Primary gastrointestinal epithelioid angiosarcoma (EAS) is an extremely rare and aggressive malignancy. Due to its epithelioid morphology and aberrant cytokeratin expression, it frequently mimics poorly differentiated carcinoma, creating significant diagnostic challenges. Furthermore, the molecular landscape of primary EAS, particularly regarding MYC status, remains underrecognized compared to radiation-associated angiosarcomas. An 82-year-old man presented with refractory melena and severe anemia. Imaging revealed multifocal lesions involving the stomach and small intestine. The patient underwent a laparoscopic exploration and multiple segmental resections. Histologically, the tumors consisted of epithelioid cells arranged in solid sheets with extensive hemorrhage. Immunohistochemistry showed strong positivity for CD31, ERG, and CD34, accompanied by diffuse CKpan expression, mimicking carcinoma. Crucially, despite the absence of prior radiotherapy, Next-Generation Sequencing (NGS) of the gastric lesion identified significant MYC gene amplification (copy number 6.7) and a PTPRD nonsense mutation. The patient died three months after surgery. This case highlights a critical diagnostic pitfall: primary EAS can diffusely express cytokeratins. More importantly, our findings challenge the traditional view that MYC amplification is exclusive to secondary, radiation-associated angiosarcomas. We propose that MYC amplification can act as a driver in primary EAS and may serve as a biomarker for aggressive clinical behavior.

Oral epithelioid angiosarcoma arising in the oral cavity is exceptionally rare. This case reports the first instance of synchronous primary epithelioid angiosarcoma in the oral cavity and oropharynx. Accurate diagnosis requires an understanding of the importance of immunohistochemistry to differentiate this vascular tumour from similar pathologic entities.

Uterine mesenchymal malignancies typically include leiomyosarcoma, carcinosarcoma and endometrial stromal sarcoma, while uterine angiosarcoma is exceptionally rare, with only a few dozen cases reported worldwide. We describe a case of high-grade epithelioid uterine angiosarcoma in a woman in her early 50s, diagnosed via outpatient endometrial pipelle biopsy. MRI and CT demonstrated endometrial and bilateral ovarian masses with multiple cavitating lung nodules, consistent with metastatic disease, stage four B according to the International Federation of Gynaecology and Obstetrics classification (FIGO stage IVB). During oral progesterone therapy for abnormal uterine bleeding, lung metastases initially regressed before subsequently progressing. The patient underwent total abdominal hysterectomy, bilateral removal of fallopian tubes and ovaries and omental biopsy. Histopathology confirmed high-grade epithelioid angiosarcoma with bilateral serous borderline ovarian tumours. Despite surgical management, she experienced rapid disease progression and died 5 months after surgery.

A Case of Epithelioid Angiosarcoma with a Difficult Diagnosis and Considerations on the Clinical Subtypes

Primary penile sarcomas are rare malignancies, accounting for less than 5% of penile cancers, with epithelioid angiosarcoma representing an exceptionally uncommon and aggressive subtype, documented in only about 30 cases worldwide. We report the case of a 59-year-old man who presented with an ulcerative lesion of the balanopreputial sulcus, initially presumed to be infectious or traumatic. Histopathological assessment following surgical excision revealed a poorly differentiated neoplasm initially suggestive of carcinoma. However, further expert pathological review and an extensive immunohistochemical panel identified a vascular neoplasm, with tumor cells expressing ERG, Fli-1, c-MYC, and focal CD31, alongside aberrant synaptophysin expression. The neoplasm lacked cytokeratins, additional neuroendocrine markers, and markers of melanocytic or myogenic differentiation. Molecular studies excluded hallmark translocations of other vascular or perivascular tumors but confirmed MYC gene amplification, supporting a definitive diagnosis of high-grade epithelioid angiosarcoma. This case highlights the diagnostic complexity of rare penile tumors and emphasizes the critical role of integrated histopathological, immunophenotypic, and molecular analyses in distinguishing aggressive vascular malignancies from their mimics.

Epithelioid Angiosarcoma Presenting as Massive Peritoneal Bleed: A Case Report of Continuous Draining and Hypertransfusion Management

Cutaneous epithelioid angiosarcoma (CEA) is a rare, aggressive vascular neoplasm predominantly affecting elderly individuals. Due to its nonspecific clinical presentation, early diagnosis can be challenging yet crucial for prognosis. We report a case of a 70-year-old male who presented with a rapidly enlarging, painful plaque on the anterior thigh. The lesion had been progressing over a few weeks and was associated with tenderness. Skin biopsy revealed sheets of large epithelioid cells with vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm. Mitotic figures were frequent. Immunohistochemistry showed strong positivity for CD31 and ERG, supporting a diagnosis of epithelioid angiosarcoma. Markers for epithelial and melanocytic tumors were negative. Kaposi’s sarcoma and metastatic carcinoma were considered but excluded based on the absence of characteristic histological features and lack of immunoreactivity for cytokeratins and HHV-8. Given the localized nature of the lesion, wide local excision was planned. Adjuvant radiotherapy was considered due to high risk of local recurrence. The patient is currently under close oncologic follow-up. Targeted therapies were discussed as potential options depending on disease progression. CEA is a rare and often misdiagnosed entity due to its variable presentation and resemblance to other cutaneous malignancies. Early histological and immunohistochemical evaluation is key to diagnosis. Prompt, multidisciplinary intervention is essential to improve patient outcomes.

Angiosarcoma is a rare, aggressive malignancy that accounts for less than 1% of sarcomas of bone. Epithelioid angiosarcoma, a subtype, is characterized by pleomorphic cells with vascular differentiation and commonly arises in deep soft tissues of the extremities. Angiosarcoma associated with orthopedic implants or retained foreign bodies, such as ballistic debris, is exceedingly rare. Here, the authors present the case of epithelioid angiosarcoma in a 54-year-old male with a history of a prior proximal femur ballistic injury and intramedullary nail fixation who was initially misdiagnosed with chronic osteomyelitis.

Primary epithelioid angiosarcoma of the thyroid: A case report

Primary spinal angiosarcoma is extremely rare with few reported cases globally. While en bloc resection is the only definitive and curative treatment modality, this case highlights the potential for curative-intent, non-surgical management of spinal epithelioid angiosarcoma using taxane-based chemoradiotherapy, especially in anatomically challenging and surgically unresectable locations. It also emphasises the role of multimodal imaging and histopathological correlation in the diagnosis and monitoring of rare spinal tumours.

Epithelioid angiosarcoma of the bladder is an exceptionally rare and aggressive vascular malignancy, characterized by a poor prognosis due to its high propensity for invasion and metastasis. Due to its rarity, the diagnosis is often challenging and may be misinterpreted as other high-grade malignancies. Patients commonly present with advanced-stage disease, including muscle invasion at the time of diagnosis, leading to unfavorable clinical outcomes. We report a 73-year-old male patient with a history of metastatic colon cancer (to the cervical lymph node) who presented with gross hematuria. Imaging and cystoscopy evaluation revealed a mobile bladder mass with possible right anterior bladder wall thickening and necrotic tissue. Transurethral resection of the bladder tumor performed outside was initially interpreted as muscle-invasive poorly differentiated carcinoma with sarcomatoid differentiation. Upon reviewing the slides at our institution, the diagnosis was revised to epithelioid angiosarcoma of the bladder. Despite an aggressive multimodal therapeutic approach, including chemotherapy and radical prostatectomy, the patient's clinical condition progressively worsened, ultimately leading to mortality 11 months post-diagnosis. This case report highlights the diagnostic challenges and aggressive nature of epithelioid angiosarcoma of the bladder, emphasizing the need for early detection and exploration of novel therapeutic strategies to improve patient outcomes.

A 64-year-old man presented with severe anemia (hemoglobin 56g/L; RBC 2.60×10 12 /L) on a background of hypertension, diabetes, coronary heart disease, and cerebral thrombosis. Contrast-enhanced abdominal CT and initial endoscopy were unremarkable. Initial 99m Tc-RBC SPECT/CT scintigraphy localized active bleeding to the descending colon. However, repeat endoscopy revealed brown stool in the terminal ileum. Subsequent 99m Tc-RBC SPECT/CT scintigraphy identified a small-bowel soft-tissue mass whose position shifted confirmed epithelioid angiosarcoma of the small intestine. This case highlights the utility of 99m Tc-RBC SPECT/CT in diagnosing challenging small intestinal angiosarcoma.

The likely first question to ask when encountering a soft tissue tumor for the first time is simply, "Is this carcinoma or sarcoma?" Lesions of unknown etiology should also nearly always include melanoma as a differential diagnosis due to its greatly elusive nature, and this case report reinforces the importance of also keeping a lymphoproliferative process at the forefront of one's mind while considering the possible overlapping features with other entities. We present a 64-year-old man with a soft tissue mass of the supraspinatus that was perceived as an epithelioid angiosarcoma due to the largely epithelioid morphology and characteristic immunohistochemical profile. However, given the patient's pertinent hematologic history and an additional array of immunohistochemical stains, the neoplasm was regarded as a myeloid sarcoma. Much like melanomas, lymphomas can present in a number of different forms and fashions. Namely, myeloid sarcomas-a mass-forming neoplasm composed of myeloid blasts effacing the surrounding tissue architecture-can masquerade as a carcinoma or sarcoma not only morphologically, but also immunohistochemically. We consider the pitfalls experienced with this entity and further elaborate on the genetics discovered within this particularly challenging lesion.

A 67-year-old woman presented with abdominal pain and fever and was found to have multiple liver masses, up to 6cm in size, that had not been detected on ultrasound 2months earlier. The rapid onset of lesions, elevated inflammatory markers, and mildly increased liver enzymes initially suggested liver abscesses based on radiographic findings. However, the patient showed no response to antimicrobial therapy, and contrast-enhanced ultrasonography indicated a primary liver tumor. Biopsy revealed a poorly differentiated carcinoma or sarcoma, and the patient died 11days after admission. Autopsy, combined with immunohistopathological analysis, confirmed primary hepatic epithelioid angiosarcoma (EAS). We presented a rare case of hepatic EAS, highlighting its clinical course, radiological features, and pathological findings.

Patient: Male, 58-year-oldFinal Diagnosis: High grade angiosarcoma transformation in schwannomaSymptoms: Associated with mild pain • skin and softClinical Procedure: —Specialty: OncologyObjective: Rare diseaseBackgroundEpithelioid angiosarcoma arising in a schwannoma is an exceedingly rare and aggressive malignancy, with less than 25 cases reported in the English-language literature. Histopathologically, it combines the spindle cell characteristics of schwannomas with the epithelioid, vascular nature of angiosarcomas. The presence of SMARCB1 frameshift loss-of-function (LOF) mutations impairs gene function, contributing to various aggressive cancers.Case ReportA 58-year-old man presented with slow-growing masses on the back and arm. Ultrasound and MRI findings were suspicious for nerve sheath tumor. He underwent surgical resection and biopsy, with results revealing SOX10-positive, S100-positive, CD31-positive, excisional margins-positive characteristics of high-grade epithelioid angiosarcoma arising in a schwannoma. A PET scan suggested metastasis to intrathoracic lymph nodes. Tempus molecular profiling showed SMARCB1 frameshift LOF. He was treated with weekly paclitaxel and tazemetostat, with slight improvement in pain; however, he developed symptomatic disease progression. Due to extensive metastatic disease precluding surgical resection, palliative radiation was added to the systemic treatment regimen. After several cycles of treatments with worsening symptoms, he decided to enter hospice care.ConclusionsPresentation of high-grade angiosarcoma arising in schwannoma can be non-specific, posing a diagnostic challenge. Histopathology and immunohistochemistry are essential in the diagnosis and may be characterized by the presence of SMARCB1 frameshift LOF as a prognostic biomarker. Surgical resection with negative margins is the cornerstone of treatment supplemented by chemotherapy and radiotherapy. Patients should be monitored closely for recurrence or metastasis.

Epithelioid hemangioma (EH) of the liver is an exceptionally rare vascular neoplasm, with only one pathology-confirmed case previously reported. We describe the second such instance, and the first to incorporate detailed radiologic characterization and RNA sequencing. A 68-year-old man presented with hepatic masses, portal lymphadenopathy, and a lytic pubic lesion initially concerning for metastatic carcinoma. Liver biopsy demonstrated a vascular proliferation of hobnail endothelial cells within myxoid stroma, with associated hemorrhage, hemosiderin, and eosinophil-rich inflammation. Immunohistochemistry showed diffuse ERG and focal FOSB expression, weak TFE3 staining, and a low proliferative index, while CAMTA1 and HMB-45 were negative. Imaging revealed multifocal, mildly FDG-avid hepatic lesions with nodal and osseous involvement. Whole-transcriptome sequencing was negative for pathogenic fusions. These findings confirmed a diagnosis of EH, illustrating its capacity to mimic malignancy. This case highlights the diagnostic value of integrating radio-genomic analysis and underscores the need for comprehensive workup to distinguish EH from epithelioid hemangioendothelioma, angiosarcoma, and Kaposi sarcoma, entities with distinct prognostic and therapeutic implications.

Pulmonary Epithelioid Hemangioendothelioma (PEHE) is an uncommon endothelial cell-derived vascular tumor of the lung. It is a form of Epithelioid Hemangioendothelioma (EHE), a low to intermediate-grade malignant vascular sarcoma which may be aggressive and can metastasize. It presents with a wide range of clinical and radiological findings, including bilateral lung nodules and pleural effusion. Diagnosis of PEHE is challenging due to its rarity and similarity to other benign and malignant vascular lesions. It is essential to distinguish PEHE from other vascular lesions of an epithelioid nature, particularly epithelioid angiosarcoma, which has a distinct prognosis and treatment options. Molecular analysis has now conclusively demonstrated this difference by detecting typical gene fusions, such as that of WWTR1-CAMTA1, which is not identified in angiosarcoma. However, even though molecular pathogenesis has been more clearly understood, PEHE lacks a universal treatment regimen, and management is often personalized, depending on therapies such as mTOR inhibitors. The present case illustrates the challenges in diagnosis, variable clinical progression, and the ongoing need for greater awareness among medical professionals regarding PEHE to facilitate earlier diagnosis, improve therapeutic strategies, and enhance patient outcomes for this rare tumor.

Vascular neoplasms of the liver encompass aspectrum ranging from the common benign hemangiomas to the very rare malignant vascular neoplasms, namely epithelioid hemangioendotheliomas (EHE) and angiosarcomas. Despite their high prevalence, hemangiomas are rarely biopsied or resected-typically only in cases with atypical imaging features or when large size raises concern for rupture. In this overview, we place particular emphasis on the newly described entity known as hepatic small vessel neoplasm (HSVN). Epithelioid hemangioendotheliomas and angiosarcomas, due to their rarity and several diagnostic pitfalls, can pose significant diagnostic challenges in histopathology. These pitfalls will be specifically addressed here.

Abstract Epithelioid angiosarcoma is an exceedingly rare and highly aggressive vascular malignancy that predominantly affects adults, with pediatric cases being exceptionally uncommon. We report the case of an 8-year-old female from Kashmir who presented with progressive pain and swelling in her right shoulder. Initially diagnosed with infantile hemangioma based on histopathological examination, the patient experienced rapid malignant transformation to epithelioid angiosarcoma within a 3-month period. The clinical course was complicated by spontaneous rupture requiring surgical intervention, with intraoperative findings revealing a large soft tissue mass extending from the deltoid to the scapular region. Subsequent comprehensive histopathological review with immunohistochemical studies confirmed the diagnosis of epithelioid angiosarcoma. The patient was treated with multimodal therapy including surgery, radiotherapy, and chemotherapy with positron emission tomography-computed tomography surveillance. This case demonstrates the diagnostic challenges inherent in pediatric vascular tumors and emphasizes the critical importance of comprehensive histopathological evaluation, vigilant clinical monitoring, and multidisciplinary management approaches to optimize patient outcomes in rare pediatric malignancies.

Rare epithelioid angiosarcoma: Clinical and imaging report