Composite hemangioendothelioma in a 2-year-old girl.

Composite hemangioendothelioma (CHE) is a rare locally aggressive vascular neoplasm of intermediate malignancy. We describe a 2-year-old patient diagnosed with this tumor. Careful documentation of patients with CHE is crucial to better define the prognosis and treatment of this entity.

Vascular tumors of intermediate malignancy: An update.

The term "hemangioendothelioma" is used for endothelial neoplasms of intermediate malignancy and describes a group of rare neoplasms having biologic behavior falling in between that of the benign hemangiomas and fully malignant angiosarcomas. The hemangioendotheliomas fall into several specific, clinicopathologically and genetically distinct entities, specifically epithelioid hemangioendothelioma, kaposiform hemangioendothelioma, papillary intralymphatic angioendothelioma and retiform hemangioendothelioma (hobnailed hemangioendothelioma), pseudomyogenic hemangioendothelioma, composite hemangioendothelioma, and YAP1::TFE3-fused hemangioendothelioma. The clinical, morphologic, immunohistochemical, and genetic features, and the differential diagnosis of each of these rare entities are discussed in this review.

Composite hemangioendothelioma- report of two cases located in bone and review of the literature.

BACKGROUND: Composite hemangioendothelioma (CHE) is a rare intermediate-grade vascular tumor characterized by a complex histologic component. It occasionally metastasizes, but local recurrence is not uncommon. CHE is mainly located in the extremities' distal dermis and subcutaneous soft tissues. It is rarely located in the bone. We report here two cases originally occurred in bone. CASE PRESENTATION: The first case of CHE occurred solely on the left pubis. The second case is a patient post-resection of CHE in the manubrium sterni 10 years ago [1], who presented with multiple lesions in the left ilium and T6, T12 vertebra. All these lesions in the two cases showed osteolytic bone destruction on computed tomography (CT) scans and showed relatively high signal intensity on the fat-suppressed sequences of T2-weighted magnetic resonance (MR) images and isointense signal intensity on T1-weighted MR images. After injection of contrast agent (Gd-DTPA), the lesions showed inhomogeneous enhancement. 2-deoxy-2 [F-18] fluoro-D-glucose positron emission tomography-computed tomography (18FDG PET-CT) showed increased FDG uptake in these osteolytic bone destruction areas with SUVmax around 5.0. Both patients underwent surgery. Lesions in the left pubis and left ilium were confirmed by postoperative pathology while lesions on the vertebrae were only biopsied, not surgically resected. The first patient had no recurrence or metastasis in 5 years after surgery. The second patient had surgery recently and is still being followed up. CONCLUSIONS: CHE occurring in bone is rarely reported. Our report provides more detailed information on the diagnosis of CHE. Given that CHE is locally aggressive and occasionally metastatic, PET-CT may be helpful in staging and follow-up.

Composite haemangioendothelioma in the heart: a case report.

Background: Primary cardiac neoplasm is rare and generally benign. Epithelioid haemangioendothelioma, a potentially malignant tumour of vascular origin, has been occasionally described in the heart. Composite haemangioendothelioma, characterized by a heterogeneous architecture of vascular components and usually located in soft tissue of the extremities, has only been reported twice in the heart. We herein report another case of this extremely uncommon cardiac tumour. Case summary: Comprehensive cardiac examination of a 59-year-old female patient with palpitations and personal history of Hodgkin's lymphoma and chest radiation revealed a mass in the left atrium. After surgical resection, histopathological and immunohistochemical analysis identified a composite haemangioendothelioma. After two years, repeated imaging revealed neither signs of local relapse nor metastasis. Conclusions: Composite haemangioendothelioma, a very uncommon form of potentially malignant vascular tumour, can also be encountered in the heart. In this present case, the outcome was favourable two years after surgical resection without adjuvant therapy.

Composite hemangioendothelioma in the cervical spine with kaposiform hemangioendothelioma features in an elderly patient: a case report.

BACKGROUND: Composite hemangioendothelioma (CHE) is an intermediate group of tumors with features between hemangioma and angiosarcoma both histologically and biologically. CHE is predominant in young and middle-aged adults, but very infrequently affects the spine. We describe the case of primary CHE in the cervical spine exhibiting kaposiform hemangioendothelioma (KHE)-like components that was associated with cervical myelopathy with vertebral body destruction in an elderly woman. We retrospectively reviewed the case of a primary cervical spinal tumor, diagnosed as CHE with KHE-like components in pathological findings, associated with cervical myelopathy and cervical vertebral body destruction. CASE PRESENTATION: An 80-year-old woman presented with progressive cervical myelopathy caused by a cervical spine tumor. Preoperative cervical MRI revealed a neoplastic lesion invading the cervical spine that strongly compressed the spinal cord, causing right upper-limb paralysis. We performed partial tumor resection along with posterior decompression and fixation. Postoperatively, pathological findings showed that the tumor was CHE with KHE-like features. Following radiotherapy, no recurrences have been observed in 21 months. CONCLUSIONS: This is the first report of CHE with features of KHE in the spine of an elderly patient. Posterior decompression and fusion of the cervical spine and subsequent radiotherapy resulted in a good outcome.

Whole Exome Sequencing Identifies Somatic Variants in an Oral Composite Hemangioendothelioma Characterized by YAP1-MAML2 Fusion.

Composite hemangioendothelioma (CHE) is considered a borderline malignant vascular tumor defined by an admixture of distinct vascular neoplastic components. A 21-year-old female is presented herein with a 1 cm painless mandibular vestibular mass of less than a year duration. The infiltrating tumor was characterized by dilated vascular channels lined by endothelial cells with bland ovoid or round nuclei exhibiting, occasionally, hobnail/matchstick-like arrangement. Intravascular cell proliferations with hyaline globular deposits were also present. Additionally, lobular spindle and epithelioid cell aggregates, as well as slit-like spaces exhibiting a retiform or angiosarcomatous morphology were observed. Intracytoplasmic signet-ring or lipoblast-like vacuolization was also noted. Mitotic activity was exceptionally rare. Vascular spaces and the stroma featured lymphocytes and plasma cells. Neoplastic cells were positive for CD31, CD34, D2-40 and ERG, negative for CAMTA1 and synaptophysin, while type IV collagen highlighted the plasmalemma of most vessels and hyaline globules. Fluorescence in situ hybridization revealed gene rearrangements in both YAP1 and MAML2 genes, in keeping with a YAP1-MAML2 fusion. Whole exome sequencing (WES) identified three missense mutations FLT1 [p.R1016G], PIK3CA [p.H1047L], and C11orf42 [p.A304P] and a mitochondrial frameshift insertion MT-ND4 [c.1107_1108insC; p.P370fs]. These WES results suggest that FLT1 and/or PIK3CA variants may contribute to tumor growth/transformation while the MT-ND4 variant may relate to proliferation, angiogenesis and/or inhibition of apoptosis.

Recurrent PTBP1::MAML2 fusions in composite hemangioendothelioma with neuroendocrine differentiation: A report of two cases involving neck lymph nodes.

Composite hemangioendothelioma (CHE) displaying neuroendocrine differentiation is a rare histologic variant that is often mistaken for angiosarcoma, having a predilection for visceral locations and being associated with an aggressive clinical course. Their pathogenesis is still evolving, with only two cases to date from separate studies reporting a recurrent PTBP1-MAML2 fusion. Herein, we report two new cases of neuroendocrine CHE harboring PTBP1-MAML2 fusions occurring in two elderly patients (70-year-old male and 71-year-old female), both involving neck lymph nodes. The first case presented with multifocal cervical lymphadenopathy, while the second case occurred unifocally in an enlarged neck lymph node. Histologically, the tumors displayed heterogenous architectural patterns with areas reminiscent of benign cavernous hemangioma, retiform hemangioendothelioma, epithelioid hemangioendothelioma, and angiosarcoma. Cytologically, the cells were monotonous with round to ovoid nuclei, open to fine chromatin, scant to moderate cytoplasm, and frequent vacuolization. In addition, the first case showed focal solid areas of large epithelioid cells with severe nuclear atypia, enlarged nuclei and prominent nucleoli, resembling epithelioid angiosarcoma. Tumor cells were diffusely positive for vascular markers and focally positive for synaptophysin. In both cases, a next-generation sequencing fusion panel confirmed an in-frame fusion between PTBP1 exon 10 and MAML2 exon 2. One case with clinical follow-up showed stable recurrent disease and metastatic lung deposits following treatment. Both patients were alive at 3 months and 1 year following initial diagnosis. Our findings lend further support to classifying CHE with PTBP1-MAML2 fusions as a distinct variant of CHE with unique clinicopathologic features, including neuroendocrine features.

Thoracic composite hemangioendothelioma with neuroendocrine marker expression.

BACKGROUND: Composite hemangioendothelioma is an extraordinarily rare form of vascular neoplasm which develops predominantly in the skins and soft tissues of the adults. Neuroendocrine marker expression in composite hemangioendothelioma is considered as specifically relevant to the more aggressive behavior. CASE PRESENTATION: The patient was a 71-year-old man complaining continuous back pain. Computed tomography (CT) showed that 10 cm of contrast-enhanced soft tissue mass was occurring on the right posterior chest wall and developing adjacent to the spinal canal. Via the laminectomy, the tumor end was identified and separated from the dura mater. Then, via the posterolateral thoracotomy, the en bloc resection was achieved by separating the tumor from the diaphragm and vertebras. Histologic examination showed a complex combination of epithelioid and retiform hemangioendothelioma areas which were positive for anti-synaptophysin staining. At 12-month follow-up, there were no signs of tumor recurrence on CT, and the patient had no symptom. CONCLUSIONS: We achieved the complete resection of a huge thoracic neuroendocrine composite hemangioendothelioma developing adjacent to the spinal canal. The combination of the posterior lumbar laminectomy and the following posterior thoracotomy is a viable approach to radically resect a thoracic neuroendocrine composite hemangioendothelioma involving chest wall.

Case Report: Cutaneous Pleomorphic Lymphangiosarcoma in a Dog Exhibiting Features of Human Composite Hemangioendothelioma.

Background: Angiosarcomas are a broad category of vascular origin neoplasms that are poorly characterized in veterinary species. Lymphangiosarcoma (LAS) is an uncommon type of angiosarcoma reported in humans and canines arising from lymphatic endothelium. LAS can be differentiated from other angiosarcomas in dogs based on expression of Prospero-related homeobox gene-1 (PROX-1) or lymphatic vessel endothelial receptor-1 (LYVE-1). Composite hemangioendothelioma (CHE) is a rare angiosarcoma subtype described in people and characterized by a variable biologic behavior and infrequent metastasis. This variant of angiosarcoma histologically combines features of retiform hemangioendothelioma and epithelioid hemangioendothelioma. Information regarding the cytologic and histopathologic appearance and clinical course of dogs with vascular tumors that exhibit features of CHE are unknown. Here, we report a case of pleomorphic LAS with features of CHE arising in a dog and treated with surgery and adjuvant chemotherapy. Case presentation: A 10-year-old intact male Labrador retriever presented with an approximately 6-cm-diameter cutaneous mass caudal to the left elbow that was progressively growing over 1.5 years. On physical examination, palpable extensions were identified coursing proximally over the triceps with concurrent loco-regional peripheral lymphadenopathy. Fine needle aspirates (FNA) and cytologic assessment of the cutaneous mass, left prescapular, and accessory axillary lymph nodes reported that this appeared to be a metastatic epithelial neoplasm, although a mixed carcinoma or collision tumor could not be excluded. An incisional biopsy of the mass was submitted for histopathology and was consistent with a well-differentiated angiosarcoma with features of CHE. The neoplasm expressed vimentin, CD31, von Willebrand factor (vWf), and PROX-1, supporting the diagnosis of LAS. Complete staging was performed, and no additional metastatic lesions were identified. Left forelimb amputation and lymph node removal were performed. Based on the diagnosis of metastatic LAS, doxorubicin chemotherapy was administered. 7 months post-amputation, the tumor recurred at the amputation site without evidence of metastatic disease. Conclusion: This report describes a malignant, locally aggressive lymphatic origin vascular tumor in a dog, with features consistent with descriptions of CHE in humans. Cytologic features in this case were discordant with its true mesenchymal etiology, obfuscating diagnosis. The morphologic features of the mesenchymal neoplastic population and immunohistochemistry (IHC) labeling ultimately supported a diagnosis of pleomorphic LAS with features of CHE.

Composite Hemangioendothelioma With Neuroendocrine Marker Expression: Report of a "Paraganglioma-Like" Paravertebral Case.

Composite hemangioendothelioma is a rare vascular tumor morphologically comprising several distinct vascular components and exhibits a borderline malignant potential. We described the case of a 53-year-old female who presented with an infiltrative mass in the paravertebral soft tissue. The tumor showed discrete nests of synaptophysin-expressing epithelioid cells accompanied by rich vasculature, features highly reminiscent of sympathetic paraganglioma. Further analysis revealed areas resembling spindle cell hemangioma, retiform hemangioendothelioma, cavernous hemangioma/lymphangioma, and epithelioid hemangioendothelioma without the myxohyaline matrix in the tumor, and a final diagnosis of composite hemangioendothelioma with synaptophysin expression was made. Critical appraisal of this recently described entity and its possible pathogenic relationship with retiform hemangioendothelioma were discussed.

Composite hemangioendothelioma of the forehead and right eye; a case report.

BACKGROUND: Hemangioendothelioma includes several types of vascular neoplasms , as well as both benign and malignant growth. CASE PRESENTATION: This study evaluated a case of a 78-year-old female diagnosed with composite hemangioendothelioma (CHE). This patient had an 18-month history of painless inflammatory lesions and erythema on the left forehead and right upper eyelid. The clinical and pathologic characteristics of the CHE were evaluated in the present study. CONCLUSION: The evidence of the coexistence of variable components of the CHE in our study emphasized the importance of distinctive morphology and biology, and should be considered in the differential diagnosis of other vascular lesions.

Reconstruction With ß-Tricalcium Phosphate After Navicular Tumor Resection.

Postresection reconstruction of the navicular bone is challenging. A composite hemangioendothelioma is an intermediate malignancy characterized by an admixture of differing vascular components. In the present report, a 40-year-old male with a composite hemangioendothelioma presented with multiple soft tissue lesions of the leg and sole and a navicular bone lesion. The navicular bone was resected and reconstructed using ß-tricalcium phosphate of strong compression resistance with plating. The current reconstruction method can be applied, not only for tumors, but also for trauma.

Composite Hemangioendothelioma of the Submandibular Region.

Composite hemangioendothelioma (HE) is a rare vascular neoplasm of intermediate malignant potential that predominantly occurs within the dermis or subcutis of the extremities, and occurs in a wide age range. It is locally aggressive with a high rate of local recurrence, and more rarely regional lymph node or distant metastasis. Histologically, it is composed of a complex admixture of benign, intermediate and malignant vascular components. Although composite HE may contain angiosarcoma-like areas, its prognosis is better than that of pure angiosarcoma. We describe a case of composite HE presenting as a submandibular mass in a 43 year-old male, which included areas of prominent 'high grade' epithelioid angiosarcoma. This adds to the range of anatomic sites of these neoplasms, highlights the importance of recognition of the head and neck as a potential site, and emphasizes the importance of accurate diagnosis for correct management (including of long term follow up) and prognostication.

Composite hemangioendothelioma: An unusual presentation of a rare vascular tumor.

OBJECTIVES: Composite hemangioendothelioma (CHE) has been recently recognized as a low- to intermediate-grade vascular tumor. CHEs are rare vascular tumors that are clinically similar to more common vascular tumors but histologically exhibit a composite of hemangioendothelioma variants. We report the first case of a CHE on the scalp and the fifth case to show findings supportive of regional metastasis. METHODS: Our patient had a multilobulated, violaceous scalp nodule, which on histologic examination revealed epithelioid, retiform, and spindle-cell components and rare foci of intermediate-grade mitotic activity consistent with CHE. RESULTS: Imaging studies were performed and revealed an abnormal uptake of contrast media in a posterior neck nodule that, when examined via fine-needle aspiration, revealed clumps of atypical cells. CONCLUSIONS: This unique case presentation is representative of the variability seen in the presentation of CHE and highlights the importance of considering CHE on the clinical and histologic differential of vascular tumors.

Composite hemangioendothelioma arising from the kidney: case report with review of the literature.

Reported herein is a medical curiosities vascular tumor primary arising from the kidney and exhibiting unique histopathological features. A 32-year-old woman underwent a total nephrectomy of right kidney because of a mass localized in the inferior pole. Distinct from other vascular lesions, on histology the tumor had a peculiar composite pattern, consisting of benign and malignant vascular components, which were haphazardly intermixed without any definite margins. The malignant component was composed of epithelioid hemangioendothelioma (45%) and angiosarcoma (50%) with moderate differentiation. Immunohistochemically, the oval to cuboidal to spindle tumor cells expressed only endothelial markers (CD31, CD34 and factor VIII-related antigen). And the angiosarcomatous component was characterized by the presence of a greater proliferation index Ki-67. Unlike other epithelial tumors, smooth muscle actin (SMA), cytokeratin, EMA and S-100 were all negative in the epithelioid tumor cells. These findings led to the diagnosis of a low-grade vascular neoplasm with morphological features consistent with so-called composite hemangioendothelioma (CHE). At 11 month follow up the patient was alive, without evidence of tumor recurrence. CHE is an extremely rare vascular neoplasm, with borderline malignant potential, which mostly occurs in distal extremity of the limbs at the cutaneous level and, only 30 cases have been previously described until now. To our knowledge, this is the first report of CHE arising from the kidney and widens the spectrum of primary vascular tumors arising in the kidney.