Despite significant advances in their molecular pathogenesis, skeletal vascular tumors remain diagnostically challenging due to their aggressive radiologic appearance and significant morphologic overlap. Within the epithelioid category and at the benign end of the spectrum, recurrent FOS/FOSB fusions have defined most epithelioid hemangiomas, distinguishing them from epithelioid hemangioendothelioma and angiosarcoma. More recently, the presence of EWSR1/FUS :: NFATC1/2 fusions emerged as the genetic hallmark of a novel group of unusual vascular proliferations, often displaying epithelioid morphology, with alternating vasoformative and solid growth, variable atypia, reminiscent of composite hemangioendothelioma. In this study, we further our understanding and morphologic spectrum of NFATC -fusion positive vascular neoplasms by describing 9 new cases, including soft tissue locations and novel fusion partners. Combining with the initial cohort of 5 cases, a total of 14 patients were analyzed, showing slight female predilection and an age range of 10 to 66 (mean 42 y). Twelve patients had solitary lesions, while 2 had multifocal polyostotic (pelvic bones) disease. Overall, 12 lesions were intra-osseous and 2 in soft tissue. By targeted RNA Fusion panels or FISH, there were 6 cases of EWSR1::NFATC1 , 4 EWSR1::NFATC2 , 2 FUS::NFATC2 , 1 EWSR1 rearrangement, and 1 with a novel FABP4::NFATC2 fusion. Follow-up was available in 4 patients. One patient experienced 2 local recurrences, 11 and 15 years postdiagnosis, and one patient experienced progressive disease despite multimodality treatment (curettings, embolization, radiation) over 3 years. In summary, our extended investigation confirms that NFATC -related fusions define a distinct group of vascular neoplasms with variable architecture, epithelioid phenotype, and cytologic atypia, commonly located in the bone, occasionally multifocal and with potential for local recurrence and aggressive behavior but no metastatic potential. Molecular analysis is recommended in diagnostically challenging cases with atypical histology to exclude malignancy.

• MeSH
• epiteloidní hemangioendoteliom * patologie   MeSH
• hemangioendoteliom * MeSH
• hemangiom * MeSH
• lidé MeSH
• transkripční faktory NFATC genetika   MeSH
• transkripční faktory genetika   MeSH
• vaskulární nádory * genetika   terapie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• NFATC1 protein, human MeSH Prohlížeč
• transkripční faktory NFATC MeSH
• transkripční faktory MeSH

BACKGROUND/AIM: Hepatic epithelioid haemangio-endothelioma (HEHE) is a very rare malignant tumor of vascular origin and uncertain biological behaviour that is difficult to diagnose using preoperative radiology diagnostic techniques. PATIENTS AND METHODS: The authors present here two patients with HEHE of different extent. The first patient had a generalised form of disease, with involvement of the liver, lungs and bones and was treated with a combination of bevacizumab and capecitabine. The second patient had a localised form of disease involving the liver and this was resolved using a combination of liver resection and radiofrequency ablation. In both patients, the radiology work-up before surgery was non-specific and metastases of another malignant process were considered. The definitive histological diagnosis was made by the pathologist on the basis of immunohistochemical analysis that demonstrated the presence of CD31, CD34 and calmodulin-binding transcription activator 1 (CAMTA 1). RESULTS: Both patients remain in an overall good condition 27 and 5 months respectively following treatment for HEHE. CONCLUSION: Preoperative radiological diagnosis of HEHE is difficult and immunohistochemical examination of the tumor tissue sample remains the key diagnostic tool. Radical surgical resection or liver transplantation is the method of choice in patients with localised liver involvement.

• Klíčová slova
• Hepatic epithelioid haemangioendothelioma, diagnostic dilemma, treatment options,
• MeSH
• bevacizumab aplikace a dávkování   MeSH
• capecitabinum aplikace a dávkování   MeSH
• dospělí MeSH
• epiteloidní hemangioendoteliom diagnóza   farmakoterapie   patologie   chirurgie   MeSH
• hepatektomie MeSH
• játra patologie   chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory jater diagnóza   farmakoterapie   patologie   chirurgie   MeSH
• nádory kostí diagnóza   farmakoterapie   patologie   sekundární   MeSH
• nádory plic diagnóza   farmakoterapie   patologie   sekundární   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• bevacizumab MeSH
• capecitabinum MeSH

Epithelioid hemangioma (angiolymphoid hyperplasia with eosinophilia, EH/ALHE) is a rare benign angioproliferative lesion which typically occurs in the region of the head and neck. In the literature, occurence on the extremity is only rarely described. A case of multiple occurence of EH/ALHE in the skin of the toes and metatarsal bone with osteolysis is reported. Occurence on the extremity, superficial and deep affection and some "atypical" microscopic features may cause diagnostic dilemma. The key diagnostic features of EH/ALHE are vascular channels lined with epithelioid endothelial cells, surrounding layer of myopericytes, absence of atypia and mitotic activity and characteristic inflammation. Immunohistochemistry may be helpful in settling the diagnosis.

• MeSH
• angiolymfoidní hyperplazie s eozinofilií diagnóza   patologie   MeSH
• dospělí MeSH
• epiteloidní hemangioendoteliom diagnóza   patologie   MeSH
• lidé MeSH
• nemoci nohy (od hlezna dolů) diagnóza   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• kazuistiky MeSH

The authors describe a locally recurrent tumor of the mandible whose microscopic structure and immunohistochemical findings corresponded to an epithelioid hemangioendothelioma. The tumorous cells had an epithelioid character, they created rudimentary vascular lumina, and they focally expressed vascular markers CD 34, CD 31, and F VIII. Locally the tumor grew aggressively. During the last recurrence, the tumor even affected the already healed and rebuilt bone graft, which was incorporated after the primary resection of the mandibular body. From the histological point of view, the tumor approximated an angiosarcoma. No metastases occurred.

• MeSH
• diferenciální diagnóza MeSH
• epiteloidní hemangioendoteliom diagnostické zobrazování   patologie   chirurgie   MeSH
• lidé MeSH
• lokální recidiva nádoru diagnostické zobrazování   patologie   chirurgie   MeSH
• mandibula diagnostické zobrazování   patologie   chirurgie   MeSH
• nádory mandibuly diagnostické zobrazování   patologie   chirurgie   MeSH
• následné studie MeSH
• počítačová rentgenová tomografie MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Epitheliolid hemangioendothelioma of the liver is a very rare vascular tumor. We report the case of this tumor found during the autopsy of a 74-year-old man. The liver was infiltrated by multiple greyish nodes (diam. 3-30 mm), partially calcified. Microscopically, the tumor was composed of dense sclerotic and fibrous stroma with focal calcifications. In this stroma, groups and cords of irregular cells of two main types were dispersed. The first type was represented by big cells with large clear eosinophilic cytoplasm. The second cell type was characterised by medium-sized elongated, sometimes bizarre-shaped cells. Tumorous cells did not produce mucin. Immunohistochemically, the tumorous cells were positive for FVIIIR--Ag, actin, vimentin, and desmin and also showed disperse weak positivity for S100 protein. Staining for epithelial membrane antigene (EMA), keratins, and CD68 was negative. Neoplastic cells were positive for Ulex europaeus lectin. Electronmicroscopically, the tumorous cells had irregular nuclei, lobular or cleft shape with one or two nucleoli. Cytoplasm contained a high amount of intermediate filaments forming large aggregates. The cells were connected by desmosomes and partially surrounded by dense basal lamina. The diagnosis of epithelioid hemangioendothelioma is based on a histological picture, supported by immunohistochemical positivity for FVIIIR: Ag and Ulex europaeus and by additional ultrastructural study.

• MeSH
• epiteloidní hemangioendoteliom chemie   patologie   MeSH
• imunohistochemie MeSH
• lidé MeSH
• nádory jater chemie   patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• kazuistiky MeSH