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Aim: Post-radiation angiosarcoma is an iatrogenic event seen in the setting of breast cancer treatment. Histopathologically, there are morphologic variants of angiosarcoma that mimic benign entities, including the capillary lobule variant of post-radiation angiosarcoma. We present the largest case series to date of this histopathologic variant of post-radiation angiosarcoma., Methods and Results: Cases of the capillary lobule variant of post-radiation angiosarcoma from institutional/consultation archives from 2008 to June 2022 were reviewed. For inclusion, tumors had to occur in irradiated skin and exhibit a multi-lobular proliferation of tightly packed capillary-like vessels, as previously described in this variant. Prior ancillary studies were also reviewed. Eight cases met the criteria. All occurred in women treated with radiation for breast cancer (median age 75 years). All cases had similar findings, including a multi-lobular proliferation of tightly packed vessels, infiltrative cords, and atypical single endothelial cells. A conventional angiosarcoma pattern was also seen in five cases. All cases tested were positive for vascular markers (CD31, CD34, and/or ERG) and MYC. MYC amplification was shown by FISH in all cases tested. Smooth muscle actin (SMA) was positive in pericytes in the capillary lobules in all five cases tested and areas of conventional angiosarcoma in two of three cases., Conclusions: The capillary lobule variant of angiosarcoma is a rare and therefore potentially under-recognized variant of post-radiation angiosarcoma. The lobular architecture and SMA positivity may mimic benign vascular proliferations. Careful attention to histopathologic features and ancillary tests may facilitate accurate diagnosis., (© 2022 The Authors. Journal of Cutaneous Pathology published by John Wiley & Sons Ltd.)

Postradiation cutaneous angiosarcoma of the breast is a rare, delayed complication of adjuvant radiation treatment for breast carcinoma and is associated with a worse prognosis than the original primary cancer. Recent studies have characterized the diagnostic utility of MYC and NOTCH1 receptor expression as markers for secondary radiation-associated angiosarcomas. Herein, we report an exophytic secondary breast angiosarcoma with MYC and NOTCH1 immunoreactivity. This case illustrates the utility of these markers for the identification of radiation-associated angiosarcoma with MYC and NOTCH1 expression, potential for targeted therapy and need to identify patients for further studies of the clinicopathologic and prognostic significance., (© 2021 Wiley Periodicals LLC.)

Secondary angiosarcoma of the breast following catheter-based brachytherapy after lumpectomy is rare. We describe a case of a patient with breast cancer treated with partial mastectomy and sentinel node biopsy followed by accelerated partial breast irradiation (APBI), who developed skin changes 6 years after completion of therapy. Punch biopsy confirmed the diagnosis of secondary angiosarcoma. This case is even more unique in that the location of the skin changes was remote to the lumpectomy site. There is a critical need to recognize secondary angiosarcoma presentation after APBI and determine the rate of occurrence compared with traditional external beam irradiation., (© 2020 Wiley Periodicals LLC.)

Background: The p53 and phosphoinositide-3-kinase, catalytic, alpha polypeptide/v-akt murine thymoma viral oncogene homolog/mechanistic target of rapamycin (PIK3CA/AKT/mTOR) pathways frequently are altered in sarcoma with complex genomics, such as leiomyosarcoma (LMS) or undifferentiated pleomorphic sarcoma (UPS). The scale of genetic abnormalities in these pathways remains unknown in angiosarcoma (AS)., Methods: The authors investigated the status of critical genes involved in the p53 and PIK3CA/AKT/mTOR pathways in a series of 62 AS., Results: The mutation and deletion rates of tumor protein 53 (TP53) were 4% and 0%, respectively. Overexpression of p53 was detected by immunohistochemistry in 49% of patients and was associated with inferior disease-free survival. Although p14 inactivation or overexpression of the human murine double minute homolog (HDM2) were frequent in LMS and UPS and could substitute for TP53 mutation or deletion, such alterations were rare in angiosarcomas. Phosphorylated ribosomal protein S6 kinase (p-S6K) and/or phosphorylated eukaryotic translation initiation factor 4E binding protein 1 (p-4eBP1) overexpression was observed in 42% of patients, suggesting frequent activation of the PIK3CA/AKT/mTOR pathway in angiosarcomas. Activation was not related to intragenic deletion of phosphatase and tensin homolog (PTEN), an aberration that is frequent in LMS and UPS but absent in angiosarcomas., Conclusions: The current results indicated that angiosarcomas constitute a distinct subgroup among sarcomas with complex genomics. Although TP53 mutation and PTEN deletion are frequent in LMS and UPS, these aberrations are rarely involved in the pathogenesis of angiosarcoma., (Copyright © 2012 American Cancer Society.)

Cutaneous angiosarcoma or lymphangiosarcoma represents an uncommon aggressive tumor known to arise on a background of chronic lymphedema secondary to various etiologies, principally following surgery or irradiation. There have been rarely reported cases of angiosarcoma following infective conditions that eventuate with lymphatic stasis. We report a case of angiosarcoma arising after 33 years within a background of filariasis. Awareness of this association can lead to early diagnosis and appropriate treatment of this potentially fatal malignant tumor., (Copyright © 2011 John Wiley & Sons A/S.)

A significant proportion of angiosarcoma arises in the setting of chronic lymphedema, often following surgery for breast carcinoma (Stewart-Treves syndrome). Massive localized lymphedema (MLL), a relatively recently described and rare pseudotumor most often occurring in morbidly obese patients, is thought to be the result of derangements in lymphatic drainage secondary to excessive adipose tissue. Only a very small number of cases of angiosarcoma have been reported in patients with MLL. We reviewed the clinical and pathological features of five patients with angiosarcoma arising in this unusual clinical setting. The tumors arose in three women and two men, who were in the age range from 36 to 81 years (median: 52 years). All patients were or had recently been morbidly obese (mean body mass index = 47.2 kg/cm(2) ; range:37.6-68.5 kg/cm(2) ) and had long-standing soft tissue changes of MLL. The tumors arose in the thigh (two cases), lower leg (two cases) and abdomen/proximal thigh (one case) and ranged from 6 to 28.5 cm in size (mean: 15.9 cm). All tumors were conventional high-grade angiosarcomas and microscopically exhibited an admixture of vasoformative, spindled and epithelioid features. Microscopic changes of MLL, including dermal fibrosis, expansion of interlobular fibrous septa and lymphangiectasia, were identified in all cases. Clinical follow-up (four cases; mean: 13.8 months; range: 2-32 months) showed one patient to be dead of disease, one patient to be dead from therapy-related complications and two patients to be alive without disease. One case was too recent for meaningful clinical follow-up. We conclude that lymphedema secondary to obesity should be recognized as a significant risk factor for the development of angiosarcoma. The clinical and pathological features of angiosarcoma arising in this distinctive clinical setting appear to be identical to those of other lymphedema-associated angiosarcomas. With the continuing epidemic of obesity in Western societies, the incidence of obesity-related angiosarcoma is probably to increase. Consequently, it is critical that lymphedematous areas in obese patients be carefully examined for clinical evidence of early angiosarcoma, with the hope that timely diagnosis may lead to improved patient outcome., (Copyright © 2011 John Wiley & Sons A/S.)

Approximately 100 cases of angiosarcoma following breast-conserving therapy have been reported. The prevalence of angiosarcoma following breast conservation has not been accurately established and optimal treatment has not been defined. The goal of this article is to clarify both issues. The Fisher's exact test was used to compare the prevalence of postirradiation angiosarcoma seen in our private practice to the prevalence reported from the two largest national database studies. A literature review was performed to determine optimal treatment guidelines. The results of the comparison indicated that the prevalence of postirradiation angiosarcoma seen in our practice was significantly higher than that reported in the two national database studies at p-values of 0.0124 and 0.0080. Also, results from the literature review suggest that early detection and aggressive treatment lead to improved outcomes. The data are insufficient to draw firm conclusions, but suggest that the current literature underestimates the prevalence of angiosarcoma following breast-conserving therapy. Since elderly women derive less benefit from radiation and may be more prone to develop postirradiation angiosarcoma, confirmation of our findings could lead to a reappraisal of the management of elderly patients with early stage breast cancer.

Background: Angiosarcoma arising in the irradiated breast after breast-conserving therapy is being reported with increasing frequency. As more women undergo breast-conserving therapy, the incidence can be expected to increase. Surgeons, medical oncologists, and radiation oncologists will be faced with difficult management decisions for this aggressive disease., Methods: A comprehensive review of all English-language reports of angiosarcomas after breast-conserving therapy was performed. Approximately 100 cases were reviewed for treatment details and outcome analysis was performed., Results: Surgical excision is associated with very high rates of disease recurrence (55 of 75 patients with at least 1 year of follow-up; 73%). Local disease recurrences in the tumor bed or along the mastectomy scar are a component of almost all recurrences (96%). Distant metastases develop simultaneously or shortly after local recurrences. Hyperfractionated radiotherapy has successfully prevented local disease recurrences in a limited number of patients., Conclusions: Angiosarcoma after breast-conserving therapy is increasingly diagnosed in a small but significant portion of breast carcinoma survivors. The aggressive nature of this disease demands further investigation of adjuvant therapy to prevent recurrence of disease after surgery., (Copyright 2003 American Cancer Society.)

Background: Angiosarcomas arise in the scalp and face in the elderly, in association with chronic lymphedema (Stewart-Treves syndrome), and in irradiated areas. Rarely in these settings, angiosarcomas exhibit pure spindle cell phenotype., Methods: Herein, the clinicopathologic features of a 72-year-old-woman with spindle cell angiosarcoma are described., Results: A 72-year-old woman presented with numerous nodules and diffuse induration from the lower abdomen to the right buttock, corresponding to the area exposed to 60Co-irradiation during treatment for cervical carcinoma 10 years earlier. Histopathological examination revealed inflitrative, atypical, spindle cells that labeled with antibodies to CD31, CD34, and factor VIII-related antigen. Ultrastructurally, these malignant spindle cells contained Weibel-Palade bodies. No features suggesting radiation dermatitis (sclerosis or bizarre, large fibroblasts) were identified, but lymphangiectases and widely spaced collagen bundles(lymphedema) were prominent in the skin surrounding the angiosarcoma. Computed tomographic scan of the abdomen highlighted this histologic finding by demonstrating tumor masses limited to areas of lymphedema. Treatment with intravenous and local injections of recombinant interleukin 2 (rIL 2) followed by electron beam irradiation were initially effective with tumor remission for 2 months. However, the recurrent tumor did not respond to a second course of one-shot injection of rIL 2 through the abdominal aorta and the patient succumbed to her angiosarcoma 19 months after diagnosis., Conclusions: Radiation-induced lymphedema may be a factor in angiosarcoma associated with radiotherapy.

Background: Second malignancies are a well recognized complication of radiation therapy., Methods: We performed a computer search of the literature using the Medline Database for Pericardial Tumors and Post-Irradiation Sarcomas., Results: The case history of a patient who developed a radiation-induced pericardial angiosarcoma is described. We present a detailed review of pericardial sarcomas., Conclusions: We believe this to be the first report of a radiation-induced pericardial sarcoma. The importance of continued long-term observation for patients who receive mediastinal irradiation is stressed.

Background: Angiosarcoma (AS) accounts for 1 to 2% of all soft tissue sarcoma. Both primary and secondary AS may occur, the latter being reported in the upper extremity with lymphedema after extended radical mastectomy for breast cancer (postmastectomy AS) or following radiotherapy of the breast, the thoracic wall, or other sites (radiation-associated AS). The authors report two cases of cutaneous radiation-associated AS and review literature regarding treatment planning and follow-up data to define the most appropriate therapy for cutaneous and noncutaneous radiation-associated AS., Methods: The clinical records of two patients with radiation-associated AS were analyzed and previously reported cases were reviewed., Results: Case 1: a female age 67 years developed cutaneous AS in the residual breast 27 months after breast-conserving therapy and conventional external beam radiotherapy (EBR). She underwent chemotherapy followed by simple mastectomy and chemotherapy with the same regimen but developed early recurrence that was treated with hyperthermia and EBR, wide excision, and second-line chemotherapy. She died 30 months after primary diagnosis of AS with multiple metastases. Case 2: a male age 59 years developed cutaneous AS in the left groin, 10 years after conservative surgery and EBR for a penile carcinoma. Early recurrence following wide excision was treated with chemotherapy, re-excision, and immunochemotherapy but the patient died 24 months after the primary diagnosis of cutaneous AS with local progression and distant metastases., Conclusions: The prognosis of radiation-associated AS is dismal, due mostly to its poor differentiation and frequent diagnostic delay. Simple mastectomy is advised for patients with cutaneous AS after breast-conserving surgery with wide tumor-free margins. If primary surgery fails, survival is seriously compromised because adjuvant or palliative treatments are not effective.

A 20-year-old man with von Recklinghausen disease had a right neck mass. Pathologic examination at excision showed angiosarcoma arising in a malignant schwannoma of the cervical brachial plexus. Comparison with previous reports revealed that angiosarcoma is a rare, highly aggressive sarcomatous element in malignant schwannoma arising in patients with neurofibromatosis (NF).

Background: Angiosarcoma (AS) is an uncommon tumor that rarely develops after external beam radiation therapy (EBRT). Thirty-six cases have been reported in the literature., Methods: The authors present two additional cases. Each of these patients received breast-conserving treatment for breast carcinoma that consisted of tylectomy and EBRT. In each case, AS developed in the field of prior irradiation., Results: Currently, seven cases of AS after radiation therapy for breast-conserving treatment of breast carcinoma have been reported. The average time interval between the administration of radiation therapy and the development of AS is 8.6 years., Conclusions: This complication is rare and should not influence the decision to offer breast-conserving therapy to patients. However, patients should be informed that AS may develop as a result of radiation therapy.

Angiosarcomas account for only 1% to 2% of all soft tissue sarcomas with the most common site of origin being skin and subcutaneous tissue particularly on the face and scalp of elderly patients. These neoplasms rarely arise in the small or large bowel with presentation as diffuse abdominal "angiosarcomatosis." Two patients are reported who were treated with adjuvant pelvic irradiation for gynecologic malignancies (squamous cell carcinoma of the cervix and adenocarcinoma of the endometrium) in whom diffuse abdominal angiosarcoma of intestinal origin developed 7 and 18 years later. Both patients were treated with standard megavoltage irradiation. The clinical course was rapid in both cases with death due to intra-abdominal hemorrhage and bowel obstruction. The pertinent literature relating to the association between radiation therapy and subsequent development of angiosarcomas of soft tissues and other sites is briefly reviewed.

The authors present an angiosarcoma of the scrotum and penis. The disease occurred in a 61-year-old man with a long history of neurofibromatosis (von Recklinghausen's disease). The histologic and ultrastructural features are described. The authors speculate that the angiosarcoma, which developed in a location without histologic evidence of neurofibromatosis, possibly represents an expression of an abnormal genome in vascular tissue. The angiosarcoma responded to radiation therapy only temporarily, recurred after surgery, and did not respond to Adriamycin, dactinomycin or cis-platinum. The patient died three years after the onset of his angiosarcoma.

This paper reports a case of angiosarcoma of the terminal ileum in a 66-year-old female. This angiosarcoma developed 8 years after postoperative irradiation for ovarian carcinoma. This case appears to be the sixth case of angiosarcoma arising at the site of therapeutic irradiation thus far reported in the literature. The fact that the angiosarcomas in these cases developed in anatomic sites, which are unusual for angiosarcomas in general, suggests that there is a cause-and-effect relationship between irradiation and angiosarcoma. Apart from the direct carcinogenic effect of irradiation, prolonged stimulation for tissue repair resulting from tissue damage secondary to irradiation-induced vascular changes may also play an etiologic role in the development of angiosarcomas in these cases.

A 47-year-old woman presented with an angiosarcoma of the terminal ileum 14 years after receiving adjuvant radiation therapy for ovarian dysgerminoma. Her clinical course is described, and the previously reported cases of radiation-induced angiosarcoma are reviewed.

Angiosarcomas are rare tumors, particularly in the head and neck region. A case report of an angiosarcoma arising in the internal carotid artery is described; such an occurrence has not previously been reported. The etiology, pathology, and treatment of this unusual tumor are discussed.

The production of tumors through solid-state mechanisms has been demonstrated in experimental animals, but foreign body tumorigenesis has not been proven definitively in man. The authors report three patients with angiosarcoma that occurred in intimate association with foreign material retained for prolonged periods. Although several etiologic factors have been defined in angiosarcoma, foreign bodies generally are not appreciated to have this potential. Review of the literature disclosed six cases of angiosarcoma and 40 cases of sarcomas of other histologic types associated with foreign material, with latency periods of from 4 months to 63 years. Implanted foreign material thus should be considered capable of inducing virtually any form of sarcoma in humans.

Six different types of bovine papillomavirus (BPV-1 to BPV-6) have been identified and classified into two subgroups: subgroup A, which induce fibropapillomas, and subgroup B, which induce true epithelial papillomas. BPV-4, a member of subgroup B, is the aetiological agent of papillomas of the upper alimentary canal, which can become a focus for transformation to squamous-cell carcinomas in animals feeding on bracken fern. Strong circumstantial evidence suggests that the progression to malignancy is due to the interplay between BPV-4 and carcinogen(s) present in the fern. The carcinomas of the upper alimentary canal are often accompanied by adenomas and adenocarcinomas of the lower bowels, and by carcinomas and hemangiosarcomas of the urinary bladder. Bracken-grazing animals are also heavily immunosuppressed. Florid papillomatosis of the upper alimentary canal and cancers of the urinary bladder have been experimentally reproduced in animals either kept on a diet of bracken or immunosuppressed with azathioprine. Several bladder cancers contained multiple episomal copies of BPV-2 DNA, suggesting that this virus, or its genome, can be present in a latent form, and that it can be implicated in malignant transformation. Further indication of latent infection is provided by the onset of skin warts in papillomatosis-free animals. These warts developed at sites of damaged skin and harboured either BPV-1 or BPV-2. BPV-4 DNA has not been found in the naturally occurring cancers of the upper alimentary canal and of the lower bowels, except in one tongue carcinoma and one transforming papilloma, indicating that the viral genome is not required for the maintenance of the malignant state in the alimentary canal.

Between 1920 and 1970, 13 patients (7 men and 6 women) with cutaneous angiosarcomas of the head or neck were treated at the Mayo Clinic; the mean age of the patients was 66 years. Three clinical patterns were noted: a superficial spreading type, a nodular type, and an ulcerating type. There were no predisposing benign lesions; however, in one patient, angiosarcoma developed in an area of previously irradiated skin. Three modes of therapy were used: surgery alone, radiation alone, and surgery with postoperative irradiation. Of the 13 patients, 2 survived more than 5 years and 2 were alive within 1 year of therapy. Because cervical lymph node spread is common, lymph node clearance is recommended for patients with lateralized lesion or with palpable lymphadenopathy at presentation.

An hepatic angiosarcoma that developed 36 years after thorotrast administration is described with radiological and autoradiographic findings. An unusual feature of this case is the remarkably long latent period.

Light and ultrastructural features of a cerebellar hemangioblastoma in a 56-year-old man are described in detail. The neoplasm was composed of three major cell types: endothelial cells, pericytes, and stromal cells. The endothelial cells lined the fenestrated vascular channels. The pericytes were ensheathed by their own basal lamina which separated them from the basal lamina covering the endothelium. The stromal cells contained, in addition to the conventional organelles, numerous membrane-bound lipid inclusions, annulate lamellae, and nuclear bodies. There were also present transitional cells which shared the fine structure of all the three major cell types. Histogenetically, the tumor was considered to be of vascular origin. The stromal cells represented the stem cells which, under the neoplastic influence, continued to proliferate and differentiate into "vasoformative" elements (pericytes and endothelium) which formed new blood vessels. The transitional forms between the stromal cells and the "vasoformative" elements suggested that the cellular components of a hemangioblastoma shared a common ancestry, most likely of an angioblastic lineage.

Malignant neoplasms known to develop following external beam radiation include squamous cell carcinoma, osteosarcoma, chondrosarcoma, malignant fibrous histiocytoma, mixed mullerian tumors, malignant schwannoma, myelogenous leukemia and angiosarcoma. Latency periods of many years characterize the onset of these tumors following the exposure. Cutaneous angiosarcoma following radiotherapy for breast carcinoma has been rarely documented, occurring up to 13 years postirradiation. Two cases of this entity are reported occurring 37 months postradiotherapy at the site of mastectomy performed for mammary duct carcinoma.

The authors discuss an angiosarcoma that developed in a 50-year-old woman's breast 10 years after she underwent conventional postoperative irradiation with cobalt 60 teletherapy. Although angiosarcoma developing in a lymphedematous arm after radical mastectomy is a well-known phenomenon, and several cases of angiosarcoma are known to have occurred in the chest wall after mastectomy with or without irradiation, only one other case of angiosarcoma in an irradiated breast has been reported. The possible role of therapeutic irradiation in inducing this malignancy is discussed.