Understanding the Efficiency of Splenic Hemangiosarcoma Diagnosis Using Monte Carlo Simulations.

Hemangiosarcoma is a common neoplasm of the spleen in older dogs. However, diagnosis is complicated by necrosis and hemorrhage, which can mimic a number of benign processes. Currently, there is no consensus about the number of sections pathologists should examine to rule out hemangiosarcoma. To answer this question, we examined 413 histopathologic sections from 50 cases of canine hemangiosarcoma (mean: 8.1 sections per case; range, 5-14). Each section had the presence or absence of hemangiosarcoma determined by 2 board-certified anatomic pathologists. Then, 100 Monte Carlo simulations were performed, randomly selecting sections from each case 10 000 times and the results averaged. These simulations suggest that examination of 5 sections from a spleen with hemangiosarcoma yields a 95.02% chance of diagnosing hemangiosarcoma, while examination of 10 sections yields a 98.59% chance of diagnosis when hemangiosarcoma is in fact present. The data emphasize the need to submit the entire spleen for histopathologic examination in suspected cases of hemangiosarcoma and suggest that 5 sections obtained by a trained individual are likely sufficient for diagnosis.

Head and neck sarcomas: epidemiology, pathology, and management.

Sarcomas of the head, neck, and skull base represent a heterogeneous group of tumors with distinct prognostic features. There have been significant improvements in characterizing these sarcomas using traditional morphologic assessments and more recent immunohistochemical analysis. Surgery is the mainstay of treatment followed by radiation therapy. Treatment modalities have changed in select pediatric sarcomas, for which new chemotherapeutic combinations have improved survival statistics. The high rate of distant failure emphasizes the need for novel systemic and directed molecular therapies. Tumor grade, size, and margin status are key factors in survival.

Mode of action associated with development of hemangiosarcoma in mice given pregabalin and assessment of human relevance.

Pregabalin increased the incidence of hemangiosarcomas in carcinogenicity studies of 2-year mice but was not tumorigenic in rats. Serum bicarbonate increased within 24 h of pregabalin administration in mice and rats. Rats compensated appropriately, but mice developed metabolic alkalosis and increased blood pH. Local tissue hypoxia and increased endothelial cell proliferation were also confirmed in mice alone. The combination of hypoxia and sustained increases in endothelial cell proliferation, angiogenic growth factors, dysregulated erythropoiesis, and macrophage activation is proposed as the key event in the mode of action (MOA) for hemangiosarcoma formation. Hemangiosarcomas occur spontaneously in untreated control mice but occur only rarely in humans. The International Programme on Chemical Safety and International Life Sciences Institute developed a Human Relevance Framework (HRF) analysis whereby presence or absence of key events can be used to assess human relevance. The HRF combines the MOA with an assessment of biologic plausibility in humans to assess human relevance. This manuscript compares the proposed MOA with Hill criteria, a component of the HRF, for strength, consistency, specificity, temporality, and dose response, with an assessment of key biomarkers in humans, species differences in response to disease conditions, and spontaneous incidence of hemangiosarcoma to evaluate human relevance. Lack of key biomarker events in the MOA in rats, monkeys, and humans supports a species-specific process and demonstrates that the tumor findings in mice are not relevant to humans at the clinical dose of pregabalin. Based on this collective dataset, clinical use of pregabalin would not pose an increased risk for hemangiosarcoma to humans.

FISH for MYC amplification and anti-MYC immunohistochemistry: useful diagnostic tools in the assessment of secondary angiosarcoma and atypical vascular proliferations.

BACKGROUND: Secondary angiosarcoma and benign but microscopically atypical vascular proliferations (herein referred to as atypical vascular lesion or AVL) are rare consequences of radiation therapy and/or chronic lymphedema most commonly seen in breast cancer patients. Differentiating angiosarcoma from AVL can be difficult due to overlapping clinical and microscopic features. Recently, amplification of MYC has been associated with 55-100% of secondary angiosarcomas but is reportedly absent in AVL. We examined a series of secondary angiosarcoma and AVL for MYC amplification by fluorescence in situ hybridization (FISH) and expression by immunohistochemistry to investigate the diagnostic utility for discriminating angiosarcoma from AVL. METHODS: Cases of secondary angiosarcoma (n = 8) and AVL (n = 4) were retrieved from our archives and examined by FISH and immunohistochemistry. RESULTS: All angiosarcoma cases (8/8 = 100%) demonstrated high-level MYC amplification by FISH, whereas all AVLs (0/4 = 0%) were negative for MYC amplification. Additionally, all angiosarcoma cases (8/8 = 100%) demonstrated nuclear positivity for MYC, whereas all AVLs (0/4 = 0%) were negative. CONCLUSION: Amplification of MYC and nuclear expression of MYC is present in secondary angiosarcoma but not AVL. These ancillary tests can be useful to distinguish angiosarcoma from AVL in difficult cases.

An immunocytochemical assessment of 19 cases of cutaneous angiosarcoma.

Four endothelial cell markers, two selective cytokeratin markers and a monoclonal smooth muscle antibody (SMA) were employed in the assessment of 19 cases of cutaneous angiosarcoma classified according to their degree of tumour differentiation. No labelling was seen for SMA or with cytokeratin markers MNF116 and CBL170. Expression of factor VIII-related antigen was seen in two tumours and positivity for CD34 (QBend 10 antibody) was found in four tumours. By contrast the pan-endothelial cell marker Ulex europeaus agglutinin 1 (UEA-1) and the CD31 marker JC70A labelled all cases of cutaneous angiosarcoma with the exception of one poorly differentiated tumour. These data confirm the endothelial cell origin of angiosarcoma, they demonstrate that CD31 and UEA1 are reliable markers in routinely processed tissue, and they suggest a lymphatic derivation for the tumour. This finding is in marked contrast to Kaposi's sarcoma where CD34 is the most reliable marker.

[Primary sarcomas of the maxillofacial area. The clinical assessment of a case of angiosarcoma with a rare location]. / I sarcomi primitivi del distretto maxillo-facciale. Valutazione clinica di un caso di angiosarcoma a rara localizzazione.

Following a short critical review of the most recent literature, the present study reports a case of angiosarcoma of the gingiva, localized at the level of the vestibular surface of the lower incisor region. The intense positive reaction of neoplastic elements to factor VIII-correlated antigen, negative for cytokeratin and positive for vimentin, allowed the vascular nature of the neoplasia to be confirmed.