Secondary Angiosarcoma Research Articles

Primary and secondary cutaneous angiosarcoma: Distinctive clinical, pathological and molecular features

Angiosarcomas are ubiquitous neoplasms involving both cutaneous and soft tissue and visceral locations. Accumulating biomolecular evidences suggest that cutaneous angiosarcomas are distinctive entities with molecular, clinical and pathological peculiarities. Despite several ongoing clinical trials with promising therapeutic agents, the prognosis of cutaneous angiosarcomas is dismal and survival still rely on early diagnosis and surgery. An accurate diagnosis and the knowledge of the underlying molecular landscape are therefore essential to improve the prognosis. We detail the molecular, clinical, dermoscopic, morphological and prognostic features of cutaneous angiosarcoma. Although the molecular landscape of cutaneous angiosarcoma is not completely understood, accumulating evidences suggest that there are characteristic molecular alterations including dysregulation of angiogenesis and several complex molecular pathways. Secondary cutaneous angiosarcomas, arising in correlation with chronic lymphedema and ionizing radiation, have different molecular hallmarks, which are also leading to the first diagnostic applications. The diagnosis of cutaneous angiosarcoma may be challenging, as well-differentiated forms can be hard to distinguish from benign and low-grade vascular neoplasms, while poorly differentiated forms can be easily confounded with other non-vascular high-grade neoplasms. An accurate and early diagnosis, which is mandatory to ensure the best survival for the patients, is mainly based on morphological hallmarks.

Primary Mammary Angiosarcoma: Literature Review.

Angiosarcomas of the breast are extremely rare, highly aggressive tumors of vascular origin comprising 0.04% of all malignant neoplasms of the breast. They can be classified into primary mammary angiosarcomas and cutaneous (secondary) angiosarcomas. Primary angiosarcomas, owing to their unusual clinical presentation, are diagnosed late. In addition, the available literature to date lacks sufficient evidence to establish standard treatment guidelines for this group of tumors, thereby resulting in poor prognosis. In medical database, most available papers concern secondary angiosarcomas, with only a few case reports of primary angiosarcomas. The aim of this paper is to review what is known hitherto about the presentation, diagnostic tools, and therapeutic modalities for primary mammary angiosarcomas.

Bilateral primary angiosarcoma of breast in young patient: A case report with review of literature

Angiosarcomas are rare tumors arising from endothelial lining of vascular channels. The first case of breast angiosarcoma was presented in 1907 by Borrman and the first case of secondary angiosarcoma described in 1987 by Body. There are 2 main types. Haemangiosarcomas in blood vessels and lymphangiosarcomas in lymphatic vessel walls.All angiosarcomas tend to be aggressive and are mostly multicentric. These tumors have very high local recurrence rate and metastasis because of their intrinsic biologic properties. They are often misdiagnosed leading to a poor prognosis and a high mortality rate. We present a case of a 21-year-old female presented with an ulcerated right breast lesion which was diagnosed as primary angiosarcoma of breast with metastasis to left breast after 4 years.

Primary Vascular Tumors of Bone: A Monoinstitutional Morphologic and Molecular Analysis of 427 Cases With Emphasis on Epithelioid Variants.

Recent molecular discoveries have refined vascular bone tumor classification. To investigate the clinical relevance of these refinements, we reviewed all cases of primary vascular bone tumors treated at our Institute. On the basis of morphology, cases were assessed immunohistochemically and molecularly. A total of 427 cases of primary vascular tumor of bone with available follow-up and histologic material were retrieved and reclassified according to the most recent diagnostic criteria as follows: 289 hemangiomas, 38 epithelioid hemangiomas, 21 epithelioid hemangioendotheliomas, 2 retiform hemangioendotheliomas, 1 intraosseous papillary intralymphatic angioendothelioma, 24 pseudomyogenic hemangioendotheliomas, and 52 angiosarcomas (of these, 45 were epithelioid angiosarcomas and 7 spindle cell secondary angiosarcoma). Both epithelioid and classic hemangiomas behave as benign tumors with excellent prognosis. The distinction between cellular and conventional type of epithelioid hemangioma was not associated with a different clinical course. Conversely, epithelioid hemangioendothelioma exhibited a more aggressive clinical behavior than hemangioma, with higher rates of multifocality and distant spread. Immunohistochemical positivity for CAMTA1 or TFE3 did not have a prognostic implication. In epithelioid hemangioendothelioma, the presence of morphologic malignant features was associated with reduced disease-free (P=0.064) and overall survival (P=0.055). Pseudomyogenic hemangioendothelioma featured local aggressiveness in 5/24 patients exhibiting a clinical behavior closer to epithelioid hemangioma than epithelioid hemangioendothelioma. Last, 32/45 patients with epithelioid angiosarcoma died of disease with a median survival time of 10 months from diagnosis. In conclusion, the integration of morphologic, immunohistochemical, and molecular features allows a better stratification of primary vascular tumors of bone with significant prognostic and therapeutic implications.

Axillary Lymph Node Dissection in Angiosarcomas of the Breast: An Asian Institutional Perspective.

Angiosarcomas of the breast (ASB) are rare, making up to less than 8% of all angiosarcomas. The surgical management for this disease continues to vary throughout centres worldwide due to the current limited evidence. We aim to examine the necessity of axillary lymph node dissection in this pathology through a retrospective study of axillary metastasis and recurrence patterns in patients treated at our institution. A retrospective review of a prospectively-maintained database was performed. All adult patients with a histologically confirmed diagnosis of ASB seen at the National Cancer Centre Singapore between 2006 and 2019 were identified. Axillary lymph node status, treatment, survival, and recurrence data were collated. Thirteen patients were identified with a confirmed diagnosis of ASB, of which there were 11 primary and 2 secondary angiosarcoma cases. Eight patients had some form of axillary lymph node dissection and 5 did not. No positive nodes were found in any examined axillary nodes despite high median number of nodes harvested (13, range 8–24). 5/13 patients had disease progression, of whom none had locoregional recurrence to the axilla. ASB continues to be rare and recurrent and presents as a challenge to treat. Axillary lymph node involvement is most likely not present in a majority of patients. Prophylactic removal is unwarranted in patients presenting without lymph node involvement due to the lack of axillary metastasis.

Recurring radiation-induced angiosarcoma of the breast that was treated with paclitaxel chemotherapy: a case report

BackgroundAngiosarcoma of the breast is very rare and can be divided into primary and secondary angiosarcoma. Radiation-induced angiosarcoma (RIAS) is classified as secondary angiosarcoma. Diagnosis of RIAS is difficult due to its rarity, and the interpretation of pathological imaging is complicated. In the National Comprehensive Care Network (NCCN) guidelines, the first choice of treatment is surgery with negative margins. Adjuvant radiotherapy (RT) for close soft tissue margins should be considered. Preoperative or adjuvant chemotherapy of nonmetastatic disease is not recommended for angiosarcoma. We report a case of RIAS, which was impossible to diagnose with core needle biopsy (CNB) but was diagnosed by excisional biopsy. The patient was then administered adjuvant chemotherapy using conjugated paclitaxel (PTX).Case presentationA 62-year-old woman noticed a tumor in her right breast. She had a history of right breast cancer and had undergone breast-conserving surgery, RT, and tamoxifen therapy 8 years previously. CNB, which was performed twice, was inconclusive. The tumor was surgically excised and pathological analysis yielded a diagnosis of angiosarcoma. She then underwent a right mastectomy. One month after she underwent right mastectomy, a nodule reappeared on the skin of her right breast, and excisional biopsy revealed recurrence of angiosarcoma. A few weeks later another nodule reappeared near the post-operative scar and excisional biopsy revealed recurrence of angiosarcoma. We assumed that surgical therapy was insufficient because the patient experienced relapse of angiosarcoma after complete mastectomy. After the second recurrence, we treated her with systemic chemotherapy using PTX. There was no evidence of recurrence 8 months after chemotherapy.ConclusionAlthough angiosarcoma is difficult to diagnose, many patients have a poor prognosis. Therefore, prompt treatment intervention is desired. Moreover, there is little evidence regarding adjuvant therapy of angiosarcoma since it is a rare disease. We consider that adjuvant therapy helped to effectively prevent recurrence in the patient after complete excision.

Prognostic Factors in a Large Nationwide Cohort of Histologically Confirmed Primary and Secondary Angiosarcomas.

Angiosarcoma (AS) is a rare sarcoma of endothelial origin, arising spontaneously (primary AS) or after external damage such as radiation therapy or UV exposure (secondary AS). To date, reliable assessment of prognostic factors has proven difficult, due to disease rarity and heterogeneity of study cohorts. Although large registries provide relatively large AS patient series, these cases often lack histological confirmation. This study aimed to analyze AS prognostic factors in a large nationwide cohort of histologically confirmed cases, established through linkage of clinical data from the Netherlands Cancer Registry and pathology data from the Dutch pathology registry (PALGA). All cases were reviewed by an expert pathologist, showing a 16% discordance rate. Multivariable Cox regression survival analysis among 479 confirmed AS patients revealed remarkably poorer overall survival (OS) for primary AS compared to secondary AS (7 vs 21 months, Hazard ratio (HR) = 1.5; 95% confidence interval (CI) = 1.2–1.9). Age above 65 years, male gender, and no surgical treatment also significantly correlated to worse OS. Overall, OS was relatively poor, with a median of 13 months (95% CI = 10–16 months) and 22% five-year survival rate. With this study, we illustrate AS heterogeneity in clinical behavior and show for the first time better survival for secondary AS compared to primary AS.

Angiosarcoma — a malignant neoplasm secondary to radiotherapy for breast cancer in a female patient following breast-conserving treatment — a case report

Angiosarcoma is a rare malignant neoplasm, accounting for 1–2% of all sarcomas. The main cause of developing secondary angiosarcoma is radiotherapy. We analysed the case of a 52-year-old woman with breast cancer, who had undergone breast-conserving therapy. Four years after finishing treatment, she was diagnosed with secondary angiosarcoma in the irradiated area. The patient underwent a mastectomy. The disease relapsed six months after the operation in form of local recurrence, as well as liver and lung metastases. The patient’s condition gradually deteriorated despite treatment (chemotherapy and symptomatic management). The patient died due to cardiorespiratory failure nine months after the diagnosis of secondary malignancy.

Abstract 756: Whole exome sequencing identifies frequent mutations of PTPRB and KDR in secondary angiosarcoma

Abstract Angiosarcoma is an uncommon malignant vascular tumor that can occur anywhere on the body, with a predilection for the skin or soft tissues of the scalp and face. By whole exome sequencing, we identified recurrent somatic mutations in PTPRB, which encodes an endothelial-specific phosphatase that negatively regulates angiogenesis, in three secondary angiosarcoma tumors (3/10). In addition, four tumors harbored missense variants in the KDR gene, including three germline substitutions. Neither the PTPRB nor the KDR alterations were found in the 5 primary tumors studied. Copy number analysis derived from the exome and methylation data revealed frequent MYC amplification in the majority of secondary angiosarcoma tumors (9/10). Altogether, our data provide a comprehensive overview of genetic and epigenetic landscapes of angiosarcoma, and demonstrate that aberrant angiogenesis associated with PTPRB and KDR mutations may contribute to the pathogenesis of angiosarcoma. Citation Format: Tenzin Gayden, Brendan C. Dickson, Hamid Nikbakht, Pierre-Olivier Fiset, Nicolas De Jay, Javad Nadaf, David L. Burk, Albert Berghuis, Rebecca Gladdy, Jay Wunder, Robert Turcotte, Jacek Majewski, Nada Jabado. Whole exome sequencing identifies frequent mutations of PTPRB and KDR in secondary angiosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 756.

A Single Institution Study Experience of Secondary Breast Angiosarcoma after Breast Conserving Treatment: Multidisciplinary Management

A Single Institution Study Experience of Secondary Breast Angiosarcoma after Breast Conserving Treatment: Multidisciplinary Management

Local therapy for radiotherapy-associated angiosarcoma of the breast after organ-sparing treatment of primary breast cancer patients. A report of two cases and review of therapeutic options

Radiotherapy-associated angiosarcoma of the breast in breast cancer patients is a rare, poor-prognosis malignancy. Surgical resection with mastectomy is the standard local treatment for this disease. We present two cases of localized secondary angiosarcoma of the breast following breast-conserving therapy for early breast cancer, who underwent salvage mastectomy with R0 resection, followed by chemotherapy in one case. Both patients developed thoracic wall recurrence, and received palliative radio- and chemotherapy. In 23 months after being diagnosed with angiosarcoma, they died of uncontrolled local and distant disease. Our cases confirmed the high risk of local failure after salvage mastectomy due to radiotherapy-induced angiosarcoma. Based on literature, better local control might be achieved with more aggressive surgical approach with excision of all irradiated skin and soft tissue, and with re-irradiation.

Molecular biology of sarcoma

Soft tissue sarcomas are a large group of heterogenous neoplasms, many of them are highly aggressive. Most of the cases are sporadic, without any well-defined pathogenetic factor. Potential risk factors are ionizing radiation, lymphatic oedema (secondary angiosarcoma of the breast), viral infections (HHV8 and Kaposi sarcoma), exposure to chemical factors (vinyl chloride and hepatic angiosarcoma). Genetic susceptibility plays a role in a minority of cases. However, mutations in TP53, ATM and ATR genes are associated with enhanced susceptibility to radiation. Li-Fraumeni syndrome (autosomal dominant TP53 mutation) predisposes to development of malignancies, one third of them are sarcomas. Genetic alterations observed in sarcomas could be divided into three major groups characterized by: (1) chromosome translocations; (2) simple karyotype and mutations; (3) variably complex karyotypes. A large part of sarcomas belong to the first group and the specific chromosal translocations could be utilized in the diagnostic process. A smaller number of sarcomas could be assigned to the second group, e.g. desmoid fibromatosis (CTNNB1 or APC mutations) and GIST (KIT, PDGFRA, or less frequently BRAF, SDH, NF1). A large number of sarcomas are characterized by complex and variable karyotypes. Gene copy number alterations are frequent in this group, e.g. in well-differentiated liposarcoma there is an amplification of MDM2, CDK4 and HMGA2 genes or sarcoma-specific chromosomal break regions present in the CHOP gene in myxoid liposarcoma and FKHR in alveolar rhabdomyosarcoma.

Secondary breast angiosarcoma: A multicentre retrospective survey by the national Italian association of Breast Surgeons (ANISC)

BackgroundBreast angiosarcoma is a malignant mesenchymal neoplasm, which accounts for approximately 2% of all soft tissue sarcomas. Secondary breast angiosarcoma (SBA) may be related to chronic lymphedema after a mastectomy with lymph node dissection (Stewart Treves syndrome) and previous radiotherapy for complications from breast radiation treatment. It is a very rare condition; therefore, diagnosis and management are still a challenge. MethodsThe ANISC collected SBA data by means of a survey sent to all Italian breast centres in the ANISC. The clinicopathological characteristics and the management of this disease were analysed. ResultsTwenty-four centres participated in this survey in which 112 cases of SBA were analysed. The median age of the women with SBA was 68.9 years and it appeared approximately 90 months after the first irradiation for breast cancer. In 92% of cases, a mastectomy was performed without axillary dissection for those patients having a high grade of SBA (74.2%). The prognosis was worse in the high-grade cases (overall survival-OS: 36 months) as compared with the low-grade cases (OS: 48 months). After a follow-up of 5 years, 50.5% of the patients were still alive.Disease-free survival (DFS) was 35 months, and there were no differences between the groups of patients with either high- or low-grade histology. ConclusionsSecondary breast angiosarcoma is a very aggressive disease associated with a short survival outcome. The surgical approach still remains an important step in the course of treatment; furthermore, an accurate histological examination is helpful in establishing the prognosis of the patient. A mastectomy is mandatory. A longer OS was observed in patients with low-grade angiosarcoma as compared to high-grade angiosarcoma (C.I. 40–57 vs. 31–41 months).

Cutaneous Angiosarcoma Secondary to Lymphoedema or Radiation Therapy — A Systematic Review

AimsSecondary angiosarcoma is known to be associated with lymphoedema or radiation after cancer treatment. This systematic review aims to evaluate the clinical features and outcomes of secondary angiosarcoma commonly arising after breast cancer treatment. Materials and methodsA systematic review was carried out according to the PRISMA protocol. Medline, EMBASE, CINAHL and Cochrane databases were searched for English articles to April 2018 with predefined strategy. Retrieved studies were independently screened and rated for relevance. Data were extracted by two researchers. ResultsThere were 72 secondary angiosarcomas of the limbs. Most patients (n = 68, 94.4%) had a history of lymphoedema. The median latent period was 15 years (range 3–40 years). Thirty-eight (52.8%) patients received wide excision or amputation as a treatment for the angiosarcoma, two (2.8%) patients received isolated limb perfusion and one (1.4%) patient received systemic chemotherapy. The remaining patients received palliative care/undocumented treatment. The pooled median duration to mortality was 10.5 months (range 1–144 months). Of note, obesity was documented in seven (9.7%) patients. There were 83 breast angiosarcomas; all with known breast cancer history. Thirty-one (37.3%) patients received mastectomy as breast cancer treatment. Fifty-four (65.1%) patients had a history of adjuvant radiotherapy for the primary breast cancer. The median latent period was 6 years (range 2–50 years); the median size was 40 mm (range 8–200 mm). Forty-one (49.4%) patients received wide excision, 19 (22.9%) patients received completion mastectomy and 23 (27.7%) patients have undocumented treatment for angiosarcoma. The pooled median duration to mortality was 31 months (range 6–168 months). ConclusionAngiosarcoma in lympedematous upper limbs or after breast cancer irradiation remains uncommon. However, its long latency and high mortality warrant long-term vigilant surveillance.

Primary and Secondary Breast Angiosarcoma

Breast angiosarcoma is a rare and aggressive tumor. The role of F-FDG PET/CT in breast angiosarcoma is poorly known. We report a series of 13 lesions in 11 patients with histologically proven primary or secondary breast angiosarcoma who underwent FDG PET/CT at the initial assessment in our institution. All breast lesions showed FDG avidity. Visually and statistically, we observed a significant difference of SUVmax uptake foci between primary and secondary breast angiosarcoma (Wilcoxon test P < 0.0046) and a significantly poorer prognosis for high SUVmax than those with low SUVmax (P = 0.049) regardless of primary or secondary origins.

A case of radiation-associated angiosarcoma after breast cancer

BackgroundRadiation-associated angiosarcoma (RAAS) is a rare subtype of secondary angiosarcoma that is characterized by rapid proliferation and extensive tissue infiltration. Although various treatments for RAAS (such as surgery, chemotherapy, and radiation therapy) have been reported, there is no consensus as to which approach is the best.Case presentationA 76-year-old woman presented with right breast cancer (T1N0M0, stage I) 9 years ago. She had undergone breast-conserving surgery and sentinel lymph node biopsy and was receiving adjuvant chemotherapy and radiation therapy for the malignancy. Six years after presenting with the tumor, she developed pigmented skin and was diagnosed with a RAAS; this angiosarcoma recurred three times within 2 years. The angiosarcoma was resected each of the three times, after which adjuvant radiation therapy was performed. At 76 years old, the patient developed a new mass on her chest skin in the vicinity of the scar. Angiosarcoma was diagnosed following a pathology report, which resulted in a second diagnosis of recurrent RAAS again since the diagnostic criteria were met. After extensive resection of the irradiated area, the patient has remained free of angiosarcoma for the last 3 years.ConclusionResection of the entire irradiated field is critical for successful treatment of RAAS.

Paclitaxel-dependent prolonged and persistent complete remission four years from first recurrence of secondary breast angiosarcoma.

Among angiosarcomas, radiation-induced breast sarcomas (RIBS) represent a well-known entity generally characterized by a poor outcome, especially in patients with advanced disease. Despite the unfavorable prognosis, some chemotherapeutic agents have been used to treat these malignancies, occasionally with success. Treatments with demonstrated activity against sarcomas include ifosfamide-based regimens and, more recently, taxane derivatives. We report a case of a patient having a secondary breast angiosarcoma recurring early after surgery, who achieved complete remission following treatment with weekly paclitaxel. After 4 years of maintenance therapy, with an interval between consecutive administrations of no longer than 3 weeks, the patient is still in complete remission. A locoregional recurrence was documented twice during this period, the first as a consequence of a brief treatment interruption and the second because of a treatment delay. Nonetheless, in both instances a new complete remission was rapidly achieved with the resumption of the same treatment, without evidence of any significant adverse effects. We discuss the highly unusual behavior of this malignancy and the possible role of the two different mechanisms of action of paclitaxel-antiangiogenic versus cytotoxic-depending on the schedule of administration, with evidence of "false" drug-resistance.

Cytokeratin positivity in secondary angiosarcoma of breast: A diagnostic pitfall

Reappearing breast lump in a known case of breast carcinoma often turns out to be a recurrence of the carcinoma. However, in patients receiving radiotherapy for the disease, possibility of secondary angiosarcoma should also be suspected. Secondary angiosarcoma can pose a challenge in pathological diagnosis especially in small trucut biopsies. Aberrant expression of epithelial marker can also add to the difficulty. In this article, we report a case wherein similar difficulties were faced during the diagnosis.

Ultrasound Elastography and Magnetic Resonance Imaging Findings of Breast Angiosarcoma Mimicking a Benign Lesion by Elastography: A Case Report

Introduction: Primary and secondary angiosarcomas of the breast are rare neoplasms. Radiologically, magnetic resonance imaging, mammography, and ultrasound (US) findings of angiosarcomas have been reported previously. However, ultrasound (US) elastography findings of angiosarcoma have not been reported yet. Currently, US elastography should be used commonly to decide biopsy or short-term follow- up of breast lesions. Case Presentation: A 39-year-old female from Adana, Turkey, was admitted to Dr.Turgut Noyan Adana Teaching and Medical Research Center at the breast center of Baskent University, with a palpable right breast mass, which had been enlarging for one year in 2015. Our breast center is a tertiary referral center. B-mode US and US elastography findings suggested that the lesion was benign; however, magnetic resonance imaging showed a mass enhancing intensely at early phases with rapid wash out. The final diagnosis of the mastectomy specimen confirmed low-grade angiosarcoma. If the recommendation would have been based on the elastography findings, it would have been catastrophic because angiosarcomas tend to rapidly increase in size. Conclusions: B-mode US and elastography findings of breast angiosarcoma may mimic benign lesions.

Prognosis and treatment of non-metastatic primary and secondary breast angiosarcoma: a comparative study

BackgroundBreast angiosarcoma is a rare malignancy with limited publications confined to small retrospective case reviews and case reports. Knowledge of this disease is limited because information from previous studies is insufficient and inconsistent.MethodsWe obtained data from the Surveillance, Epidemiology, and End Results Program for non-metastatic primary and secondary breast angiosarcoma, and performed analysis to determine clinicopathological characteristics and estimate their associations with overall survival (OS).ResultsMedian age was 50–54 years in primary breast angiosarcoma and 70–74 years in secondary breast angiosarcoma, while median OS was 93 and 32 months, respectively. Age, tumor grade and tumor spread were associated with poor survival outcomes. Compared with primary breast angiosarcoma, patients with secondary breast angiosarcoma had a “nominal” increased death risk (HR = 1.89, 95% CI, 1.43–2.50, p < 0.001), which was driven by older age and more aggressive tumor phenotype at presentation. Mastectomy was associated with worse OS compared with breast conservative surgery (BCS) (adjHR = 2.47, 95% CI, 1.29–4.74) in primary angiosarcoma patients. Adjuvant radiation was associated with worse OS in secondary angiosarcoma patients (adjHR =1.77, 95% CI, 1.01–3.12).ConclusionsThere is a “nominal” increased death risk in secondary breast angiosarcoma due to advanced clinicopathological features. Both BCS and mastectomy are feasible in primary and secondary angiosarcoma if R0 can be achieved. Routine radiation in unselected breast angiosarcoma should be cautious because there is no survival benefit in primary AS and appeared to be associated with a worse OS in secondary AS.