Hemangioendothelioma of the spleen: a case study of post-mortem observation with immunohistochemical confirmation

Objective. To provide a clinical and morphological description of a case of splenic hemangioendothelioma with liver metastases, and to analyze its pathomorphological and immunohistochemical characteristics in accordance with current diagnostic and differential diagnostic criteria.

Materials and methods. A case of epithelioid hemangioendothelioma (EHE) of the spleen with metastatic liver involvement in a 73‐year‐old woman admitted to the hospital with complaints of left upper quadrant pain, abdominal distension, and jaundice was presented.

Results. Post‐mortem examination revealed a massive splenic tumor measuring 15×12×10 cm, with widespread metastases to the liver. Histologically, the tumor was characterized with a biphasic pattern, featuring solid nests of epithelioid cells and anastomosing vascular channels. Immunohistochemical analysis demonstrated diffuse positive expression of CD31, CD34, and ERG, confirming the endothelial nature of the tumor, with a Ki‐67 proliferation index of 10–15%.

Conclusion. This clinical observation demonstrates typical pathomorphological features of epithelioid hemangioendothelioma of the spleen and underscores the importance of comprehensive immunohistochemical analysis for the differential diagnosis of rare vascular tumors. The late diagnosis at the stage of disseminated disease reflects the non‐specific nature of clinical manifestations and explains the poor prognosis. This case study contributes significantly to the Russian‐language medical literature, given the extreme rarity of this pathology.

1. Morgado de Abreu MAM, Ferreira CAA, Nai GA. Composite hemangioendothelioma: report of a rare neoplasm. An Bras Dermatol. 2025;100(5):501166. DOI: https://doi.org/10.1016/j.abd.2025.501166

2. Anderson WJ, Doyle LA. Updates from the 2020 World Health Organization Classification of Soft Tissue and Bone Tumours. Histopathology. 2021;78(5):644-657. DOI: https://doi.org/10.1111/his.14265

3. Rosenbaum E, Jadeja B, Xu B, et al. Prognostic stratification of clinical and molecular epithelioid hemangioendothelioma subsets. Mod Pathol. 2020;33:591-602. DOI: https://doi.org/10.1038/s41379-019-0368-8

4. Paulson KG, Ravi V, Rubin BP, Park M, Loggers ET, Cranmer LD, Wagner MJ. Incidence, demographics, and survival of malignant hemangioendothelioma in the United States. Cancer Med. 2023;12(14):15101-15106. DOI: https://doi.org/10.1002/cam4.6181

5. Liu Z, He S. Epithelioid hemangioendothelioma: incidence, mortality, prognostic factors, and survival analysis using the surveillance, epidemiology, and end results database. J Oncol. 2022;2022:2349991. DOI: https://doi.org/10.1155/2022/2349991

6. Korobkova IZ, Dremin DA, Kakalov SM, Kirsan’ IV, Skrynnikov IS, Ugrimov AA, Sorokin MN. Hepatic Epithelioid Hemangioendothelioma. Journal of Radiology and Nuclear Medicine. 2019;100(6):372-378. (In Russ.). DOI: https://doi.org/10.20862/0042-4676-2019-100-6-372-378

7. Zhang S, Liang Y, Yang Y, Guo L, Li W, Shi S. Clinicopathological features, risk model and prognosis of 115 cases of epithelioid hemangioendothelioma: A single-center study. Front Oncol. 2025;15:1577968. DOI: https://doi.org/10.3389/fonc.2025.1577968

8. Scalora N, DeWane G, Drebot Y, Khan AA, Sinha S, Ghosh K, Robinson D, Cogswell P, Bellizzi AM, Snow AN, Breheny P, Chimenti MS, Tanas MR. EHE cell cultures are a platform for mechanistic and therapeutic investigation. Sci Rep. 2025;15:35516. DOI: https://doi.org/10.1038/s41598-025-19453-1

9. Driskill JH, Zheng Y, Wu BK, Wang L, Cai J, Rakheja D, et al. WWTR1(TAZ)-CAMTA1 reprograms endothelial cells to drive epithelioid hemangioendothelioma. Genes Dev. 2021;35(7-8):495-511. DOI: https://doi.org/10.1101/gad.348221.120

10. Errani C, Zhang L, Sung YS, Hajdu M, Singer S, Maki RG, Healey JH, Antonescu CR. A novel WWTR1-CAMTA1 gene fusion is a consistent abnormality in epithelioid hemangioendothelioma of different anatomic sites. Genes Chromosom Cancer. 2011;50(9):644-653. DOI: https://doi.org/10.1002/gcc.20886

11. Flucke U, Vogels RJC, de Saint Aubain Somerhausen N, Creytens DH, Riedl RG, van Gorp JM, et al. Epithelioid hemangioendothelioma: clinicopathologic, immunhistochemical, and molecular genetic analysis of 39 cases. Diagn Pathol. 2014;9:131. DOI: https://doi.org/10.1186/1746-1596-9-131

12. Pimenta EM, Goyal A, Farber ON, Lilley E, Shyn PB, Wang J, Wagner MJ. Epithelioid Hemangioendothelioma: Treatment Landscape and Innovations for an Ultra-Rare Sarcoma. Curr Treat Options Oncol. 2025;26(6):516-523. DOI: https://doi.org/10.1007/s11864-025-01328-2

13. Liu X, Yang P, Liu L, Si S, Zhou R, Liu T, et al. Long-term prognosis and treatment modalities of hepatic epithelioid hemangioendothelioma: a retrospective study of 228 patients. BMC Cancer. 2024;24:1285. DOI: https://doi.org/10.1186/s12885-024-13053-4

14. Wu X, Li B, Zheng C, Hong T, He X. Clinical characteristics of epithelioid hemangioendothelioma: a single-center retrospective study. Eur J Med Res. 2019;24:16. DOI: https://doi.org/10.1186/s40001-019-0375-8

15. Denolf M, Rappaport A, Delvaux S. Epithelioid Hemangioendothelioma of Spleen and Bone: A Case Report. J Belg Soc Radiol. 2024;108(1):64. DOI: https://doi.org/10.5334/jbsr.3600

16. Shibuya R, Matsuyama A, Shiba E, Harada H, Yabuki K, Hisaoka M. CAMTA1 is a useful immunohistochemical marker for diagnosing epithelioid haemangioendothelioma. Histopathology. 2015;67(6):827-835. DOI: https://doi.org/10.1111/his.12713

17. Tansir G, Rastogi S, Barwad A, Yadav R, Shamim SA, Dhamija E, Pandey R, Garg R, Shrivastava S. Management and outcomes of advanced hemangioendothelioma at a medical oncology clinic in an Indian tertiary care center. Future Sci OA. 2023;8(10):FSO827. DOI: https://doi.org/10.2144/fsoa-2021-0132

18. Li X, Ma X, Hao J, Dong C, Wang Y. Primary splenic epithelioid hemangioendothelioma with diffuse metastases revealed by FDG PET/CT imaging: A case report. Medicine (Baltimore). 2021;100(13):e25065. DOI: https://doi.org/10.1097/MD.0000000000025065

19. Meng K, Yang X, Guo S, Tao J. Hepatic epithelioid hemangioendothelioma with TFE3 rearrangement: a case report and literature review. Front Oncol. 2025;15:1442233. DOI: https://doi.org/10.3389/fonc.2025.1442233

20. Fotiadis C, Georgopoulos I, Stoidis C, Patapis P. Primary tumors of the spleen. Int J Biomed Sci. 2009;5(2):85-91.

21. Ramkumar S. Epithelioid Haemangioma of Bone: A case series and comprehensive literature review reappraising the diagnostic classification of all epithelioid vascular neoplasms of bone. Cureus. 2021;13(6):e15371. DOI: https://doi.org/10.7759/cureus.15371

22. Vasquez M, Ordóñez NG, English GW, Mackay B. Epithelioid hemangioendothelioma of soft tissue: report of a case with ultrastructural observations. Ultrastructural Pathology. 1998;22(1):73-78. DOI: https://doi.org/10.3109/01913129809032260

23. Anderson T, Zhang L, Hameed M, Rusch V, Travis WD, Antonescu CR. Thoracic epithelioid malignant vascular tumors: a clinicopathologic study of 52 cases with emphasis on pathologic grading and molecular studies of WWTR1-CAMTA1 fusions. Am J Surg Pathol. 2015;39(1):132-139. DOI: https://doi.org/10.1097/PAS.0000000000000346

24. Tan Y, Yang X, Dong C, Xiao Z, Zhang H, Wang Y. Diffuse hepatic epithelioid hemangioendothelioma with multiple splenic metastasis and delayed multifocal bone metastasis after liver transplantation on FDG PET/CT images: A case report. Medicine (Baltimore). 2018;97(22):e10728. DOI: https://doi.org/10.1097/MD.0000000000010728

25. Guo Q, Xue J, Xu L, Shi Z, Zhou B. The clinical features of epithelioid hemangioendothelioma in a Han Chinese population: A retrospective analysis. Medicine (Baltimore). 2017;96(26):e7345. DOI: https://doi.org/10.1097/MD.0000000000007345

26. Sardaro A, Bardoscia L, Petruzzelli MF, Portaluri M. Epithelioid hemangioendothelioma: an overview and update on a rare vascular tumor. Oncol Rev. 2014;8(2):259. DOI: https://doi.org/10.4081/oncol.2014.259

27. Zhao J, Dang Y. Case report of misdiagnosis: a rare case of hepatic epithelioid hemangioendothelioma characterized primarily by fever. Front Oncol. 2025;15:1606872. DOI: https://doi.org/10.3389/fonc.2025.1606872

28. Sawma T, Sultan A, Abdulmoneim S, Grotz T, Rosen CB, Taner T, Heimbach JK, Warner SG, Siontis BL, Ho TP, Robinson SI. Management and long-term outcomes of patients with hepatic epithelioid hemangioendothelioma. J Surg Oncol. 2024;130(5):1062-1069. DOI: https://doi.org/10.1002/jso.27807

29. Tumanova UN, Dubova EA, Karmazanovskiy GG, Shchegolev AI, Stepanova YuA. Hemangioma of the spleen (clinical observation and literature review). Diagnostic and Interventional Radiology. 2011;5(1):81-93. (In Russ.). DOI: https://doi.org/10.20862/0042-4676-2011-5-1-81-93

30. Weiss SW, Enzinger FM. Epithelioid hemangioendothelioma: a vascular tumor often mistaken for a carcinoma. Cancer. 1982;50(5):970-981. DOI: https://doi.org/10.1002/1097-0142(19820901)50:5<970::aid-cncr2820500527>3.0.co;2-z

31. Tsuneyoshi M, Dorfman HD, Bauer TW. Epithelioid hemangioendothelioma of bone. A clinicopathologic, ultrastructural, and immunohistochemical study. Am J Surg Pathol. 1986;10(11):754-764. DOI: https://doi.org/10.1097/00000478-198611000-00002

32. Scoazec JY, Degott C, Reynes M, Benhamou JP, Feldmann G. Epithelioid hemangioendothelioma of the liver: an ultrastructural study. Hum Pathol. 1989;20(7):673-681. DOI: https://doi.org/10.1016/0046-8177(89)90155-x

33. Wang Z, Zhang L, Zhang B, Mu D, Cui K, Li S. Hemangioendothelioma arising from the spleen: A case report and literature review. Oncol Lett. 2015;9(1):209-212. DOI: https://doi.org/10.3892/ol.2014.2693

34. Ji F, Liu Y, Shi J, Liu C, Fu S, Wang H, Ren B, Mi D, Gao S, Sun D. Single-cell transcriptome analysis reveals mesenchymal stem cells in cavernous hemangioma. Front. Cell Dev. Biol. 10:916045. DOI: https://doi.org/10.3389/fcell.2022.916045

35. Petronella P, Scorzelli M, Luise R, Iannaci G, Sapere P, Ferretti M, Costanzo RM, Freda F, Canonico S, Rossiello R. Primary thyroid angiosarcoma: an unusual localization. World J Surg Oncol. 2012;10:73. DOI: https://doi.org/10.1186/1477-7819-10-73