Kaposi sarcoma (KS) is an HHV-8–associated vascular malignancy that most commonly occurs in the setting of HIV infection but may also develop in immunosuppressed, HIV-negative solid-organ transplant recipients. Post-transplant KS is rare, accounting for only 0.4–5% of malignancies, and visceral involvement—particularly of the gastrointestinal (GI) tract—is highly uncommon. We describe a case of disseminated KS with gastric, duodenal, and colonic involvement in an HIV-negative renal transplant recipient presenting with chronic diarrhea.

We present the case of a 56-year-old HIV-negative woman with a history of renal transplantation who developed disseminated Kaposi sarcoma following prolonged immunosuppression. The patient had been receiving azathioprine after previous intolerance to mycophenolate. She presented with chronic diarrhea and progressive painful cutaneous lesions involving the genital, perineal, and perianal regions. Skin biopsy demonstrated spindle cell proliferation with HHV-8 positivity, confirming KS. Subsequent PET/CT imaging revealed extensive nodal, cutaneous, and pulmonary involvement, along with nonspecific FDG uptake in the stomach and colon.

Gastrointestinal evaluation was pursued due to persistent diarrhea and abnormal imaging findings. Laboratory studies, including thyroid function, fecal calprotectin, fecal elastase, celiac serology, and infectious GI PCR panel, were unremarkable. Endoscopic assessment revealed multiple raised, erythematous lesions throughout the stomach, duodenum, and colon. Histology from these sites confirmed Kaposi sarcoma with spindle cell proliferation and HHV-8 positivity.

This case reflects the role of chronic immunosuppression as the primary pathogenic driver of KS in HIV-negative transplant recipients. Calcineurin inhibitors and azathioprine are recognized to potentiate HHV-8 reactivation and tumor development. Conversely, mTOR inhibitors such as sirolimus and everolimus possess anti-angiogenic and antiproliferative properties and have been associated with regression of KS lesions. Based on this evidence, immunosuppression was modified by discontinuing azathioprine and transitioning to everolimus with low-dose tacrolimus. Systemic treatment with liposomal doxorubicin was initiated due to disseminated disease.

Although well documented in HIV-positive individuals, colonic Kaposi sarcoma remains rare in HIV-negative transplant recipients. Review of the literature demonstrates only a small number of comparable cases, emphasizing that gastrointestinal KS can present with nonspecific symptoms such as diarrhea and may only be diagnosed through endoscopic biopsy.