Pleural epithelioid hemangioendothelioma in a 39-Year-old female: a case report.

BACKGROUND: Epithelioid hemangioendothelioma (EHE) is a rare malignancy of vascular origin which can be primarily be seen in various tissues. EHE originating from the pleura is an even more uncommon subtype which may mimic mesothelioma and pleural carcinomatosis. The prognosis of pleural EHE is poor and there is no consensus on the optimal therapeutic approach. CASE PRESENTATION: A 39-year-old middle-eastern female presented with progressive dyspnea and left shoulder discomfort. Chest computed tomography scan revealed a left side pleural effusion and pleural thickening. Pleuroscopy was done and biopsies were taken which were positive for CD31, CD34, CK, factor 8-R-antigen, and vimentin. Patient was diagnosed with pleural epithelioid hemangioendothelioma (PEHE) and chemotherapy was started and underwent extrapleural pneumonectomy 7 months later. Unfortunately, the patient passed away 10 months after diagnosis due to disease complications. CONCLUSIONS: Once PEHE is suspected in histology it can be confirmed with immunohistochemistry. Chemotherapy, surgery or a combination of both is currently used as the treatment but the standard treatment remains a question.

Primary pulmonary epithelioid hemangioendothelioma.

Pulmonary epithelioid hemangioendothelioma (PEH) is a rare tumour of vascular origin with low to intermediate malignancy. Typical radiological finding on CT is multiple small nodules in bilateral lungs, and some will have punctate calcifications and pleural thickening. The diagnosis of PEH is confirmed by histopathological findings and positive immunohistochemistry staining. We report a case of a woman in her 50s with a medical history of lung adenocarcinoma. Later, regular chest CT during a routine cancer follow-up revealed multiple small pulmonary nodules and increased sizes of these nodules on serial images, initially misdiagnosed as multiple lung metastases. The histopathological diagnosis was made on a pulmonary wedge resection. Finally, PEH was diagnosed on the basis of positive immunohistochemical staining for CD31, ERF and TFE3. In the current study, the clinicopathological features and review of the literature were investigated. Our case highlights the importance of a histological diagnosis to avoid misdiagnosis.

A Case Presentation of Metastatic Hepatic Epithelioid Hemangioendothelioma: A Rare Vascular Tumor.

Epithelioid hemangioendothelioma (EHE) is an uncommon vascular tumor that can present in various organs, including the liver. Hepatic EHE (HEHE) may showcase with metastases at initial presentation, as patients have vague symptoms such as right upper quadrant pain leading to the risk of delayed diagnosis. There is no standard treatment. Fortunately, prognosis is good. This remains true for some patients with metastatic disease who are not being actively treated. In this report, we present a unique case of metastatic HEHE in a 65-year-old Caucasian male who has not received treatment and continues to remain in stable condition after his initial diagnosis three years ago.

An extremely rare case of pulmonary epithelioid hemangioendothelioma.

Epithelioid emangioendothelioma (EHE) is a rare tumor originating from vascular endothelial cells, which belongs to malignant vascular tumors with low to moderate differentiation and potential metastatic ability and its incidence rate is less than one in a million. We herein report a rare case of EHE of pulmonary origin and a review of the literature concerning the clinical and pathological features of this disease. The patient underwent left upper lobectomy to completely extirpate the lesion by video-assisted thoracic surgery. Our findings suggest the difficulty of making a diagnosis before surgery and that more cases need to be reported in order to facilitate the preoperative diagnosis of such a rare tumor.

NR1D1::MAML1 epithelioid and spindle cell sarcoma mimicking pseudomyogenic hemangioendothelioma in core biopsy: A case report and review of the literature.

Epithelioid and spindle cell sarcomas with NR1D1::MAML1/2 gene fusions are rare and emerging entities. Only six cases of NR1D1-rearranged mesenchymal tumors have previously been reported in the literature; they are often characterized by an epithelioid morphology, at least focal pseudogland formation, prominent cytoplasmic vacuoles, and focal to diffuse immunohistochemical expression of keratin. We herein report the first case of an NR1D1::MAML1 epithelioid and spindle cell sarcoma with dual immunohistochemical expression of ERG and FOSB, mimicking a pseudomyogenic hemangioendothelioma (PHE) on core biopsy. The sarcoma arose in the left forearm of a 64-year-old man. Initial biopsy showed a mesenchymal neoplasm composed of epithelioid and spindle cells dispersed in myxoid stroma with scattered stromal neutrophils. The morphologic features, combined with the dual immunohistochemical expression of ERG and FOSB, initially mimicked PHE, representing an important potential diagnostic pitfall. The patient subsequently underwent a radical resection, which showed a much more diffuse epithelioid appearance with nested architecture and pseudogland formation. Next-generation sequencing was performed on the resection specimen, which revealed an NR1D1::MAML1 gene fusion, confirming the final diagnosis. Given the fully malignant potential of this tumor, knowledge and recognition of this rare entity are essential to ensure proper management, prevent misdiagnosis, and further characterize the clinical course of this emerging entity. Comprehensive molecular testing can help to identify these rare tumors and exclude the possibility of epithelioid mimics, including PHE.

A Rare Case of Primary Adrenal Epithelioid Angiosarcoma.

BACKGROUND Primary adrenal epithelioid angiosarcoma (PAEA) is a very uncommon primary adrenal gland tumor that usually occurs around the age of 60 years and is more common among males. Owing to its rarity and histopathological features, PAEA could be misdiagnosed as adrenal cortical adenoma, adrenal cortical carcinoma, or other metastatic cancers, such as metastatic malignant melanoma and epithelioid hemangioendothelioma. CASE REPORT A 59-year-old male patient presented to our hospital with a complaint of abdominal bloating that started 2 months prior. His vital signs and the results of his physical and neurological examinations were unremarkable. A computed tomography scan showed a lobulated mass arising from the hepatic limb of the right adrenal gland but no evidence of metastasis to the chest or abdomen. The patient underwent right adrenalectomy, and the macroscopic pathological findings from a right adrenalectomy specimen revealed atypical tumor cells with an epithelioid appearance in the background of an adrenal cortical adenoma. Immunohistochemical staining was performed to confirm the diagnosis. The final diagnosis was epithelioid angiosarcoma involving the right adrenal gland with a background adrenal cortical adenoma. The patient had no postoperative complications, pain in the surgical wound, or fever. Therefore, he was discharged with a schedule for followup appointments. CONCLUSIONS PAEA may be misinterpreted as adrenal cortical carcinoma, metastatic carcinoma, or malignant melanoma radiologically and histologically. Immunohistochemical stains are essential for diagnosing PAEA. Surgery and strict monitoring are the main treatments. In addition, early diagnosis is essential for patient recovery.

Epithelioid hemangioendothelioma of the retroperitoneal giant type treated with Toripalimab: A case report.

Epithelioid hemangioendotheliomas (EHEs), low-grade malignant tumors of vascular endothelial cell origin, are characterized by vascular endothelial proliferation. In 2002, the World Health Organization classified EHEs as locally aggressive tumors with the potential to metastasize. Currently, the diagnosis of EHE is based on pathology, histological and immunohistochemical examinations. There are no standard treatment guidelines. We here report a 69-year-old man who presented with left-sided chest and abdominal pain for more than 2 months. Enhanced computed tomography of the thorax and abdomen in another hospital suggested a mass in the left adrenal region that was considered malignant. Positron emission tomography- computed tomography in our hospital suggested a large multi-loculated, hypermetabolic, cystic mass in the left adrenal region that was considered malignant. Accordingly, a puncture biopsy of the mass was performed and the diagnosis of EHE confirmed by pathological examination, including immunohistochemical staining. This patient was treated with the programmed death 1 (PD-1) immune checkpoint inhibitor toripalimab with long-term success. The best response was stable disease (SD) with a progression-free survival (PFS) of more than 13 months. The patient is still alive now. Because the sample size of previous studies was small, further studies are needed to determine the safety and efficacy of toripalimab in the treatment of EHE.

New Molecular Insights, and the Role of Systemic Therapies and Collaboration for Treatment of Epithelioid Hemangioendothelioma (EHE).

OPINION STATEMENT: Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated vascular sarcoma. EHE can have different clinical presentations from indolent to rapidly evolving cases, behaving as a high-grade sarcoma. Serosal effusion and systemic symptoms such as fever and severe pain are known as adverse prognostic factors; however, outcome prediction at disease onset remains a major challenge. In spite of its rarity, an international collaborative effort is in place with the support of patient advocates to increase the knowledge of EHE biology, develop new treatment options, and improve patient access to new active medications. Currently, systemic therapies are indicated only for patients suffering from progressive and/or symptomatic disease and in patients with a high risk of organ dysfunction. Standard systemic agents available so far for treatment of sarcomas, and in particular anthracycline-based chemotherapy, have marginal activity in EHE. On this background, EHE patients should be always considered for clinical study when available. The MEK inhibitor trametinib has been recently investigated prospectively in advanced EHE showing some activity, but the publication of the full dataset is still awaited to better interpret the results. Besides, there are data on response to antiangiogenics such as sorafenib and bevacizumab and, from retrospective studies, interferon, thalidomide, and sirolimus. Unfortunately, none of these agents is formally approved for EHE patients and access to treatments varies greatly between countries causing a huge disparity in patient care from one country to another.

Clinicopathological study of pseudomyogenic hemangioendothelioma.

OBJECTIVES: Pseudomyogenic hemangioendothelioma (PHE) is a rare intermediate hemangioendothelioma. This article aims to study the clinicopathological features of PHE. METHODS: We collected the clinicopathological features of 10 new PHE, and examined their molecular pathological features by fluorescence in situ hybridization. In addition, we summarized and analyzed the pathological data of 189 reported cases. RESULTS: The case group consisted of six men and four women aged 12-83 years (median: 41 years). Five instances occurred in the limbs, three in the head and neck, and two in the trunk. Tumor tissues were composed of spindle cells and round or polygonal epithelioid cells, which were either arranged in sheets or interwoven, along with areas of transitional morphology. Scattered or patchy stromal neutrophil infiltration was observed. Tumor cells had abundant cytoplasm, and some contained vacuoles. The nuclei had mild to moderate atypia, with visible nucleoli, and mitosis was rare. PHE tissues diffusely expressed CD31 and ERG, but not CD34, Desmin, SOX-10, HHV8 or S100, while some samples expressed CKpan, FLI-1 and EMA. INI-1 stain is retained. The proliferation index of Ki-67 is 10-35%. Seven samples were detected by fluorescence in situ hybridization, six of which had breakages in FosB proto-oncogene (AP-1 transcription factor subunit). Two patients experienced recurrence; however, no metastasis or death occurred. CONCLUSIONS: PHE is a rare soft tissue vascular tumor, which has biologically borderline malignant potential, local recurrence, little metastasis, and good overall survival and prognosis. Immunomarkers and molecular detection are valuable for diagnosis.

Successful chemotherapy with continuous immunotherapy for primary pulmonary endovascular epithelioid hemangioendothelioma: A case report.

RATIONALE: Epithelioid hemangioendothelioma (EHE) is a rare, low to moderate-grade malignancy, even less in pulmonary endovascular neoplasm. Patients with pulmonary EHE have no optimal treatment, resulting in poor prognoses. PATIENT CONCERNS: We reported a 42-year-old man with multiple mild metabolic uptakes in pulmonary endovascular filling defect with a maximum standardized uptake value of 4.5 by 18-fluorodeoxyglucose/fibroblast associated protein inhibitor-positron emission tomography/ computed tomography. Anticoagulant treatment was not effective with the diagnosis of acute pulmonary embolism. DIAGNOSES: A primary endovascular EHE pulmonary endovascular epithelioid hemangioendothelioma was diagnosed by endovascular biopsy with positive stains for molecular CD31, CD34 and CAMTA1, and it had low proliferative capacity characterized by Ki-67 of 5%. The mutation gene MSH2 (p.Y656 in exon 12) (mutation abundance of 0.07%) from peripheral blood indicates the potential benefit of an immune checkpoint inhibitor, pembrolizumab. INTERVENTIONS AND OUTCOMES: The patient was treated with tri-weekly paclitaxel (175mg/m2) and carboplatin (AUC 5) chemotherapy regimen. He exerted a remarkable response after 5 cycles (21 days per cycle) and Pembrolizumab (200mg once monthly) as maintenance treatment. LESSONS: This case highlights the diagnostic challenge of differentiating endovascular lesions and optimal therapy for pulmonary EHE. Importantly, it indicated that the mutation gene MSH2 (p.Y656) might influence the pathogenesis of EHE.

Poor response to sintilimab plus chemotherapy in a pulmonary epithelioid hemangioendothelioma patient: a case report.

Pulmonary epithelioid hemangioendothelioma (PEH) is a rare vascular tumor with no established treatment protocol. The authors report the case of a young woman diagnosed with PEH. DNA and RNA analysis by next-generation sequencing was performed on the tumor tissue. A novel germline PALB2 mutation and classical WWTR1-CAMTA1 fusion were identified. She experienced a poor response to sintilimab (a PD-1 inhibitor) plus platinum-based chemotherapy as the first-line treatment. PEH patients harboring a germline PALB2 mutation and WWTR1-CAMTA1 gene fusion may respond poorly to treatment with PD-1 inhibitors plus chemotherapy.

Pulmonary epithelioid hemangioendothelioma (PEH) is a rare vascular tumor with no established treatment protocol. Although PD-1 inhibitors have dramatically improved the prognosis of some tumors, the efficacy is unknown in PEH patients. The authors report an advanced PEH patient treated with sintilimab plus platinum-based chemotherapy, who died after two cycles of treatment. The authors inferred that PEH patients with a germline PALB2 mutation and WWTR1-CAMTA1 fusion may not benefit from PD-1 inhibitors plus chemotherapy.

Hemangioendotelioma epitelioide cutáneo extenso multifocal agresivo. Informe de un caso / Aggressive multifocal extensive cutaneous epithelioid haemagioendothelioma. A case report

El hemangioendotelioma epitelioide es un tumor vascular infrecuente, descrito por primera vez en 1975 por Dail y Liebow como un carcinoma bronquioloalveolar. Habitualmente, se comporta como una neoplasia de bajo grado; sin embargo, se han descrito casos en los que el tumor manifiesta una elevada agresividad, extendiéndose con rapidez por todo el organismo. Presentamos el caso de un hombre de 41 años con dermatosis en muslo izquierdo y extensión rápida a abdomen, cuyo diagnóstico inicial fue de un carcinoma metastásico vs. linfoma. En la revisión de laminillas, se confirmó el diagnóstico de hemangioendotelioma epitelioide de piel, iniciando tratamiento con radioterapia. Este tumor afecta excepcionalmente la piel, habiéndose descrito pocos casos en la literatura médica.(AU)

Epithelioid haemangioendothelioma is a rare vascular tumor, first described in 1975 by Dail and Liebow as a bronchioloalveolar carcinoma. Although it usually behaves like a low-grade neoplasm, cases have been reported in which the tumor shows a high grade of malignancy, spreading rapidly throughout the body. We present the case of a 41-year-old man with dermatosis in the left thigh with rapid extension to the abdomen; the initial differential diagnoses were metastatic carcinoma versus lymphoma. When the histopathology was re-examined, a diagnosis of skin epithelioid hemangioendothelioma was confirmed and treatment with radiotherapy was initiated. This tumour rarely affects the skin; there are only a few previously reported cases.(AU)

[Aggressive multifocal extensive cutaneous epithelioid haemagioendothelioma. A case report]. / Hemangioendotelioma epitelioide cutáneo extenso multifocal agresivo. Informe de un caso.

Epithelioid haemangioendothelioma is a rare vascular tumor, first described in 1975 by Dail and Liebow as a bronchioloalveolar carcinoma. Although it usually behaves like a low-grade neoplasm, cases have been reported in which the tumor shows a high grade of malignancy, spreading rapidly throughout the body. We present the case of a 41-year-old man with dermatosis in the left thigh with rapid extension to the abdomen; the initial differential diagnoses were metastatic carcinoma versus lymphoma. When the histopathology was re-examined, a diagnosis of skin epithelioid hemangioendothelioma was confirmed and treatment with radiotherapy was initiated. This tumour rarely affects the skin; there are only a few previously reported cases.

Epithelioid hemangioendothelioma - an unexpected diagnosis of a mediastinal tumor with extensive local thrombosis.

Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor and the mediastinal localization is amongst the most infrequent. We present the case of a 37-year-old woman with a history of resected left thyroid tumor that presented to our department for evaluation of a left supraclavicular palpable mass in close contact with local vascular structures, and with heterogeneous contrast enhancement as described by computed tomography (CT) and magnetic resonance imaging (MRI). Considering the history of the patient, the presumptive diagnosis of thyroid tumor recurrence was established, and the patient was referred to surgical department. During procedure, we encountered important bleeding from a ruptured jugular vein branch, which we assumed to be a newly formed tumor blood vessel. After surgery (48 hours postoperatively), the patient developed important local thrombosis that encompassed the left internal jugular vein, left subclavian vein and the left brachiocephalic trunk that partially subsided after anticoagulant therapy. The histological examination revealed the presence of a vascular tumor proliferation of epithelioid endothelial cells that was characteristic of an EHE confirmed later on the immunohistochemical studies as Yes-associated protein 1-transcription factor E3 (YAP1-TFE3) subtype. In addition to the case report, some relevant information from the scarce literature data about mediastinal EHE were reviewed here.

The challenging surgical management of hepatic epithelioid hemangioendothelioma: a narrative review.

BACKGROUND AND OBJECTIVE: Hepatic epithelioid hemangioendothelioma (HEHE) is an uncommon vascular endothelial cell cancer involving the hepatic tissue with full malignant potential. HEHE diagnosis is challenging because blood tests and radiological findings are often non-pathognomonic. Therapeutic possibilities are manifold, ranging from a simple "wait and see" to surgical approaches, up to systemic therapies with vascular endothelial growth factor (VEGF) and mechanistic target of rapamycin (mTOR) inhibitors. The standardized adoption of the surgical approaches, namely resection or transplantation, still remains unclear. Aim of this review is to clarify the role of the surgical strategies for the management of HEHE. METHODS: A review of the literature was done with the intent to focus on the relevant studies exploring the role of the different surgical therapies. A search of these studies was done using the electronic database MEDLINE-PubMed. KEY CONTENT AND FINDINGS: The surgical approaches, namely resection or transplantation, represent the best option in treating well-selected patients with HEHE. Resection is indicated in the case of single lesion or oligonodular monolobar disease. Liver transplantation is indicated in the case of multifocal bilobar disease, even in the presence of resectable extrahepatic disease. The potential role of a minimally invasive approach should represent a relevant field to explore. CONCLUSIONS: The impact of surgery for the treatment of HEHE requires further studies to further clarify its relevant role. Standardized approaches are required.

Epithelioid Vascular Lesions: The Differential Diagnosis and Approach in Cytology and Small Biopsies.

Vascular neoplasms are rare tumors with a multitude of clinical presentations and behavior, which make accurate identification and subclassification challenging on limited small biopsies. Within the spectrum of these lesions, the ones with epithelioid morphology, such as epithelioid hemangioendothelioma and epithelioid angiosarcoma, are particularly challenging given the morphologic overlap with nonvascular lesions and the limited cells due to hemodilution on sampling. Herein, we review the differential diagnosis of epithelioid vascular neoplasms, with a focus on the cytomorphology, differential diagnoses, and ancillary studies that pathologists should be aware of when evaluating small biopsies and aspirates, including novel translocations, and associated monoclonal immunohistochemistry antibodies, that can help in the diagnosis of some of these tumors. Awareness of these morphologic and ancillary study findings in these rare tumors will hopefully allow pathologists to recognize and render-specific diagnoses on limited samples of these challenging lesions.

Case of metastatic epithelioid haemangioendothelioma from an unknown primary site associated with membranous nephropathy and hypercoagulable state.

We report a rare case of metastatic epithelioid haemangioendothelioma from an unknown primary site presenting with axillary lymph node metastases. The patient also had a new-onset membranous glomerulonephritis and thromboembolism, which we postulate were paraneoplastic. The pathogenesis of this rare cancer, the risk of misdiagnosis and membranous glomerulonephritis as a paraneoplastic syndrome are discussed.

Trasplante hepático en hemangioendotelioma epiteloide hepático con metástasis pulmonares: reporte de un caso / Liver transplantation in hepatic epitheloid hemangioendothelioma and lung metastases: a case report

El hemangioendotelioma epiteloide hepático (HEHE) es un tumor vascular raro de menor malignidad que el hemangiosarcoma. En los poco frecuentes casos unilobulares, puede indicarse hepatectomía parcial con riesgo de recurrencia agresiva; en enfermedad hepática extensa, incluso con compromiso extrahepático, el trasplante hepático ha resultado efectivo. Las metástasis son más frecuentes en pulmón,peritoneo, ganglios linfáticos, bazo y sistema nervioso. Se presenta el caso de un adolescente asintomático con HEHE con metástasis pulmonares y compromiso ganglionar abdominal que recibió trasplante hepático con evolución favorable.

Hepatic epithelioid hemangioendothelioma (HEHE) is a rare vascular tumor of less malignancy than hemangiosarcoma. In the rare unilobar cases, partial hepatectomy may be indicated with risk of aggressive recurrence; in extensive liver disease, even with extrahepatic involvement, liver transplantation has been performed successfully. Metastases are more common in the lung, peritoneum, lymph nodes, spleen, and nervous system. We present the case of an asymptomatic adolescent with HEHE with lung metastases and abdominal lymph node involvement who received a liver transplant with a favorable outcome.