Prognostic stratification of clinical and molecular epithelioid hemangioendothelioma subsets

Self Cite

The diagnosis of epithelioid hemangioma (EH) remains challenging due to its rarity, worrisome histologic features, and locally aggressive clinical and radiographic presentation. Especially in the bone, EH can be misdiagnosed as a malignant vascular neoplasm due its lytic, often destructive or multifocal growth, as well as atypical morphology. The discovery of recurrent FOS and FOSB gene fusions in the pathogenesis of most EH has strengthened its stand-alone classification, distinct from other malignant epithelioid vascular lesions, such as epithelioid hemangioendothelioma or angiosarcoma. In this study we investigate a group of molecularly confirmed skeletal EH by the presence of FOS or FOSB gene rearrangements to better define its clinical and pathologic characteristics within a homogenous molecular subset. The cohort included 38 patients (25 males, 13 females), with a mean age at diagnosis of 38 years (range, 4-75). Regional, multifocal presentation was noted in 10 cases. Only six cases were correctly recognized as EH by the referring institutions, while most were misdiagnosed as other vascular tumors. Of the 17 patients with follow-up data available, five patients (29%) developed local recurrence after marginal en bloc excision (n = 3) or curettage (n = 2). Local recurrence-free survival rates were 84% at 3 years and 38% at 5 years. No metastasis or disease-related death was identified. Imaging studies exhibited no specific features, showing cortical bone destruction and soft-tissue extension in 14 (38%) cases. FOS gene rearrangements were detected in 28 (74%) of cases, while FOSB rearrangements in 10 (26%) cases. Our results highlight the significant challenges encountered in establishing a correct diagnosis exclusive of the molecular testing, mainly due to its overlap to other malignant epithelioid vascular tumors. Skeletal EH emerges as a genetically defined locally aggressive vascular neoplasm, with a high rate of local recurrence, but lacking the propensity for distant spread.

Section: Clinical Findingsmentioning

confidence: 96%

Epithelioid hemangioma of bone harboring FOS and FOSB gene rearrangements: A clinicopathologic and molecular study

Tsuda

Suurmeijer

Sung

et al. 2020

Self Cite

“…In addition to tumor grade, the presence of multifocal disease, pleural involvement, and lymph node or distant metastases had significant power in predicting prognosis. Moreover, EHE with WWTR1‐CAMTA1 fusions had a less favorable clinical outcome than EHE with YAP1‐TFE3 , with a five‐year survival rate of 59% and 86%, respectively …”

Section: Discussionmentioning

confidence: 97%

“…Soft tissue EHE larger than 3 cm and with increased mitotic rate (>3 mitoses in 50 HPF) are considered high‐risk tumors apt to develop metastases in up to 40% of cases, whereas smaller EHE with low nuclear grade and scant mitoses are considered to be low‐risk tumors . In a large cohort of 93 molecularly confirmed EHE involving different sites, it was found that most soft tissue EHE are solitary . In addition to tumor grade, the presence of multifocal disease, pleural involvement, and lymph node or distant metastases had significant power in predicting prognosis.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Variant WWTR1 gene fusions in epithelioid hemangioendothelioma—A genetic subset associated with cardiac involvement

Suurmeijer

Dickson

Swanson

et al. 2020

Self Cite

The genetic hallmark of epithelioid hemangioendothelioma (EHE) is a recurrent WWTR1-CAMTA1 fusion, which is present in most cases bearing a conventional histology. A subset of cases is characterized by a distinct morphology and harbors instead of YAP1-TFE3 fusion. Nevertheless, isolated cases lack these canonical fusions and remain difficult to classify. Triggered by an index case of a left atrial mass in a 76-year-old female with morphologic features typical of EHE, but which showed a WWTR1-MAML2 fusion by targeted RNA sequencing, we searched our files for similar cases displaying alternative WWTR1 fusions. A total of 6 EHE cases were identified with variant WWTR1 fusions, four of them presenting within the heart. There were three females and three males, with a wide age range at diagnosis (21-76 years, mean 62, median 69). The four cardiac cases occurred in older adults (mean age of 72, equal gender distribution); three involved the left atrium and one the right ventricle. One case presented in the vertebral bone and one in pelvic soft tissue. Microscopically, all tumors had morphologic features within the spectrum of classic EHE; two of the cases appeared overtly malignant. All cases were tested by FISH and four were investigated by targeted RNA sequencing. Two tumors harbored WWTR1-MAML2 fusions, one WWTR1-ACTL6A, and in three cases, no WWTR1 partner was identified. Of the four patients with follow-up, two died of disease, one was alive with lung metastases, and the only patient free of disease was s/p resection of a T11 vertebral mass. Our findings report on additional genetic variants involving WWTR1 rearrangements, with WWTR1-MAML2 being a recurrent event, in a small subset of EHE, which appears to have predilection for the heart.

“…9,10 A recent analysis of 93 cases suggested that worse outcome is associated with advanced stage, and WWRT1-CAMTA1A mutation. 11…”

Section: Introductionmentioning

confidence: 99%

Case of epithelioid hemangioendothelioma occurring in the postradiation setting for breast cancer

Hahn

Dickson

Gupta

et al. 2020

Epithelioid hemangioendothelioma (EHE) is a rare malignant vascular tumor, which is typically characterized by recurrent fusion genes. EHEs most commonly occur in the lung, liver, bone, and internal organs. EHE has rarely been reported to occur in the post‐radiotherapeutic setting, the breast site or in association with breast cancer. The differential diagnosis for radiation‐associated vascular lesions of the breast is classically limited to atypical vascular lesion and angiosarcoma and does not include EHE. We present the case of a woman with a history of breast cancer and post‐surgical radiotherapy who went on to develop an EHE of the chest wall skin within 3 years of the completion of radiotherapy. Microscopically, the lesion was infiltrative and composed of anastomosing nests of epithelioid‐to‐spindled cells with eosinophilic and vacuolated cytoplasm. By immunohistochemistry, the cells were positive for ERG, D2‐40, and CD31. The diagnosis was confirmed by identification of a characteristic WWTR1‐CAMTA1 fusion gene using RNA sequencing. This case expands our understanding of radiation‐associated tumors.