Int J Clin Exp Pathol 2020;13(6):1421-1425 www.ijcep.com /ISSN:1936-2625/IJCEP0110515 Case Report Intramuscular composite hemangioendothelioma: case report of an unusual tumor in an unusual location Susie Chin1, Jiyoon Kim1, Min Jung Jung1, Min Ju Kim1, Ahrim Moon1, Hee Kyung Kim1, Young Hwan Kim2, Eun Suk Koh1 Departments of 1Pathology, 2Orthopedic Surgery, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea Received March 8, 2020; Accepted April 14, 2020; Epub June 1, 2020; Published June 15, 2020 Abstract: Composite hemangioendothelioma (CHE) is an extremely rare locally aggressive vascular neoplasm com- prising various benign, intermediate, and malignant vascular components. It is usually located superficially, in the dermis and subcutis of the extremities. Herein, we report a first case of CHE arising from the skeletal muscle in a 67-year-old woman who presented with a palpable mass on her right forearm. Magnetic resonance imaging revealed a 3.0 × 2.7-cm intramuscular mass with high-signal intensity on contrast-enhanced T2-weighted images. Excision was performed, and microscopic examination revealed a heterogeneous mixture of vascular components, consist- ing of arteriovenous malformation, spindle cell hemangioma, retiform hemangioendothelioma, and angiosarcoma- like areas. Moreover, we present a brief review of previously reported cases of CHE arising from the extremities. Keywords: Hemangioendothelioma, angiosarcoma, vascular neoplasm Introduction identified 3 years ago, and the patient under- went surgical excision at another hospital. Composite hemangioendothelioma (CHE) has However, the pathologic diagnosis of the ex- been recently described, and it was first report- cised lesion was unknown. Then, the mass ed by Nayer et al. in 2000 [1]. CHE has an inter- started to increase in size and cause pain for mediate malignant potential and is character- the past year. On physical examination, a 5-cm ized by an admixture of benign, low-grade ma- fixed mass was observed on her distal forearm. lignant, and malignant vascular components Magnetic resonance imaging revealed a 3-cm [2]. It is an extremely uncommon neoplasm, mass-like lesion in the flexor muscle of the right with fewer than 40 cases reported in the forearm, and the lesion exhibited a low-signal English literature [3]. In most cases, the mass intensity on T1-weighted images and a hyper- develops in the extremities, and the other sites signal intensity on T2-weighted images (Figure involved include the head and neck region, oral 1). Moreover, the adjacent muscles exhibited a mucosa, and viscera of the kidney and spleen slightly higher intensity on T2-weighted images. [3-6]. Most CHEs occur in the superficial layer A malignant tumor was suspected, and hence, of the skin, such as the dermis and subcutane- percutaneous needle biopsy was performed. ous tissue. To the best of our knowledge, there Pathologic examination of the biopsy specimen has been no reported case of CHE arising from revealed proliferation of small-sized vessels the skeletal muscle in previous studies [4]. consisting of capillaries, venules, and arterioles Herein, we report a first case of CHE arising admixed with fibroadipose tissue. Benign vas- from the skeletal muscle. cular lesions, including arteriovenous malfor- mations (AVMs) with small vessel components, Case presentation were considered histologically. Surgical exci- sion of the mass was performed. During the A 67-year-old woman presented with a growing operation, a 5.0 × 3.0-cm intramuscular mass mass on her right forearm. The mass was first that had irregular margins and adhered to the Intramuscular composite hemangioendothelioma surrounding soft tissues was found to be attached to the interosseous membrane and periosteum of the radius and ulna. Based on gross examination, the size of the tumor was 3.5 × 3.0 × 2.5 cm, and it had a red- dish purple, soft, hemorrhagic cut surface and an ill-defined border (Figure 2A). Histologic examination revealed a poorly Figure 1. Magnetic resonance imaging revealed a mass-like lesion in the circumscribed vascular lesi- flexor muscle. The intramuscular lesion had (A) A low-signal intensity on a on with a variety of histolog- T1-weighted image and (B) A high-signal intensity on a T2-weighted image. ic appearances consisting of benign, intermediate, and ma- lignant vascular neoplasms. Malformed large arteries and veins, with proliferation of sm- all capillary-sized vessels simi- lar to that observed on the pre- vious needle biopsy specime- ns, were identified at the peri- pheral portion of the tumor, and these were consistent with AVM (Figure 2C). More- over, spindle cell hemangioma, which is a benign vascular component composed of dilat- ed thin-walled vessels lined by a flattened endothelium with cellular and spindled stroma was identified Figure( 2D). The areas of intermediate vascular tumor resembled retiform he- mangioendothelioma, with a proliferation of narrow, arboriz- ing vessels with hobnail-like endothelial cells (Figure 2E). Well-differentiated angiosarco- Figure 2. Based on gross examination, (A) The 3.5 × 3.0-cm tumor was poorly ma-like areas, with more com- circumscribed with a hemorrhagic cut surface. Microscopic examination of plex, anastomosing vascular the tumor revealed varying benign, intermediate, and malignant vascular channels lined by multilayer- components, and (B) The vascular lesions were haphazardly intermixed, thereby providing a heterogeneous appearance (hematoxylin & eosin [H&E] ed atypical endothelial cells, stain, × 40). (C) Areas resembling arteriovenous malformation are com- were also observed (Figure posed of a mixture of arteries and veins with proliferation of small vessels 2F). These benign (AVMs, (H&E, × 100). (D) Spindle cell hemangioma has dilated thin-walled vessels 30%; spindle cell hemangio- with solid areas comprising histologically bland spindle cells (H&E, × 100). mas, 40%), intermediate (reti- (E) Retiform hemangioendothelioma is composed of long, arborizing vascu- lature lined by endothelial cells showing occasional hobnail pattern (H&E, × form hemangioendothelioma, 200). (F) Angiosarcoma-like area revealing complex vascular channels lined 20%), and malignant (angio- by multilayered, atypical endothelial cells (H&E, × 200). sarcoma, 10%) vasculatures 1422 Int J Clin Exp Pathol 2020;13(6):1421-1425 Intramuscular composite hemangioendothelioma search for articles in PubMed, and only 18 articles on CHE cases in the extremities were found [1, 4, 9-14]. Cases that did not fulfill the histologic cri- teria of CHE were excluded. The clinicopathologic features of the reported CHE cases arising from the extremities are sum- Figure 3. A. Immunohistochemical staining revealed that the Ki-67 prolif- marized in Table 1. eration index increased to 10% in the angiosarcoma-like area (× 200). B. Analysis of desmin revealed the destruction of atrophic skeletal muscle fi- In the previous cases of CHE bers caused by the tumor, thereby revealing the intramuscular location of the tumor (× 100). arising from the extremities, the age at presentation varied from 8 to 75 years, with a mean were closely and haphazardly intermixed age of 39.9 years, and the female-to-male ratio (Figure 2B). was 1.25:1. Most cases revealed a relatively long duration of neoplasm (several years until By immunohistochemical examination, the tu- diagnosis). The size of the tumors was approxi- mor had immunoreactivity to CD31 and CD34. mately 10-300 (mean: 52.3) mm. Surgical exci- The Ki-67 proliferation index increased up to sion was performed on all patients, except for 10% in the angiosarcoma-like area, whereas one patient who received chemotherapy only. the rest of the tumor had an extremely low pro- Retiform HE with arborizing vasculature mim- liferation index (<1%) (Figure 3A). Analysis of icking the rete testis lined by hobnail endothe- desmin revealed a destruction of atrophic skel- lial cells, as observed in the current case, was etal muscle fibers caused by the tumor, thereby found in 17 of 19 cases [1, 4, 9-14]. Epithelioid confirming the intramuscular location of the HE was also observed in 14 of 19 cases [1, 4, tumor (Figure 3B). Based on the various his- 10-12]. The most commonly noted benign vas- tologic appearances of vascular neoplasms, cular component of CHE was spindle cell hem- the patient was finally diagnosed with CHE. angioma (10/18), which is composed of cavern- Although the tumor was marginally excised, no ous vessels and some solid areas of spindle- additional surgical excision or adjuvant therapy shaped cells [1, 9-14]. Lymphangioma, AVM, was performed. No recurrence or metastasis of and cavernous hemangioma were also found to the tumor was identified 4 months after the be benign components [1, 11, 13]. Of the 19 operation. cases, 12, 9, 1, and 1 case involved areas resembling malignant vascular tumors, angio- Discussion sarcoma, Kaposi sarcoma, and both angiosar- coma and Kaposi sarcoma, respectively [1, 4, Hemangioendothelioma (HE) refers to a vascu- 9, 11, 13]. All the previously described CHE lar neoplasm that has a borderline biologic cases arising from the extremities were located behavior between a hemangioma and an angio- in the superficial layers of the skin such as the sarcoma. It is considered a locally aggressive dermis and subcutis [1, 4, 9-14]. Follow-up data tumor. However, it rarely metastasizes [7]. CHE were available for 16 cases. Moreover, seven is the most recently described entity of the HE (44%) patients