Primary cardiac angiosarcoma masquerading as intracardiac thrombus.

A 49-year-old man with a recent history of atrial tachycardia and intracardiac thrombus presented to the emergency department with melena and cardiac tamponade. Physical examination was notable for a vascular mass at the right lower gingival sulcus and a right chest wall nodule. Enteroscopy revealed a target lesion with friable ulcer in the gastric body. Cardiac MRI revealed a large right atrial mass, previously thought to represent thrombus. The patient was ultimately diagnosed with primary cardiac angiosarcoma (PCAS) by histopathology of gingival, gastric and subcutaneous lesions. This case illustrates the significant morbidity and mortality resulting from aggressive local invasion and growth of PCAS, as well as the challenge of differentiating between primary thrombosis and vascular malignancy. Misdiagnosis of this elusive clinical entity may be costly, potentially resulting in delay of intervention and adverse effects of alternate therapies such as anticoagulation.

[Diagnostic difficulties and legal analysis of potential claims to occupational medicine specialists based on a case of unrecognizable cardiac angiosarcoma]. / Trudnosci diagnostyczne i analiza prawna potencjalnych roszczen wobec lekarza medycyny pracy na przykladzie nierozpoznanego naczyniakomiesaka serca.

The article presents a case of sudden death of a 56-year-old woman at the workplace, caused by a very rare primary cardiac tumor. The patient's family reported a crime to the prosecutor's office suggesting participation of third parties in causing the death or malpractice in physical examinations before the death. A review of clinical data concerning cardiac angiosarcoma, available in electronic databases (e.g., Web of Science, PubMed), was presented, which could be useful in the practice of occupational medicine specialists. A legal analysis of potential claims to occupational medicine specialist in the case of failure to recognize primary cardiac tumors was also included in the article. Med Pr. 2020;71(6):757-64.

Intra-Axial Metastatic Angiosarcoma of the Central Nervous System Associated with Anemia, Pulmonary Tuberculosis and Short Survival

Introduction Angiosarcoma (AG) is a malignant mesenchymal neoplasm that predominantly affects the soft tissues and, to variable degrees, expresses themorphological and functional characteristics of the endothelium. The incidence of sarcomas of the central nervous system(CNS) is low (0.5% to 2.7%), and AGs involving the brain are even rarer. Case Description A 45-year-old male patient presented with complaints of headache, nausea, and vomiting. An examination showed bilateral papilledema and a right lung pleurotomy. The patient's previous history included drug addiction, pulmonary tuberculosis, lung abscess, pleural empyema, and pulmonary artery embolization for severe hemoptysis. Computed tomography/magnetic resonance imaging scans revealed a large intra-axial lesion extending into the right parietal and temporal lobes, with hemorrhagic zones. The patient underwent surgical resection of the lesion. Microscopy showed a poorly-differentiated, high-grade malignant tumor composed of plump/epithelioid cells forming small vascular spaces and solid nests, compatible with AG.In the postoperative period, the patient developed recurrent hemoptysis. A biopsy of the tissues adjacent to the pleurotomy determined the diagnosis of pulmonary AG. At 30 days after the resection, the patient died from hemoptysis, hemothorax, lung atelectasis, and intracranial hypertension related to the recurrence of the brain tumor. Conclusion Angiosarcoma is a rare neoplasia related to short survival due to the high proliferative index, which must be considered in patients presenting hemorrhagic tumors. No specific genetic abnormalities have been described for this neoplasia.

Identification of the JAK-STAT pathway in canine splenic hemangiosarcoma, thyroid carcinoma, mast cell tumor, and anal sac adenocarcinoma.

Dysregulation of the Janus Kinase (JAK) - Signal Transducer and Activator of Transcription (STAT) cellular signaling pathway has been associated with the development and progression of multiple human cancers. STAT3 has been reported to be present and constitutively active in a number of veterinary cancers, and few studies have reported mutations or activation of JAK1 or JAK2. Archived tissue samples from 54 client-owned dogs with histologically-diagnosed HSA, MCT, TC, or AGASACA were evaluated by immunohistochemical scoring of JAK1, JAK2, STAT3, and the phosphorylated counterparts pJAK1, pJAK2, and pSTAT3. IHC scoring was retrospectively analyzed with retrospectively-collected clinical parameters, including patient characteristics, metastasis, and survival. JAK1, pJAK1, JAK2, pJAK2, STAT3, and pSTAT3 were present in all tumor types evaluated. Significant correlations between JAK 1/2 or STAT3 and activated or downstream components were identified in all tumor types. Clinically, pSTAT3 was correlated with development of metastasis in dogs with MCT, while increased JAK1 expression or activation may impact survival in dogs with MCT or HSA. These findings provide a foundation to further investigate the JAK-STAT pathway in canine malignancies for additional therapeutic options.

Prognostic and predictive factors for angiosarcoma patients receiving paclitaxel once weekly plus or minus bevacizumab: an ancillary study derived from a randomized clinical trial.

BACKGROUND: We report here a correlation analysis conducted along with a phase II trial assessing bevacizumab in combination with weekly paclitaxel. METHODS: Circulating pro/anti-angiogenic factors were assessed on day 1 (D1) and day 8 (D8). The prognostic value for progression-free survival (PFS) was evaluated using a Cox model with biomarkers as continuous variables. RESULTS: Among the 51 patients enrolled and treated in this trial, biomarker analysis was performed for 42: 18 in Arm A (single-agent) and 24 in Arm B (combination). With a median follow-up of 46 months, PFS was 5.5 versus 5.7 months, respectively (p = 0.75). According to univariate analysis, factors associated with a poor PFS were as follows: visceral angiosarcoma, de novo angiosarcoma, and high PlGF and low VEGF-C baseline values. In multivariate analysis, de novo angiosarcoma (HR = 2.5; p = 0.024) and baseline VEGF-C value (HR = 0.7; p = 0.003) were significant prognostic factors. We observed a significant increase in circulating PlGF (< 0.001) and a decrease in VEGF (< 0.001) during bevacizumab treatment. An increase in FGF was associated with a poor outcome. CONCLUSIONS: De novo angiosarcoma and a low baseline level of VEGF-C were found to be associated with a poor prognosis. Addition of bevacizumab induces major changes in circulating biomarkers (VEGF and PlGF) in a short timeframe without impacting PFS. TRIAL REGISTRATION: Retrospectively registered on EudraCT N° 2009-017020-59 and NCT01303497 (February 24, 2011).

A new preclinical ultrasound platform for widefield 3D imaging of rodents.

Noninvasive in vivo imaging technologies enable researchers and clinicians to detect the presence of disease and longitudinally study its progression. By revealing anatomical, functional, or molecular changes, imaging tools can provide a near real-time assessment of important biological events. At the preclinical research level, imaging plays an important role by allowing disease mechanisms and potential therapies to be evaluated noninvasively. Because functional and molecular changes often precede gross anatomical changes, there has been a significant amount of research exploring the ability of different imaging modalities to track these aspects of various diseases. Herein, we present a novel robotic preclinical contrast-enhanced ultrasound system and demonstrate its use in evaluating tumors in a rodent model. By leveraging recent advances in ultrasound, this system favorably compares with other modalities, as it can perform anatomical, functional, and molecular imaging and is cost-effective, portable, and high throughput, without using ionizing radiation. Furthermore, this system circumvents many of the limitations of conventional preclinical ultrasound systems, including a limited field-of-view, low throughput, and large user variability.

Primary Epithelioid Angiosarcoma of Finger Masquerading as Epithelioid Hemangioma: Report of a Case and Analysis of Mutational Pattern in Epithelioid Hemangiomas and Angiosarcomas by Next-generation Sequencing.

AIMS: We report an unusual case of epithelioid angiosarcoma (AS) mimicking an epithelioid hemangioma (EH) and analyze mutational patterns in EHs and ASs. METHODS AND RESULTS: A 58-year-old woman presented with a finger lump and metastatic lung nodules. Initial needle biopsies showed an EH, with only focal atypical histologic features. The patient underwent finger amputation and resection of lung nodules. The amputation specimen and lung nodules revealed features of AS. Fluorescence in situ hybridization for FOS and FOSB gene rearrangements were negative in the primary tumor as well as in the lung metastasis. Intrigued by the unique morphologic features of an AS masquerading as an EH, we expanded our study by analyzing mutations in EHs versus ASs using a targeted next-generation sequencing of 50 cancer-related genes. Seven EHs and 6 ASs including the present case were subjected to mutation analysis using the Ion AmpliSeq Cancer Hotspot Panel v2 assay of 50 cancer-related genes. The present case lacked mutation. Novel somatic variants were detected in 2 of 7 EHs and 1 of 6 ASs. Sorting intolerant from tolerant and polymorphism phenotyping analysis revealed benign/tolerated and deleterious variants in both tumor types. Deleterious variants TP53 c.707T>C (p.Tyr236Cys), FLT3 c.1995C>T (p.Met665Ile), and SMO c.1919C>T (p.Thr640Ile) were detected in EH, while AS revealed deleterious variant PTPN11 c.226G>A (p.Glu76Lys). CONCLUSIONS: We present an epithelioid AS mimicking EH. We report novel somatic variants in EHs and AS. Benign variants may not be associated with development of these tumors. Whereas, deleterious variants, especially PTPN11 c.226G>A, may be linked to tumorigenesis of AS.

Primary angiosarcoma of neck nodes with bony metastasis - A case report.

This is a case of a 30 year old female who presented in February 2012 with a large painless left neck swelling since 5 months. Her biopsy was done but the result was inconclusive. Later on after proper staging workup it was found to be bony metastatic disease. Her repeated biopsy showed spindle cell lesion. She was advised surgery, which was done revealing poorly differentiated angiosarcoma involving 27 out of 33 lymph nodes. Angiosarcoma is an uncommon malignant neoplasm characterized by rapidly proliferating, extensively infiltrating anaplastic cells derived from blood vessels and lining irregular blood-filled spaces. Cutaneous angiosarcoma of the scalp and face is the most common form of angiosarcoma. Angiosarcoma of the cervical lymph node without a primary scalp or oral cavity lesion is a very rare presentation and has been reported only once. Thus, this case reported with bony metastasis can be labeled as the first of its kind.

Identification of the two KIT isoforms and their expression status in canine hemangiosarcomas.

BACKGROUND: KIT is a tyrosine kinase growth factor receptor. High expression of KIT has been found in several tumors including canine hemangiosarcoma (HSA). This study investigated the correlation of KIT expression and c-kit sequence mutations in canine HSAs and benign hemangiomas (HAs). RESULTS: Immunohistochemistry (IHC) staining confirmed KIT expression in 94.4 % (34/36) of HSAs that was significantly higher than 0 % in HAs (0/16). Sequencing the entire c-kit coding region of HSAs and normal canine cerebellums (NCCs) revealed GNSK-deletion in exon 9. As for exon 9 genotyping by TA-cloning strategy, GNSK-deletion c-kit accounted for 48.6 % (68/140) colonies amplified from12 KIT-positive HSAs, a significantly higher frequency than 14.1 % (9/64) of colonies amplified from six NCCs. CONCLUSIONS: Due to the distinct expression pattern revealed by IHC, KIT might be used to distinguish benign or malignant vascular endothelial tumors. Moreover, the high incidence of GNSK-deletion c-kit in canine HSAs implicates KIT isoforms as possibly participating in the tumorigenesis of canine HSAs.

Pleural Myiasis Associated With Pleural Angiosarcoma.

Myiasis refers to a parasitic infestation of vertebrate mammals by dipterous larvae (maggots) of higher flies. Infections in humans typically occur in tropical and subtropical regions, regions with limited medical access, and areas with poor hygiene and living conditions. Infestations in humans have been described in subcutaneous, nasal, ocular, oropharyngeal, and orotracheal cases; however, reports of pulmonary myiasis in humans in the United States and other developed countries are extremely rare. We describe a patient with recently diagnosed primary pleural angiosarcoma who presented to our clinic for the management of a thoracostomy tube and was diagnosed with pleural myiasis.

Angiosarcoma of the head and neck

Introduction Angiosarcoma of the head and neck is a rare vascular sarcoma associated with high rates of local recurrence and distant metastasis and a poor prognosis. Objective We describe our experience treating patients with angiosarcoma of the head and neck to evaluate the outcomes, patterns of failure, and current treatments. Methods We identified six patients with angiosarcoma of the head and neck and treated at our institution between 2000 and 2013. We compared our results to the literature from 1979 to 2013. Results Mean follow-up was 42 months. Local recurrence rate was 50% with diseasespecific survival and 2-year disease-free survival rates of 33.3 and 20%, respectively. Prognostic factors included tumor size > 5 cm and surgical margin status, with no correlation between histologic grade and survival. Combined-modality therapy was only used for aggressive tumors with positive surgical margins but is suggested to improve local control and overall survival. Conclusions Our data series supports that angiosarcoma of the head and neck has a high rate of recurrence and is associated with a poor prognosis, despite current combined-modality therapy. The study highlights the importance of attaining negative margins during surgical resection, the utility of adjuvant therapies, as well as the need for continued research in developing new management strategies.

Association of Sphingosine-1-phosphate (S1P)/S1P Receptor-1 Pathway with Cell Proliferation and Survival in Canine Hemangiosarcoma.

BACKGROUND: Sphingosine-1-phosphate (S1P) is a key biolipid signaling molecule that regulates cell growth and survival, but it has not been studied in tumors from dogs. HYPOTHESIS/OBJECTIVES: S1P/S1P1 signaling will contribute to the progression of hemangiosarcoma (HSA). ANIMALS: Thirteen spontaneous HSA tissues, 9 HSA cell lines, 8 nonmalignant tissues, including 6 splenic hematomas and 2 livers with vacuolar degeneration, and 1 endothelial cell line derived from a dog with splenic hematoma were used. METHODS: This was a retrospective case series and in vitro study. Samples were obtained as part of medically necessary diagnostic procedures. Microarray, qRT-PCR, immunohistochemistry, and immunoblotting were performed to examine S1P1 expression. S1P concentrations were measured by high-performance liquid chromatography/mass spectrometry. S1P signaling was evaluated by intracellular Ca(2+) mobilization; proliferation and survival were evaluated using the MTS assay and Annexin V staining. RESULTS: Canine HSA cells expressed higher levels of S1P1 mRNA than nonmalignant endothelial cells. S1P1 protein was present in HSA tissues and cell lines. HSA cells appeared to produce low levels of S1P, but they selectively consumed S1P from the culture media. Exogenous S1P induced an increase in intracellular calcium as well as increased proliferation and viability of HSA cells. Prolonged treatment with FTY720, an inhibitor of S1P1 , decreased S1P1 protein expression and induced apoptosis of HSA cells. CONCLUSIONS AND CLINICAL IMPORTANCE: S1P/S1P1 signaling pathway functions to maintain HSA cell viability and proliferation. The data suggest that S1P1 or the S1P pathway in general could be targets for therapeutic intervention for dogs with HSA.

An unexpected cause of diffuse alveolar hemorrhage in a kidney transplant patient.

Diffuse alveolar hemorrhage (DAH) is a life-threatening condition requiring urgent treatment. There are many different treatment-relevant causes of DAH, making the diagnostic approach to these patients complex and necessitating a multidisciplinary team. We report the case of a kidney transplant recipient in whom all diagnostic efforts did not reveal the cause of DAH, and only autopsy was able to establish an unexpected diagnosis.

[Cardiac angiosarcoma in a pregnant women].

We present a case of cardiac angiosarcoma in a pregnant women. Clinical manifestations of angiosarcoma were unspecific and progressed rapidly as hemopericardium, cardiac tamponade, heart failure, fever, chest pain. Pregnancy was interrupted at 22-nd week. The patient died in 6 months after appearance of first symptoms.

Stewart-Treves syndrome: pathogenesis and management.

Stewart-Treves syndrome is a malignancy that arises within chronic lymphedema. Although classically described as a consequence of radical mastectomy, this lymphangiosarcoma has been documented to occur in cases of congenital and other causes of chronic secondary lymphedema. The development of this aggressive lymphangiosarcoma at sites of chronic lymphedema renders it a possible model for Kaposi sarcoma. Because of the increase in conservative treatment for breast carcinoma and improvement of operative and radiation therapy techniques, the prevalence of Stewart-Treves syndrome has decreased. Regardless, this malignancy significantly worsens patients' outcomes and needs to be diagnosed and treated early. Chemotherapy and radiation therapy have not improved survivorship significantly. Early amputation or wide local excision offers the best chance for long-term survival. Yet, overall prognosis remains dismal. Untreated patients usually live 5 to 8 months after diagnosis.