Comparison of tumor-associated YAP1 fusions identifies a recurrent set of functions critical for oncogenesis.

YAP1 is a transcriptional coactivator and the principal effector of the Hippo signaling pathway, which is causally implicated in human cancer. Several YAP1 gene fusions have been identified in various human cancers and identifying the essential components of this family of gene fusions has significant therapeutic value. Here, we show that the YAP1 gene fusions YAP1-MAMLD1, YAP1-FAM118B, YAP1-TFE3, and YAP1-SS18 are oncogenic in mice. Using reporter assays, RNA-seq, ChIP-seq, and loss-of-function mutations, we can show that all of these YAP1 fusion proteins exert TEAD-dependent YAP activity, while some also exert activity of the C'-terminal fusion partner. The YAP activity of the different YAP1 fusions is resistant to negative Hippo pathway regulation due to constitutive nuclear localization and resistance to degradation of the YAP1 fusion proteins. Genetic disruption of the TEAD-binding domain of these oncogenic YAP1 fusions is sufficient to inhibit tumor formation in vivo, while pharmacological inhibition of the YAP1-TEAD interaction inhibits the growth of YAP1 fusion-expressing cell lines in vitro. These results highlight TEAD-dependent YAP activity found in these gene fusions as critical for oncogenesis and implicate these YAP functions as potential therapeutic targets in YAP1 fusion-positive tumors.

New risk factors and molecular landscapes of hepatic angiosarcoma in the Taiwanese population†.

Hepatic angiosarcoma is a rare, highly aggressive malignancy of the liver. The tumorigenesis of hepatic angiosarcoma has been relatively understudied in terms of aetiology and molecular properties. A recent study published in The Journal of Pathology revealed a strong association between hepatic angiosarcoma incidence and chronic kidney disease, particularly in end-stage renal disease using population-based data from the National Health Insurance Research Database in Taiwan and an institutional cohort. The study also revealed enrichment in the mutational signature of aristolochic acid exposure and is the first reported observation of this mutational signature in human sarcomas. © 2023 The Pathological Society of Great Britain and Ireland.

Molecular Analysis of Renal/Adrenal Angiosarcomas Reveals High Frequency of Recurrent Genetic Alterations.

Angiosarcomas of the kidney and adrenal gland are rare, highly aggressive vascular neoplasms. Their genomic profile has not been systematically studied to date. We report the clinicopathologic and molecular features of six angiosarcomas centered in the kidney/adrenal gland. All patients were male adults, ranging from 58 to 77 years of age. Tumor sizes ranged from 2.5 to 22.5 cm. Half of the cases demonstrated hot spot mutations in the KDR gene, while one-third demonstrated mutations in the PIK3CA gene; both of these gene alterations being previously described, preferentially in breast angiosarcomas. In addition, two cases each demonstrated BRIP1 gene amplification, CTNNB1 and ETV6 mutations, which have not been previously reported in angiosarcoma. Notably, molecular studies were critical in establishing the correct diagnoses in three cases: one was an epithelioid angiosarcoma originally misdiagnosed as metastatic adenocarcinoma to the adrenal gland, the second was a vasoformative angiosarcoma that mimicked hemangioma, and the third was a collision tumor between a high-grade angiosarcoma and a chromophobe renal cell carcinoma which was originally diagnosed as a sarcomatoid renal cell carcinoma. In summary, angiosarcomas of the kidney and adrenal gland have a high frequency of recurrent genetic alterations, some of them being shared with other angiosarcoma subtypes, while other appear to be novel. In particular, activating hot spot KDR and PIK3CA mutations represent potential therapeutic targets for these highly aggressive cancers.

Clinicopathologic and molecular correlates to neoadjuvant chemotherapy-induced pathologic response in breast angiosarcoma.

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.

Imaging features of hepatic angiosarcoma: retrospective analysis of two centers.

PURPOSE: Identifying primary hepatic angiosarcoma (PHA) preoperatively is challenging, often relying on postoperative pathology. Invasive biopsy increases bleeding risk, emphasizing the importance of early PHA diagnosis through imaging. However, comprehensive summaries of ultrasound, abdominal computed tomography (CT), magnetic resonance imaging (MRI), and whole- body positron emission tomography-CT (PET-CT) in this context are lacking. This study aimed to investigate the comprehensive imaging characteristics of PHA. PATIENTS AND METHODS: Imaging data were collected from 7 patients diagnosed with PHA via pathology between January 2000 and December 2019 in two provincial grade III hospitals. All patients underwent routine color ultrasound examinations before surgery, with 3 patients receiving contrast-enhanced ultrasound (CEUS).CT scans, both plain and enhanced, were performed on 5 patients, and whole-body PET-CT examinations were conducted on 2 patients. RESULTS: Among the 7 patients with PHA, 4 presented with a single solid intrahepatic mass (2 of which were large), 1 with a single exophytic macroblock type, 1 with a mixed type featuring multiple masses and nodules, and 1 with a multiple nodule type. Conventional ultrasound of PHA showed uneven echoes within the tumor, potentially accompanied by septal zone echoes, and a blood flow grade of 0-I. CEUS displayed early-stage circular high enhancement, a central non-enhancement area, and a "vascular sign" around the tumor. CT scans revealed low-density shadows in the plain scan stage, high peripheral ring enhancement, and punctate nodular enhancement in the arterial phase, with varying intensities and the presence of a "vascular sign." During the portal vein stage, the interior of the tumor was consistently unfilled and exhibited structural disorder. PET-CT showed low-density lesions in the liver and low fluorodeoxyglucose metabolism. CONCLUSIONS: Imaging diagnosis plays a crucial role in PHA diagnosis. When liver tumor imaging matches the above characteristics, consider PHA.

Use of neoadjuvant paclitaxel in breast angiosarcoma-Impact on surgical resection and response rates.

OBJECTIVE: Breast angiosarcoma is a tumor that can arise as a primary breast tumor or in association with prior radiation therapy. Angiosarcomas are uniquely sensitive to paclitaxel. This study evaluated the impact neoadjuvant paclitaxel (NAC) therapy has on surgical outcomes, tumor recurrence, and survival in breast angiosarcomas. METHODS: Patients with angiosarcoma of the breast, either primary or radiation-associated, were identified from a prospective institutional database. Patients receiving NAC were compared to those treated with upfront surgery. Clinical and pathological variables were compared using Student's t-test or Fisher's exact test, differences in survival were calculated using Kaplan-Meier methods. RESULTS: Twenty-four patients with angiosarcoma of the breast were identified, 10 with primary angiosarcoma and 14 with radiation-associated angiosarcoma. Twelve patients received NAC, 6 of each with primary angiosarcoma or radiation-associated angiosarcoma. Of these 12 patients, 11 had a margin negative resection (91%) of which, nine had a complete pathological response on surgical pathology. Of the 12 surgery-first patients, four (n = 4/12, 33%) had positive surgical margins, two of the four underwent reoperation. With a median follow-up of 16 months, four NAC patients had recurrence (33%) compared to six patients in the surgery-first group (58%) (p = 0.41). While not statistically significant, NAC patients had a 33% less risk of recurring compared to surgery-first patients ([hazard ratio =0.67 (95% confidence interval 0.16-2.72; p = 0.6]). CONCLUSION: NAC for breast angiosarcoma may be associated with high rates of complete pathological response and margin-negative resection. However, this did not impact overall survival. Future prospective control studies and longer follow-up periods are warranted to understand the impact on recurrence and survival.

Association between hepatic angiosarcoma and end-stage renal disease: nationwide population-based evidence and enriched mutational signature of aristolochic acid exposure.

Hepatic angiosarcoma (HAS) is an aggressive mesenchymal malignancy that remains underexplored with respect to its etiology and mutational landscapes. To clarify the association between HAS and end-stage renal disease (ESRD), we used nationwide data of the National Health Insurance Research Database (NHIRD) in Taiwan, covering ~99% of the population, from 2001 to 2016. To investigate molecular signatures, we performed whole-exome sequencing (WES) in 27 surgical specimens, including nine ESRD-associated cases. The NHIRD analysis demonstrated that HAS ranked second among all angiosarcomas in Taiwan, with the incidence rates of HAS being 0.08, 2.49, and 5.71 per 100,000 person-years in the general population, chronic kidney disease (CKD), and ESRD patients, respectively. The standardized incidence ratios of HAS in CKD and ESRD patients were 29.99 and 68.77, respectively. In comparison with nonhepatic angiosarcoma, the multivariate regression analysis of our institutional cohort confirmed CKD/ESRD as an independent risk factor for HAS (odds ratio: 9.521, 95% confidence interval: 2.995-30.261, p < 0.001). WES identified a high tumor mutation burden (TMB; median: 8.66 variants per megabase) and dominant A:T-to-T:A transversion in HAS with frequent TP53 (81%) and ATRX (41%) mutations, KDR amplifications/gains (56%), and CDKN2A/B deletions (48%). Notably, ESRD-associated HAS had a significantly higher TMB (17.62 variants per megabase, p = 0.01) and enriched mutational signatures of aristolochic acid exposure (COSMIC SBS22, p < 0.001). In summary, a significant proportion of HAS in Taiwan is associated with ESRD and harbors a distinctive mutational signature, which concomitantly links nephrotoxicity and mutagenesis resulting from exposure to aristolochic acid or related compounds. A high TMB may support the eligibility for immunotherapy in treating ESRD-associated HAS. © 2023 The Pathological Society of Great Britain and Ireland.

Distinct genomic landscapes in radiation-associated angiosarcoma compared with other radiation-associated sarcoma histologies.

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.

Survival outcomes of rare cutaneous malignancies within an insured cohort of patients, 1988-2018.

BACKGROUND: There are limited survival data on cutaneous angiosarcoma (CAS), dermatofibrosarcoma protuberans (DFSP), Merkel cell carcinoma (MCC), and sebaceous carcinoma (SC). OBJECTIVE: To analyze survival trends in CAS, DFSP, MCC, and SC among a racially diverse, insured cohort of patients. METHODS: Using data from the Kaiser Permanente Southern California Cancer Registry, we identified adults diagnosed with CAS, DFSP, MCC, or SC between January 1, 1988 and December 31 2018, followed through December 31, 2021. RESULTS: Our cohort consisted of 83 diagnoses of CAS, 490 diagnoses of DFSP, 411 diagnoses of MCC, and 249 diagnoses of SC. Our analysis revealed no significant differences in overall or disease-specific 1000 person-years mortality rates among our populations of non-Hispanic Whites, Hispanics, African American/Blacks, and Asian American/Pacific Islanders diagnosed with CAS, DFSP, MCC, or SC. On multivariate analysis, controlling for patient and tumor characteristics, there was similarly no increased risk of overall mortality for minorities diagnosed with CAS, DFSP, MCC, or SC. LIMITATIONS: Retrospective nature of the analysis and small sample size. CONCLUSION: Contrary to existing literature, our results show a notable lack of racially driven survival disparities among insured individuals with CAS, DFSP, MCC, and SC, emphasizing the importance of health care coverage.

Evaluation of PRAME immunohistochemistry in cutaneous vascular neoplasms reveals frequent expression in primary and post-irradiation cutaneous angiosarcomas.

BACKGROUND: Preferentially expressed antigen in melanoma (PRAME) has been extensively studied in cutaneous melanocytic tumors and has proven valuable as a diagnostic adjunct in routine dermatopathology practice. However, its expression in cutaneous vascular neoplasms, particularly angiosarcomas (AS), remains largely unexplored. METHODS: To further explore PRAME expression in cutaneous AS, 18 cases of post-irradiation and 13 cases of primary cutaneous AS were evaluated for PRAME. For comparison, sections from 11 deep soft tissue/visceral AS, 10 Kaposi sarcomas, 8 microvenular hemangiomas, 7 infantile hemangiomas, 8 atypical vascular lesions, 6 epithelioid hemangioendotheliomas, 6 pyogenic granulomas, 6 papillary endothelial hyperplasias, 6 epithelioid hemangiomas, 3 capillovenous malformations, 3 hobnail hemangiomas, 2 spindle cell hemangiomas, 2 pseudomyogenic hemangioendotheliomas, and 2 composite hemangioendotheliomas were also retrieved. RESULTS: Overall, 22 of 31 (70.9%; 12 post-irradiation and 10 primary) cutaneous AS were positive for PRAME. In contrast, only 1 of 11 (9.1%) deep soft tissue/visceral AS showed diffuse and strong PRAME nuclear staining. All other tumor types were negative for PRAME, except for 5 of 7 (71.4%) infantile hemangiomas, which demonstrated rare (<5%; four cases) and 1+ (5-25%; one case) nuclear staining. CONCLUSIONS: In this study, we have demonstrated frequent nuclear PRAME expression in cutaneous AS. PRAME immunohistochemistry may serve as a valuable additional marker in selected clinical settings.

Case of a CIC::DUX4 fusion gene in a vascular neoplasm extends the spectrum of CIC-rearranged sarcomas.

CIC-rearranged sarcomas comprise a group of exceptionally aggressive round-cell sarcomas. These tumors most commonly demonstrate CIC::DUX4 fusion and show similar histopathology to Ewing sarcomas, though lesions mimicking vascular neoplasms have recently been described. Here, we describe a case of a patient with CIC::DUX4 fusion sarcoma identified using RNA-based molecular testing who was initially diagnosed with an endothelial neoplasm. The tumor showed extensive vasoformative growth, complete WT1 negativity, and global positive staining for ERG, CD31, and DUX4 by immunohistochemistry. Methylation testing of the tumor clustered more closely with angiosarcomas than with CIC-rearranged sarcomas. Our findings suggest that CIC::DUX4 fused neoplasms may demonstrate a more diverse phenotypic range than previously appreciated and offer evidence that both molecular and immunohistochemical studies are needed for accurate diagnosis.

Numerous multinucleated giant cells in cutaneous epithelioid angiosarcoma and pulmonary metastasis: A unique observation with potential diagnostic pitfalls.

The histopathologic diagnosis of poorly differentiated cutaneous angiosarcoma can be challenging. We report a case of cutaneous epithelioid angiosarcoma with numerous multinucleated giant cells (MGCs) developing pulmonary metastasis. A 79-year-old man presented with a red-purple plaque on the scalp. A skin biopsy revealed epithelioid cell proliferation, admixed with numerous MGCs, and background hemorrhage. Vascular spaces were focally present and lined by atypical endothelial cells, including MGCs. Immunohistochemically, tumor cells, including MGCs, were positive for CD31, D2-40, and ERG. The patient received radiation therapy and chemotherapy, after which a follow-up CT scan revealed symptomless pneumothorax and pulmonary metastases. The patient received palliative partial lung resection, and the specimen revealed histopathological and immunohistochemical features similar to the primary cutaneous lesion. Our report expands the morphologic spectrum of cutaneous epithelioid angiosarcoma. Cutaneous angiosarcoma is an aggressive neoplasm; thus, awareness of this rare manifestation is important.

A Novel TEK::GAB2 Gene Fusion in Pediatric Angiosarcoma of Pelvic soft Tissue: A Case Report and Literature Review.

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.

Chalazion-mimicked eyelid angiosarcoma in a young Asian with good prognosis: a case report.

BACKGROUND: Angiosarcoma is an extremely rare malignant tumor. So far, only about 42 cases of angiosarcoma involving the eyelids have been reported. Eyelid angiosarcoma occurs more frequently in elderly Caucasian males and is prone to misdiagnosis. We present a case report in a young Asian male patient with eyelid angiosarcoma that was misdiagnosed as a chalazion. CASE PRESENTATION: A 46-year-old South Korean male with no underlying disease had a right lower lid mass. The lesion was initially misdiagnosed as a chalazion at a local clinic, but a diagnosis of eyelid angiosarcoma was made after the first biopsy trial. PET-CT was performed to ensure that there was no metastasis in the whole body. Surgical excision with enough surgical margin was used alone for treatment and reconstruction was performed with a tarsoconjunctival advancement flap (modified Hughes procedure), which helped ensure good cosmesis. No recurrence was observed 4 years and 5 months after the surgery. CONCLUSIONS: The current study presents the first case of chalazion-mimicked eyelid angiosarcoma in a young Asian male aged under 50 years. This case shows that even if a benign eyelid disease is suspected in a young patient, an incisional biopsy must be performed to confirm whether the lesion is malignant. Since the prognosis is good for the case of eyelid angiosarcoma, if there is no clear evidence of distal metastasis, surgical resection should be performed with an enough safety margin.

Primary cardiac angiosarcoma: Imaging characterization.

This case report describes a 35-year-old female patient who presented with palpitations and shortness of breath. Imaging findings suggested a cardiac tumor, histopathology confirmed primary cardiac angiosarcoma. This tumor is highly aggressive, usually occurs in the right atrium, lacks specificity in clinical presentation, is prone to early metastasis, and has a poor prognosis. Echocardiography is the method of choice for early detection and is important in assessing tumor size, location, mode of attachment and whether cardiac function is impaired.

Pediatric primary intracranial angiosarcoma with epithelioid differentiation: a surgeon's dilemma.

Angiosarcoma is a rare form of soft tissue sarcoma originating from endothelial tissue, accounting for < 1% of all sarcomas. Primary epithelioid angiosarcomas of the central nervous system (CNS) are even more elusive, with only four reports described in the literature. In this article, we describe the first case in pediatric population, with a brief literature review regarding this entity. A 13-year-old girl presented to emergency services with raised intracranial pressure. MRI demonstrated a heterogenous lesion in the temporal lobe. She underwent emergency craniotomy and subtotal excision of the tumor. Eventually the patient developed multiple infarcts and succumbed post operatively. Pre-operative diagnosis on radiology is difficult considering the rarity of this entity and heterogeneity in radiological appearance. One needs to have a high degree of suspicion to consider angiosarcoma as a radiological differential. Overall prognosis remains poor. Early adjuvant treatment may improve overall survival.

Imaging features of pediatric angiosarcomas: clinical, pathologic, and radiological review.

BACKGROUND: Angiosarcomas are rare malignant vascular tumors and there is scarcity of data on their imaging features. OBJECTIVE: To review and illustrate the imaging, clinical, and pathologic features of angiosarcoma in children. MATERIALS AND METHODS: A list of pathologically proven angiosarcoma seen between Nov 1992 and Jan 2023 was obtained from a pathology database and picture archiving and communication system. Those with pre-treatment imaging available on our PACS were included in the study. Imaging studies were reviewed by two readers in consensus. RESULTS: A total of six children (two males and four females; median age of 8.8 years; range 2.9 years to 15.5 years) had angiosarcoma during the study period. Organ of origin included breast (n = 2), liver (n = 2), spleen (n = 1), and paranasal sinuses (n = 1). The patient with splenic angiosarcoma had Li-Fraumeni syndrome. Five patients had a single lesion while one had multifocal lesions. The tumors were large with a median diameter of 12.9 cm (range 2.7 cm to 24 cm). Most tumors were heterogeneous on T2-weighted imaging with hemorrhage and necrosis and showed heterogeneous enhancement. Three had well-defined borders and three had infiltrative borders. None of the tumors showed calcifications. Two tumors in the liver showed gradual non-centripetal progressive diffuse enhancement on dynamic imaging. One patient had metastases at presentation and four patients subsequently developed metastases on follow-up. Five patients underwent surgical resection and chemotherapy; one patient with a liver lesion underwent arterial embolization followed by liver transplant. Three patients died at the last follow-up. CONCLUSION: The imaging features of angiosarcomas are nonspecific, but the tumors are large heterogeneously enhancing masses with hemorrhage and necrosis. Hepatic angiosarcomas may show non-centripetal progressive and heterogeneous enhancement on dynamic imaging.

Paediatric hepatic angiosarcoma with consumptive hypothyroidism-an important diagnostic pitfall to avoid during evaluation of hepatic vascular tumours.

Hepatic angiosarcoma is an extremely rare primary malignant vascular tumour in children with very poor prognosis. Radiological diagnosis of hepatic angiosarcoma is challenging due to overlapping imaging features with other benign vascular hepatic tumours, particularly infantile hepatic haemangioma. Consumptive hypothyroidism is a condition that is almost exclusively associated with infantile hepatic haemangioma and has never been reported in angiosarcoma. We present a case of hepatic angiosarcoma in a 20-month-old girl, associated with consumptive hypothyroidism and, as a result, initially misdiagnosed as infantile hepatic haemangioma. Radiologists should be aware that consumptive hypothyroidism is not a reliable feature to use in excluding paediatric hepatic angiosarcoma. Biopsy should be performed in patients older than 1 year of age or with atypical imaging features.

Epithelioid angiosarcoma of the calf: a case report of an atypical imaging appearance.

Angiosarcoma is an uncommon cause of soft tissue malignancy, accounting for approximately 2% of all soft tissue sarcomas. Of these, epithelioid angiosarcoma represents a morphologic subtype, where the malignant endothelial cells demonstrate a predominantly or exclusively epithelioid appearance. Overall, epithelioid angiosarcoma shares similar imaging characteristics to conventional angiosarcoma including a T1 hypointense to isointense and T2 hyperintense mass, which demonstrates avid enhancement, serpentine feeding vessels, and overlying skin thickening on MRI. The case herein describes a case of epithelioid angiosarcoma in a 65-year-old female presenting with an enlarging calf mass and lower extremity pain. Initial imaging features, particularly on MRI, were highly unusual for angiosarcoma which was thus not strongly considered in the initial differential diagnosis. However, once diagnosis of epithelioid angiosarcoma was confirmed following resection, pathologic correlates were utilized to account for the unusual imaging findings retrospectively. The goal of this study is to not only describe an atypical presentation of an uncommon diagnosis but also attempt to rationalize the unexpected imaging findings with gross and microscopic correlates. Further, the utility of radiology-pathology correlation demonstrated in this case may be useful to others when evaluating similar lesions with unexpected MRI characteristics.

Ovarian angiosarcoma: A systematic review of literature and survival analysis.

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.