Angiosarcoma Research Articles

Atypical Vascular Lesions of the Breast: Clinicopathological and Immunohistochemical Study of 24 Cases from a Single Institution

INTRODUCTION: Atypical Vascular Lesions (AVL) of the breast after radiation exposure show heterogeneous clinical and histopathologic features. Most data on outcomes reported previously favored a benign process, but some studies have challenged this concept, suggesting that AVL and post-radiation angiosarcoma represent a morphologic continuum, implying AVL as a precursor to angiosarcoma. However, the risk of malignancy is still undefined due to small number of reported cases with follow-up information. OBJECTIVES: To characterize AVL of the breast clinically and histopathologically, and to study their behavior, trying to establish whether they are a true benign process or a risk factor for developing angiosarcoma. MATERIAL AND METHODS: All cases of AVL of the breast diagnosed at the Department of Anatomic Pathology at the European Institute of Oncology (EIO), Milan, from 1999 to 2009 were selected. Histo-pathologic review and immunohistochemical studies for podoplanin (D2-40), CD31, Ki67 and endoglin (CD105) were performed. RESULTS: Twenty-four female patients treated at the EIO were diagnosed with AVL of the breast after radiotherapy for breast carcinoma. The median age was 58 years old (range: 36-81 years), and AVL size ranged from 0.3cm to 1.1cm (median, 0.5cm). The latency interval between radiotherapy and AVL diagnosis was 49 months (range: 17-124 months). The most common clinical presentation of AVL was an erythematous or violet unique papule in the irradiation field (62.5% of the cases). Microscopically, AVL did not infiltrate the subcutaneous tissue and did not have endothelial multilayering, prominent nucleoli, mitoses or lakes of blood. A patchy chronic inflammatory infiltrate accompanied all AVL to varying degrees. Thirteen cases were classified as lymphatic type (LT) AVL and 11 cases as vascular type (VT) AVL, according to positive staining for D2-40. The endothelial cells stained for CD31 (18 cases), Ki-67 (5 cases), and CD105 (12 cases). One patient with VT-AVL with positive margin developed local recurrence. Two patients, one with VT-AVL, and the other with LT-AVL with compromised margin, developed high grade angiosarcoma in the previous biopsy site, 19 and 89 months later, respectively. Both cases showed overexpression of Ki-67 in the endothelial cells of the AVL. Margin involvement was associated to unfavorable outcome. DISCUSSION: Our data indicate that post-radiation angiosarcoma and AVL may represent a morphologic continuum. AVL cases of both types, VT and LT-AVL, showed similar risk of progressing to angiosarcoma, as well as AVL with high Ki-67 expression. CONCLUSION: Although our data are not conclusive, the development of local recurrence and subsequent angiosarcoma indicate that AVL must be completely excised, with free surgical margins, and patients must be accompanied by clinical exams and imaging until the natural history of the AVL is better explained.

Bilateral Angiosarcoma of the Breast: Case Report and Review of the Literature

INTRODUCTION: The Angiosarcoma of the breast is a malignant mesenchymal neoplasia that has its origin at endothelial cells of blood vessels of the breast. It is a rare pathology, which represents 0. 04% of the primary tumors of the breast and about 8% of the sarcomas presented at the mammary gland. It occurs mainly in women under 40 years old. The incidence of synchronic contralateral breast Angiosarcoma is about 20%. The dissemination of the tumor is mainly hematogenic. It is usually presented as tumor, with a diameter of about 5 centimeters with soft consistence and badly bounded borders. The diagnosis is histopathological. The prognosis is unfavorable due to the high aggressiveness of the tumor, with recurrence taxes around 50% and a survival index of about 41% in 3 years. The usually recommended treatment is the surgical approach through mastectomy. CASE REPORT: SNPM, female, 44 years old. She was sent to Hospital Federal da Lagoa for having a touchable nodule in the left breast two months before the first interview. The physical examination showed medium-volume breasts, with a palpable tumor at the union of internal quadrants of the left breast with four centimeters in diameter, badly defined bounds, mobile, with a slightly hard consistence and negative papillary discharge bilaterally. Mammography presented with no suspicious lesions. Ultrasonography of the breasts showed at the union of the internal quadrants of the left breast a hypoechogenic, heterogeneous and irregular nodule with. This nodule measured 3. 2 x 1. 3 x 2. 8 centimeters category BI-RADS 4. We made then a core biopsy of this nodule, with a hystopathological report compatible with breast Angiosarcoma of a low degree. An MRI was performed after this diagnosis. The MRI revealed an irregular and heterogeneous nodule, with intense precocious impregnation by the contrast medium and signals of limited distribution at the union of medium quadrants of the left breast. The nodule measured 4. 7 x 3. 8 x 3.5 centimeters corresponding to what was found at the USG performed previously. The MRI showed also a small irregular nodule with intense heterogeneous impregnation of the contrast medium and ascending curve placed in the third medium of the union of the superior quadrants of the right breast classified as BI-RADS 4. At this point, we performed core biopsy of the nodule of the right breast, which made the same diagnosis of the left breast lump. Skin bilateral sparing mastectomy with expander placement bilaterally was performed as the surgical treatment. Histopathological examination of the surgical right breast revealed a low-grade breast angiosarcoma with free surgical margins. The result of the left breast surgical specimen was breast angiosarcoma of intermediate histological grade with foci of high grade, focal necrosis, angiolymphatic invasion was not observed, surgical margins were also free. CONCLUSION: This is a rare and very agressive disease. In the case reported, the patient is at the age when the most cases of this kind of sarcoma appear. The patient had a bilateral tumor. Although the prognosis is dark and there is a high recurrence of the disease, we have decided for the bilateral adenectomy that spare the skin and areolopapilar complexes with expander placement bilaterally, respecting the desire of a young and depressive patient.

Breast Sarcoma: A Case Report in Young Patient

INTRODUCTION: Sarcomas are defined as mesenchymal tumors are usually found in soft tissues and present as a large mass palpable. Metastatic lymph nodes are rare because the spread occurs most commonly by hematogenous, being the lung an important metastatic site. (Robbins, 2004). This condition is considered a rare cancer that affects mainly elderly women. Belong to this group of neoplasms filoides malignant tumors, a heterogeneous group of sarcomas, including liposarcomas, osteosarcoma, angiosarcomas, malignant histiocitofibroma, leiomiosarcomas, among others. (Gustalla, 1997). This condition has clinical aspect as breast mass palpable, painless, fast growing, leading to a diffuse increase of the breast. This study aims to discuss the clinical and histological sarcoma of the breast, from the case report, considered to be an uncommon clinical condition. CASE REPORT: LR, 41, white, married, teacher, born and raised in Lucena-PB, sought outpatient Mastology presenting breast enlargement 4 months ago. Gesta II to II, breastfeeding for 5 years. Lack of oral hormonal contraception and family history of breast cancer. There was no report of alcohol consumption or smoking. On physical examination, there was a bulky mass in the left breast, with areas of necrosis and increased vascularity of the skin. Palpable axillary lymph nodes in left axilla, measuring about 2 cm the largest one. It was performed a core needle biopsy that revealed mesenchymal neoplasm and after immunohistochemical evaluation it was confirmed the diagnosis of undifferentiated sarcoma of the breast. DISCUSSION: The breast sarcomas represent 1% of malignant breast diseases, making it a rare malignant neoplasm. It mainly affects women of advanced age, over 60 years, but it can also affect more rarely women in adolescence. The histopathological diagnosis of the lesion can be accomplished by core biopsy, a minimally invasive method, which has high sensitivity and specificity in the evaluation of mammary lesions. In order to ensure the accuracy diagnosis, immunohistochemistry is a valuable procedure to confirm the diagnosis (Cezar, 1995). Most publications do not define what is the best follow-up treatment in terms of surgery, chemotherapy and radiotherapy. However, it is common to consider total mastectomy without axillary dissection, in the absence of palpable lymph nodes. The role of wide excision and adjuvant therapy remain uncertain (Amaral 2008). The prognosis is difficult to define, although local invasion and the degree of cellular atypia appear to have some predictive value, while the tumor size and mitotic activity less correlated with the result. (Barnes, 1977).

Hamartoma Associated to Pseudoangiomatous Stromal Hyperplasia (Pash) of the Breast and Chondroid Metaplasia

INTRODUCTION: Hamartoma of the breast is rare benign lesion, generally detected through the screening mammographic. PURPOSE: Case report of two rare histopathological alterations in the breast: PASH and Chondroid metaplasia associated to the hamartoma. For the attention of us, in this case was the compound of “chondroid metaplasia” (unusual in benign lesion) associated PASH that is histologically benign myofibroblastic proliferation of mammary stroma, and complex network of anastomosing slit-like spaces within a dense collagenous stroma. REPORT: RCM, female, 47 years old, history of the left breast nodule painless, for 5 years ago, detected by mammographic screening. Physical exam: right breast without palpable tumour. Left breast: size nodule 5. 0mm in inferomedial quadrant (IMQ), elastic, mobile, free skin and deep plans surface localized in junction medial quadrants (JMQ), Axillary lymph nodes uninvolved. MMG: ovale hyperdense nodule, margins partially defined, associated with calcifications, measuring 45mm in IMQ left breast BIRADS zero. USG: Heterogeneous nodular image, irregular with calcifications measuring 59 per 33 per 44 mm, localized at 9 o’clock position left breast. Core biopsy: PASH and cartilagenous differentiation. It was suggested total resection of lesion. Freezing exam: its didn’t conclude. Surgical pathological report: left breast quadrant, mammary hamartoma, chondroid metaplasia, and PASH with tubular microcystic adenosis and fat. Immunohistochemical: positive P63 and Calponin in the myo-epithelial cells. Immunohistochemical profile together morphological findings consistent to mammary hamartoma. DISCUSSION: Hamartoma has been incidence of 0. 1-0. 7%, average 45 years old, in the mammographic shows circumscribed lesion lobular pseudocapsular and heterogenous density. The classical mammography appearance is circumscribed area consisting of both soft tissue and lipomatous elements, surrounded by a thin radiolucent zone. Despite the pathogenic of the lesion is not clear, it’s thought to result from a mesenchymal dysgenesis rather than a true tumoral process. Histologically, the most characteristic is appearance otherwise normal breast and fat tissue distributed in a nodular fashion within a fibrous stroma. Some cases have been reported to a genetic defect named Cowden’s disease. The current management of hamartoma is surgical removal. CONCLUSION: The aim of this report was the presents rare hamartoma benign breast lesion associated to chondroid metaplasia, uncommon lesions that leads us to do a differential diagnostic with fibroadenoma and benign phyllodes tumours, as well PASH areas although benign lesion that histologically need the differential diagnosis with low grade mammary angiosarcoma. The patient is very well and she is in follow up uneventful.

Breast Sarcoma in a 16 Year-Old Girl

INTRODUCTION: Sarcomas are histologically heterogeneous nonepithelial tumors, which may develop in the connective tissue of the breast, only in around 4, 6 cases per million women/year. They represent less than 1% of all the breast cancers; however their grim prognosis implies an importance in the study of these tumors. Sarcomas usually occur in women over 45 years of age. Furthermore, these malignancies can be classified according to their histology, as fibrosarcoma, angiosarcoma, and pleomorphic sarcoma. The patient appears with a fast growing mass in her breast. The prognosis depends on stage and histological grade, and treatment is mainly surgery. This case report is of a teenager without any family history who developed this rare malignancy. CASE REPORT: APLV, female, 16 years old, white, natural from and resident in Rio de Janeiro, Brazil, student, single, was referred to the senology department for further investigation of breast mass. The patient denied any previous illnesses, contact with Tuberculosis or anything important in the family history. Her physical exam presented with a 20cm tumor occupying the whole left breast, stretching the skin but without infiltrating it, with a hard consistency, and an areas of fluctuation. This area was drained and the liquid was sent to pathology for research for neoplastic cells, Tuberculosis, and other pathogens. The axillary lymph nodes were not palpable. A core-biopsy of the tumor was performed for diagnosis, and the patient was submitted to a breast sonogram and mammography. The cytology showed no signs of disease. The result of the core- biopsy was malignant mesenchymal neoplasm. The sonogram and the mammography showed a large hypoechoic/hyperdense mass occupying all quadrants of the left breast, of about 14 cm, suggesting a solid lesion. The immunohistochemistry research showed fusiform cells neoplasm with intense pleomorphism and necrosis, positive for vimentine, and negative for CD31, CD34, estrogen receptor, progesterone receptor and CK5. The screening for metastatic disease was negative, and the patient was submitted to mastectomy with immediate reconstruction with skin graft. The final result from pathology of the left breast was a malignant mesenchymal neoplasm with necrosis, and pronounced nuclear pleomorphism and high mitotic index. Nipple, skin, and surgical margins free from neoplasm. The patient was followed up at the hospital for one year and she has had a favorable outcome, with good healing and no metastasis so far. DISCUSSION: The diagnosis of breast sarcoma is very rare, and it is usually followed by a poor prognosis for the patient. It is important to report the rare cases in order to further understand and to clarify the aspects of this disease. The patient in this case report, epidemiologically different from the usual breast sarcoma patient, shows that anything is possible in oncology.

Widespread epithelioid angiosarcoma with ventricular wall involvement in a dog.

This paper reports on a canine angiosarcoma, presenting as an "undifferentiated metastasizing tumor". A 14-year-old female Cocker Spaniel was referred to the University of Extremadura Veterinary Clinic for clinical examination after suffering rapid deterioration, with chronic cough, anorexia and cachexia. One week after clinical examination, the dog died of right congestive heart failure and ventricular arrhythmia. Blood counts revealed lymphopenia and platelet depletion. The biochemistry profile was within normal limits, except for a drop in blood urea nitrogen. Cytological evaluation of liver and spleen biopsies revealed clustered anaplastic cells that lacked convincing tissue differentiation. Major findings at necropsy were enlarged spleen and multiple, beige to dark-red nodules ranging from 0.5 to 3 cm in diameter in the heart, lung, liver and spleen. At histological examination, multiple nests of anaplastic epithelioid cells were found in sections from all affected organs. Immunohistochemistry revealed widespread expression of CD31 and Factor VIII-related antigen. The neoplastic cells were negative for CD 18. The diagnosis of epithelioid angiosarcoma, localized in the myocardium, lung, liver and spleen was made. The primary site of the neoplasm could not be determined.

Angiosarcoma of the Scalp Successfully Treated With a Single Therapy of Sorafenib

Angiosarcoma (AS) of the scalp is a rare and aggressive neoplasm with one of the worst prognoses among malignant skin tumors. The overall 5-year survival rate is less than 30%. Specific treatment guidelines are absent, and treatment options include surgical excision, radiation therapy, chemotherapy (CT), and biological therapy such as recombinant interleukin 2 (rIL-2). Surgical excision with negative margins combined with CT is the most successful strategy for improving the prospect for survival. Considering that (1) the age range of patients with AS of scalp and face is 70 to 75 years; that (2) the strong toxicity of current first-line CTs, including taxanes, often requires treatment cessation; and that (3) tumors gradually become unresponsive during the course of treatment in many cases, patients with AS require a new, effective, and safe treatment. Sorafenib inhibits KIT, FLT-3, VEGFR-1, 2, 3, and PDGFRin a dose-dependent manner. Recently, a multicenter phase 2 study found that single-agent sorafenib was safe and especially active against recurrent and metastatic AS. Progression-free survival and overall survival rates were 3.8 months and 14.9 months, respectively. The study recommended sorafenib, 400 mg twice daily, for AS.

Alterations of the p53 and PIK3CA/AKT/mTOR pathways in angiosarcomas

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). The authors investigated the status of critical genes involved in the p53 and PIK3CA/AKT/mTOR pathways in a series of 62 AS. 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. 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.

Localized angiosarcomas (AS): Identification of prognostic factors (PF) and analysis of treatment impact—Series from the French Sarcoma Group (GSF/GETO).

10018 Background: AS represents less than 2% of all adult soft tissue sarcoma. PF and role of respective (neo)-adjuvant treatments in management of localized AS remain badly established. Methods: We have conducted a retrospective multicentre study (June 1980-October 2009) of 107 patients with localized AS. All cases have been centrally reviewed by pathologist expert. Univariate and multivariate analysis were conducted to identify independent PF. Overall survival (OS) and Local Recurrence Free Survival (LRFS) were estimated using the Kaplan-Meier method. Impact of treatments had been explored with Cox Model after adjustment to the PF. Results: The sex ratio was 18/89 (0.2). Median age was 71 years. 22% (24/107) and 62% (67/107) of patients developed AS in preexisting lymphoedema and in irradiated field, respectively. 71 cases (66%) were superficial. The most frequent primary locations were: limbs (35, 33%), chest wall (32, 29%) and breast (22, 20%). Grade was 1 in 21/103 (20%), 2 in 35/103 (34%) and 3 in 47/103 cases (46%). Treatments consisted in surgery, adjuvant radiotherapy and (neo)-adjuvant chemotherapy in, respectively, 95, 27 and 27 cases. R0 margin was obtained in 49 cases. The median OS and LRFS were, respectively, 38.8 months and 27 months. In multivariate analysis, the following PF influenced the OS: lymphedema (HR=2.02 [1.15-3.55]) and size>5 cm (HR=1.48 [1.01-2.45]). After adjustment to these PF, R0 margins was the sole treatment parameter improving the OS (HR=0.19 [0.05-0.73]). In multivariate analysis, the following PF influence the LRFS: Age>70 (HR=1.68 [1.02-2.76]) and pre-existing lymphedema (HR=2.07 [1.15-3.75]). After adjustment to these prognostic factors, R0 margins (HR=0.48 [0.38-0.69]) and adjuvant radiotherapy (HR=0.29 [0.10-0.83]) improved the LRFS. Conclusions: Pre-existing lymphedema, tumour size and age>70 are the major PF in patients with localized AS. The achievement of R0 margins is of major importance for improving the outcome whatever the endpoint (OS, LRFS) Adjuvant radiotherapy decreased the local recurrence. (Neo)-adjuvant chemotherapy does not influence survivals.

Activity of sorafenib in radiation-associated breast angiosarcomas harboring MYC and FLT4 amplifications.

10019 Background: Angiosarcomas (ASs) are rare, aggressive vascular malignancies of endothelial cell differentiation which arise de novo or secondary to radiation therapy (RAS.) A subset of patients(pts) with AS harbor mutations in KDR (VEGFR-2) or overexpression of MYC and/or FLT4(VEGFR-3). MYC & FLT4 gene amplifications occur almost exclusively in RAS. These alterations provide a rationale for investigating agents that target angiogenesis in RAS. In a phase II trial of sorafenib, AS pts had a partial response (PR) of 14%; targeting the appropriate pt population may be essential. We hypothesize that co-amplification of MYC & FLT4 may be predictive of response to sorafenib. Methods: Using our institutional sarcoma database & data query system, we identified AS patients treated with sorafenib at Memorial Sloan-Kettering Cancer Center between 1992-2011. Molecular analysis performed on available tissue. With IRB approval, clinical information was collected. Results: We identified 10 women with RAS that received sorafenib. Average age 68 (range 51-84.) 7 pts had distant metastatic disease. Median lines of systemic therapy prior to sorafenib: 2 (range 1-4.) Sorafenib was first line in 60% of pts, administered at 400mg daily and adjusted for toxicity. Best responses included: complete response (CR) 2/9(22%), PR 1/9(11%), stable disease (SD) 5/9(56%) range 5-23m, progressive disease 1/9(11%) for a clinical benefit rate of (CR+PR+SD) 89%. Responses were seen in patients with lung metastases (n=2) and locally advanced disease (n=1) and were durable for 17, 42 and 26 months. Median duration on therapy was 15 months (range 0-42 months.) 7 pts underwent molecular analysis: co-amplification of MYC & FLT4 3 pts (30%); MYC amplification 4 pts (40%); KDR mutation 0 patients. Of the 3 responders, MYC & FLT4 co-amplification were observed in 2 patients and not evaluated in one. Conclusions: Sorafenib is active against RAS of the breast. In this small series, complete and partial responses were seen in patients with co-amplification of MYC & FLT4. This observation requires further study. Performing molecular studies on all AS pts will help define the pathophysiology of this deadly disease to guide rationale clinical trials.

Cardiac Angiosarcoma Management and Outcomes: 20-Year Single-institution Experience

To identify the clinicopathologic characteristics, treatments, and outcomes of a series of patients with primary cardiac angiosarcoma (AS). This retrospective case series was set in a tertiary referral center with a multidisciplinary clinic. Consecutive patients with institutionally confirmed pathologic diagnosis of cardiac AS from January 1990 to May 2011 were reviewed. Main outcome measures included patient demographics, tumor characteristics, management strategies, disease response, and survival. Data from 18 patients (78 % male) were reviewed. Sixteen patients (89 %) had AS originating in the right atrium. At diagnosis, eight patients (44 %) had localized/locally advanced disease and ten patients (56 %) had metastatic disease. Initial treatment strategies included resection (44 %), chemotherapy (39 %), and radiotherapy (11 %). Of the eight patients with localized/locally advanced AS, two underwent macroscopically complete resection with negative microscopic margins, one underwent macroscopically complete resection with positive microscopic margins, one underwent macroscopically incomplete resection, two received chemotherapy followed by surgery and intraoperative radiotherapy, one received chemotherapy alone, and one died before planned radiotherapy. Median follow-up was 12 months. Median overall survival (OS) was 13 months for the entire cohort; median OS was 19.5 months for those presenting with localized/locally advanced AS and 6 months for those with metastatic disease at presentation (p = 0.08). Patients who underwent primary tumor resection had improved median OS compared with patients whose tumors remained in situ (17 vs. 5 months, p = 0.01). Cardiac AS is associated with poor prognosis. Resection of primary tumor should be attempted when feasible, as OS may be improved. Nevertheless, most patients die of disease progression.

The miR‐17‐92 cluster and its target THBS1 are differentially expressed in angiosarcomas dependent on MYC amplification

Angiosarcomas (ASs) represent a heterogeneous group of malignant vascular tumors that may occur spontaneously as primary tumors or secondarily after radiation therapy or in the context of chronic lymphedema. Most secondary ASs have been associated with MYC oncogene amplification, whereas the role of MYC abnormalities in primary AS is not well defined. Twenty-two primary and secondary ASs were analyzed by array-comparative genomic hybridization (aCGH) and by deep sequencing of small RNA libraries. By aCGH and subsequently confirmed by fluorescence in situ hybridization, MYC amplification was identified in three out of six primary tumors and in 8 out of 12 secondary AS. We have also found MAML1 as a new potential oncogene in MYC-amplified AS. Significant upregulation of the miR-17-92 cluster was observed in MYC-amplified AS compared to AS lacking MYC amplification and the control group (other vascular tumors, nonvascular sarcomas). Moreover, MYC-amplified ASs were associated with a significantly lower expression of thrombospondin-1 (THBS1) than AS without MYC amplification or controls. Altogether, our study implicates MYC amplification not only in the pathogenesis of secondary AS but also in a subset of primary AS. Thus, MYC amplification may play a crucial role in the angiogenic phenotype of AS through upregulation of the miR-17-92 cluster, which subsequently downregulates THBS1, a potent endogenous inhibitor of angiogenesis. © 2012 Wiley Periodicals, Inc.

Aneurysmal fibrous histiocy toma: a clinical and histopathologic review of five cases

Objective To understand the clinical and histopathologic diagnostic criteria for aneurysmal fibrous histiocytoma (AFH).Methods The clinical and histopathological features of 5 patients with AFH were retrospectively reviewed.Results There were 3 males and 2 females in these patients.All the tumors clinically manifested as dark erythematous or brown nodules.Three cases had a recent history of rapid growth.The lesions were located on the limbs (n =3),or chest and lower mandible (n =2).Histopathological examination of skin biopsies showed typical features of dermatofibroma,accompanied by many irregular cleftlike or cavernous blood-filled spaces with numerous hemosiderin pigments in all of these cases.Immunohistochemically,the tumor cells were immunoreactive to vimentin and CD68 but negative for CD34 or CD31.Conclusions In view of a history of recent rapid growth,the presence of hemorrhagic pseudocysts and high vascularity,AFH should be differentiated from angiosarcoma and angiomatoid fibrous histiocytoma. Key words: Histiocytoma, benign fibrous; Clinical and histological features

Does a common vascular origin confer similar prognosis to malignant tumors of the liver?

186 Background: Unlike the ubiquitous hepatic hemangioma, malignant vascular tumors (MVT) of the liver are uncommon and poorly understood. We hypothesized that tumor histology is a predominant factor associated with survival in these tumors. Methods: Patients with hepatic angiosarcoma (AS), hemangioendothelioma (HE) and its epithelioid variant (EHE), or hemangiopericytoma (HP) were identified using the SEER database (1973-2007). Standardized incidence rates were calculated based on the 2000 U.S. population. Prognostic factors were studied with Cox regression modeling. Results: We included 297 patients with MVT (207 AS, 28 HE, 56 EHE, 6 HP) with an annual standardized incidence of 3 per million. Patients with AS were likely to be older at diagnosis (median 63 yrs, p = 0.001) and less likely to be female (38%, p < 0.001). All tumors demonstrated metastatic potential, although EHE and AS had the highest rate of regional or distant metastases (75% each, p = 0.05, Table 1). Patients with EHE had the overall longest median survival of 75 (30-183) months (p < 0.001). Surgical resection and transplant did not improve the overall survival of patients with EHE in multivariate models (p = 0.2, 0.9). Conclusions: Histology is an important factor in determining survival for patients with hepatic MVT. Patients with EHE have the longest OS even in the absence of surgical intervention, whereas patients with AS have shorter survival but appear to benefit from surgery. [Table: see text]

Primary cardiac angiosarcoma and diffuse pulmonary hemorrhage: a case report

Primer kardiyak anjiyosarkom, cok kotu seyreden, oldukca nadir gorulen kotu huylu bir tumordur. Hastalik semptomlari nonspesifiktir. Ender klinik gorunumlerinden biri de, diffuz pulmoner hemorajidir. Altmis bir yasinda erkek olgu, 10 gundur devam eden sag yan agrisi, oksuruk ve kan tukurme yakinmalari ile klinigimize basvurdu. Akciger grafisinde iki tarafli noduler lezyonlar ve kardiyotorasik indekste artis izlendi. Toraks bilgisayarli tomografide, kardiyomegali, sag atrium anterolateral komsulugunda 7x5 cm kitle lezyonu, her iki akcigerde orta ve alt zonlarda buzlu cam gorunumleri izlendi. Ekokardiyografide sol ventrikul dilate ve hipertrofik idi. Olgu miksoma on tanisi ile ameliyat edildi. Ameliyat sirasinda kardiyak anjiyosarkom saptandi. Hasta, ameliyattan kisa bir sure sonra, solunum yetmezligi nedeniyle kaybedildi. Bu makalede, birtakim tanisal zorluklar ile birlikte, pulmoner semptomlar goz onunde bulundurularak yurutulen tanisal surecin ayrintili olarak irdelenmesi amaciyla bir olgu calismasi sunuldu. Anah tar soz cuk ler: Anjiyosarkom; diffuz pulmoner hemoraji; kalp tumoru. Primary cardiac angiosarcoma is a very rare malignant tumor with very poor prognosis. Symptoms of the disease are nonspecific. One of the rare clinical presentations is diffuse pulmonary hemorrhage. A 61-year-old male was admitted to our clinic with the complaints of right side pain lasting for 10 days, cough and hemoptysis. The chest X-ray showed bilateral nodular lessions and increased cardiothoracic index. Thoracic computed tomography revealed cardiomegaly, showing a mass in 7x5 cm in the anterolateral right atrium with ground-glass appearance, predominantly in the mid and lower zones of bilateral lung fields. Echocardiography showed dilatation and hypertrophy of the left ventricle. The case underwent surgery with the initial diagnosis of myxoma. During surgery, cardiac angiosarcoma was diagnosed. The patient died due to respiratory failure soon after surgery. In this article, we present a case report, discussing the details of the diagnostic process based on pulmonary symptoms along with certain challenges.

Epithelioid angiosarcoma metastases to the bone marrow manifesting as erythroblastic anemia and leukocytosis: a and review of the literature

Bone marrow is an exceptionally uncommon site of metastatic dissemination in angiosarcoma (AS) as only single case reports have been published so far. We report a case of a 72-year-old male with epithelioid angiosarcoma of the liver who subsequently developed erythroblastic anemia. The trephine bone marrow biopsy revealed total replacement of the normal hematopoiesis by diffuse infiltrate of AS. This rare complication of the clinical course of this tumor should be taken into account in the pathological diagnosis of patients with AS presenting with hematological abnormalities.

Functional studies in two angiosarcoma cell lines.

e20511 Background: Angiosarcomas (AS) are rare vascular tumours. A series of studies were performed to characterise and contrast two human cutaneous AS cell lines (ASM and ISO-HAS) with human dermal micro-vascular endothelial cells (HuDMECs). The effects of inhibition of vascular endothelial growth factor (VEGF) receptors were investigated using the selective tyrosine kinase inhibitor (TKI) axitinib (A). Methods: The relative expression of angiogenic proteins and phospho-tyrosine kinases (pTK) were investigated using Proteome Profiler Arrays (R&D Systems). Basement membrane extract (Matrigel) tubule formation and Boyden chamber migration functional assays were performed and the effects of A studied. Cell proliferation assays compared A with chemotherapy (doxorubicin (D) and paclitaxel (P)) and drugs suggested by the pTK array (everolimus (E) and the checkpoint-2 (ChkII) inhibitor C3742 (C)). Results: The AS cell lines demonstrated an increased expression of angiogenin, coagulation factor III, fibroblastic growth factor (FGF) 1 and 2, HGF, TGF-β1, VEGF and the pTKs mTOR, p70 S6, p53 and ChkII relative to HuDMEC controls. On Matrigel HuDMECs developed a more extensive network of tubules than the malignant endothelial cells (total network length HuDMECs 810 units vs ASM 129 vs ISOHAS 589 (p=0.008)). ASM and ISO-HAS demonstrated significantly increased migration (mean migration HuDMECs 17 cells per hpf (x20) vs ASM 91 vs ISO-HAS 60.7 (p=0.018)). The addition of A 50ng/ml reduced tubule formation by 24% (p=0.005) and migration by 14% (p=0.071) across all cell lines. Results were not significant for individual cell lines. Estimated IC50 for single agent drugs (ng/ml) were P 6.5, D 21 and A 500. Single agent E reduced proliferation by 20% in all doses studied. A+P and E+D combinations showed an additive rather than synergistic effect. Single agent C and C+D combinations had no significant effect. Conclusions: ASM and ISO-HAS exhibited different responses compared to HuDMECs in the functional assays. The effects of single agent A on endothelial behaviour were modest but may be of benefit in the treatment of AS in combination with chemotherapy. mTOR is a potential drug target in AS. Results from array studies are being validated in AS tumor samples.

Benign “Waxing–Waning” Vascular Proliferations in Previously Irradiated Skin

Benign “Waxing–Waning” Vascular Proliferations in Previously Irradiated Skin

Multi-slice CT findings of hepatic angiosarcoma with pathological correlation

Multi-slice CT findings of hepatic angiosarcoma with pathological correlation

Tumour suppressor gene TP53 mutations in atypical vascular lesions of breast skin following radiotherapy

Atypical vascular lesions (AVL) occurring at the site of radiotherapy represent an uncommon but well-documented complication in the setting of breast-conserving therapy for breast carcinoma. Although the biological behaviour of AVL has been regarded as benign, it has been suggested that AVL may represent a precursor of angiosarcoma. A better understanding of the biology of AVL is essential in order to assess appropriate patient management. The aim of the present study was to investigate alterations of tumour suppressor gene TP53 in a series of radiation-induced AVL and angiosarcomas (AS). Direct sequencing analysis of the TP53 gene showed the presence of at least one variation in 10 of 12 (83.3%) AVL and in seven of eight (87.5%) AS. The most common alteration in both categories was the P72R polymorphism in exon 4. One angiosarcoma sample carried a pathogenetically relevant disruptive mutation c.592delG, a frameshift deletion in exon 6, causing a premature stop codon. The presence of TP53 alterations suggests that its mutational inactivation may be implicated in the pathogenesis of radiation-associated vascular proliferations. The common mutational pathway suggested by our data supports the hypothesis that AVL and AS are biologically related entities, most probably representing the extremes of a morphological continuum.