms after discontinuation of the drug, supports a probable causal association. Clinicians should remain vigilant for unusual infections or neoplasms in patients undergoing JAK inhibitor therapy.