上皮样血管内皮瘤12例临床病理学分析

doi:10.3969/j.issn.1674-8115.2025.07.011

摘要/Abstract

摘要：

目的·探索上皮样血管内皮瘤（epithelioid hemangioendothelioma，EHE）患者的临床、病理及分子遗传学特征及其预后。方法·收集2016年9月至2023年12月上海交通大学医学院附属仁济医院确诊的12例EHE患者的临床及随访资料，组织样本分别行苏木精-伊红（hematoxylin-eosin，H-E）染色、免疫组织化学（immunohistochemistry，IHC）染色和荧光原位杂交（fluorescence in situ hybridization，FISH）检测。结果·12例患者中男性患者3名、女性9名，平均年龄（47.17±11.15）岁；肿瘤分布为肝脏6例、肺4例、纵隔1例、右锁骨上1例；无症状患者9例，其余3例患者因胸闷、乏力等轻微不适症状就医。CT检查显示发生在肝脏和肺部的EHE患者均为多发结节，其中2例同时累及肝脏和肺；发生在锁骨上及纵隔的EHE患者为单发结节。H-E染色显示：肿瘤组织由上皮样细胞、树突状细胞和中间细胞构成，排列呈腺泡状、条索状或簇状；上皮样细胞具有圆形泡状核及嗜酸性胞质，部分细胞呈印戒样外观伴胞质空泡；间质含黏液样基质。IHC染色显示：肿瘤组织的间叶源性血管内皮标志物波形蛋白、CD31、ETS转录因子ERG、凝血第Ⅷ因子相关抗原均为阳性，而上皮源性标志物阳性率低且仅呈弱阳性，Ki-67指数也较低。FISH检测显示：10例患者存在钙调素结合转录激活因子1（calmodulin-binding transcription activator 1，CAMTA1）基因断裂，另2例患者存在转录因子E3（transcription factor E3，TFE3）基因断裂。12例患者中11例获得随访结果，随访时间2~38个月，平均21.7个月，其中3例无瘤生存，6例带瘤生存，1例术后4个月死亡，1例术后24个月因心脏病死亡。结论·EHE临床特征不典型、易复发、预后差异较大；组织病理学结合IHC及分子检测有助于明确诊断。

关键词: 上皮样血管内皮瘤, 组织病理学, 免疫组织化学, 分子检测

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

中图分类号:

R732.2

隋成亮, 沈艳莹, 刘泽兵. 上皮样血管内皮瘤12例临床病理学分析[J]. 上海交通大学学报（医学版）, 2025, 45(7): 892-899.

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.

图/表 5

表1 12例EHE患者的临床资料和随访结果

Tab 1 Clinical data and follow-up of 12 EHE cases

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

图1 EHE的CT增强典型影像Note： CT-enhanced venous phase of EHE in the mediastinum (A), supraclavicular nodule (B), liver (C), and lung (D). The tumor tissues appeared as masses or nodular hypodense shadows (red arrows). In particular, the hepatic EHE (C) showed a distinct target sign on CT imaging, characterized by a hyperdense central core surrounded by a peripheral hypodense rim.

Fig 1 Typical CT-enhanced images of EHE

图2 EHE的组织病理学表现（H-E染色）Note： A. Tumor cells distributed in the mucus-rich background (×200). B. Tumor cells arranged in a nodular pattern (×40). C. Signet-ring-like tumor cells (red arrows, ×400). D. Formation of original lumen of the blood vessels containing red blood cells (red arrows, ×200). E. Dendritic cells with elongated, and stellate nuclei (red arrows, ×400). F. Tumor cells infiltrating the walls of blood vessels (red arrows, ×200). G. Tumor cells arranged in a nodular pattern (red arrows, ×100). H/I. Signet-ring-like tumor cells (red arrows, ×400). The tissues were respectively from the liver (A‒F), lung (G), mediastinum (H), and supraclavicular nodule (I).

Fig 2 Histopathological manifestations of EHE (H-E staining)

图3 EHE的IHC染色结果（×200）Note： A. CD34. B. CD31. C. Vimentin. D. ERG. E. FⅧ-Rag. F. CK.

Fig 3 IHC staining results of EHE (×200)

图4 EHE的分子病理学检测结果Note： A. FISH results for CAMTA1 gene split (×1 000). B. FISH results for TFE3 gene split (×2 000). C/D. The enlarged images of the white boxes of A (C) and B (D) (×4 000). The gene split showed the separated red and green signals or the loss of green signals (yellow arrows).

Fig 4 Molecular pathological results of EHE

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