Understanding multicentric haemangioendothelioma: diagnostic dilemmas and treatment strategies.

Epithelioid haemangioendothelioma (EH) is a rare malignant vascular tumour occurring mainly in the liver and lungs, with bones being a rare site and primarily seen in the adult population. This case presents a male patient in his 40s who presented to the outpatient department with a chief issue of a painless swelling over the inguinal region for 4 months, gradually increasing in size, along with a history of a gradually enlarging, painless mass on his left knee over the past 5 years. Despite occasional discomfort during physical activities, the mass exhibited no associated trauma, fever, weight loss or systemic symptoms. Physical examination revealed a firm mass on the left knee and a matted lymph nodal swelling in the left inguinal region. Subsequent imaging studies identified multiple soft tissue lesions, osseous involvement and pulmonary metastases, suggestive of multicentric haemangioendothelioma. The patient underwent surgical excision of the inguinal mass and fixation of a pathological fracture in the left femur. He is currently undergoing chemotherapy and is scheduled for regular follow-up appointments. This case underscores the importance of thorough diagnostic evaluation and multidisciplinary management in complex oncological conditions like multicentric haemangioendothelioma.

Epithelioid Hemangioendothelioma as a Dangerous, Easy to Miss, and Nearly Impossible to Clinically Diagnose Condition: Case Report.

Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor with metastatic potential. EHE can have single- or multiorgan involvement, with presentations ranging from asymptomatic disease to pain and systemic symptoms. The extremely heterogeneous clinical presentation and disease progression complicates EHE diagnosis and management. We present the case of a 24-year-old woman with two periauricular erythematous papules, leading to the discovery of metastatic EHE through routine biopsy, despite a noncontributory medical history. Histology revealed the dermal proliferation of epithelioid cells and vacuoles containing red blood cells. Immunohistochemistry markers consistent with EHE solidified the diagnosis. Although extremely rare, prompt diagnosis of EHE is essential for informed decision-making and favorable outcomes. Key clinical and histopathological findings are highlighted to aid dermatologists in diagnosing and managing this uncommon condition.

The observational EURACAN prospective clinical registry dedicated to epithelioid hemangioendothelioma: The protocol of an international and collaborative effort on an ultra-rare entity.

INTRODUCTION: Epithelioid hemangioendothelioma (EHE) is an ultra-rare sarcoma, marked by distinctive molecular and pathological features and with a variable clinical behavior. Its natural history is still partially understood, reliable prognostic and predictive factors are lacking and many questions are still open on the optimal management. In the context of EURACAN, a prospective registry specifically dedicated to EHE was developed and launched with the aim of providing, through high-quality prospective data collection, a better understanding of this disease. STUDY DESIGN: Registry-based cohort study including only new cases of patients with a pathological and molecularly confirmed diagnosis of EHE. OBJECTIVES: To improve the understanding of EHE natural history, validate and identify new prognostic and predictive factors, clarify the activity and efficacy of currently available treatment options, describe treatment pattern. METHODS: Settings and participantsIt is an hospital-based registry established in centers with expertise in EHE including adult patients with a new pathological and molecularly confirmed diagnosis of EHE starting from the 1st December 2023. The characteristics of each patient in the facility who meets the above-mentioned inclusion criteria will be collected prospectively and longitudinally with follow-up at cancer progression and / or cancer relapse or patient death. It is a secondary use of data which will be collected from the clinical records. The data collected for the registry will not entail further examinations or admissions to the facility and/or additional appointments to those normally provided for routine patient follow-up. VariablesFull details on patients and disease features, treatment and outcome will be collected, according to common clinical practice guidelines developed and shared with all the contributing centers. In addition, data on potential confounders (e.g. comorbidity; functional status etc.) will also be collected. Statistical methodsThe data analyses will include descriptive statistics and analytical analyses. Multivariable Cox's proportional hazards model and Hazard ratios (HR) for all-cause or cause-specific mortality will be used to determine independent predictors of overall survival, recurrence and progression. RESULTS: The registry has been joined by 21 sarcoma reference centers across EU and UK, covering 10 countries. Patients' recruitment started in December 2023. The estimated completion date is December 2033 upon agreement on the achievement of all the registry objectives. The already established collaboration and participation of EHE patient's associations involved in the project will help in promoting the registry and fostering accrual.

[MRI manifestations of 40 cases with the hepatic epithelioid hemangioendothelioma classification based on the morphology and size].

Objective: To explore the MRI characteristics of the hepatic epithelioid hemangioendothelioma (HEHE) classification according to morphology and size. Methods: The clinical, pathological, and MRI imaging data of 40 cases with HEHE confirmed pathologically from December 2009 to September 2021 were retrospectively analyzed. A paired sample t-test was used for comparison between the two groups. Results: There were 40 cases (5 solitary, 24 multifocal, 9 local fusion, and 2 diffuse fusion) and 214 lesions (163 nodules, 31 masses, and 20 fusion foci). The most common features of lesions were subcapsular growth and capsular depression. The signal intensity of lesions ≤1cm was usually uniform with whole or ring enhancement. Nodules and mass-like lesions ≥1cm on a T1-weighted image had slightly reduced signal intensity or manifested as a halo sign. Target signs on a T2-weighted image were characterized by: target or centripetal enhancement; fusion-type lesions; irregular growth and hepatic capsular retraction, with ring or target-like enhancement in the early stage of fusion and patchy irregular enhancement in the late stage; blood vessels traversing or accompanied by malformed blood vessels; focal bleeding; an increasing proportion of extrahepatic metastases and abnormal liver function with the type of classified manifestation; primarily portal vein branches traversing; and reduced overall intralesional bleeding rate (17%). Lollipop signs were presented in 19 cases, with a high expression rate in mass-type lesions (42%). The fusion lesions were expressed, but the morphological manifestation was atypical. The diffusion-weighted imaging mostly showed high signal or target-like high signal. An average apparent diffusion coefficient of lesions was (1.56±0.36) ×10(-3)mm(2)/s, which was statistically significantly different compared with that of adjacent normal liver parenchyma (t=8.28, P<0.001). Conclusion: The MRI manifestations for the HEHE classification are closely related to the morphology and size of the lesions and have certain differences and characteristics that are helpful for the diagnosis of the disease when combined with clinical and laboratory examinations.

Primary pulmonary epithelioid hemangioendothelioma metastatic to the pleura and mediastinal lymph node with a prominent rhabdoid cytomorphology showing CAMTA1::WWTR1 fusion and novel PRDM1 and TNFRSF14 mutations.

Cases of epithelioid hemangioendothelioma with WWTR1::CAMTA1 fusion can show rhabdoid cytomorphology. Lack of intracytoplasmic luminal spaces, marked rhabdoid cytomorphology, and variability in the expression of vascular markers makes the diagnosis of EHE challenging. Therefore, a high level of suspicion and ancillary studies (immunohistochemistry and next generation sequencing) help reach a definitive diagnosis in these cases.

The Profuse Bleeding Potential of Orbital Epithelioid Hemangioendotheliomas.

Epithelioid hemangioendothelioma is a rare vascular tumor originating from vascular endothelial or pre-endothelial cells. We present the case of a 4-month-old male with a rapidly enlarging left zygomatico-orbital tumor causing mass effect on the eye globe. Examination revealed a large, nontender, solid lesion. CT angiography showed no major feeder or intralesional vessels. Complete surgical excision was performed, which was complicated by life-threatening intraoperative bleeding and successfully controlled with electrocautery. Microscopically, tumor cells exhibited varying morphologies. Immunohistochemistry confirmed the diagnosis of epithelioid hemangioendothelioma (positive for CD31 and CD34, negative for CK AE1/AE3). We also highlight 2 similar case reports with life-threatening bleeding complications. Surgeons should be aware of this condition and optimize surgical preparation, including blood products, to manage potential bleeding complications.

Proposed diagnostic and prognostic markers of primary malignant hepatic vascular neoplasms.

INTRODUCTION: Primary malignant hepatic vascular tumors with various malignant potentials include epithelioid hemangioendothelioma (EHE) and angiosarcoma (AS), which may overlap pathologically. This study aimed to compare the pathological findings of hepatic EHE with those of AS, in association with patient outcomes. METHODS: Fifty-nine histologically confirmed patients with 34 EHE and 25 AS were admitted to a tertiary hospital from 2003 to 2020. Their EHE and AS pathological features were compared. Immunohistochemistry for CD31, ERG, CAMTA-1, TFE3, P53, and Ki-67 labeling was performed on paraffin-embedded blocks. Markers, along with histological findings, were analyzed for the purposes of diagnostic and prognostic significance by multivariate analysis. RESULTS: CAMTA-1 was 91.2% positive in EHE, but negative in AS (p = < 0.001). AS was significantly correlated to an aberrant p53 expression, high Ki-67 labeling, and high mitotic activity, compared to EHE (all, p = < 0.001). EHE can be classified as low grade (LG) and high grade (HG) using the prognostic values of mitotic activity and ki-67 labeling (sensitivity = 1, specificity = 1). Low grade-EHE showed significantly better overall survival than high grade-EHE (p = 0.020). CONCLUSIONS: Immunohistochemistry for CAMTA-1, P53, and Ki-67 labeling may help distinguish EHE and AS in histologically ambiguous cases, especially small biopsied tissue. Moreover, the combination of mitotic activity and Ki-67 labeling can be a prognostic factor for EHE with various clinical features.

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.

Multifocal intraosseous pseudomyogenic (epithelioid sarcoma-like) hemangioendothelioma: A rare presentation of an uncommon tumor.

ABSTRACT: Pseudomyogenic hemangioendothelioma (PHE) is an uncommon mesenchymal neoplasm of intermediate malignant potential showing endothelial differentiation. Around 20 cases of primary osseous PHE have been reported to date. A 16-year-old boy presented with complaints of pain in his right leg. Imaging revealed multifocal intramedullary and cortical-based lytic lesions involving long and small bones. Microscopic examination revealed plump, spindled cells arranged in fascicles and admixed "epithelioid" and "rhabdoid" cells sans vasoformative areas. By immunohistochemistry, the lesional cells were reactive for AE1/AE3, CD31, Erg, Fli1, and SMA, while immunonegative for CD34, myogenin, and S100. Nuclear expression of the INI1/SMARCB1 protein was retained. PHE is a rare entity, more so as a primary osseous lesion; therefore, awareness of the presence of this entity in the bone is the key to making a diagnosis. We discuss its clinicopathological features, differential diagnosis, and an attempt a short review of the literature.

Primary Adrenal Epithelioid Angiosarcoma: A Case Report.

Primary adrenal angiosarcomas are exceedingly rare with a rapidly progressive clinical course and a poor outcome. Establishing the diagnosis can be challenging, and it is complicated by the fact that there are no characteristic clinical or imaging features that are pathognomonic for angiosarcoma. Histologically, they can overlap with other more commonly encountered adrenal tumors. Herein, we present an otherwise healthy 41-year-old woman diagnosed with a primary adrenal epithelioid angiosarcoma. We aim to expand the knowledge of the sparse literature existing on primary adrenal angiosarcomas to help better understand the diagnostic features, clinical behavior, and management of these rare tumors.

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.

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.

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.