Gastrointestinal Kaposi Sarcoma: Histopathological Features and Diagnostic Challenges - Insights from a Single Center.

Objectives: Gastrointestinal Kaposi sarcoma (GI-KS) is a rare vascular neoplasm associated with human herpesvirus 8 (HHV 8), most often emerging in immunosuppressed individuals. Its endoscopic appearance-ranging from nodular and polypoid lesions to ulcerations-can be subtle. In addition, histopathological features of KS may mimic benign inflammatory conditions or other mesenchymal tumors, delaying accurate diagnosis. This study aimed to evaluate the histopathological features of GI-KS and to clarify the neoplastic and non-neoplastic diagnostic challenges in a single-center cohort. Methods: We retrospectively reviewed 13 GI-KS cases diagnosed between 2005 and 2025. Clinical data and endoscopic findings were retrieved from the hospital's electronic medical records. Hematoxylin and eosin-stained sections, along with HHV-8 immunohistochemistry (IHC) slides, were retrospectively evaluated. Results: Thirteen patients (11 male; mean age 47±18 years) were identified, of whom 84.6% were immunosuppressed (eight HIV-positive, two renal transplant recipients, and one receiving corticosteroids). Cutaneous or extraintestinal KS lesions were present in 11 cases. Endoscopic evaluation revealed nodular lesions (30.8%), polypoid lesions (23.1%), snake-skin-like hemorrhagic areas (7.7%), infiltrative lesions (7.7%), erythematous elevated lesions (7.7%), or nonspecific erythematous changes (7.7%). Suspicion of KS was documented in only three endoscopy reports. Lesions were most commonly located in the stomach (76.9%), followed by the rectum (15.4%) and colon (7.7%). Histologically, slit-like vascular channels and erythrocyte extravasation were observed in 84.6% of cases, hemosiderin deposits in 53.8%, chronic inflammatory infiltrates including plasma cells in 76.9%, and foveolar epithelial hyperplasia in 70% of gastric cases. The histologic spectrum included diagnostic pitfalls such as chronic gastritis-like features in three cases, reactive gastropathy-like changes in one case, granulation tissue-like appearance in one case, and GIST/leiomyoma-like spindle cell morphology in one case. Conclusion: The histologic features of GI-KS can mimic both neoplastic and inflammatory conditions. Therefore, histopathological evaluation should be conducted alongside clinical information, as GI-KS may present with subtle or nonspecific findings. Given the potential for life-threatening complications such as obstruction, bleeding, or perforation, accurate diagnosis and timely treatment are critically important. Routine application of HHV-8 IHC -even in cases with minimal suspicion- is essential for ensuring diagnostic accuracy, guiding appropriate management, and preventing serious outcomes.