Recurrent USP6 gene rearrangements underlie a subset of mesenchymal neoplasms, including nodular fasciitis and aneurysmal bone cyst. These rearrangements place USP6 under the regulatory control of another gene's constitutively active promoter, resulting in USP6 overexpression. Recently, it has been demonstrated in a limited number of cases that detection of USP6 overexpression by RNA chromogenic in situ hybridization (CISH) can serve as a surrogate marker for USP6-rearranged tumors. To further assess the diagnostic utility of USP6 RNA CISH, we evaluated its application in 1210 bone and soft tissue tumors, using a combination of whole tissue sections and tissue microarrays. USP6 overexpression, defined as RNA CISH staining in >1% of lesional cells, was observed in 92% (36/39) of nodular fasciitis cases and in 85% (17/20) of primary aneurysmal bone cysts. All examples of nodular fasciitis (15/15) and primary aneurysmal bone cyst (8/8) with USP6 fusion confirmed by molecular genetic testing were positive for overexpression. Other tumors staining positive for USP6 included cellular fibroma of tendon sheath (3/3, 100%) and myositis ossificans (3/3, 100%). Although USP6 RNA CISH proved to be highly specific for USP6-rearranged lesions when assessed in 1145 negative control cases reflecting 53 other tumor types, positivity was rarely seen in isolated cases of angiosarcoma (1/16, 6%), malignant peripheral nerve sheath tumor (1/80, 1%), and carcinosarcoma (1/7, 14%). Taken together, these findings indicate that USP6 RNA CISH represents a useful diagnostic tool; careful interpretation remains critical to its successful implementation, given that isolated examples of non-USP6-rearranged tumors rarely stain positive.

Hemangiosarcoma (HSA) is a highly malignant tumor of endothelial origin that is infrequently reported in cats, accounting for less than 2% of nonhematopoietic neoplasms. Feline HSA is typically classified into dermal and visceral subtypes, both of which exhibit metastatic potential. While HSA is the tumor most commonly reported to metastasize to the brain in dogs, intracranial involvement in cats remains rare, with only one previously documented metastatic case. This case report details the clinical presentation, magnetic resonance imaging (MRI) features, histopathological findings, and gross post-mortem brain changes in a cat diagnosed with intracranial hemangiosarcoma.

Angiosarcomas are rare and aggressive malignant neoplasms of vascular or lymphatic endothelial origin, accounting for approximately 2% of soft-tissue sarcomas. They occur predominantly in the skin and superficial soft tissues, particularly in the head and neck region and the breast, whereas gastrointestinal involvement is exceptionally rare. Previous radiotherapy is a well-established risk factor for secondary angiosarcoma. However, radiation-associated gastrointestinal angiosarcomas are extremely uncommon and have been reported predominantly in the small bowel. We report the case of a 55-year-old woman who presented with abdominal pain, hemorrhagic ascites, intermittent rectal bleeding, severe anemia, anorexia, and weight loss 16 years after pelvic radiotherapy and cisplatin-based chemotherapy for cervical squamous cell carcinoma. Computed tomography revealed circumferential thickening of the cecum and right colon with abundant hyperdense ascites. Colonoscopy showed an obstructing, ulcerated, and contact-bleeding mass involving the cecum and right colon. Histopathological examination of endoscopic biopsies revealed a poorly differentiated malignant vascular neoplasm. Immunohistochemical staining was positive for cluster of differentiation (CD)31 and CD34 and negative for cytokeratin, CD3, CD20, and Human Herpesvirus (HHV)8, with a Ki-67 proliferation index of 40%, supporting the diagnosis of colonic angiosarcoma. Surgical resection was considered; however, the patient developed a massive bilateral pulmonary embolism and died seven days after admission. Given the prolonged latency and the histological distinction from the primary cervical carcinoma, a possible radiation-associated etiology was considered. Nevertheless, the original radiotherapy plan was unavailable, preventing definitive confirmation that the tumor arose within the irradiated field. This case highlights the diagnostic difficulty, aggressive clinical course, and poor prognosis of colonic angiosarcoma following pelvic radiotherapy.

Primary cardiac tumors are rare, whereas cardiac metastases are more common forms of cardiac involvement in patients with advanced malignancies; both are clinically important because of their potential cardiovascular consequences. This review summarizes current evidence on the immune microenvironment, immune-evasion mechanisms, immunotherapeutic opportunities, multi-omics-based immune decoding, and cardiovascular toxicity in cardiac tumors and cardiac metastases. Cardiac myxoma is discussed as a benign primary cardiac tumor with inflammatory, cytokine-mediated, metabolic, and candidate immune-regulatory features, whereas malignant primary cardiac tumors, particularly cardiac sarcomas such as cardiac angiosarcoma, are reviewed in relation to immunosuppressive niches, macrophage-rich microenvironments, T-cell dysfunction, and heterogeneous responses to immune checkpoint inhibitors. Cardiac metastases are considered as a clinically relevant setting in which immunotherapy may be feasible for selected patients with careful cardiovascular assessment. Key mechanisms discussed include immune checkpoint pathways, tumor-associated macrophages, metabolic reprogramming, cytokine signaling, vascular abnormalities, and spatial immune organization. The review also highlights the role of single-cell sequencing, spatial transcriptomics, proteomics, metabolomics, and integrative multi-omics approaches in defining tumor-specific immune landscapes and potential biomarkers. Finally, immune checkpoint inhibitor-associated cardiotoxicity, particularly myocarditis, is discussed with emphasis on baseline cardiovascular assessment, biomarker monitoring, multimodality imaging, and multidisciplinary cardio-oncology management.

Chronic expanding hematoma (CEH) is a rare condition characterized by progressive enlargement of a hematoma long after an initial hemorrhagic event and may mimic malignancy. We report a 61-year-old woman who developed a progressively enlarging left axillary mass 15 years after modified radical mastectomy followed by adjuvant chemotherapy and radiotherapy for breast cancer. The lesion became ulcerated and spontaneously bled, raising concern for locoregional recurrence. Ultrasonography demonstrated heterogeneous mixed cystic-solid lesions, while systemic evaluation revealed no evidence of distant metastatic disease. Ultrasound-guided core needle biopsy showed hemorrhage, fibrin deposition, and fibrous tissue without malignant cells but was considered inconclusive because of potential sampling limitations. Surgical excision and extensive debridement were therefore performed. The 7 × 5 × 2 cm excised specimen was extensively sampled in 20 tissue blocks and demonstrated organized hematoma, fibrosis, hemosiderin-laden macrophages, and chronic inflammatory changes, without atypical endothelial proliferation or malignant tumor cells. CEH was definitively diagnosed. Following staged wound management with vacuum sealing drainage, the axillary defect was successfully reconstructed using a pedicled scapular artery perforator propeller flap. This case emphasizes the importance of considering CEH, recurrent carcinoma, and angiosarcoma in the differential diagnosis of delayed hemorrhagic masses after breast cancer treatment and highlights the importance of adequate histopathological sampling for definitive diagnosis.

Women treated for breast cancer with lumpectomy and radiation therapy are at risk for disease recurrence, as well as radiation-associated (secondary) angiosarcoma. Hematomas are rarely responsible for new masses in this setting. We examined a series of breast hematomas with papillary endothelial hyperplasia (PEH), some of which raised concern for angiosarcoma, to identify features that aid in distinguishing these benign lesions from angiosarcoma in diagnostically challenging cases. Hematomas diagnosed in twenty-eight breast biopsy and/or resection specimens from nineteen women within our institutional archive were studied (2013-2026). Clinical, imaging, and pathology data were correlated. Immunohistochemical evaluation included PRAME, MYC, p53 and ERG IHC, along with Martius-Scarlet-Blue (MSB) histochemical staining. The mean age at hematoma presentation was 72.4 years, with patients presenting long after surgery (mean: 18.5 years) and radiotherapy (mean: 17.5 years). Several patients were on medications interfering with coagulation (13). Most masses were categorized as BI-RADS 4 and underwent multiple diagnostic procedures. In hematomas, reactive endothelium dissected organizing fibrin rather than collagen, highlighted by MSB or trichrome stains. PRAME was negative while MYC and p53 demonstrated wild type expression in all tested lesions. With the breast cancer survivor population increasing in number, age, and use of anti-coagulation, late breast hematomas are increasingly encountered by breast pathologists and radiologists. Careful evaluation to distinguish organizing hematoma with PEH from angiosarcoma is necessary.

Cutaneous angiosarcoma (cAS) is an aggressive vascular malignancy comprising idiopathic primary cutaneous angiosarcoma (PCAS) and secondary cutaneous angiosarcoma (SCAS) arising after radiation therapy or chronic lymphedema. Comparative genomic analyses delineating these subtypes in Asian populations remain limited. We retrospectively evaluated 15 Japanese cAS patients (10 PCAS, 5 SCAS) who underwent comprehensive genomic profiling (CGP) using FoundationOne CDx or liquid CDx between 2020 and 2026. Variants of unknown significance (VUS) and potential clonal hematopoiesis (CH)-derived mutations were systematically excluded. The cohort demonstrated a uniformly low tumor mutational burden (median 4 mut/Mb) with no MSI-H cases. TP53 was the most frequent driver mutation (47%), followed by CDKN2A (33%), MYC (33%), KDR (27%), CDKN2B (27%), MTAP (27%), KIT (27%), and PDGFRA (27%). A molecular separation was observed between the two clinical subtypes, where focal MYC amplification was confined to SCAS cases (5/5, 100%), whereas PCAS lesions were enriched with cell-cycle pathway alterations via co-deletions of CDKN2A, CDKN2B, and MTAP, alongside variable receptor tyrosine kinase (RTK) gains (KIT/PDGFRA). RAS pathway mutations presented only as three cases of missense variants across both subtypes. Although limited by sample size, these findings suggest subtype-associated genomic patterns in Japanese cAS and may serve as preliminary observations that warrant validation in larger East Asian cohorts.

Ear neoplasms are growths that commonly affect light-coated, unpigmented felines exposed to prolonged sunlight. Another factor associated with these growths is the constant tissue trauma caused by intense pruritus in cases of chronic otitis. Any tissue making up the structure of the pinna can undergo changes and initiate pathogenic cell proliferation. In this context, cutaneous hemangiosarcomas may arise from alterations in the ear's vascular endothelium, albeit less frequently. This report describes the case of a 12-year-old, white, mixed-breed cat with a history of prior pinnectomy and local recurrence. To treat the new lesion, total ear canal ablation combined with cryotherapy of the surgical bed was selected to maximize recurrence-free survival. Histopathological analysis of the surgical specimen confirmed a moderate grade hemangiosarcoma associated with chronic otitis, with clear margins. The patient was referred to for oncological follow-up and remains free of recurrence one year after the procedure.