Angiosarcoma is so rare, no reports on its epidemiology and prognosis using nationwide population-based data exist. The present study aimed to clarify the characteristics and clinical outcomes of angiosarcoma using the National Cancer Registry (NCR) in Japan. We analyzed data from 23,522 patients with soft-tissue sarcomas (STS), entered in the NCR in 2016-2019 using the International Classification of Diseases-Oncology, Third Edition cancer topography and morphology codes. We extracted demographics, tumor details, treatment, and prognosis for each patient. Of 23,522 STS patients, 1,973 patients were enrolled in the angiosarcoma group and 21,549 in the non-angiosarcoma group. Angiosarcoma accounts for 8.4% of all STS (adjusted incidence: 0.18/100,000/year). Most angiosarcoma patients were men (58.7%) and the most common tumor location was the head/neck (51.0%). In the angiosarcoma group (compared to the non-angiosarcoma group): age at diagnosis was significantly older; more tumors were localized; chemotherapy and radiotherapy were more common; surgery was less common; and the overall survival was significantly worse (P < 0.001). Several factors were associated with worse overall survival in the multivariate analyses. The present study is the first to have clarified the epidemiology, clinical features, treatment, prognosis, and significant factors affecting prognosis of patients with angiosarcoma in Japan.

Angiosarcoma is a rare and aggressive malignancy of endothelial cells with multiple subtypes. Foamy cell angiosarcoma is a rare variant in which endothelial cells demonstrate "foamy" cytoplasmic change. We present the case of a 59-year-old male who presented with progressive erythema and swelling of the midface and bilateral eyelids. Two biopsies obtained 3 months apart showed an infiltrate of foamy mononuclear cells in the deep dermis, resembling a xanthomatous histiocytic process. Clinical work-up for disorders including Erdheim-Chester disease, Langerhans cell histiocytosis, and necrobiotic xanthogranuloma was negative. Nine months later, a third set of biopsies was performed showing a similar infiltrate of foamy histiocyte-like cells within the deep dermis. However, there was also a dermal proliferation of irregular vascular spaces lined by atypical endothelial cells, diagnostic of angiosarcoma. Subsequent immunohistochemical stains demonstrated expression of CD31 and ERG within the foamy cells in both sets of biopsies, strongly suggesting endothelial lineage and supporting a diagnosis of foamy cell angiosarcoma. CD34 was negative. This case represents a very unusual presentation of angiosarcoma and a diagnostic conundrum. In cases such as these, especially when features of a vascular proliferation are absent, ERG appears to be the most useful marker for differentiating foamy cell angiosarcoma from histopathologic mimickers.

Hepatic mesenchymal tumors (HMTs) are non-epithelial benign and malignant tumors with or without specific mesenchymal cell differentiation. They are relatively uncommon. Except for mesenchymal hamartoma, calcified nested stromal-epithelial tumor, and embryonal sarcoma, most mesenchymal lesions are not specific to the liver. Pathologists face challenges in diagnosing HMTs due to their diverse morphologies and phenotypic variations. Accurate diagnosis is critical for directing appropriate patient care and predicting outcomes. This review focuses on mesenchymal tumors with a relative predilection for the liver, including vascular and non-vascular mesenchymal neoplasms. It provides a thorough and up-to-date overview, concentrating on clinical and pathological features, differential diagnosis, and diagnostic approaches.

The prognostic impact of subclassifying tumors as primary and secondary cutaneous angiosarcoma (cAS) in terms of the risk of local recurrence, metastasis, disease-specific mortality, and overall survival has not been extensively investigated in previous studies. This study aimed to characterize the clinicopathological features and estimate the 2-, 5-, and 10-year rates of local recurrence, metastasis, disease-specific death, and overall survival for patients with primary and secondary cAS, and to propose a follow-up recommendation for these patients.

All Danish patients diagnosed with cAS between 2000 and 2023 were included. The prognosis was estimated using age- and sex-standardized stratified cause-specific Cox-regression with all-cause mortality as a competing risk.

A total of 192 patients were included, comprising 99 patients with primary cAS and 93 with secondary cAS. The 5-year local recurrence rate was similar between primary (42 %) and secondary cAS (39 %). However, patients with primary cAS exhibited a higher 5-year rate of metastasis (50 %) compared to those with secondary cAS (33 %). Similarly, the 5-year disease-specific mortality was substantially higher in patients with primary cAS (57 %) compared to secondary cAS (35 %). Correspondingly, the 5-year overall survival rate was low in both primary (32 %) and secondary cAS (49 %).

Primary cAS is associated with poorer 5-year outcomes of metastasis, disease-specific death, and overall survival compared with secondary cAS. Follow-up could be limited to 5 years, as >95 % of the relapses occurred within this period and may include clinical examinations and local MRI to detect local recurrences, and cross-sectional imaging to detect regional and distant metastases.

Angiosarcoma (AS) is a rare malignancy with considerable heterogeneity seen in its aetiology, anatomical location, and clinicopathological behaviour. Diagnosis is often delayed and prognosis poor. The purpose of this study was to perform a retrospective review of all cases of AS over 10 years at a high-volume regional UK referral centre.

We reviewed all cases of AS discussed at the sarcoma multidisciplinary meetings of University Hospitals Birmingham NHS Foundation Trust from September 2013 to August 2023. Demographic and clinicopathologic features at diagnosis, approaches to treatment, and outcomes were compared between four AS subtypes.

A total of 130 cases were identified. The median age at diagnosis was 71 years, with the majority being female (78%). The most common AS subtype was radiation-induced AS (RIAS) (n = 72; 55%), followed by primary cutaneous (n = 28; 22%), primary non-cutaneous (n = 25; 19%), and AS secondary to lymphoedema (n = 5; 4%). Metastases were present at diagnosis in 18% of patients. Treatment was with surgery in the majority of patients (71%). The median survival for the cohort was 30 months (95% CI 20-40), although this differed significantly by AS subtype (p < 0.001), ranging from 5 months in primary non-cutaneous AS to 76 months in RIAS.

RIAS is the most common AS subtype, with surgery the only potentially curative treatment modality. Overall prognosis varies significantly by subtype. An international consensus on classification of AS subtypes is required to allow meaningful comparisons across studies and/or a prospective multi-centre registry.

Primary (PAS) and radiation-associated angiosarcomas (RAAS) of the breast are rare tumors of vascular origin with poor survival. In this retrospective cohort study, we aimed to assess the impact of multidisciplinary treatment optimization on the prognosis of patients who underwent surgery at a national referral center.

Cases of operable angiosarcoma of the breast evaluated by a multidisciplinary team including surgeons, medical oncologists and radiation oncologists expert in the field and treated from January 2012 to January 2023 were retrieved from a prospectively maintained database. The outcomes of three treatment groups, defined by the timing of surgery in relation to adjuvant and neoadjuvant therapies, were compared.

Fifty-nine patients with operable angiosarcomas of the breast (49 RAAS and 10 PAS) were retrospectively identified. The five-year overall survival was 85.2 % (95 % CI 73.9-98.2) and event-free survival was significantly better in patients with grade 1 than those with grade 2 or 3 tumors. Patients receiving neoadjuvant chemotherapy had significantly better outcomes than those treated with primary surgery. Pathological complete response was significantly higher in patients receiving neoadjuvant radiotherapy after neoadjuvant chemotherapy, and a trend towards better distant-disease-free survival was found for patients with complete response at time of surgery.

Optimization of angiosarcoma treatment based on specialized, multidisciplinary assessment regarding the type and timing of surgery and the use of neoadjuvant chemoradiotherapy can improve outcomes. The findings of this study support the use of neoadjuvant chemotherapy as well as adjuvant and neoadjuvant radiotherapy in clinical practice.

Ovarian angiosarcoma (OA) is rare, with only sporadic cases reported in English literature. We performed a systematic review of cases published in the PubMed, Science Direct, and Google Scholar databases with the aim of describing the reported clinicopathological features of OA. Fifty-three articles that reported 60 patients were reviewed. Of the 60 patients, 7 (11.6 %) were diagnosed with secondary (metastatic) ovarian angiosarcoma and 53 (88.3 %) were diagnosed with primary ovarian angiosarcoma. The mean age at presentation for ovarian angiosarcoma was 38.3±17.8 years. The average tumor size for ovarian angiosarcoma was 11.9±6.1 cm. Abdominal distention was reported in 45/60 (75 %). Microscopic examination revealed necrosis in 28/60 (46.7 %), pleomorphism in 32/59 (54.2 %), mitotic figures in 44/60 (73.3 %), spindle-shaped cells in 27/36 (75 %), epithelioid-shaped cells in 20/36 (55.5 %), and mixed epithelioid and spindle-shaped cells in 12/36 (33.3 %) patients. On immunohistochemistry CD 31 was positive in 41/41 (100 %), CD 34 in 38/39 (97.4 %), and Factor VIII related antigen in 18/21 (85.7 %) patients. Metastasis was present in 43/60 (71.6 %) patients. Chemotherapy and surgery was performed in 36/52 (69.2 %). The median follow-up time for ovarian angiosarcoma was 7 months (IQR1-IQR3:2-13.5 months). 24 (48 %) of the 50 patients with available survival data were alive and 26/50 (52 %) were dead of disease. Survival analyses (KM curves) revealed that the presence of necrosis (log-rank test; p = 0.05) and absence of spindle-shaped cells (log rank test; p = 0.04) on histopathology were associated with worse outcomes, while treatment with combined chemotherapy and surgical excision was associated with better survival (P < 0.001) therefore, prompt diagnosis and early treatment with combined chemotherapy and surgical excision can prolong survival in OA.

Soft tissue sarcomas are a diverse and heterogeneous group of cancers of mesenchymal origin. Each histological type of soft tissue sarcoma has unique clinical particularities, which makes them challenging to diagnose and treat. Multidisciplinary management of these rare diseases is thus key for improved survival. The role of surgery has been well established, and it represents the cornerstone curative treatment for soft tissue sarcomas. To date, local recurrence is the leading cause of death in low-grade sarcomas located at critical sites, and distant metastasis in high-grade sarcomas, regardless of the site of origin. Management must be tailored to each individual histologic type. We describe the most common types of extremity, trunk, abdominal, and retroperitoneal soft tissue sarcoma along with characteristics to consider for optimized management.

The spleen is occasionally referred to as the 'forgotten organ' because splenic lesions are less common and encountered rarely compared to pathologies of other abdominal solid organs. Therefore, although well-demonstrated using various abdominal imaging modalities, radiologists tend to be less familiar with splenic diseases, making interpretation challenging. This study aimed to review common and uncommon splenic diseases and illustrate the multimodal imaging (including ultrasonography, CT, MRI, and PET/CT) features of these lesions in correlation with their histopathology. Recognizing the radiological findings of various splenic lesions helps narrow down the differential diagnosis and guide appropriate clinical decision-making for radiologists.

Radiation associated angiosarcoma (RAAS) of the breast is a rare malignancy with poor survival. Optimal treatment strategies remain uncertain due to a lack of data, and vary between surgery alone and a combination of surgery with (neo)adjuvant chemotherapy (NACT) and/or re-irradiation. The aim of this study was to evaluate the potential benefit of taxane based NACT.

In this retrospective single center study, all patients with RAAS of the breast treated between 1994 and 2024 are included. Since 2018, NACT is considered a treatment option for this patient population in our institute. The difference in oncological outcomes of patients with and without NACT were compared.

Thirty-five women were included. Thirteen (37 %) received NACT of which five (39 %) also had neoadjuvant re-irradiation with hyperthermia. Eleven patients (85 %) received paclitaxel, the other two (15 %) had doxorubicine/docetaxel. Complete pathological response was found in 69 % (n = 9). Median follow up was 41 months (range 24-56) for patients with NACT and 44 (range 20-108) for patients without NACT. In the NACT group, only one patient developed a recurrence after 6.5 years. Patients with NACT had improved oncological outcomes compared to patients without NACT in terms of 3-year local recurrence free survival (100% vs. 63.9 %, p = 0.14), distant metastasis free survival (100 % vs. 47.5 %, p = 0.005), and overall survival (100% vs. 56.1 %, p = 0.016).

In this study, neoadjuvant taxanes for RAAS of the breast leads to improved distant metastasis free survival and overal survival in patients treated with NACT compared to no NACT.

Angiosarcoma is a rare endothelial-derived malignancy that is extremely diverse in anatomy, aetiology, molecular and immune characteristics. While novel therapeutic approaches incorporating targeted agents and immunotherapy have yielded significant improvements in patient outcomes across several cancers, their impact on angiosarcoma remains modest. Contributed by its heterogeneous nature, there is currently a lack of novel drug targets in this disease entity and no reliable biomarkers that predict response to conventional treatment. This review aims to examine the molecular and immune landscape of angiosarcoma in association with its aetiology, anatomical sites, prognosis and therapeutic options. We summarise current efforts to characterise angiosarcoma subtypes based on molecular and immune profiling. Finally, we highlight promising technologies such as single-cell spatial "omics" that may further our understanding of angiosarcoma and propose strategies that can be similarly applied for the study of other rare cancers.

Angiosarcoma of the bone is very rare, accounting for less than 1% of all malignant bone tumors. We report our experience with an epithelioid hemangiosarcoma arising in the proximal tibia and a review of the literature. The patient, an 85-year-old male, was referred to our institution because of left knee pain that had persisted for five months, and bone radiolucency was observed in the proximal tibia. A bone and prostate biopsy was performed due to a suspicion of prostate cancer and bone metastasis. The positron emission tomography-computed tomography (PET-CT) showed accumulation in the prostate and proximal tibia, and the prostate-specific antigen (PSA) level was high at 14.11 ng/mL. Therefore, we diagnosed the patient with bone metastasis of prostate cancer and performed curettage and cement filling. However, postoperative pathological diagnosis revealed an epithelioid hemangiosarcoma, and we considered amputation. Two months after curettage, the patient underwent transfemoral amputation because of local recurrence. Eight months after amputation, he died due to multiple metastases. Approximately 20% of cases with epithelioid hemangiosarcoma have multiple metastases at the time of initial diagnosis, and it is sometimes difficult to distinguish from bone metastases of cancer because they may be arranged in foci or on cords. There are few reports of effective adjuvant therapy, and the clinical course can be rapid, so early amputation should be considered.

The most primary sites of angiosarcoma are the skin, breast gland, and soft tissues. Primary hepatic angiosarcoma (PHA) is a rare malignant tumor of mesothelial tissue originating from the liver. PHA often presents with multiple intrahepatic foci or metastasis at the time of presentation due to its nonspecific clinical presentation and highly aggressive nature. There are no established or effective treatment guidelines for PHA, so early detection and early treatment are of great value for patient survival. Unfortunately, there is a paucity of literature on the imaging features of PHA, making the diagnosis and treatment of this disease a considerable challenge.

In this case report, we present a 59-year-old man who initially presented with abdominal pain and radiating pain in the right shoulder. Magnetic resonance imaging and positron emission tomography-computed tomography revealed multiple intrahepatic nodules that needed to be differentiated from tumors of vascular epithelial origin and tumors with progressive enhancement features, and signs of tumor metastasis were assessed. The patient was then subjected to contrast-enhanced ultrasonography (CEUS) to further clarify the extent of tumor infiltration and the state of microcirculatory perfusion. The manifestations observed on CEUS were similar to the classical characteristic presentation of hepatocellular carcinoma, called "quick wash-in and quick wash-out". In addition, CEUS showed that the lesion exhibited gradual infiltration and growth along the liver pedicle structures with no invading blood vessels. Finally, based on pathological and immunohistochemical tests and the above imaging manifestations, it was confirmed that the patient had infiltrating PHA, which is a rare pathological type of PHA. The patient underwent transcatheter arterial chemoembolization and chemotherapy. Four months after the onset of symptoms, the follow-up radiological examination revealed poor treatment efficacy and rapid deterioration.

This case report complements the imaging modalities of a rare infiltrative PHA, in which CEUS and quantitative analysis are found to offer substantial advantages in characterizing the microcirculatory perfusion of the lesion, providing clinicians with diagnostic information at the earliest opportunity to make a diagnosis and develop a treatment strategy to prolong the patient survival.

This study sought to investigate oncological outcomes and prognostic factors for patients with angiosarcomas (AS).

This single-center, retrospective cohort study, analyzed histopathologically confirmed AS cases. Primarily diagnosed, locally recurrent and metastatic AS were included. Overall survival (OS), local control (LC) and local progression-free survival (LPFS) were assessed by Kaplan-Meier estimator. Multivariable Cox regression analysis was performed to detect factors associated with OS and LPFS.

In total, 118 patients with a median follow-up of 6.6 months were included. The majority presented with localized disease (62.7%), followed by metastatic (31.4%) and locally recurrent (5.9%) disease. Seventy-four patients (62.7%) received surgery, of which 29 (39.2%) were treated with surgery only, 38 (51.4%) with surgery and perioperative radiotherapy or chemotherapy, and 7 (9.4%) with surgery, perioperative radiotherapy and chemotherapy. Multivariable Cox regression of OS showed a significant association with age per year (hazard ratio (HR): 1.03, p = 0.044) and metastatic disease at presentation (hazard ratio: 3.24, p = 0.015). For LPFS, age per year (HR: 1.04, p = 0.008), locally recurrent disease at presentation (HR: 5.32, p = 0.013), and metastatic disease at presentation (HR: 4.06, p = 0.009) had significant associations. Tumor size, epithelioid components, margin status, and perioperative RT and/or CTX were not significantly associated with OS or LPFS.

Older age and metastatic disease at initial presentation status were negatively associated with OS and LPFS. Innovative and collaborative effort is warranted to overcome the epidemiologic challenges of AS by collecting multi-institutional datasets, characterizing AS molecularly and identifying new perioperative therapies to improve patient outcomes.

Angiosarcoma is a rare aggressive and understudied soft tissue sarcoma with pending evidence-based treatment guidelines due to varying study cohorts and inconsistent outcome measures. Surgery with wide resection is currently considered to be the cornerstone in management. In a population-based cohort identified from Danish National Health Registers between 2000 and 2017, this study aimed to define prognostic factors in patients with newly diagnosed soft tissue angiosarcoma. Kaplan-Meier survival analysis demonstrated 5-year overall survival of 28%. Competing risk analysis demonstrated cumulative incidence of local recurrence of 30% and metastasis of 43%. Multivariable Cox models among 154 included patients demonstrated age above 60 years and metastasis to be independently associated with worse overall survival. Cutaneous tumors, surgery, and negative resection margin were independently associated with improved overall survival. Adjuvant oncological treatment did not improve overall survival, risk of metastasis, or recurrence. Negative margin was not associated with lower risk of recurrence and metastasis. We conclude that, despite demonstrated improved survival after surgery with wide resection, overall survival remains poor.

Angiosarcomas are rare and highly malignant soft tissue sarcomas originating from endothelial cells lining the lymphatic or vascular system. While they predominantly emerge from (sub)cutaneous regions, occurrences have been reported throughout the body. The etiology of angiosarcoma remains elusive in most clinical cases. Nevertheless, several prognosis risk factors play a pivotal role, including chronic lymphedema, therapeutic irradiation, environmental carcinogens, familial syndromes, and the presence of foreign materials like metallic objects and biomedical implants. Despite evidence implicating retained foreign material in angiosarcoma development, understanding its prognosis and pathogenesis remains limited. The pathogenesis of angiosarcoma appears to involve a complex interplay of chronic inflammation, tissue remodeling, and genetic factors that create a conducive microenvironment for malignant transformation. Management of these sarcomas remains challenging due to their infiltrative nature owing to the high chance of metastasis and local recurrence. The primary treatment modalities currently include surgery, radiotherapy, and chemotherapy, but recent advances in targeted immunotherapy and gene therapy hold promise for more effective approaches. This comprehensive review delves into the potential etiological and pathogenic roles of foreign materials, such as metallic objects, biomedical implants, and biomaterials, in the development of angiosarcoma. Further research into the underlying molecular mechanisms could provide valuable insights for tailored management and developing novel targeted therapeutic strategies.

Both primary and secondary breast angiosarcoma (AS) are characterized by multifocal presentation and aggressive behavior. Despite multimodality therapy, local and distant relapse rates remain high. Therefore, neoadjuvant chemotherapy (NACT) is employed to improve the R0 resection rates and survival, but its benefits remain controversial. Herein, we investigate pathologic and molecular correlates to NACT-induced histologic response in a group of 29 breast AS, 4 primary and 25 radiation-associated (RA). The two NACT regimens applied were anthracycline- and non-anthracycline-based. The pathologic response grade was defined as: I: ≤ 50%, II: 51%-90%, III: 91%-99%, and IV: 100%. An additional 45 primary AS and 102 RA-AS treated by surgery alone were included for survival comparison. The genomic landscape was analyzed in a subset of cases and compared to a cohort of AS without NACT on a paired tumor-normal targeted DNA NGS platform. All patients were females, with a median age of 31 years in primary AS and 68 years in RA-AS. All surgical margins were negative in NACT group. The NACT response was evenly divided between poor (Grades I-II; n = 15) and good responders (Grades III-IV; n = 14). Mitotic count >10/mm2 was the only factor inversely associated with pathologic response. By targeted NGS, all 10 post-NACT RA-AS demonstrated MYC amplification, while both primary AS harbored KDR mutations. TMB or other genomic alterations did not correlate with pathologic response. All four patients with Grade IV response remained free of disease. The good responders had a significantly better disease-specific survival (p = 0.04). There was no survival difference with NACT status or the NACT regimens applied. However, NACT patients with MYC-amplified tumors showed better disease-free survival (p = 0.04) compared to MYC-amplified patients without NACT. The overall survival of NACT group correlated with size >10 cm (p = 0.02), pathologic response (p = 0.04), and multifocality (p = 0.01) by univariate, while only size >10 cm (p = 0.03) remained significant by multivariate analysis.

Angiosarcoma (AS) represents a rare and aggressive vascular sarcoma, posing distinct challenges in clinical management compared to other sarcomas. While the current European Society of Medical Oncology (ESMO) clinical practice guidelines for sarcoma treatment are applicable to AS, its unique aggressiveness and diverse tumor presentations necessitate dedicated and detailed clinical recommendations, which are currently lacking. Notably, considerations regarding surgical extent, radiation therapy (RT), and neoadjuvant/adjuvant chemotherapy vary significantly in localized disease, depending on each different site of onset. Indeed, AS are one of the sarcoma types most sensitive to cytotoxic chemotherapy. Despite this, uncertainties persist regarding optimal management across different clinical presentations, highlighting the need for further investigation through clinical trials. The Italian Sarcoma Group (ISG) organized a consensus meeting on April 1st, 2023, in Castel San Pietro, Italy, bringing together Italian sarcoma experts from several disciplines and patient representatives from "Sofia nel Cuore Onlus" and the ISG patient advocacy working group. The objective was to develop specific clinical recommendations for managing localized AS within the existing framework of sarcoma clinical practice guidelines, accounting for potential practice variations among ISG institutions. The aim was to try to standardize and harmonize clinical practices, or at least highlight the open questions in the local management of the disease, to define the best evidence-based practice for the optimal approach of localized AS and generate the recommendations presented herein.

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.

Angiosarcoma is a rare and aggressive type of soft-tissue sarcoma with high propensity to metastasize. For patients with metastatic angiosarcoma, prognosis is dismal and treatment options are limited. To improve the outcomes, identifying patients with poor treatment response at an earlier stage is imperative, enabling alternative therapy. Consequently, there is a need for improved methods and biomarkers for treatment monitoring. Quantification of circulating tumor-DNA (ctDNA) is a promising approach for patient-specific monitoring of treatment response. In this case report, we demonstrate that quantification of ctDNA using SiMSen-Seq was successfully utilized to monitor a patient with metastatic angiosarcoma. By quantifying ctDNA levels using 25 patient-specific mutations in blood plasma throughout surgery and palliative chemotherapy, we predicted the outcome and monitored the clinical response to treatment. This was accomplished despite the additional complexity of the patient having a synchronous breast cancer. The levels of ctDNA showed a superior correlation to the clinical outcome compared with the radiological evaluations. Our data propose a promising approach for personalized biomarker analysis to monitor treatment in angiosarcomas, with potential applicability to other cancers and for patients with synchronous malignancies.

A 63-year-old woman was admitted to our department for the investigation of superior vena cava (SVC) syndrome. Computed tomography revealed an azygos tumor extending into the SVC. Video-assisted thoracic surgery (VATS) was performed to remove the distal end of the azygos vein in the left lateral position, followed by complete resection of the entire tumor under median sternotomy in the supine position. The histological diagnosis was a primary angiosarcoma of the azygos vein. The patient was discharged without any complications and is now alive and tumor-free 24 months after surgery. In addition, contrast-enhanced computed tomography revealed no graft occlusion in the two reconstructed brachiocephalic veins. Thoracoscopic surgery in the lateral position is useful for safe and reliable complete resection of a tumor arising from the azygos vein.

Primary vascular tumors of bone are a heterogeneous group of neoplasms, ranging from benign hemangiomas to frankly malignant epithelioid hemangioendotheliomas and angiosarcomas. Over the years, their classification has been a matter of discussion, due to morphologic similarities and uncertainty regarding biologic behavior. Over the past decade, with the development of next-generation sequencing, there has been a significant improvement in the molecular characterization of these lesions. The integration of their morphologic, immunohistochemical and molecular features has led to a better stratification, with important prognostic and therapeutic implications. Nevertheless, primary vascular bone tumors still represent a challenge for medical oncologists. Given their rarity and heterogeneity, in the last few years, there has been no significant progress in medical treatment options, so further research is needed. Here we present a review of the current knowledge regarding primary vascular tumors of the bone, correlating clinicopathologic features with tumor behavior and therapeutic approaches.

Recent studies have described several molecular subtypes and deregulation of immuno-oncologic signaling pathways in angiosarcoma. Interestingly, mast cells were enriched in subsets of angiosarcoma, although their significance remains unknown. In this study, we aim to verify this observation using immunohistochemistry (H scores) and NanoString transcriptomic profiling and explore the association between mast cells with clinical and biological features. In the study cohort (N = 60), H scores showed a significant moderate correlation with NanoString mast cell scores (r = 0.525; P < .001). Both H score and NanoString mast cell scores showed a significant positive correlation (P < .05) with head and neck location, nonepithelioid morphology, and lower tumor grade. Mast cell enrichment significantly correlated with higher NanoString regulatory T-cell scores (H score, r = 0.32; P = .01; NanoString mast cell score, r = 0.27; P = .04). NanoString mast cell scores positively correlated with signaling pathways relating to antigen presentation (r = 0.264; P = .0414) and negatively correlated with apoptosis (r = -0.366; P = .0040), DNA damage repair (r = -0.348; P = .0064), and cell proliferation (r = -0.542; P < .001). Interestingly, in the metastatic setting, patients with mast cell-enriched angiosarcoma showed poorer progression-free survival (median, 0.2 vs 0.4 years; hazard ratio = 3.05; P = .0489) along with a trend toward worse overall survival (median, 0.2 vs 0.6 years; hazard ratio, 2.86; P = .0574) compared with patients with mast cell-poor angiosarcoma. In conclusion, we demonstrated the presence of mast cells in human angiosarcoma and provided initial evidence of their potential clinical and biological significance. Future research will be required to elucidate their specific roles and mechanisms, which may uncover novel avenues for therapeutic intervention.

Angiosarcoma of bone is very rare entity, accounting for less than 1% of all primary bone sarcomas with associated poor prognosis. We hereby present a case report of angiosarcoma of tibia in a young boy and reviewed its literature and management of the disease. A 21-year young male presented to us with complaints of pain and swelling over left lower leg since last 3 months. On evaluation, MRI lower leg revealed multiloculated lesion of size 32×36×52 mm showing multiple fluid-fluid levels which was hyperintense on T2 images in left distal tibial metaphysis showing endosteal scalloping with cortical destruction along lateral border and abuts the physis. Image-guided biopsy was done. PET CT revealed no evidence of metastasis. Histopathology report revealed tumor involving bone and soft tissue comprising of plump ovoid to epitheloid/spindled cells in nests and focal fascicles with marked nuclear atypia, prominent nucleoli and mitotic figures with vascular pattern with thick walled vessels, many haemosiderophages. Differentials of telangiectatic osteosarcoma/adamantioma was made. On further IHC studies, tumor cells were found positive for SATB2, CD31, ERG while negative for CK, P40, DESMIN, MYOGENIN, TLE-1, S-100. Diagnosis of angiosarcoma of tibia was confirmed. Decision to give neo-adjuvant chemotherapy with doxorubin/Ifosfamide-based regimen was made followed by later with limb salvage surgery. He received 5 cycles of chemotherapy 3 weekly regimen which he tolerated well. Repeat MRI leg showed partial reduction in tumor size but there was presence of pathological fracture seen with some extraosseous component of tumor. Limb salvage surgery was not possible and he underwent below knee amputation. His postoperative recovery was eventful. Final histopathology confirmed diagnosis of angiosarcoma tibia. Case was discussed in multidisciplinary tumor board and he was started on alternate chemotherapy with Injection docetaxel and gemcitabine-based regimen. He had received 3 cycles of this regimen till now and is disease free from last 3 months. Angiosarcoma of bone is a very rare entity; the literature is limited regarding treatment and outcome of patients with this tumor. Most information is currently available from case reports, and treatments are based on guidelines for other types of primary bone sarcomas. We hereby present a case report of angiosarcoma of tibia in a young boy and reviewed its literature, diagnostic dilemmas associated with it and management of the disease after discussing in multidisciplinary board. Role of chemotherapy, surgery, and their sequencing is not well defined. Prospective trials are required to manage this rare entity.

Soft tissue sarcoma is a broad family of mesenchymal malignancies exhibiting remarkable histological diversity. We portray the proteomic landscape of 272 soft tissue sarcomas representing 12 major subtypes. Hierarchical classification finds the similarity of proteomic features between angiosarcoma and epithelial sarcoma, and elevated expression of SHC1 in AS and ES is correlated with poor prognosis. Moreover, proteomic clustering classifies patients of soft tissue sarcoma into 3 proteomic clusters with diverse driven pathways and clinical outcomes. In the proteomic cluster featured with the high cell proliferation rate, APEX1 and NPM1 are found to promote cell proliferation and drive the progression of cancer cells. The classification based on immune signatures defines three immune subtypes with distinctive tumor microenvironments. Further analysis illustrates the potential association between immune evasion markers (PD-L1 and CD80) and tumor metastasis in soft tissue sarcoma. Overall, this analysis uncovers sarcoma-type-specific changes in proteins, providing insights about relationships of soft tissue sarcoma.

Angiosarcomas are rare tumors that can be difficult to diagnose due to subtle changes in the vascular endothelium. When there is evidence to suggest malignancy, such as a pathologic fracture, further investigation is needed, and a high suspicion for angiosarcoma needs to be present so that appropriate immunohistochemical stains are utilized on biopsied tissue. In situations where such suspicion is high and prior biopsies have been negative, performance of splenectomy, can be both diagnostic and therapeutic when splenomegaly is present.

This is a case of a 52-year-old woman with splenomegaly, initially attributed to infection, in the setting of upper respiratory symptoms and thrombocytopenia. Three months later, however, she presented with back pain. Imaging showed lytic bone lesions with pathologic vertebral fracture and numerous liver lesions that were too small to characterize further. Initial biopsies of the liver and bone did not reveal a pathologic process. Several months later, still without a unifying diagnosis, she presented to our institution. MRI of the brain was done for neurologic concerns and showed pathologic enhancement in the calvarium. A PET scan showed diffuse avidity of the skeleton and spleen. After discussing the case with a hematologist, splenectomy was performed for both diagnostic and therapeutic purposes. Angiosarcoma was identified in the spleen and in a PET-directed bone biopsy. With a definitive diagnosis, she returned home and subsequently elected to pursue hospice care.

When there is a high clinical suspicion for malignant angiosarcoma, a multidisciplinary approach is necessary to direct both tissue acquisition and necessary histochemical staining.

Angiosarcomas (ASs) are rare malignant vascular entities that can affect several regions in our body, including the heart. Cardiac ASs comprise 25-40% of cardiac sarcomas and can cause death within months of diagnosis. Thus, our aim was to identify potential differences and/or similarities between cardiac and extra-cardiac ASs to enhance targeted therapies and, consequently, patients' prognosis. Whole-transcriptome analysis of three cardiac and eleven extra-cardiac non-cutaneous samples was performed to investigate differential gene expression and mutational events between the two groups. The gene signature of cardiac and extra-cardiac non-cutaneous ASs was also compared to that of cutaneous angiosarcomas (n = 9). H/N/K-RAS and TP53 alterations were more recurrent in extra-cardiac ASs, while POTE-gene family overexpression was peculiar to cardiac ASs. Additionally, in vitro functional analyses showed that POTEH upregulation conferred a growth advantage to recipient cells, partly supporting the cardiac AS aggressive phenotype and patients' scarce survival rate. These features should be considered when investigating alternative treatments.

Since the domestication of dogs 10,000 years ago, they have shared their living environment with humans and have co-evolved. The breeding process that dogs have undergone in only a few centuries has led to a significant accumulation of specific genetic alterations that could induce particular diseases in certain breeds. These canine diseases are similar to what is found in humans with several differences; therefore, comparing such diseases occurring in humans and dogs can help discover novel disease mechanisms, pathways, and causal genetic factors. Human angiosarcoma (AS) and canine hemangiosarcoma (HSA), which are sarcomas originating from endothelium, are examples of diseases shared between humans and dogs. They exhibit similar characteristics and clinical behaviors, although with some critical differences resulting from evolution. In this review, we will describe the similarities and differences in terms of clinical and molecular characteristics between human AS and canine HSA, and discuss how these similarities and differences can be applied to advance the treatment of these diseases.

Angiosarcoma is a very rare soft tissue sarcoma that originates from endothelial cells and typically has a poor prognosis. It is most commonly found in elderly white men and can occur anywhere in the body, particularly in the head, neck, and scalp. Patients who have undergone previous radiation treatment or who have chronic lymphedema also face an elevated risk of this condition. Various genetic changes are suspected to contribute to the development of angiosarcoma, and these changes have been identified as potential targets for treatment. For localized disease, wide surgical resection is often the prudent course of action. A multidisciplinary approach, which may include surgery, radiotherapy, systemic chemotherapy, or immunotherapy, is typically the most effective way to achieve favorable outcomes. In this review, we discuss the general understanding of angiosarcoma and its management, with a particular focus on the current evolving treatments for the disease.

Primary adrenal angiosarcoma is an extremely rare malignant tumor with challenging diagnosis. A 66-year-old woman had a 4.3 cm right adrenal mass suspicious for adrenal cortical carcinoma. Pathological examination demonstrated a hemorrhagic adrenal cyst with numerous irregularly shaped anastomosing vascular channels lined by atypical endothelial cells that had frequent atypical mitotic figures (12/10 HPF, Ki67 10%). The tumor cells were positive for CD31, ERG, and FLI-1, but negative for adrenal and other tumor lineage markers by immunohistochemistry. NGS fusion gene testing ruled out epithelioid hemangioendothelioma. Accurate diagnosis and differential inclusion are important for appropriate treatment of this rare tumor.

We investigated outcomes and prognostic factors for patients treated for cutaneous angiosarcoma (CA).

We conducted a retrospective review of patients treated for CA of the face and scalp from 1962 to 2019. All received definitive treatment with surgery, radiation (RT), or a combination (S-XRT). The Kaplan-Meier method was used to estimate outcomes. Multivariable analyses were conducted using the Cox proportional hazards model.

For the 143 patients evaluated median follow-up was 33 months. Five-year LC was 51% and worse in patients with tumors >5 cm, multifocal tumors, those treated pre-2000, and with single modality therapy (SMT). These remained associated with worse LC on multivariable analysis. The 5-year disease-specific survival (DSS) for the cohort was 56%. Tumor size >5 cm, non-scalp primary site, treatment pre-2000, and SMT were associated with worse DSS.

Large or multifocal tumors are negative prognostic factors in patients with head and neck CA. S-XRT improved outcomes.

We explored features of the angiosarcoma (AS) tumor microenvironment to discover subtypes that may respond to immunotherapy.

Thirty-two ASs were included. Tumors were studied by histology, immunohistochemistry (IHC), and gene expression profile using the HTG EdgeSeq Precision Immuno-Oncology Assay.

Comparing cutaneous and noncutaneous ASs, the second group showed 155 deregulated genes, and unsupervised hierarchical clustering (UHC) delineated two groups: the first mostly cutaneous AS and the second mainly noncutaneous AS. Cutaneous ASs showed a significantly higher proportion of T cells, natural killer cells, and naive B cells. ASs without MYC amplification revealed a higher immunoscore in comparison with ASs with MYC amplification. PD-L1 was significantly overexpressed in ASs without MYC amplification. UHC showed 135 deregulated genes differentially expressed when comparing ASs from the non-head and neck area with patients who had AS in the head and neck area. ASs from the head and neck area showed high immunoscore. PD1/PD-L1 content was significantly more highly expressed in ASs from the head and neck area. IHC and HTG gene expression profiling revealed a significant correlation between PD1, CD8, and CD20 protein expression but not PD-L1.

Our HTG analyses confirmed a high degree of tumor and microenvironment heterogeneity. Cutaneous ASs, ASs without MYC amplification, and ASs located in the head and neck area seem to be the most immunogenic subtypes in our series.

Angiosarcoma is a mesenchymal soft tissue sarcoma with a tendency for vascular endothelial differentiation. It is highly malignant with a poor prognosis but has a low incidence. Epithelioid angiosarcoma of the gastrointestinal tract is rare, and simultaneous multiple lesions of the stomach and small intestine are even rarer. It is easy to be misdiagnosed clinically. We report on a case of preoperative misdiagnosis of gastric cancer and postoperative diagnosis of epithelioid angiosarcoma with multiple lymph node metastases.

A 75-year-old patient who was admitted to the hospital because of fatigue, melena and dysuria for >1 month.

Gastroscopy revealed gastric fundus ulcer and the biopsy revealed poorly differentiated adenocarcinoma of the fundus. We performed a radical gastrectomy for gastric cancer during which multiple ulcers were found in the jejunum and resected. Postoperative pathology showed multiple epithelioid angiosarcoma in the stomach and small intestine with lymph node metastases. The patient did not receive further treatment and died 2 month after the surgery.

Gastrointestinal epithelioid angiosarcoma is one of the differential diagnoses of gastrointestinal adenocarcinoma and surgery is the main treatment. The lymph nodes are one of the main sites of metastasis.

Angiosarcomas are a rare subtype representing 1-2% of soft tissue sarcomas. Risk factors are rarely elucidated but radiotherapy and lymphedema are the most common ones, usually following local treatment for local breast cancer. Despite the improvement of our knowledge, the prognosis remains poor with 35-40% of 5 year-overall survival. Local treatment when feasible should include a R0 surgery completed with adjuvant radiation. When metastatic, front lines chemotherapies include doxorubicine or weekly paclitaxel. If possible, in oligometastatic patients, metastasectomy should always be considered allowing the best responses. The knowledge of angiosarcoma's biology is rapidly increasing and new biomarkers are emerging. The use of immunotherapy in particular subtypes including head and neck angiosarcomas shows promising results. The model of the angiosarcoma project, a patient-participating study, seems to be an excellent way to study rare tumors. We should focus our efforts on understanding the underlying molecular biology to propose the best precision medicine for those patients.

Fueled by support from the National Cancer Institute's "Cancer Moonshot" program, the past few years have witnessed a renewed interest in the canine spontaneous cancer model as an invaluable resource in translational oncology research. Increasingly, there is awareness that pet dogs with cancer provide an accessible bridge to improving the efficiency of cancer drug discovery and clinical therapeutic development. Canine tumors share many biological, genetic, and histologic features with their human tumor counterparts, and most importantly, retain the complexities of naturally occurring drug resistance, metastasis, and tumor-host immune interactions, all of which are difficult to recapitulate in induced or genetically engineered murine tumor models. The utility of canine models has been particularly apparent in sarcoma research, where the increased incidence of sarcomas in dogs as compared to people has facilitated comparative research resulting in treatment advances benefitting both species. Although there is an increasing awareness of the advantages in using spontaneous canine sarcoma models for research, these models remain underutilized, in part due to a lack of more permanent institutional and cross-institutional infrastructure to support partnerships between veterinary and human clinician-scientists. In this review, we provide an updated overview of historical and current applications of spontaneously occurring canine tumor models in sarcoma research, with particular attention to knowledge gaps, limitations, and growth opportunities within these applications. Furthermore, we propose considerations for working within existing veterinary translational and comparative oncology research infrastructures to maximize the benefit of partnerships between veterinary and human biomedical researchers within and across institutions to improve the utility and application of spontaneous canine sarcomas in translational oncology research.

Primary hepatic angiosarcoma (PHA) is extremely rare, and its imaging findings are similar to those of other liver tumors including hepatocellular carcinoma (HCC). Here, we report a case of hepatitis C virus (HCV)-related HCC followed by PHA that showed remarkable clinical response to atezolizumab plus bevacizumab (Atezo/Bev) therapy.

A 78-year-old man with recurrent HCC had a liver tumor with lymphadenopathy. Although considered as HCC recurrence, microscopic examination of the resected liver and lymph node showed PHA. Three months later, a solitary lung nodule was newly detected and subsequently resected. The pathological diagnosis was poorly differentiated HCC. Therefore, the patient was finally diagnosed with double cancer of PHA and HCC. Thereafter, he developed a new liver tumor with lymphadenopathy and received Atezo/Bev therapy. Liver tumor biopsy was carried out before the treatment. The pathological diagnosis was angiosarcoma. The patient showed a partial response after two courses of Atezo/Bev therapy.

To our best knowledge, this report is the first case to present HCV-related HCC followed by PHA and to show that Atezo/Bev therapy is beneficial for PHA.