Clinicopathological features of 12 cases of epithelioid hemangioendothelioma

doi:10.3969/j.issn.1674-8115.2025.07.011

Abstract

Abstract:

Objective ·To investigate the clinical, pathological, and molecular genetic features and prognosis of epithelioid hemangioendothelioma (EHE) patients. Methods ·Clinical and follow-up data of 12 EHE patients diagnosed at Renji Hospital, Shanghai Jiao Tong University School of Medicine from September 2016 to December 2023 were collected. Tissue samples were analyzed using hematoxylin-eosin (H-E) staining, immunohistochemistry (IHC), and fluorescence in situ hybridization (FISH). Results ·Among the 12 patients, there were 3 males and 9 females, with a mean age of (47.17±11.15) years. Tumors were located in the liver (6 cases), lung (4 cases), mediastinum (1 case), and supraclavicular region (1 case). Nine patients were asymptomatic, while 3 presented with mild symptoms such as chest tightness and fatigue. CT imaging revealed that EHE patients with involvement of livers and lungs exhibited multiple nodules, and 2 cases had tumors in both organs. Patients with tumors in the supraclavicular region and mediastinum presented with solitary nodules. H-E staining demonstrated that tumor tissues were composed of epithelioid, dendritic, and intermediate cells, arranged in acinar, cord-like, or clustered patterns. Epithelioid cells had round vesicular nuclei and eosinophilic cytoplasm, with some showing a signet-ring appearance and cytoplasmic vacuoles. The stroma contained a mucoid matrix. IHC staining revealed that mesenchymal endothelial markers, including vimentin, CD31, ETS transcription factor ERG, and factor Ⅷ-related antigen, were positive in the tumor tissues, while epithelial markers showed low positivity with weak staining. The Ki-67 indexes were also low. FISH analysis showed that 10 patients had a calmodulin-binding transcription activator 1 (CAMTA1) gene break, while 2 patients had a transcription factor E3 (TFE3) gene break. Of the 12 patients, 11 were followed up for 2 to 38 months, with a mean follow-up time of 21.7 months. Three patients achieved tumor-free survival, 6 were alive with tumors, 1 died 4 months after surgery, and 1 died of heart disease 24 months after surgery. Conclusion ·EHE has atypical clinical features, a tendency to recur, a and variable prognosis. Accurate diagnosis requires a combination of histopathology, IHC, and a molecular testing.

Key words: epithelioid hemangioendothelioma (EHE), histopathology, immunohistochemistry (IHC), molecular testing

CLC Number:

R732.2

SUI Chengliang, SHEN Yanying, LIU Zebing. Clinicopathological features of 12 cases of epithelioid hemangioendothelioma[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025, 45(7): 892-899.

Figures/Tables 5

TrendMD

References 23

[1]	李卓, 杜强, 马沛卿, 等. 肝上皮样血管内皮瘤14例临床病理学特点分析[J]. 中华病理学杂志, 2021, 50(5): 511-513.
	LI Z, DU Q, MA P Q, et al. Clinicopathological characteristics of hepatic epithelioid hemangioendothelioma[J]. Chinese Journal of Pathology, 2021, 50(5): 511-513.
[2]	STUDER L L, SELBY D M. Hepatic epithelioid hemangioendothelioma[J]. Arch Pathol Lab Med, 2018, 142(2): 263-267.
[3]	弋春燕, 马捷, 曾显荣, 等. 前纵隔上皮样血管内皮瘤CT表现与病理相关征象分析[J]. 中国CT和MRI杂志, 2023, 21(1): 89-91.
	YI C Y, MA J, ZENG X R, et al. Analysis of pathological and CT features of anterior mediastinum epithelioid hemangioendothelioma[J]. Chinese Journal of CT and MRI, 2023, 21(1): 89-91.
[4]	TSUCHIHASHI K, BABA E S. Epithelioid hemangioendothelioma-its history, clinical features, molecular biology and current therapy[J]. Jpn J Clin Oncol, 2024, 54(7): 739-747.
[5]	魏淑飞, 韩永良, 张卢舜, 等. 肝脏上皮样血管内皮瘤44例临床病理观察[J]. 临床与实验病理学杂志, 2022, 38(12): 1492-1496.
	WEI S F, HAN Y L, ZHANG L S, et al. Clinicopathological observation of hepatic epithelioid hemangioendothelioma: a study of 44 cases[J]. Chinese Journal of Clinical and Experimental Pathology, 2022, 38(12): 1492-1496
[6]	LAU K, MASSAD M, POLLAK C, et al. Clinical patterns and outcome in epithelioid hemangioendothelioma with or without pulmonary involvement: insights from an internet registry in the study of a rare cancer[J]. Chest, 2011, 140(5): 1312-1318.
[7]	LYTLE M, BALI S D, GALILI Y, et al. Epithelioid hemangioendothelioma: a rare case of an aggressive vascular malignancy[J]. Am J Case Rep, 2019, 20: 864-867.
[8]	陈少芳, 庄丹萍, 金红涛, 等. 肝脏、双肺同时发生的上皮样血管内皮瘤影像表现一例并文献复习[J]. 磁共振成像, 2024, 15(3): 187-189.
	CHEN S F, ZHUANG D P, JIN H T, et al. Epithelioid hemangioendothelioma involving both liver and lung: one case report[J]. Chinese Journal of Magnetic Resonance Imaging, 2024, 15(3): 187-189.
[9]	方燕红, 刘向一, 倪云燕, 等. 肝脏上皮样血管内皮瘤的影像学表现[J]. 中国卫生标准管理, 2023, 14(24): 82-86.
	FANG Y H, LIU X Y, NI Y Y, et al. Imaging manifestations of hepatic epithelioid hemangioendothelioma[J]. China Health Standard Management, 2023, 14(24): 82-86.
[10]	叶枫, 蒋力明, 宋颖, 等. 肝脏上皮样血管内皮瘤的影像学特征[J]. 中华消化外科杂志, 2017, 16(2): 201-206.
	YE F, JIANG L M, SONG Y, et al. Imaging features of hepatic epithelioid hemangioendothelioma[J]. Chinese Journal of Digestive Surgery, 2017, 16(2): 201-206.
[11]	董淑慧, 杨勇, 刘爱东, 等. 骨原发性上皮样血管内皮瘤2例临床病理学分析并文献复习[J]. 诊断病理学杂志, 2024, 31(8): 711-714.
	DONG S H, YANG Y, LIU A D, et al. Clinicopathological features of primary epithelioid hemangioendothelioma originated in bone: report of two cases and literature review[J]. Chinese Journal of Diagnostic Pathology, 2024, 31(8): 711-714.
[12]	王帅, 吕明, 梅丽. 上皮样血管内皮瘤6例临床病理分析[J]. 中国实验诊断学, 2024, 28(9): 1075-1078.
	WANG S, LÜ M, MEI L. Clinicopathological analysis of 6 cases of epithelioid hemangioendothelioma[J]. Chinese Journal of Laboratory Diagnosis, 2024, 28(9): 1075-1078.
[13]	马晓燕, 方建强, 石艳宏, 等. 肝脏上皮样血管内皮瘤穿刺标本的病理特征[J]. 诊断病理学杂志, 2023, 30(8): 799-801.
	MA X Y, FANG J Q, SHI Y H, et al. Pathological features of hepatic epithelioid hemangioendothelioma of needle biopsy specimen[J]. Chinese Journal of Diagnostic Pathology, 2023, 30(8): 799-801.
[14]	NOH O K, KIM S S, YANG M J, et al. Treatment and prognosis of hepatic epithelioid hemangioendothelioma based on SEER data analysis from 1973 to 2014[J]. Hepatobiliary Pancreat Dis Int, 2020, 19(1): 29-35.
[15]	倪海春, 谢永辉, 章宏峰. 肺上皮样血管内皮瘤4例临床病理观察[J]. 临床肿瘤学杂志, 2023, 28(9): 836-841.
	NI H C, XIE Y H, ZHANG H F. Pulmonary epithelioid hemangioendothelioma: a clinicopathological analysis of four cases[J]. Chinese Clinical Oncology, 2023, 28(9): 836-841.
[16]	王湛博, 安晓静, 邓晋芳, 等. 肝脏恶性血管源性肿瘤中ERG、Fli-1、CD34、CD31、FⅧRAg的表达特征[J]. 中华病理学杂志, 2017, 46(11): 760-763.
	WANG Z B, AN X J, DENG J F, et al. Characteristics of ERG, Fli-1, CD34, CD31 and FⅧRAg expression in hepatic malignant vascular tumors[J]. Chinese Journal of Pathology, 2017, 46(11): 760-763.
[17]	FLUCKE U, VOGELS R J C, DE SAINT AUBAIN SOMERHAUSEN N, et al. Epithelioid Hemangioendothelioma: clinicopathologic, immunohistochemical, and molecular genetic analysis of 39 cases[J]. Diagn Pathol, 2014, 9: 131.
[18]	ROSENBAUM E, JADEJA B, XU B, et al. Prognostic stratification of clinical and molecular epithelioid hemangioendothelioma subsets[J]. Mod Pathol, 2020, 33(4): 591-602.
[19]	DOYLE L A, FLETCHER C D M, HORNICK J L. Nuclear expression of CAMTA1 distinguishes epithelioid hemangioendothelioma from histologic mimics[J]. Am J Surg Pathol, 2016, 40(1): 94-102.
[20]	LOTFALLA M M, FOLPE A L, FRITCHIE K J, et al. Hepatic YAP1-TFE3 rearranged epithelioid hemangioendothelioma[J]. Case Rep Gastrointest Med, 2019, 2019: 7530845.
[21]	WU X, LI B L, ZHENG C J, et al. Clinical characteristics of epithelioid hemangioendothelioma: a single-center retrospective study[J]. Eur J Med Res, 2019, 24(1): 16.
[22]	ATYAH M M, SUN Y L, YANG Z Y. The challenges of hepatic epithelioid hemangioendothelioma: the diagnosis and current treatments of a problematic tumor[J]. Orphanet J Rare Dis, 2024, 19(1): 449.
[23]	TORRENCE D, ANTONESCU C R. The genetics of vascular tumours: an update[J]. Histopathology, 2022, 80(1): 19-32.

No.	Gender	Age/year	Lesion location	Symptom/detection way	Lesion number	Other organs involved	Maximal lesion diameter/cm	Therapy	Follow-up/month	Prognosis
1	Male	42	Liver	PE	2	‒	‒	Surgery	0	Unknown
2	Female	40	Liver	PE	Multiple	Bilateral lung	2.7	Surgery+TT+Chemo	38	Recurrence, survival with tumors
3	Female	50	Liver	Feeling unwell	Multiple	‒	2.3	Surgery	2	Tumor-free survival
4	Male	59	Liver	Fatigue	Multiple	‒	7.3	Surgery	4	Death
5	Female	49	Liver	PE	Multiple	‒	2.0	Surgery+interferon	21	Recurrence, survival with tumors
6	Female	25	Liver	PE	Multiple	Bilateral lung	5.6	TT+surgery	29	Recurrence, survival with tumors
7	Male	44	Supraclavicular	Self-detected	Multiple	‒	2.0	RT	35	Tumor-free survival
8	Female	52	Mediastinum	Chest tightness	1	‒	8.0	TT	8	Survival with tumors
9	Female	43	Lung	PE	Multiple	‒	1.4	TT+RT	36	Survival with tumors
10	Female	70	Lung	PE	Multiple	‒	8.2	Surgery	24	Death due to a heart attack
11	Female	40	Lung	PE	Multiple	‒	0.8	Surgery	27	Recurrence, survival with tumors
12	Female	52	Lung	PE	Multiple	‒	0.7	Surgery	15	Tumor-free survival

No.	Gender	Age/year	Lesion location	Symptom/detection way	Lesion number	Other organs involved	Maximal lesion diameter/cm	Therapy	Follow-up/month	Prognosis
1	Male	42	Liver	PE	2	‒	‒	Surgery	0	Unknown
2	Female	40	Liver	PE	Multiple	Bilateral lung	2.7	Surgery+TT+Chemo	38	Recurrence, survival with tumors
3	Female	50	Liver	Feeling unwell	Multiple	‒	2.3	Surgery	2	Tumor-free survival
4	Male	59	Liver	Fatigue	Multiple	‒	7.3	Surgery	4	Death
5	Female	49	Liver	PE	Multiple	‒	2.0	Surgery+interferon	21	Recurrence, survival with tumors
6	Female	25	Liver	PE	Multiple	Bilateral lung	5.6	TT+surgery	29	Recurrence, survival with tumors
7	Male	44	Supraclavicular	Self-detected	Multiple	‒	2.0	RT	35	Tumor-free survival
8	Female	52	Mediastinum	Chest tightness	1	‒	8.0	TT	8	Survival with tumors
9	Female	43	Lung	PE	Multiple	‒	1.4	TT+RT	36	Survival with tumors
10	Female	70	Lung	PE	Multiple	‒	8.2	Surgery	24	Death due to a heart attack
11	Female	40	Lung	PE	Multiple	‒	0.8	Surgery	27	Recurrence, survival with tumors
12	Female	52	Lung	PE	Multiple	‒	0.7	Surgery	15	Tumor-free survival