Cutaneous angiosarcoma (cAS) is a rare and aggressive malignant vascular tumor that arises from endothelial cells lining the blood vessels. It can occur in any part of the body, but most commonly, it affects the skin and soft tissues. cAS has a poor prognosis with a 5-year survival rate of only 9%. This review summarizes the current understanding of angiosarcoma pathogenesis, clinical presentation, diagnosis, and treatment approaches. Recent advances in molecular characterization have identified recurrent genetic alterations that may lead to the development of novel targeted therapies. Multidisciplinary management combining surgery, radiation, and systemic therapy remains the mainstay of treatment; however, outcomes remain poor for metastatic disease. Ongoing research into the molecular drivers of cAS and immunotherapeutic approaches offers hope for improving the outcomes of this challenging malignancy.

Patients treated with radiotherapy (RT) for prostate cancer (PC) have increased risk of secondary rectal cancer (SRC) and more limited treatment options.

To assess the tumor molecular profile, clinical characteristics, and oncologic outcomes of SRC after PC and compare them with those of primary rectal cancer (PRC).

This case-control study included patients with SRC diagnosed 5 or more years after RT for PC and patients with PRC who were treated at Memorial Sloan Kettering Cancer Center in New York between February 1, 1994, and September 31, 2022.

Clinical information and DNA sequencing data were analyzed. Oncologic outcomes were compared between patients with SRC and clinically matched patients with PRC using log-rank tests and Cox proportional hazards regression models. Numerical and categorical variables were compared using the Wilcoxon rank sum test and Fisher exact test, respectively.

The analysis included 604 male patients with PRC (71.6%; median age, 55 [IQR, 46-66] years) and 64 male patients with SRC (median age, 78 [IQR, 72-82] years). Patients with SRC had more distal rectum (37 of 63 [58.7%] vs 131 of 581 [22.5%]; P < .001) and anterior rectal wall (20 of 57 [35.1%] vs 67 of 496 [13.5%]; P < .001) tumors, were less likely to receive neoadjuvant treatment (33 of 64 [51.6%] vs 570 of 604 [94.4%]), and had shorter 5-year overall survival (45.7% vs 64.9%; P = .01) and disease-free survival (40.3% vs 71.2%; P = .006) compared with clinically matched patients with PRC. Targeted DNA sequencing data from 31 SRC tumors identified lower mutational burden (median, 4.4 [IQR, 3.2-6.7] per megabase [Mb] vs 5.8 [IQR, 4.4-7.0] per Mb; P = .047), lower frequency of APC alterations (15 [48.4%] vs 432 [79.9%]; P < .001), and higher rates of SMAD4 inactivation (8 [25.8%] vs 54 [10.0%]; P = .01) compared with 541 PRC tumors. Whole-exome sequencing data from 17 SRC tumors identified a higher rate of frameshift deletions compared with 28 PRC tumors (median, 5.0 [IQR, 4.0-9.0] vs 2.5 [IQR, 1.0-4.2] variants; P < .001).

In this case-control study, patients with SRC after RT for PC had worse survival and different molecular profiles than patients with PRC. These findings may help improve the clinical management of SRC.

Angiosarcoma (AS) of the breast, a rare mesenchymal neoplasm, exhibits distinct forms based on etiological and genetic features. While cases with typical clinical presentation and morphology allow for a straightforward diagnosis, challenges arise when clinical data are scarce, diagnostic material is limited, or morphological characteristics overlap with other tumors, including undifferentiated carcinomas. The trichorhinophalangeal syndrome protein 1 (TRPS1), once regarded as highly specific for breast carcinomas, now faces doubts regarding its reliability. This study explores TRPS1 expression in breast AS. Our investigation revealed that 60% of AS cases displayed TRPS1 labeling, contrasting with the 40% lacking expression. Scoring by four independent readers established a consensus, designating 12/35 ASs as unequivocally TRPS1-positive. However, uncertainty surrounded nine further cases due to a lack of reader agreement (being substantial as reflected by a kappa value of 0.76). These findings challenge the perceived specificity of TRPS1, shedding light on its presence in a noteworthy proportion of breast ASs. Consequently, the study underscores the importance of a comprehensive approach in evaluating breast ASs and expands the range of entities within the differential diagnosis associated with TRPS1 labeling.

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.

Angiosarcomas are a type of soft-tissue sarcoma characterized by aggressive malignant tumors originating from endothelial cells of blood vessels or lymphatic vessels. Limited studies have been done to explore the molecular pathophysiology of the disease, with rather limited studies involving transcriptomic analyzes. This study was undertaken to identify the shared molecular signatures and gene modules associated with angiosarcomas of various origin. Transcriptomic data analysis of publicly available data was done followed by WGCNA to identify shared signature gene modules. The Maximal Clique Centrality algorithm was applied to gene modules, and unclustered network analysis was conducted on differentially expressed genes to identify true hub genes. The expression of candidate genes in various cancer types was analyzed using GEPIA. WGCNA analysis identified five significant modules, with the most enriched module being associated with angiogenesis and cell junction regulators. The intersection of true hub genes from MCC analysis of WGCNA modules and high-degree nodes from an unclustered network revealed eight consistently overexpressed genes in all angiosarcoma samples.Among the eight enriched genes, CHRNA5 and CTLA4, are exclusively overexpressed in angiosarcoma and not in other cancers of the same tissue origin, with significant drug-protein interactions suggesting their potential as therapeutic targets.

Pediatric angiosarcoma of soft tissue, an extremely rare entity, remains poorly understood from a genetic standpoint. Herein, we present the case of a previously healthy 17-year-old girl with acute left hip pain. Subsequent magnetic resonance imaging revealed a 21.8 cm left pelvic sidewall mass with heterogeneous enhancement and multiple lung nodules. Biopsy of the tumor showed an infiltrative, hemorrhagic neoplasm composed primarily of atypical spindle to epithelioid cells. Focal vasoformative architecture was appreciated. Immunohistochemically, the tumor cells were strongly positive for CD31, ERG, and FLI-1, supporting the diagnosis of angiosarcoma. Genetic analysis identified a novel TEK::GAB2 gene fusion. TEK belongs to the angiopoietin receptor family, and its fusion with GAB2 is predicted to mediate tumorigenesis. This report expands the current knowledge on the spectrum of gene rearrangements of angiosarcoma.

Li-Fraumeni syndrome (LFS) is one of the most common hereditary cancer predisposition syndromes in Brazil. The high frequency of the syndrome is due to a founding variant (R337H) in the country. LFS is characterized by a wide variety of malignant phenotypes. Despite the great epidemiological importance of the R337H variant, the frequency of other types of pathogenic variants is like other populations, with the majority of these being missense variants. There is strong evidence that radiotherapy is associated with secondary sarcomas, including angiosarcomas, and this finding is especially true for LFS patients. Angiosarcoma is not described as overrepresented in individuals with LFS, except in patients submitted to radiotherapy. Germline testing in all breast cancer patients under 65 will reveal many germline mutations in TP53 without a family history of cancers associated with the syndrome. We present a case of a previously undescribed pathogenic variant in TP53 (c788del, pAns263llefs⁣∗82) in a patient with no family history of cancer, with a previous diagnosis of breast carcinoma treated with radiotherapy, who developed angiosarcoma after a few years leading to germline testing. The presence of angiosarcoma in a radiotherapy bed should raise suspicion for LFS. The recent recommendation of testing breast cancer patients under the age of 65, even without any family history, can be a source of discoveries of new mutations and assist in therapeutic decisions.

Mesenchymal neoplasms within the genitourinary tract include a wide spectrum of tumors, ranging from benign to malignant, and tumors of uncertain malignant potential. Except for stromal tumors of the prostate, which originate from the specific prostatic stroma, these neoplasms generally resemble their counterparts in other body sites. The rarity of these neoplasms and the limitation associated with small biopsy samples present unique diagnostic challenges for pathologists. Accurate diagnosis is paramount, as it significantly influences prognosis and guides management and treatment strategies. This review addresses common diagnostic scenarios, discusses key differential diagnoses, and sheds light on potential diagnostic pitfalls.

Mesenchymal tumors of the skin are rare and clinically heterogeneous, and can represent diagnostic challenge for pathologists. Most of these lesions have overlapping clinical and histological features, thus the understanding of architectural patterns, cytoplasmic and stromal features can facilitate proper diagnosis. Anatomic site may be an important factor in the differential diagnosis, as are patient's age and sex. Ancillary tests are often required and can be useful to rule out other entities. Molecular diagnostics is playing an increasingly important role in the diagnosis of soft tissue neoplasms. Here, we review clinical, histological, and molecular features of some of the most common of these uncommon entities including benign and malignant lesions.

Angiosarcoma (AS) is a malignant vascular neoplasm comprising neoplastic endothelial cells accounting for 1%-4% of soft tissue sarcomas. While lymphedema-associated and post-irradiation ASs are almost always driven by a high-level amplification of MYC (8q24), sporadic ASs, including those of breast parenchymal origin, typically lack MYC amplification. Here, we report a case of sporadic breast MYC-amplified AS in a 19-year-old female with no history of lymphedema or irradiation, who was referred to our hospital for an enlarging right breast mass. After needle biopsy, the patient underwent right mastectomy and axillary lymphadenectomy. Microscopically, atypical endothelial cells proliferated and formed well-defined or slit-like vascular channels that invaded and dissected the breast parenchymal fat, ducts, and lobules. In a limited area, the tumor cells showed solid sheet-like proliferation with increased mitotic figures of 40 per 2 mm2 with a small area of necrosis. Immunohistochemical analysis revealed strong positivity for c-Myc. Fluorescence in situ hybridization (FISH) with MYC break-apart probes showed a high-level 5' single signal amplification. The patient was disease-free 16 months post-surgery. Nanopore sequencing successfully detected not only a high-level amplification of the 8q24 region, including MYC, but also multiple structural variants of the 8q24 region. In-depth analysis revealed extrachromosomal circular DNA amplification including the MYC protein-coding region and upstream region but not the downstream region. We also performed methylation classification using nanopore-based methylation data to successfully categorize the tumor as AS. This case report highlights the potential utility of nanopore sequencing in the diagnosis of sarcomas.

Introduction: Radiation-induced breast angiosarcoma (RIBAS) is a rare adverse event associated with postoperative breast irradiation. The data from the literature indicate that RIBAS occurs in less than 0.3% of patients treated with adjuvant radiotherapy for breast cancer. Given the rarity, diverse clinical presentation, poor prognosis, and lack of consensus on the management, this study aimed to present experiences of our specialized cancer center with RIBAS, in terms of the incidence, presentation, management, and outcomes. Methods: We reviewed the medical records of 10,834 breast cancer patients treated at the Institute for Oncology and Radiology of Serbia between January 2013 and June 2024 to detect patients that had breast-conserving surgery, followed by postoperative irradiation, and developed angiosarcoma in the irradiated area at least 3 years after radiotherapy, without distant metastases. The incidence, latency period, management, and treatment outcomes were analyzed. Results: A total of nine female patients with RIBAS were identified and included in this study. The median age at RIBAS diagnosis was 64 years (range: 36-68), with a median latency of 64 months (95% CI > 57) from irradiation to diagnosis. The mean tumor size was 55 mm (SD 32.78). Patients were followed for a median of 30 months (range: 7-40) after initial RIBAS surgery. Local recurrence occurred in seven patients (77.8%), with five undergoing re-do surgery with curative intent. Three patients developed distant metastases during follow-up. The median overall survival (OS) was 31 months (95% CI > 30), with a 3-year survival rate of 15.2% (95% CI 2.5-91.6%). The median local recurrence-free interval was 10 months (95% CI > 3). Median OS after RIBAS local recurrence and after breast cancer treatment was 17 months (95% CI > 15) and 108 months (95% CI > 88), respectively. Conclusions: RIBAS is a rare but increasingly prevalent adverse event associated with BC irradiation, marked by an aggressive disease course and high relapse rates. Awareness, prompt diagnosis, and a radical surgical approach with wide clear margins are critical for improving patients' outcomes.

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.

Compared to primary breast sarcoma (BSs), radiotherapy-induced sarcoma (RIS) is a less frequent type of secondary breast sarcoma. Undifferentiated pleomorphic sarcoma (UPS) is an even rarer occurrence within the RIS category. This study aimed to present the clinicopathologic and molecular features of breast radiotherapy-induced UPS.

A retrospective study was conducted at the Third Affiliated Hospital of Soochow University to analyze three patients with radiation-induced undifferentiated pleomorphic sarcoma (UPS) following breast cancer, spanning from 2006 to 2023. The clinical and pathological variables were extracted from the medical records, while immunohistochemistry was employed to analyze the immunophenotypes of these tumors. Genomic characteristics were assessed through DNA and RNA sequencing techniques. Another 15 cases from the literature were also reviewed to better characterize the tumor.

The affected areas encompass the chest wall and breasts, with an incubation period ranging from 6 to 17 years. The tumor cells exhibit pleomorphism and demonstrate a high degree of pathological mitosis. Notably, two cases displayed an accelerated disease progression, characterized by recurrent tumors and metastases occurring within short intervals of 48 and 7 months respectively subsequent to the initial diagnosis. The two prevailing identified genes were TP53 (2/3, 66.7%) and RB1 (1/3, 33.3%). Through analysis of somatic copy number variation (CNV), it was discovered that two oncogenes, MCL1 (1/3, 33.3%) and MYC (1/3, 33.3%), had experienced gains in CNV. The Tumor Mutational Burden (TMB) values for case 1, case 2, and case 3 were 5.9 mut/Mb, 1.0 mut/Mb, and 3.0 mut/Mb, respectively. Moreover, the analysis of RNA-NGS (next-generation sequencing) revealed the presence of a novel gene fusion, named COL3A1-GULP1, in case 2.

Based on our thorough analysis of research findings and previous reports, it is evident that radiotherapy-induced UPS exhibits a highly diverse and frequently severe clinical and biological behavior. Identifying tumor formation using genome sequencing can help understand its biological behavior and determine personalized treatments.

Considering the increasing number of conservative surgeries (quadrantectomies) for primary breast carcinoma, especially in the early stages, often followed by adjuvant radiotherapy, the incidence of radiation-associated angiosarcoma (RAS) is expected to rise in the coming decades, and it will represent a clinical and therapeutic challenge, as limited data are available due to the rarity and heterogeneity of the disease. Though the prognosis of these patients is poor, a number of clinical and pathological factors can be evaluated to better understand the course of RAS. The aim of this systematic review is to explore the available clinical-pathological, therapeutic, and prognostic data regarding RAS to evaluate its occurrence, diagnosis, treatment, and outcomes.

RAS clinical data were identified by a systematic review conducted in five different databases (Medline, Web of Knowledge, Google Scholar, Scopus, and Cochrane). Only RAS works published in English, with access to the full manuscript text, and with clear results, were considered as eligible.

We considered 52 papers comprising 319 RAS cases. The patient age at diagnosis ranged from 37 to 93 years, with most cases occurring from 5 to 10 years after breast irradiation. The most common clinical presentation was an aggressive development of macules, papules, or erythematous-violaceous skin discoloration at the site of previous radiation treatment for primary breast carcinoma. Complete surgical excision appeared to be the first-line treatment of the disease, in some cases followed by adjuvant local and/or systemic therapies. Despite different treatments, local recurrence rates ranged from 40% to 90%, leading to negative outcomes and poor prognosis for patients.

Although the literature is limited and the data are heterogeneous and contentious, our review aims to highlight the importance of early diagnosis, multimodal treatment, and long-term follow-up of RAS in order to limit and prevent the aggressiveness of this neoplasm.

We report on a series of consecutive patients with localized radiation-associated angiosarcoma (RAAS) of the breast region (BR) treated at two Italian sarcoma reference centers.

We retrospectively reviewed all cases of primary, localized, resectable RAAS of the BR, treated at one of the two participating institutions from 2000 to 2019. Relapse-free survival (RFS) and overall survival (OS) were calculated. The prognostic role of several variables was investigated. A propensity score matched (PSM) analysis was carried out.

Eighty-four patients were retrospectively identified. Nineteen out of 84 patients (22.6%) were pretreated with an anthracycline-based regimen for previous cancer. All patients but one underwent surgery, with 37/84 (44.1%) receiving surgery alone and 46/84 (54.8%) a multimodal approach: 18/84 (21.4%) received radiation therapy (RT) and 46/84 (54.9%) received chemotherapy. An anthracycline-based regimen was used in 10/84 patients (11.9%), while a gemcitabine-based regimen was used in 33/84 (39.3%). With a median follow-up of 51 months (interquartile range: 30-126 months), 36/84 patients (42.9%) relapsed and 35/84 patients (41.7%) died (8/84, 9.5% in the lack of metastatic disease). Five-year OS and 5-year RFS were 57% [95% confidence interval (CI) 43% to 68%] and 52% (95% CI 39% to 63%), respectively. Both (neo)adjuvant RT and chemotherapy were associated with better RFS [hazard ratio (HR) 0.25, 95% CI 0.08-0.83; HR 0.45, 95% CI 0.23-0.89] with a trend towards a better OS (HR 0.51, 95% CI 0.18-1.46; HR 0.60, 95% CI 0.29-1.24). Gemcitabine-based regimens seemed to perform better (HR 4.28, 95% CI 1.29-14.14). PSM analysis retained the above results.

This retrospective study supports the use of (neo)adjuvant RT and chemotherapy, in primary, localized resectable RAAS of the BR. An effort to prospectively validate the role of (neo)adjuvant RT and chemotherapy is warranted.

Radiation-associated sarcomas (RASs) are rare tumors with limited contemporary data to inform prognostication and management. We sought to identify the clinical presentation, patterns of care, and prognostic factors of RASs. RAS patients treated at a single institution from 2015 to 2021 were retrospectively reviewed for clinicopathologic variables, treatment strategies, and outcomes. Thirty-eight patients were identified with a median follow-up of 30.5 months. The median age at RAS diagnosis was 68.4 years (27.9-85.4), with a median latency from index radiotherapy (RT) of 9.1 years (3.7-46.3). RAS histologies included angiosarcoma (26%), undifferentiated pleomorphic sarcoma (21%), and osteosarcoma (18%). Most were high-grade (76%). Genomic profiling revealed low tumor mutational burden, frequent inactivating TP53 mutations (44%), CDKN2A deletions (26%), and MYC amplifications (22%), particularly in breast angiosarcomas. Of 38 patients, 33 presented with localized disease, 26 of whom were treated with curative intent. Overall, the median progression-free survival (PFS) was 9.5 months (1.4-34.7), and the overall survival (OS) was 11.1 months (0.6-31.6). Patients with localized vs. metastatic RASs had a longer PFS (HR, 3.0 [1.1-8.5]; p = 0.03) and OS (HR, 3.0 [1.04-8.68]; p = 0.03). Among localized RAS patients, high grade was associated with shorter OS (HR, 4.6 [1.04-20.30]; p = 0.03) and resection with longer OS (mean 58.8 vs. 6.1 months, HR, 0.1 [0.03-0.28]; p < 0.001). Among patients undergoing resection, negative margins were associated with improved OS (mean 71.0 vs. 15.5 months, HR, 5.1 [1.4-18.2]; p = 0.006). Patients with localized disease, particularly those undergoing R0 resection, demonstrated significantly better outcomes. Novel strategies are urgently needed to improve treatment outcomes in this challenging group of diseases.

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 is an aggressive vascular malignant neoplasm presenting either as a primary or secondary cancer, often arising after radiotherapy or in the context of preexisting lymphedema. Comprehensive data describing its incidence and presentation patterns are needed.

To describe the incidence, presenting characteristics, and change over time of angiosarcoma in the US.

This retrospective cross-sectional study used data from the US Cancer Statistics (USCS) National Program of Cancer Registries-Surveillance, Epidemiology, and End Results Combined Database, which captures more than 99% of newly diagnosed cancers in the US. The study included all 19 289 patients in the US with a new diagnosis of angiosarcoma between 2001 and 2020 captured in the USCS database. Statistical analysis was performed from June to September 2023.

Incidence of angiosarcoma, demographics of patients with angiosarcoma, and extent of disease at presentation.

The study included 19 289 patients (median age, 71 years [IQR, 59-80 years]; 10 506 women [54.5%]) with a new diagnosis of angiosarcoma. The US incidence of angiosarcoma doubled between 2001 (657 cases) and 2019 (1312 cases), reflecting both an increase in the adjusted incidence rate of 1.6% per year (P = .001), to 3.3 cases per 1 000 000 person-years (95% CI, 3.1-3.5 cases per 1 000 000 person-years), and an increase in the population at risk. In 2020, the reported incidence rate (3.0 cases per 1 000 000 person-years) and cases of angiosarcoma (n = 1159) were modestly lower than in 2019. Overall, 72.3% of cases of angiosarcoma (n = 13 955) were cutaneous, subcutaneous, or breast angiosarcomas; 24.4% were visceral (n = 4701); and 3.3% were located in unknown or rare primary sites (n = 633). Secondary breast and chest wall angiosarcomas among women represented the largest contribution to increasing incidence. Among breast angiosarcomas, 99.2% (2684 of 2705) were in women and 71.9% (1944 of 2705) were secondary. A total of 80.4% of chest wall or thorax cases among women (1861 of 2316) were secondary vs 26.5% among men (112 of 422), and 63.9% of upper extremity cases among women (205 of 321) were secondary vs 26.8% (56 of 209) among men (P = .001). Rates of secondary angiosarcoma in the abdomen and lower extremities were similar between men and women. The incidence rate of visceral angiosarcoma was also found to be increasing (1.5% per year; P = .001).

This cross-sectional study describes angiosarcoma presentation patterns and incidence rates in the US over a 20-year period and shows that the number of cases in men and women increased, with the greatest increase among women with secondary angiosarcoma of the chest, breast, and upper extremity. These data increase awareness of a rare but highly morbid disease and highlight the need for improved early detection of angiosarcoma among patients at high risk, such as women with a history of breast cancer.

Radiation-induced angiosarcoma (RIA) is an uncommon but morbid complication after radiotherapy for breast cancer.

Retrospective analysis of breast RIA patients at Cambridge University Hospital (CUH), a regional treatment centre in the East of England.

22 patients were identified between 2010 and 2022. Median age of diagnosis was 65 years (range 41-78). Median time from breast radiotherapy to RIA diagnosis was 6.5 years (range 2.4-16.0)-this interval has decreased over the last 24 years (r2 = 0.6601). 9% had metastasis at presentation. All patients underwent surgery (55% at CUH, 45% at local hospitals). 27% received peri-operative pegylated liposomal doxorubicin in the first-line setting. 62% relapsed following their primary curative-intent treatments after a median of 28 months. Metastases occurred in 36%, the commonest sites being lung (100%) and lymph node (50%). 2-year and 5-year overall survival (OS) rates for all patients were 73% and 60%, respectively. No correlation between progression-free survival (PFS) and OS was found with tumour size, margin, peri-operative chemotherapy, and whether surgery was performed at CUH. Patients with multifocal disease on their breasts had shorter PFS following surgery compared to single-lesion disease (median 10 vs 65 months; HR = 4.359 [95% CI 1.342-14.16]; P = 0.0143). Patients aged > 72 years had a median OS of 45 months vs 102 months for those ≤ 72 years (HR = 7.129 [95% CI 1.646-30.88]; P = 0.0086).

RIA has high rates of recurrence and mortality and appears to be occurring sooner after breast radiotherapy. Further studies on its pathogenesis and effective treatment are warranted.

Angiosarcoma is a rare complication of breast-conserving therapy. This study evaluated the change in incidence between 1992 and 2016 of secondary breast angiosarcoma (SBA) in patients with a history of breast cancer and the impact of management strategies for the original breast carcinoma on angiosarcoma treatment.

Breast cancer and angiosarcoma cases were abstracted from the Surveillance, Epidemiology, and End Result (SEER) database. SBAs were defined as angiosarcomas located in the breast occurring after a prior breast cancer diagnosis. Primary breast angiosarcomas (PBAs) were defined as an angiosarcoma diagnosis listed as "one primary only." Incidence rates were estimated using a proportion of the US total population. Survival was analyzed by the Kaplan-Meier method, and Cox proportional hazard models were used to assess the association of clinicopathologic characteristics on overall survival.

Between 1992 and 2016, 193 cases of SBA were reported in the SEER dataset in patients with a prior history of breast cancer. The incidence of breast angiosarcoma in patients with a prior diagnosis of breast cancer increased 3-fold from about 10 cases per 100,000 person-years to about 30 cases per 100,000 person-years over this same period ( P =0.0037). For treatment of SBA (n=193), almost all (95%) had surgery. Nine percent received radiation (compared with 35% of patients with PBA, P <0.001) and 23% received chemotherapy (vs. 45% for PBA, P =0.11).

We demonstrate an increasing incidence of SBA over the study period. These data can help inform shared decision-making for optimal management of locoregional breast cancer and raise awareness of secondary angiosarcoma.

Radiation-induced sarcomas (RIS) tend to have aggressive behaviour and because of their rarity, the most appropriate management for these malignancies is uncertain.

Using the Canadian Sarcoma Research and Clinical Collaboration (CanSaRCC) database, a national sarcoma registry, we aimed to investigate prognostic factors and outcomes for RIS.

Retrospective study of RIS patients treated from 1996 to 2021 at three Canadian centres.

RIS was defined as a sarcoma arising in a previously irradiated field following a 3+ year latency period, whose histology was distinct from the initially irradiated tumour. Clinicopathologic and treatment-related information was extracted from the CanSaRCC database. Overall survival (OS) was defined as the time from RIS diagnosis to death from any cause. Response rate (RR) to neoadjuvant chemotherapy (NACT) was based on physician assessment. Time-to-event analyses were estimated using the Kaplan-Meier method, with Cox regression for multivariate analysis. We considered a two-tailed p-value of <0.05 as statistically significant.

One hundred seven tumours met the criteria for RIS and were divided into three subgroups: breast angiosarcoma (BAS, n = 54), osteosarcoma (OST, n = 16), and other soft-tissue sarcomas (STS, n = 37). Patients were mostly female (n = 85, 79%), treated initially for breast carcinomas (n = 54, 50.5%), and diagnosed with high-grade tumours (n = 61/71, 86%). None had evidence of synchronous metastasis. Patients with OST were younger (median age: 48 years, p < 0.001), and BAS had the shortest latency interval (8 versus 18 years for OST/STS, p < 0.001). Most patients underwent surgery, 76% (n = 76/100) R0; 24% (n = 26) received radiation therapy, mostly (n = 15, 57.7%) neoadjuvant. Among those receiving chemotherapy, 30 (75%) underwent NACT; among patients with documented response assessment, the RR was 68% (n = 17/25), being even higher in the BAS population (89.5%, n = 13/17). Median OS was 53 months (95% CI 34-101), with a 5-year OS of 47.6%; larger tumour size, high histologic grade and older age were independent prognostic factors for worse OS.

Surgery is standard, and NACT might be useful to downsize large lesions, especially in BAS patients. Raising RIS awareness is fundamental to promoting appropriate management and fostering research through multi-institutional collaborations.

Breast pathology has many mimics and diagnostic pitfalls. Evaluation of malignant breast lesions, particularly in the biopsy setting, can be especially challenging, with diagnostic errors having significant management implications.

To discuss the pitfalls encountered when evaluating ductal carcinoma in situ and invasive breast carcinomas, providing histologic clues and guidance for appropriate use and interpretation of immunohistochemistry to aid in the correct diagnosis.

Data were obtained from review of pertinent literature of ductal carcinoma in situ and invasive breast carcinomas and from the experience of the authors as practicing breast pathologists.

Awareness of the pitfalls in diagnosing breast cancers is important when creating a differential diagnosis for each breast lesion evaluated. This review will cover some of these scenarios to aid in the diagnostic process.

Human angiosarcoma and canine hemangiosarcoma reveal similarities not only in their aggressive clinical behaviour, but especially in molecular landscape and genetic alterations involved in tumorigenesis and metastasis formation. Currently, no satisfying treatment that allows for achieving long overall survival or even prolonged time to progression does not exist. Due to the progress that has been made in targeted therapies and precision medicine the basis for a new treatment design is to uncover mutations and their functions as possible targets to provide tailored drugs for individual cases. Whole exome or genome sequencing studies and immunohistochemistry brought in the last few years important discoveries and identified the most common mutations with probably crucial role in this tumour development. Also, despite a lack of mutation in some of the culprit genes, the cancerogenesis cause may be buried in main cellular pathways connected with proteins encoded by those genes and involving, for example, pathological angiogenesis. The aim of this review is to highlight the most promising molecular targets for precision oncology treatment from the veterinary perspective aided by the principles of comparative science. Some of the drugs are only undergoing laboratory in vitro studies and others entered the clinic in the management of other cancer types in humans, but those used in dogs with promising responses have been mentioned as priorities.

Mesenchymal neoplasms of the liver can be diagnostically challenging, particularly on core needle biopsies. Here, I discuss recent updates in neoplasms that are specific to the liver (mesenchymal hamartoma, undifferentiated embryonal sarcoma, calcifying nested stromal-epithelial tumor), vascular tumors of the liver (anastomosing hemangioma, hepatic small vessel neoplasm, epithelioid hemangioendothelioma, angiosarcoma), and other tumor types that can occur primarily in the liver (PEComa/angiomyolipoma, inflammatory pseudotumor-like follicular dendritic cell sarcoma, EBV-associated smooth muscle tumor, inflammatory myofibroblastic tumor, malignant rhabdoid tumor). Lastly, I discuss metastatic sarcomas to the liver, as well as pitfalls presented by metastatic melanoma and sarcomatoid carcinoma.

Preferentially expressed antigen in melanoma (PRAME) immunohistochemistry is currently used in pathology for the assessment of melanocytic neoplasms; however, knowledge of its expression patterns in soft tissue tumors is limited. PRAME immunohistochemistry (clone QR005) was assessed on whole tissue sections of 350 soft-tissue tumors and mimics (> 50 histotypes). PRAME immunoreactivity was evaluated as follows: 0 "negative" (0% positive cells); 1+ (1-25% positive cells); 2+ (26-50% positive cells); 3+ (51-75% positive cells), and 4+ "diffuse" (> 75% positive cells). PRAME was expressed in 111 lesions (0 benign, 6 intermediate malignancy, and 105 malignant), including fibrosarcomatous dermatofibrosarcoma protuberans (2/4, 0 diffuse), NTRK-rearranged spindle cell neoplasm (2/4, 0 diffuse), atypical fibroxanthoma (1/7, 0 diffuse), Kaposi sarcoma (1/5, 0 diffuse), myxoid liposarcoma (11/11, 9 diffuse), synovial sarcoma (11/11, 6 diffuse), intimal sarcoma (7/7, 5 diffuse), biphenotypic sinonasal sarcoma (3/3, 1 diffuse), angiosarcoma (10/15, 6 diffuse), malignant peripheral nerve sheath tumor (9/12, 4 diffuse), pleomorphic rhabdomyosarcoma (2/3, 2 diffuse), alveolar rhabdomyosarcoma (2/6, 0 diffuse), embryonal rhabdomyosarcoma (7/7, 4 diffuse), undifferentiated pleomorphic sarcoma (2/12, 1 diffuse), leiomyosarcoma (2/15, 1 diffuse), clear cell sarcoma of soft tissue (1/10, 0 diffuse), low-grade fibromyxoid sarcoma (1/5, 0 diffuse), Ewing sarcoma (2/10, 1 diffuse), CIC-rearranged sarcoma (8/8, 4 diffuse), BCOR-sarcoma (2/5, 1 diffuse), melanoma (20/20, 14 diffuse), and thoracic SMARCA4-deficient undifferentiated tumor (5/5, all diffuse). All tested cases of spindle cell lipoma, dedifferentiated/pleomorphic liposarcoma, dermatofibrosarcoma protuberans, solitary fibrous tumor, inflammatory myofibroblastic tumor, myxoinflammatory fibroblastic sarcoma, nodular fasciitis, myxofibrosarcoma, epithelioid hemangioendothelioma, atypical vascular lesion, hemangioma, lymphangioma, vascular malformation, papillary endothelial hyperplasia, GIST, gastrointestinal clear-cell sarcoma, malignant melanotic nerve sheath tumor, neurofibroma, schwannoma, granular cell tumor, alveolar soft part sarcoma, epithelioid sarcoma, extraskeletal myxoid chondrosarcoma, myoepithelioma, ossifying fibromyxoid tumor, angiomatoid fibrous histiocytoma, PEComa, dermatofibroma, pleomorphic dermal sarcoma, and chordoma were negative. PRAME shows imperfect specificity in soft-tissue pathology but may serve as a diagnostic adjunct in selected differential diagnoses that show contrasting expression patterns.

MYC amplifications have been frequently detected in radiation (RT)-associated angiosarcomas (ASs) by low-resolution molecular methods. However, large-scale next-generation sequencing (NGS) studies to investigate the genomic landscape of RT-AS are scarce, particularly compared with other RT-associated sarcomas. We performed a detailed comparative genomic investigation of RT-AS versus other RT-associated histotypes, as well as sporadic sarcomas with similar histologies. Our institutional targeted DNA-NGS assay database was searched for RT-associated sarcomas. Clinical outcome data, pathologic diagnosis, and the types and frequencies of genomic alterations, including single nucleotide variants (SNVs) and copy number alterations (CNAs), were analyzed. The cohort consisted of 82 patients, 68 (83%) females and 14 (17%) males, aged 37-88 (mean 64) years. Forty-four RT-ASs (38 from breast) and 38 RT sarcomas of other histologies, including 12 malignant peripheral nerve sheath tumors (RT-MPNSTs), 14 undifferentiated pleomorphic sarcomas (RT-UPSs), and 12 osteosarcomas (RT-OSs), were included. Median time intervals from radiation to initial diagnosis in RT-AS (8.0 years) were significantly lower than those in RT-MPNST and RT-UPS (12.5 and 18.5 years), respectively. Each RT-sarcoma histotype harbored distinct mutations and CNAs. RT-associated AS had more frequent MYC, FLT4, CRKL, HRAS, and KMT2D alterations than sporadic AS (enriched in TP53, KDR, ATM, ATRX), whereas the mutational landscapes of MPNST, UPS, and OS were similar in both RT and non-RT settings. CDKN2A/B deletions and TP53 alterations were infrequent in RT-AS compared with other RT sarcomas. Among RT sarcomas, RT-AS harbored the lowest fraction of genome altered (FGA), while RT-MPNST showed the highest FGA. RT-AS had the lowest insertion:SNV and deletion:SNV ratios, while RT-UPS had the highest. The predominant mutational signatures were associated with errors in DNA repair and replication. In conclusion, RT-AS has a distinct genomic landscape compared with other RT sarcomas and sporadic AS. Potential molecular targets for precision medicine may be histotype-dependent. © 2023 The Pathological Society of Great Britain and Ireland.

Bone and soft tissue tumors are generally classified into complex karyotype sarcomas versus those with recurrent genetic alterations, often in the form of gene fusions. In this review, we provide an overview of important co-occurring genomic alterations, organized by biological mechanisms and covering a spectrum of genomic alteration types: mutations (single-nucleotide variations or indels) in oncogenes or tumor suppressor genes, copy number alterations, transcriptomic signatures, genomic complexity indices (e.g. CINSARC), and complex genomic structural variants. We discuss the biological and prognostic roles of these so-called secondary or co-occurring alterations, arguing that recognition and detection of these alterations may be significant for our understanding and management of mesenchymal tumors. On a related note, we also discuss major recurrent alterations in so-called complex karyotype sarcomas. These secondary alterations are essential to sarcomagenesis via a variety of mechanisms, such as inactivation of tumor suppressors, activation of proliferative signal transduction, telomere maintenance, and aberrant regulation of epigenomic/chromatin remodeling players. The use of comprehensive genomic profiling, including targeted next-generation sequencing panels or whole-exome sequencing, may be incorporated into clinical workflows to offer more comprehensive, potentially clinically actionable information. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Angiosarcoma of the breast is a rare breast cancer, which can arise de novo (primary breast angiosarcoma, PBA) or as a secondary malignancy (secondary breast angiosarcoma, SBA) as a result of a biological insult. In the latter case, it is usually diagnosed in patients with a previous history of radiation therapy following a conserving treatment for breast cancer. Over the years, the advances in early diagnosis and treatment of breast cancer, with increasing use of breast-conserving surgery and radiation therapy (instead of radical mastectomy), brought about an increased incidence of the secondary type. PBA and SBA have different clinical presentations and often represent a diagnostic challenge due to the nonspecific imaging findings. The purpose of this paper is to review and describe the radiological features of breast angiosarcoma, both in conventional and advanced imaging to guide radiologists in the diagnosis and management of this rare tumor.

Molecular diagnostics, with the subsequent development of novel immunohistochemical markers, continues to advance and expand the field of soft tissue pathology. As such, the ever-evolving molecular diagnostic landscape will continue to shape and refine our understanding and classification of neoplasms. This article reviews the current literature on various tumors of mesenchymal origin, including fibroblastic/fibrohistiocytic, adipocytic, vascular, and tumors of uncertain origin. We aim to give the reader a detailed understanding and pragmatic approach to various new and established immunohistochemical stains in diagnosing these neoplasms and also discuss various pitfalls with significant repercussions.

A small proportion of rectal adenocarcinomas develop in patients many years after the treatment of a previous cancer using pelvic radiation, and the incidence of these rectal cancers depends on the length of follow-up from the end of radiotherapy. The risk of radiation-associated rectal cancer (RARC) is higher in patients treated with prostate external beam radiotherapy than it is in patients treated with brachytherapy. The molecular features of RARC have not been fully investigated, and survival is lower compared to non-irradiated rectal cancer patients. Ultimately, it is unclear whether the worse outcomes are related to differences in patient characteristics, treatment-related factors, or tumor biology. Radiation is widely used in the management of rectal adenocarcinoma; however, pelvic re-irradiation of RARC is challenging and carries a higher risk of treatment complications. Although RARC can develop in patients treated for a variety of malignancies, it is most common in patients treated for prostate cancer. This study will review the incidence, molecular characteristics, clinical course, and treatment outcomes of rectal adenocarcinoma in patients previously treated with radiation for prostate cancer. For clarity, we will distinguish between rectal cancer not associated with prostate cancer (RCNAPC), rectal cancer in non-irradiated prostate cancer patients (RCNRPC), and rectal cancer in irradiated prostate cancer patients (RCRPC). RARC represents a unique but understudied subset of rectal cancer, and thus requires a more comprehensive investigation in order to improve its treatment and prognosis.

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.

Despite a wide spectrum of clinical presentations, including primary or secondary, most angiosarcomas are considered high grade. One exception is primary breast angiosarcoma, where historically, histologic grading has shown to predict outcome using the Rosen 3-tier system. However, more recent studies have challenged this concept suggesting that even in this specific clinical context angiosarcomas should be considered high grade. This study aimed to critically reevaluate the impact of histologic grade in a clinically uniform cohort managed at a single institution using a newly proposed grading system. Our study included 49 primary breast angiosarcomas diagnosed during 1994 to 2022 (median follow-up: 33 mo), classified as low grade (29%), intermediate grade (20%), and high grade (51%), based on mitotic count, extent of solid components, and necrosis. At last follow-up, 22% patients developed locoregional recurrences, 63% distant metastases, and 47% patients died of disease. As patients with low and intermediate-grade angiosarcomas had relatively similar outcomes, our cohort was further analyzed using a 2-tier system (low grade and high grade). Targeted-DNA next-generation sequencing (505 cancer gene panel) performed in 11 cases found KDR mutations in 78% and PIK3CA mutations in 44% of high-grade lesions. Histologic grade, by either 3-tier or 2-tier grading systems, had a strong impact on survival, with the 2-tier system being an independent predictor of disease-specific survival and overall survival. Based on 2-tier system, the 5-year overall survival was 38% for high-grade angiosarcoma and 74% for low-grade angiosarcoma. PIK3CA mutations alone or concurrent with KDR alterations were identified in angiosarcomas with worse prognosis.

Angiosarcomas are a heterogeneous group of rare endothelial malignancies with a complex, not completely unravelled biology. They encompass primary (sporadically occurring) angiosarcomas of several origins and secondary angiosarcomas, which often arise due to DNA damaging factors including radiotherapy or ultraviolet light exposure. The optimal treatment of metastatic angiosarcomas is unclear and the prognosis is poor. In order to discover novel treatment strategies for angiosarcomas it is important to take the heterogeneity of these tumors into account. For this reason it is also important to have preclinical models available for the different clinical subtypes. Owing to the rarity of angiosarcomas, models are scarce. So far, only five human cell lines of angiosarcomas (all of the scalp after UV exposure) are available worldwide. In this paper we describe a novel established patient-derived xenograft model of a radiotherapy-induced angiosarcoma of the breast. The tumor was characterized by a MYC amplification, CD31 and ERG immunohistochemical positivity and was further characterized by using next generation sequencing (TruSight Oncology 500) in combination with the R-package XenofilteR to separate mouse from human sequence reads.

Mesenchymal lesions of the breast are a heterogeneous range of entities with diverse clinical, histological, and molecular features, as well as biological behaviour. Their morphologic overlap with non-mesenchymal lesions (such as metaplastic carcinoma and phyllodes tumour) and relative rarity also pose significant diagnostic challenges. In this review, we summarize the salient features of selected mesenchymal lesions of the breast, emphasizing those that are the most common and problematic. Vascular, fibroblastic/myofibroblastic, adipocytic, and smooth muscle lesions are each covered with regard to their clinicopathological features and differential diagnosis, while recent advances and the role of immunohistochemistry and molecular tests are also highlighted.

Radiation-associated sarcomas (RAS) are rare but aggressive malignancies. We sought to characterize the histology-specific presentation and behavior of soft tissue RAS to improve individualized prognostication.

A single-institutional prospectively maintained database was queried for all patients with primary, nonmetastatic RAS treated with surgical resection from 1982 to 2019. Patients presenting with the five most common RAS histologies were propensity-matched to those with sporadic tumors of the same histology. Incidence of disease-specific death (DSD) was modeled using cumulative incidence analyses.

Among 259 patients with RAS, the five most common histologies were malignant peripheral nerve sheath tumor (MPNST; n = 19), myxofibrosarcoma (n = 20), leiomyosarcoma (n = 24), undifferentiated pleomorphic sarcoma (UPS; n = 55), and angiosarcoma (AS; n = 62). DSD varied significantly by histology (P = .002), with RAS MPNST and UPS having the highest DSD. In unadjusted analysis, RAS MPNST was associated with increased DSD compared with sporadic MPNST (75% v 38% 5-year DSD, P = .002), as was RAS UPS compared with sporadic UPS (49% v 28% 5-year DSD, P = .004). Unadjusted DSD was similar among patients with RAS AS, leiomyosarcoma, or myxofibrosarcoma and sporadic sarcoma of the same histology. After matching RAS to sporadic patients within each histology, DSD only differed between RAS and sporadic MPNST (83% v 46% 5-year DSD, P = .013). Patients with RAS AS presented in such a distinct manner to those with sporadic AS that a successful match was not possible.

The aggressive presentation of RAS is histology-specific, and DSD is driven by RAS MPNST and UPS histologies. Despite the aggressive presentation, standard prognostic factors can be used to estimate risk of DSD among most RAS. In MPNST, radiation association should be considered to independently associate with markedly higher risk of DSD.

Angiosarcomas are rare mesenchymal sarcomas that can present as primary cutaneous or noncutaneous disease. They express a variety of vascular endothelial growth factor receptors. The authors hypothesized that the treatment of angiosarcoma with pazopanib, a multikinase inhibitor with activity against vascular endothelial growth factor receptors, would result in disease response and prolonged disease stabilization.

This was an open-label, phase 2 trial of pazopanib in patients who had incurable angiosarcoma. The co-primary end points were response according to the Response Evaluation Criteria in Solid Tumors and progression-free survival (PFS) at 3 months. The starting dose of pazopanib was 800 mg daily.

Twenty-nine patients were accrued between 2011 and 2018, and 22 patients were evaluable for response. Toxicities were similar to those identified in prior reports. There was one partial response (3%), and the clinical benefit rate (including complete responses, partial responses, and stable disease) was 48%, which was observed more frequently in patients who had cutaneous disease. The median PFS was 14.4 weeks, and the 3-month PFS rate determined by Kaplan-Meier estimate was 54.6% (95% CI, 36.0%-82.9%), meeting the primary study objective. The Kaplan-Meier overall survival estimate was 16.1 months.

Pazopanib therapy in patients who had incurable angiosarcoma was associated with meaningful disease control, especially in those who had cutaneous disease with limited objective responses.

Angiosarcoma is a rare cancer that can be found on the skin or in internal organs. This study tested pazopanib, an oral targeted medication, to determine its benefit in patients with angiosarcoma who could not undergo the removal of their tumors by surgery. Pazopanib treatment was safe, and no new side effects were reported. The study showed that pazopanib controlled tumor growth in one half of patients at 3 months and was more common in angiosarcomas of the skin; it led to tumor shrinkage in a minority of patients (1 of 29).