Metastatic Angiosarcoma Research Articles

A unique presentation of pericardial epithelioid angiosarcoma with multifaceted complications

Introduction and importance: Angiosarcomas are rare tumors of endothelial origin and may arise in any organ. Epithelioid angiosarcomas are a subtype of angiosarcoma that are rapidly progressive and typically fatal. Case presentation: The authors report a case of a 25-year-old previously healthy female who presented initially for dyspnea and palpitations, on further evaluation she was found to have large bilateral pleural effusions and cardiac tamponade. Clinical discussion: Pericardiocentesis and thoracentesis were performed alongside biopsies that revealed atypical cellular proliferation. Fluorodeoxyglucose-positron emission tomography (FDG-PET) showed avid uptake in the anterior mediastinum, perivascular, paratracheal, subcarinal and pleural lymph nodes with large FDG uptake in the bilateral pleural effusion. Mediastinoscopy was done and biopsies showed an overtly malignant, epithelioid neoplasm with foci of vaso-formation; Keeping with high-grade epithelioid angiosarcoma of the pericardium. She received six cycles of weekly paclitaxel, but imaging for abdominal pain incidentally showed evidence of metastasis to the liver and spine so she was switched to Adriamycin-Ifosfamide for which she received one cycle so far. Her hospital course was complicated by high-output pleural effusions, chylothorax, left atrial thrombus formation and an intensive care unit stay for septic shock. Conclusion: Pericardial epithelioid angiosarcoma has been reported rarely in the literature. The authors aim to report a case of extensive metastatic pericardial epithelioid angiosarcoma in a young patient; which we believe can be an addition to the literature of a malignancy associated with poor prognosis and no definitive proven treatment regimen.

A durable response to gemcitabine monotherapy in metastatic cardiac angiosarcoma

Introduction: Primary cardiac angiosarcoma is a rare neoplasm with high rates of local recurrence and distant metastasis for which optimum treatment is poorly defined. Case Report: We present the case of a 49-year-old man with cardiac angiosarcoma with distant metastases who exhibits durable response to gemcitabine monotherapy. At initial diagnosis, he underwent complete resection with adjuvant Adriamycin and Ifosfamide for four cycles as well as external beam radiation for possible residual disease. He had recurrence with liver and bone metastases four years later. He received Gemcitabine and Docetaxel for six cycles followed by Gemcitabine monotherapy with no evidence of recurrence for the next three years. Conclusion: This patient’s consistent response to gemcitabine maintenance therapy in metastatic cardiac angiosarcoma adds to relative paucity of data regarding the management of this rare malignancy, offering insight into best practice and hope for patients afflicted with this disease.

Abstract PO3-20-12: A Case Report on the Management of a Patient with Local Breast Cancer, BIA-ALCL and Radiation Induced Metastatic Angiosarcoma: A Multidisciplinary Approach

Abstract A Case Report on the Management of a Patient with Local Breast Cancer, BIA-ALCL and Radiation-Induced Metastatic Angiosarcoma: A Multidisciplinary Approach Abstract: Breast cancer recurrence presents a complex challenge in clinical practice. We present the case of a 60-year-old female with a history of stage 2A right breast cancer diagnosed on 12/1/2013. The patient underwent bilateral mastectomy and adjuvant chemotherapy, followed by breast reconstruction. The patient subsequently developed asymmetric right breast swelling, which was biopsied and was positive for T lymphocyte markers CD30, CD43, CD45, CD4 and she was diagnosed with anaplastic large cell lymphoma in 12/14/2018, which was thought to be associated with her breast implants. In May 2022, a right chest wall mass was detected, which demonstrated growth and increased vascularity on imaging. A biopsy on 5/5/22 confirmed poorly differentiated carcinoma initially thought to be a secondary intraductal carcinoma of the breast, invading the chest wall by metastasis or direct extension, negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Further workup confirmed this mass to be angiosarcoma, most likely associated with the patient’s prior radiation therapy. The patient was started on neoadjuvant carboplatin/paclitaxel/pembrolizumab on 6/9/2022, and continued with Doxorubicin/Cyclophosphamide and pembrolizumab, which was completed on 11 November 2022. Imaging studies post-treatment showed a slightly smaller mass in the right mastectomy bed, indicating a partial response to treatment. However, a subsequent PET scan revealed a recurrence of breast cancer in the right chest wall. Considering the patient's history of prior radiation therapy and the inability to administer further radiation, the treatment plan was revised. She underwent reconstructive chest wall surgery on 1/4/2023, with complete resection and negative margins. She started on adjuvant pembrolizumab planned for one year, but the patient presented on 3/3/2023 with the growth of a chest wall mass and bleeding, consistent with progression. Liquid Tempus testing was obtained but negative for an actionable target. Options such as hyperthermia, enrollment to clinical trial, and re-irradiation were discussed, and the patient was restarted on weekly paclitaxel on 3/31/2023 due to a previous response. The patient had further local disease progression on 5/26/2023, and this regimen was stopped. The patient is planning to get Tempus testing on tumor tissue and start the next line palliative regimen with either doxorubicin or gentamicin and repeat re-irradiation if no response to these regimens. This case report highlights the challenges in managing breast cancer therapy-induced adverse conditions with two secondary tumors, both associated with the patient’s prior therapy. The importance of a multidisciplinary approach, including medical oncology, surgical oncology, radiation oncology, and sarcoma specialists, is emphasized. The use of molecular testing and consideration of clinical trials may provide additional treatment options. Further research and clinical trials are warranted to optimize the management of recurrent breast cancer with transformation to rare histological subtypes such as angiosarcoma. Citation Format: Liubou Varanitskaya, Serhan Unlu, Christina Clemow. A Case Report on the Management of a Patient with Local Breast Cancer, BIA-ALCL and Radiation Induced Metastatic Angiosarcoma: A Multidisciplinary Approach [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-20-12.

Aortic Angiosarcoma Manifesting as Multiple Musculoskeletal Metastases: A Case Report.

Aortic angiosarcomas are rare. Due to its rarity and metastatic presentation, it is difficult to diagnose metastatic aortic angiosarcoma. We describe the clinicopathological and radiologic features of a metastatic aortic angiosarcoma presenting as musculoskeletal metastases. A 59-year-old male patient presented with left thigh pain. Plain radiographs revealed multifocal osteolytic lesions in the left femur shaft. Abdominopelvic computed tomography showed a lobulated osteolytic lesion in the left iliac bone. Magnetic resonance images revealed multifocal soft tissue lesions in the thigh musculature. A positron emission tomography/computed tomography (PET/CT) scan demonstrated multiple foci of increased uptake in the left femur bone, pelvis, left thigh, and calf musculature. Focal increased uptake in the lower abdominal aorta was newly detected. Pelvis biopsy showed tumor cell nests of epithelioid cells. The tumor cells showed vasoformative features. Immunohistochemically, the tumor cells showed positivity for vimentin, CD31, and ERG. The pathologic diagnosis of epithelioid angiosarcoma was established. The origin of the tumor was presumed to be the aorta. This case underscores the importance of PET scans in identifying primary lesions. In terms of the histopathologic diagnosis of biopsy samples with tumor cells exhibiting epithelioid neoplastic morphology, employing appropriate ancillary techniques such as immunocytochemistry with vascular markers may assist in accurately diagnosing metastatic angiosarcoma.

A155 METASTATIC EPITHELIOID ANGIOSARCOMA AND RECURRENT GASTROINTESTINAL BLEEDING: A CASE REPORT

Abstract Background Angiosarcomas are aggressive tumors of the vascular endothelium that represent less than 3% of all sarcomas. Epithelioid angiosarcomas are a distinct subtype, and in exceedingly rare circumstances can involve the gastrointestinal tract leading to significant bleeding. Aims Report a case of metastatic epithelioid angiosarcoma as a cause of recurrent gastrointestinal bleeding and the utility of endoscopy in obtaining a diagnosis. Methods A retrospective case report. Results A 71 year old female with a history of type two diabetes and coronary artery disease presented to a peripheral hospital with a two week history of fatigue, abdominal pain, and intermittent fevers for which she was diagnosed with pyelonephritis. Computed tomography (CT) scan of the abdomen/pelvis was unremarkable on admission. Her stay was complicated by cardiac ischemia prompting the initiation of dual antiplatelet therapy and anticoagulation. After a few days she developed melena and an acute hemoglobin drop requiring red blood cell (RBC) transfusion. Gastroscopy revealed a few superficial erosions in the stomach and duodenum. She went on to develop hypercalcemia prompting a repeat CT abdomen/pelvis which showed multiple lytic bone lesions, innumerable small lung nodules, and areas of hypoattenuation in the liver. Contrast enhanced MRI abdomen was performed to better assess the liver, showing a geographic area of signal abnormality without mass like features. The patient was transferred to a tertiary centre for ongoing work-up and management. Shortly after arrival, a bone biopsy from a lytic lesion of the iliac crest was taken. Initial histopathology was inconclusive for malignancy. During this time, she had ongoing melena and need for intermittent RBC transfusions. Enteroscopy revealed multiple centrally ulcerated, hemorrhagic, erythematous/purpuric lesions throughout the stomach and proximal small bowel (Figure 1a). A duodenal lesion with fresh clot was clipped and multiple biopsies were taken from the stomach and duodenum. Histopathology from a gastric biopsy confirmed the diagnosis of epithelioid angiosarcoma (Figure 1b). PET scan revealed uptake in bone, lungs, and liver. The patient received 1 cycle of palliative chemoradiation, however this was discontinued due to frailty. Overt bleeding and intermittent RBC transfusions continued. The patient was transferred to full comfort care and died within 4 months of initial presentation to hospital. Conclusions Epithelioid angiosarcoma involving the gastrointestinal tract should be considered as a cause for upper gastrointestinal bleeding. Our case highlights the endoscopic characteristics and the importance of endoscopic biopsy in obtaining a histopathologic diagnosis. Figure 1a. Enteroscopy showing metastatic angiosarcoma to the stomach and small bowel. A. Gastroesophageal junction; B. Cardia and fundus; C. Duodenal bulb; D. Second portion of duodenum. Figure 1b. Metastatic epithelioid angiosarcoma to the stomach. A-B. Low and medium power H&E; C. Cytokeratin AE1/3; D. Ber-EP4; E. CD31; F. ERG. Funding Agencies None

Abstract 14933: A Rare Case of Cardiac Angiosarcoma Presenting as Hemorrhagic Pericardial Effusion

Cardiac sarcomas are exceptionally rare, with an incidence of only 0.02% and comprising less than 1% of all primary cardiac tumors. Consequently, diagnosis of the disease can be challenging due to non-specific presenting symptoms and diverse clinical manifestations. We present a unique case of cardiac sarcoma that highlights these challenges. A 70-year-old man with a history of hypertension, hyperlipidemia, and latent tuberculosis presented with palpitations, chest pain, and dyspnea, was found to have hemorrhagic pericardial effusion with tamponade. Pericardial fluid studies were negative for malignancy, and echo not suggestive of cardiac mass or pericardial abnormalities. He presented several months later with hemoptysis and was found to have innumerable pulmonary nodules on CT chest and a mediastinal mass adjacent to the right atrium. Bronchoscopy was negative for infection or malignancy. Ultimately the patient underwent CT-guided lung biopsy, which showed a malignant spindle cell neoplasm with a positive stain for vimentin and vascular markers suggestive of angiosarcoma of unknown primary. Given unclear relation of his mediastinal mass, cardiac MRI was done which showed a rapidly enhancing bulky neoplasm with abnormal contrast enhancement arising from the lateral right atrium (Figure 1) consistent with metastatic cardiac angiosarcoma. Patient was started on systemic anthracycline-based chemotherapy; however the overall prognosis remains poor. Given the rarity of cardiac sarcomas, prognosis is generally poor due to the advanced stage at the time of diagnosis. These tumors exhibit aggressive behavior and have a high propensity for metastasis. Due to their infrequency, knowledge and research is limited regarding effective treatments. This case highlights the significance of considering cardiac angiosarcoma in cases of hemorrhagic pericardial effusion even in the absence of obvious cardiac mass or pericardial nodularity on initial presentation.

Rapidly Progressive Metastatic Angiosarcoma of the Heart: A Case Report.

Cardiac angiosarcoma is a rare, malignant neoplasm affecting the heart. We present the clinical history of a 40-year-old patient diagnosed with metastatic angiosarcoma of the heart. The patient complained of shortness of breath, and a cardiac computed tomography scan revealed a mass in the right atrium and pericardial effusion. Transthoracic and transesophageal echocardiography provided detailed anatomical and functional information, and cardiac magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography/computed tomography were used to assess distant metastasis and characterize the mass in detail. Early differential diagnosis and comprehensive evaluation of a cardiac mass are vital for determining appropriate treatment strategies to improve patient outcomes. The pathological results from the endocardial biopsy confirmed the diagnosis of primary angiosarcoma. The patient underwent surgical resection of the right atrial mass but died within one month because of the locally advanced nature of the angiosarcoma and its rapid progression. The patient's medical journey sheds light on the challenges associated with diagnosing and treating this rare condition, particularly the rapid progression of its cardiac manifestations.

Cytological Features of a Metastatic Angiosarcoma in the Lymph Node Diagnosed via Liquid-Based Cytology.

Angiosarcoma is a soft tissue sarcoma of vascular origin, with more than half of the cases arising in the skin and affecting primarily the face and scalp of elderly males. Furthermore, cutaneous angiosarcoma exhibits a higher incidence of lymph node metastases than other types of sarcomas. Angiosarcomas are rarely aspirated and are occasionally encountered on cytological samples. It is a diagnostic challenge in evaluating fine needle aspiration (FNA) from a metastatic angiosarcoma without the knowledge of prior history. We present a case of scalp angiosarcoma with disease progression to erythroderma and cervical lymphadenopathy 20 months after. FNA of the cervical node revealed vasoformative features, including hemophagocytosis, formation of an intracytoplasmic lumen/vacuole, endothelial wrapping, and cell grasping. The diagnosis of nodal metastasis by angiosarcoma was confirmed with immunohistochemistry (IHC) using two vascular markers on cell block sections. Our case demonstrates the recognizable cytomorphologic clues for this rare metastatic malignancy.

Treatment response prediction with circulating tumor cell-derived organoids for soft tissue sarcoma.

e23521 Background: Pharmacologic treatment for soft tissue sarcoma (STS) remains challenging. There is a lack to predict treatment responses to chemotherapy or targeted therapy to oncologic drivers. We hypothesize that circulating tumor cells may enrich cancer initiating cells and represent a window to probe personalized drug treatment response. In this study, we test if drug sensitivity profile of short-term culture of tumor organoids derived from circulating tumor cells (CTCs) correlates to clinical treatment response. Methods: From April 2019 to December 2020, 50 patients with biopsy-confirmed STS, who had either recurrent or metastatic tumors, were enrolled in a prospective observational study in Taipei Medical University Hospital. The median age of the patients was 47, and the top 3 diagnoses were leiomyosarcoma, aggressive fibromatosis and rhabdomyosarcoma. 74% of patients had metastatic diseases at the time of blood collection. Fifty-five blood samples were collected and processed for CTC organoid culture and drug sensitivity analysis (EVASelect, CancerFree Biotech, Taipei, Taiwan), which involves culturing nucleated blood cells on a binary colloid crystal-coated surface. Clinical response was evaluated using RECIST criteria 3 months after blood collection. The relationship between CTC viability and clinical response was analyzed using a contingency table and Chi-square analysis. Results: The success rate of CTC expansion was 87.2% (48/55), as defined by ATP abundance higher than 3000 U2OS cells after 18 days of culture. Clinical information from 32 of the 50 cases was eligible for analysis, and the results showed that CTC viability at a 70% cutoff correlated with clinical disease control at 3 months after blood collection. The odds ratio, sensitivity, specificity, and diagnostic accuracy were 12 (p = 0.036), 92.3%, 50%, and 79%, respectively. A demonstration of the interaction between this research and the Molecular Tumor Board (MTB) in the Taipei Medical University Healthcare System is presented through a case study of metastatic angiosarcoma and its correlation. Conclusions: The study highlights the potential of using CTC drug sensitivity as a biomarker for precision medicine in STS, despite limitations such as small sample size, short follow-up, and disease and treatment heterogeneity. Advancements in gene-based precision medicine have been made in the past decade, but only a small number of STS patients have seen benefits from it. This emphasizes the need for further research to thoroughly evaluate the potential of CTC drug sensitivity as a predictive biomarker in clinical practice. Key words: soft tissue sarcoma; circulating tumor cells; liquid biopsy; predictive biomarker; precision medicine.

Primary and secondary angiosarcomas of the liver: a multi-institutional study of 32 cases

Angiosarcomas involving the liver can be hepatic primary or metastasis from another anatomic site, which have not been systematically compared. We analyzed a series of liver biopsy or resection specimens carrying a diagnosis of angiosarcoma collected between 2005 and 2022 at 3 tertiary medical centers. The cohort included 32 patients (20M and 12F) with a median age of 64 years. Nineteen were primary hepatic angiosarcoma (PHA) and 13 metastatic angiosarcoma to liver (MA). Males were predominant in PHA (15/19, 78%) compared to MA (5/13, 38%, P=.025). There was no age difference between the 2 groups. Five cases had background hepatic cirrhosis, which more likely harbored PHA (4/5, 80%). Multifocality and multiorgan involvement were common in both groups. Tumor size was significantly larger in PHA than in MA (10.4 versus 4.7cm, P<.01). Histologically, there were no differences in terms of tumor morphology (spindled versus epithelioid) and growth patterns (vasoformative versus solid) between the 2 groups. Immunohistochemically, all tumor cells were positive for CD31 (28/28, 100%) and ERG (18/18, 100%). Molecular analysis in 5 cases demonstrated different mutation profiles involving different genes, including MTOR, PIK3CA, ARID1A, CDKN2A, PTEN, TP53, ATRX, KDR/VEGFR2, and so forth. On follow-up, 30patients (93%) died of disease, with a median survival of 114 days. Univariate and multivariate analyses revealed PHA and epithelioid morphology to be associated with worse survival (P<.05), while treatment was associated with better survival (P<.001). Our results confirmed that angiosarcoma, particularly PHA, is extremely aggressive. Epithelioid morphology is an adverse prognosticator and may be used for tumor subclassification.

A RARE TUMOR – ADRENAL ANGIOSARCOMA

Background. Primary adrenal angiosarcoma is an exceptionally rare tumor with an incidence of &lt;1% of soft tissue sarcomas. Less than 50 cases being described in literature; most of them were nonfunctional presenting with symptoms of abdominal lump, weight loss, fatigue or weakness. The treatment remains multi-modal with involvement of surgeon as well as medical oncologist. Objective. The aim of this case report is to describe an entity which is rare in terms of incidence. It was functional as well as metastatic and managed with multimodality therapy. Methods. The case is a 47-year-old man diagnosed with metastatic adrenal angiosarcoma. The patient was managed with chemotherapy followed by surgery. Results. The final histopathological examination of the specimen and immunohistochemistry revealed angiosarcoma. At present the patient is under follow-up. Conclusion. Even though surgery forms the main stay of management, the role of multi-modality therapy forms the cornerstone for adrenal angiosarcomas.

Some CNS sarcomas seen: A 22-year series.

Central nervous system (CNS) and spine are seldom impacted by primary or metastatic sarcomas. We reviewed our 22-year experience with metastatic versus primary mesenchymal sarcomas in adults versus pediatric patients, additionally asking how many might today undergo nomenclature changes using CNS World Health Organization, 5th edition criteria. Case identification via text word search of pathology databases from our adult and pediatric referral hospitals, 2000 to August 2022, with exclusion of peripheral nervous system and primary chondro-osseous and notochordal tumors. Demographic, immunohistochemical, fluorescence in situ hybridization (FISH), and fusion results performed at the time of original diagnosis were acquired from reports. 57 cases were identified, with a 16 : 15 primary and 19 : 7 metastatic ratio in adult versus pediatric patients. Ewing sarcoma was the most frequent type (n = 18, 7 adult, 11 pediatric), with a rare primary PEComa, 2 alveolar soft part sarcomas, and metastatic angiosarcoma in the cohort. Only 3 cases, an intracranial sarcoma, DICER-1 mutant formerly diagnosed as rhabdomyosarcoma, an intracranial mesenchymal tumor, FET::CREB fusion-positive formerly diagnosed as angiomatoid fibrous histiocytoma, and a CIC-rearranged sarcoma required nomenclature updating by CNS WHO5 criteria. Few primary or metastatic, adult or pediatric, CNS/spinal sarcomas required nomenclature updates; almost all had been satisfactorily classified at the time of diagnosis, using immunohistochemistry, FISH, or fusion results.

PD-1 blockader-associated atypical hemophagocytic lymphohistiocytosis: A cautionary case report

Hemophagocytic lymphohistiocytosis (HLH) is a fatal immune hyperactivity syndrome with high mortality. It seriously endangers human health. HLH associated with immune checkpoint inhibitors is rare, and no particular diagnostic guidelines or treatment regimens exist. A 36-year-old patient with metastatic right atrial angiosarcoma was treated with programmed cell death-1 (PD-1) blockader toripalimab and pazopanib, a vascular endothelial growth factor receptor blockader. However, the patient presented to our center with HLH, and he accepted combination therapy of therapeutic plasma exchange (TPE) and immunotherapy. The patient improved quickly, after only one TPE procedure. Finally, he was discharged after completing two TPE procedures. We summarize a case of PD-1 blocker associated atypical HLH that was successfully treated with TPE. Further evidence is needed to elucidate whether TPE has therapeutic potential for immunotherapy associated HLH.

NCMP-01. CEREBRAL ANGIOSARCOMA AND DISTANT RADIATION THERAPY

Abstract Angiosarcoma is a rare malignant tumor originating from vascular endothelial cells. Typically, the diagnosis of angiosarcomas carry poor prognosis. Radiation exposure is one of the most common risk factors for angiosarcomas. Due to the rarity of angiosarcoma, there is sparse literature, hence it is mostly seen in case reports. We describe a case of cerebral angiosarcoma with an unknown primary malignancy in a patient with distant history of non-Hodgkin’s lymphoma treated with chemotherapy and radiation therapy to the thorax. A 54 year old male with a history of Non-Hodgkin’s Lymphoma was treated with ABVD chemotherapy and thoracic radiation therapy in 1995,presented for bilateral vision loss. Neurologic examination revealed a left homonymous hemianopia .Further investigation with brain Magnetic Resonance Imaging revealed hemorrhagic lesions in the bilateral frontal and in the right parietal-occipital lobes. Computed tomography of the chest, abdomen, and pelvis was negative for malignancy. The patient underwent a right occipital craniotomy with resection of right parietal occipital lesion. Histopathology revealed metastatic angiosarcoma. It has been acknowledged that exposure to external beam radiotherapy puts patients at risk for angiosarcoma in the future. It is believed that radiation may induce the development of AS by several mechanisms. One mechanism is the direct oncogenic effect of ionizing radiation, which can damage DNA, leading to genome instability and mutation of cancer-related genes. A prior literature review noted twenty cases of angiosarcoma developing following therapeutic irradiation. Our particular patient’s prior exposure to irridation did not include a brain radiation field, so it is unlikely this patient had radiation induced angiosarcoma.Furthermore, it does not appear that his prior radiation exposure explains the location of his angiosarcoma as his radiation field was localized to chest. Although angiosarcoma is rare, it deserves further investigation to increase the knowledge base on etiology of metastasis.

Rare Case of Epitheloid Angiosarcoma Posing a Diagnostic Challenge in Duodenal Biopsy

Abstract Introduction/Objective Angiosarcoma (AS) is an aggressive tumor usually arising in the skin and soft tissue. We report a unique case of AS presenting as multiple nodules in duodenum with epithelioid histomorphology without prior diagnosis. Methods/Case Report An 80-year-old man presented with dyspnea on exertion, fatigue and severe anemia. Initial work up showed bilateral pleural effusions; a wedge biopsy of the left lung was done, but results were inconclusive. The patient required repeated blood transfusions over the next three months due to persistent anemia, and gastroenterology was consulted to further investigate the cause of anemia. Occult blood was found on rectal examination. Endoscopy revealed multiple mucosal nodules and polyps in the duodenum. Biopsy showed sheets of markedly atypical, lamina propria infiltrating large epithelioid cells with vesicular nuclei, prominent nucleoli, and eosinophilic cytoplasm undermining an adenoma. The atypical cells showed strong positivity for vimentin, CD31 and ERG, patchy positivity for MNF 116; and negative for HHV-8, S-100, CK20, and various other markers. Ki-67 index was approximately 30%. The diagnosis of duodenal angiosarcoma was made and referred for expert consultation, who concurred with the diagnosis. The patient’s previous lung wedge biopsy was reviewed, and determined to represent small foci of metastatic epithelioid angiosarcoma. The patient received radiotherapy but remained dependent on frequent transfusions, and died 7 weeks after the duodenal biopsy. Results (if a Case Study enter NA) NA. Conclusion Angiosarcoma occurring in the GI tract is rare and has a poor prognosis. In our case, the patient presented with an occult GI bleed and was found to have metastatic disease on presentation. AS presenting with epithelioid morphology in the GI tract can cause significant diagnostic challenges; therefore, pathologist should be aware and may benefit from including vascular immunohistochemical markers in work up to rule out this clinically aggressive vascular malignancy.

Angiosarcoma of the lungs, liver, and bones in a 27-year-old male patient

Angiosarcoma is a rare (from 1% to 2% of all soft tissue sarcomas), highly aggressive endothelial tumor that may affect any organ. The prognosis for the disease is poor, particularly if it is metastatic by the time of diagnosis. The etiology is unclear; however, there are definite risk factors including chronic lymphedema, radiation therapy, familial syndromes, and exposure to environmental chemical toxins and foreign bodies. Although the final diagnosis is histopathological, radiological tools such as ultrasound, CT, and MRI are still necessary to determine the stage of cancer. Treatment includes surgery, chemotherapy, and radiation therapy. Chemotherapy is the main treatment strategy for metastatic angiosarcoma, however, the toxicity level of frequently used agents is high. The research focuses on targeted medicines and immunotherapy as potential therapeutic options. We present a case of angiosarcoma in a young man without chronic illnesses with metastatic spread to the lungs, liver, and bones at the time of diagnosis

Thyroid angiosarcoma: A case report and review of literature.

Thyroid angiosarcoma is a very aggressive and rare malignancy that is mostly seen in elderly of Alpine regions, related to high prevalence of iodine deficient goiter. The major diagnostic challenge is to distinguish between this entity and anaplastic carcinoma and to specify whether it is a primary or metastatic angiosarcoma. The objective of this work is to clarify this distinction through our case report and a revue of literature. We report the case of a 55 years-old female patient, with no medical history, admitted to the General Surgery Department of Ibn Sina Hospital in Rabat for the management of a cervical mass classified sonographically TI-RADS 6. It was also noted a lesion of the skin next to the thyroid lodge. The patient underwent total thyroidectomy with simple post-operative course. A third tumor location was discovered in the stomach during Oesophago-Gastro-Duodenoscopy (OGD). Microscopically, the thyroid, cutaneous and gastric tumors showed rows of oval to spindle-shaped cells, with marked cytonuclear atypia and high mitotic activity. The stroma was richly vascularized and fibro-inflammatory. Immunohistochemical studies demonstrated that the tumor cells showed positive staining for cytokeratin (AE1/AE3), CK7, ERG and CD31, while they exhibited no immunoreactivity for CK20, thyroglobulin or CD34. The first diagnostic challenge is to rule out anaplastic carcinoma. Using and the classification proposed by Cutlan et al. and a large immunohistochemical panel the diagnosis of epithelioid angiosarcoma was retained. Based on epidemiological and clinical criteria, the primary site in our case was more likely to be cutaneous. In summary, thyroid angiosarcoma is an uncommon thyroid neoplasm which poses a problem of differential diagnosis with anaplastic carcinoma and metastatic angiosarcoma. The use of a large panel of antibodies as well as the epidemiological and clinical data can solves the problem in the most difficult cases. • Thyroid angiosarcoma is a very rare malignancy that is mostly seen in elderly of Alpine regions, related to high prevalence of iodine deficient goiter. • It is a very aggressive tumor that can rapidly spread to the cervical lymph nodes, lungs, and brain or can metastasize to the duodenum, small bowel and large bowel. • Metastatic disease is associated with poor prognosis and limits the mean survival time to a few months after diagnosis and surgical treatment. • The first diagnostic challenge is to rule out an angiomatoid anaplastic carcinoma, using a large panel of antibodies. • The second challenge is to specify whether it is a primary or metastatic angiosarcoma especially when other sites are involved, based on clinical and epidemiological criteria.

Blockade of beta-adrenergic receptors reduces cancer growth and enhances the response to anti-CTLA4 therapy by modulating the tumor microenvironment

The development of immune checkpoint inhibitors (ICI) marks an important breakthrough of cancer therapies in the past years. However, only a limited fraction of patients benefit from such treatments, prompting the search for immune modulating agents that can improve the therapeutic efficacy. The nonselective beta blocker, propranolol, which for decades has been prescribed for the treatment of cardiovascular conditions, has recently been used successfully to treat metastatic angiosarcoma. These results have led to an orphan drug designation by the European Medicines Agency for the treatment of soft tissue sarcomas. The anti-tumor effects of propranolol are suggested to involve the reduction of cancer cell proliferation as well as angiogenesis. Here, we show that oral administration of propranolol delays tumor progression of MCA205 fibrosarcoma model and MC38 colon cancer model and increases the survival rate of tumor bearing mice. Propranolol works by reducing tumor angiogenesis and facilitating an anti-tumoral microenvironment with increased T cell infiltration and reduced infiltration of myeloid-derived suppressor cells (MDSCs). Using T cell deficient mice, we demonstrate that the full anti-tumor effect of propranolol requires the presence of T cells. Flow cytometry-based analysis and RNA sequencing of FACS-sorted cells show that propranolol treatment leads to an upregulation of PD-L1 on tumor associated macrophages (TAMs) and changes in their chemokine expression profile. Lastly, we observe that the co-administration of propranolol significantly enhances the efficacy of anti-CTLA4 therapy. Our results identify propranolol as an immune modulating agent, which can improve immune checkpoint inhibitor therapies in soft tissue sarcoma patients and potentially in other cancers.

Diagnosis of metastatic angiosarcoma of the aorta in colonic lesion biopsies.

Angiosarcomas are rare tumors that usually entail a poor prognosis because of extensive invasiveness and high rates of distant metastasis. Gastrointestinal tract involvement is uncommon but may cause digestive bleeding. A definitive diagnosis requires histological and immunohistochemical testing. Metastatic lesions to the gut usually have a typical morphology, which must be identified in order to avoid delay in the diagnosis and potential treatment of this malignant condition.

Bone Marrow Metastasis in a Suspected Case of Angiosarcoma Unravelled by Immunohistochemistry.

A 40-year-old female presented with progressive fatigue and left upper abdominal discomfort for 1 month. CT scan revealed ill-defined hypervascular lesions in the liver and diffuse enlargement of the spleen. She had severe anemia with leukoerythroblastic reaction. Bone marrow smears revealed clusters and discrete spindle cells, few plump and round cells. Trephine biopsy revealed an infiltrative spindle-cell neoplasm replacing the marrow with the focal presence of epithelioid cell clusters. On immunostaining, the tumor cells were positive for CD34, CD31, Friend Leukemia Virus Integration-1 (FLI1), and vimentin, consistent with metastatic angiosarcoma. There were multiple small aggregates of 5-10 MIB-1 positive tumor cells (overall positivity < 1%). She succumbed to her illness before initiation of any therapy. Bone marrow metastasis of angiosarcoma is extremely rare. The aggressive clinical course and judicious use of immunohistochemical markers are required for definitive diagnosis.