This rare sarcoma arises from neoplastic transformation of endothelial cells, the cells which give rise to blood vessels. Most of the interest in these tumors has focused upon the association of chemical exposure and the development of liver angiosarcomas. A distinct association with arsenic, Thorotrast (a radioactive contrast dye once used in radiology), and polyvinyl chloride (PVC used in plastics) has been established. No convincing association with soft tissue tumors has been established. The recent use of anti-angiogenesis drugs may open the door to treatment of this rapidly fatal disease.
Other Diagnostic Testing
Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/
Differential Diagnosis Prognosis Treatment Commonly Used Terms Internet Links
PATHOGENESIS CHARACTERIZATION ARF-p53
Abnormalities of the ARF-p53 pathway in primary angiosarcomas of the liver.
Weihrauch M, Markwarth A, Lehnert G, Wittekind C, Wrbitzky R, Tannapfel A.
Institute of Occupational Medicine, University of Hannover, Germany.
Hum Pathol 2002 Sep;33(9):884-92 Abstract quote
This study was done to investigate the contribution of the INK4a-ARF locus in tumorigenesis of angiosarcoma of the liver. Alterations of p14(ARF), p16(INKa), and p53 in primary liver angiosarcoma from 19 patients were analyzed by methylation-specific polymerase chain reaction (MSP), restriction enzyme-related polymerase chain reaction (RE-PCR), microsatellite analysis, and DNA sequencing. As a control group, 12 angiosarcomas from other organs were analyzed. Promoter methylation of p14(ARF) was found in 5 of 19 cases (26%), and p16(INKa) showed aberrant promoter methylation in 12 of 19 cases (63%). One tumor (5%) had homozygous deletion of the INK4a-ARF locus. Methylation and deletion correlated with loss of mRNA transcription. Methylated p14(ARF) appeared in the context of a methylated p16(INKa) promoter in 3 cases of the 5 angiosarcomas methylated at p14(ARF). p14(ARF) aberrant methylation was not related to the presence of p53 mutations, which was detected in 6 of 19 (32%) cases. Alterations of the INK4a-ARF locus or p53 as were not established independent prognostic factors in these tumors.
In conclusion, our data indicate that the INK4a-ARF locus is frequently inactivated in angiosarcoma of the liver and occurs independently of p53 mutations.
DISEASE ASSOCIATIONS CHARACTERIZATION BREAST CONSERVING SURGERY AND RADIATION
J Am Acad Dermatol. 2006 Mar;54(3):499-504. Abstract quote
The development of angiosarcoma of the breast is a recognized complication of breast conservation therapy (BCT), but the evolution, prevalence, and outcome have not been accurately established.
We sought to evaluate and review the clinicopathologic, prognostic, and treatment attributes of angiosarcoma arising in the irradiated breast after BCT. We conducted a retrospective chart and slide review of 8 patients seen between 1996 and 2004 with a diagnosis of secondary angiosarcoma. All were treated with mastectomy.
Clinical and histopathologic findings were studied and previously reported cases were reviewed. Primary surgery-related breast edema and cellulitis was observed in 7 and 5 patients of the 8 patients studied, respectively. Postirradiation breast edema and grade 2/3 fibrosis occurred in 5 and 8 patients, respectively. The mean age of the patients at onset of the breast cancer and angiosarcoma was 65 and 72 years, respectively. The mean latency period between the treatment of the breast cancer and the diagnosis of angiosarcoma was 75 months. The actuarial rate of 2-year survival for patients presented with single (n = 4) compared with multiple (n = 4) skin lesions was 50% and 0%, respectively (P = .0233). The estimated incidence of angiosarcoma after BCT was found to be 0.14 %.
- BCT-associated angiosarcoma arises after a relatively brief interval, and breast edema-fibrosis can possibly contribute to its development. Special attention should be paid to skin changes occurring after BCT. The extent of skin lesions is predictive of survival. As shown by a review of the literature, angiosarcomas are often resistant to surgery, chemotherapy, and radiotherapy, and targeted therapy against tumor biological properties may be a new approach to angiosarcoma treatment.
Cutaneous angiosarcoma following breast-conserving surgery and radiation: an analysis of 27 cases.
Billings SD, McKenney JK, Folpe AL, Hardacre MC, Weiss SW.
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
Am J Surg Pathol. 2004 Jun;28(6):781-8. Abstract quote
Iatrogenic angiosarcomas (AS), following treatment of breast carcinomas and attributed to chronic lymphedema, were first described by Stewart and Treves. With emphasis on breast-conserving therapy combined with adjuvant radiation, a recently recognized form of cutaneous postradiation angiosarcoma of the breast (CPRASB) has emerged.
To more completely characterize CPRASB, 27 cases were analyzed. Histologic features studied included pattern of growth (vasoformative, sieve-like, or solid), nuclear grade, necrosis, and mitotic rate. Clinical and follow-up information was obtained. The patients received relatively standard radiation treatment.
The median interval to diagnosis of CPRASB was 59 months; 5 occurred in less than 3 years. Lymphedema was largely absent, and when present was only mild in nature.
CPRASB was frequently multifocal at presentation (13 of 27). All tumors had a vasoformative pattern of growth; the majority (16 of 27) had areas with a sieve-like pattern. The solid pattern was less frequent (7 of 27). The majority had high-grade nuclear features (16 grade 3, 8 grade 2, 3 grade1). The mean mitotic rate was 9/10 HPF. Necrosis was rare (2 of 27). All were treated with wide excision or mastectomy.
Follow-up was available on 22 of 27 cases (median 44 months). Fourteen experienced local recurrence and 6 had multiple recurrences. Metastasis was documented in 9 of 22 patients and involved lungs (6), contralateral breast (3), skeleton (2), lymph nodes (1), and soft tissue (1). Eight patients died of disease, 2 died with disease, 4 were alive with disease, and 8 are alive without disease. The median interval to death was 33.5 months. All 4 patients with disease have documented metastasis.
CPRASB differs from Stewart-Treves AS by its shorter latency period and lack of association with lymphedema.
Angiosarcoma arising in hemangioma/vascular malformation: report of four cases and review of the literature.
Rossi S, Fletcher CD.
Am J Surg Pathol 2002 Oct;26(10):1319-29 Abstract quote
Malignant change in a benign vascular tumor is exceedingly rare, and there have been only five previously reported convincing cases. Four new cases of angiosarcoma (AS) arising in a hemangioma/vascular malformation (HVM) are described. All patients were in the 6th or 7th decade of life (two female, two male).
Development of an enlarging deep-seated mass was the main presenting symptom. MRI disclosed the presence of two separate soft tissue masses in both thighs in one patient. No patient had a history of prior radiotherapy at the same site. Preoperative duration, known in three cases, ranged from 1 to 24 months (median 12 months). Three tumors were located in the lower extremities (thigh and buttock), one in the retroperitoneum, and one in the parotid region. Three patients were treated by marginal excision; in one case only a biopsy was performed. Radiotherapy/chemotherapy was given in all cases. Two patients were disease free 2 and 14 months after surgery and two developed metastases.
Grossly, the tumors were described as frankly hemorrhagic masses or as firm, whitish areas with hemorrhagic nodules and were centered in skeletal muscle in three cases. Size ranged between 2.2 cm and 8 cm (median 4.3 cm).
Histologically, all the tumors had two distinct components. In three cases the benign and the malignant components were variably intermixed, whereas in one case the HVM was mainly located at the edge of the malignant tumor. The benign component showed features of an arteriovenous hemangioma (three cases) or intramuscular capillary hemangioma. AS showed epithelioid morphology in three cases and a well-differentiated dissecting pattern in one case. An imperceptible transition between the two components was noted in two cases. The two anatomically separate masses excised from one patient appeared almost identical. All cases were positive for at least two endothelial markers (CD31, CD34, VWF) and negative for the epithelial markers (EMA, AE1/AE3, Pan-keratin). Possible mechanisms for this exceptional phenomenon are discussed.
Cutaneous angiosarcoma arising in a gouty tophus: report of a unique case and a review of foreign material-associated angiosarcomas.
Folpe AL, Johnston CA, Weiss SW.
Department of Pathology and Laboratory Medicine, Emory University Medical Center, Atlanta, USA.
Am J Dermatopathol 2000 Oct;22(5):418-21 Abstract quote
Rare cases of angiosarcoma have been reported to arise in the setting of retained foreign material or in association with arteriovenous fistulae. No previous case of angiosarcoma, or any other malignancy, has been reported to arise with a gouty tophus.
We present a case of an 86-year-old man with a high-grade angiosarcoma that arose within a long-standing tophus.
Angiosarcoma in a chronically immunosuppressed renal transplant recipient: report of a case and review of the literature.
Ahmed I, Hamacher KL.
Departments of Dermatology (I.A., K.L.H.) and Laboratory Medicine and Pathology (I.A.), Mayo Clinic and Mayo Foundation, Rochester, Minnesota, U.S.A.
Am J Dermatopathol 2002 Aug;24(4):330-5 Abstract quote
Angiosarcomas are rare malignant tumors of endothelial origin that occur predominantly in the adult population. To date, only 12 cases have been described after renal transplantation.
We review the literature and present an additional case of a 59-year-old patient in whom lower-extremity lesions of cutaneous angiosarcoma developed several years after transplantation. Of the 13 patients, clinical details were available in only 12 cases. There were 10 male and 2 female patients. The mean age at diagnosis was 47.6 years (age range, 28-71 years). Almost all patients were on a combination immunosuppressive regimen, and the interval between transplantation and the development of the tumor was variable in the range of 8 months to 12 years. In five patients, the tumor arose within or adjacent to an arteriovenous fistula site. Cutaneous involvement was observed in only four cases.
The histologic spectrum consisted of both well-differentiated and poorly differentiated tumors. In one patient, features of the hemophagocytic syndrome were clinically present and the tumor morphologically displayed prominent erythrophagocytosis. In two of the cases, including the patient described in the current report, polymerase chain reaction was performed on lesional tissue for human herpesvirus-8 and the result was negative for the presence of viral DNA. Despite the use of multimodal aggressive therapy in most patients, death as a result of disease dissemination occurred over variable time periods (range, 1-15 months).
Cutaneous Angiosarcoma Complicating Morbid Obesity
Muhammad Azam, etal.
Arch Pathol Lab Med 2001;125:531–533 Abstract quote
Herein, we report a case of cutaneous angiosarcoma in a 35-year-old, morbidly obese woman. The tumor arose in the most dependent portion of the lower abdominal panniculus and showed typical changes of chronic lymphedema. The patient underwent a radical resection of her lower abdominal wall panniculus, which showed a multicentric, high-grade angiosarcoma with bilateral superficial inguinal lymph node metastases.
Histologically, conventional vasoformative areas were admixed with poorly differentiated sheets of spindle and epithelioid cells. Factor VIII was focally positive (membranous), whereas CD31 showed robust, diffuse positivity (membranous and cytoplasmic). The initial margins of resection were negative, and no follow-up radiation or chemotherapy was given. Following a recurrence at the previous excision site, the patient died 7 months after the surgery. Postmortem examination revealed a widely metastatic tumor that involved multiple organ systems.
We believe this is the second report of cutaneous angiosarcoma occurring in a chronically lymphedematous abdominal panniculus due to morbid obesity.
Am J Surg Pathol. 2005 Aug;29(8):983-996. Abstract quote
Cutaneous angiosarcoma is a rare but well-recognized complication after radiation therapy. Atypical post-radiation vascular lesions (AVLs) with a benign course have been described recently, but few cases with limited follow-up have been studied so far.
A total of 42 cases diagnosed as either radiation-associated cutaneous vascular lesions or angiosarcoma were retrieved from departmental and consultation files from 1995 to 2003. Hematoxylin and eosin-stained sections and clinical as well as follow-up data were evaluated. All patients were female with a median age of 59 years (range, 36-90 years).
Presentation ranged from small erythematous/violaceous papules or nodules to large plaques with discoloration located on the chest wall (35), abdomen (2), shoulder, groin, flank, axilla, and lower leg (1 each). Reasons for radiation included breast carcinoma (35 cases) and a variety of other lesions (mainly malignant disease). Size range was 0.1 to 20 cm. Angiosarcomas presented as larger lesions (median, 7.5 cm) compared with AVLs (median, 0.5 cm).
The time interval from radiation was significantly shorter for the development of AVL (median, 3.5 years) compared with cutaneous angiosarcoma (median, 6 years). Histologic evaluation revealed 26 lesions meeting criteria for angiosarcoma, ranging from morphologically low-grade to high-grade; 16 cases were classified as AVLs. These were fairly well-circumscribed lesions confined within superficial to mid dermis and composed of complex anastomosing and focally dilated vascular spaces. Some showed prominent hyperchromatic endothelial cells, while others were characterized by areas with a dissecting growth pattern within dermal collagen. Endothelial multilayering was absent.
Clinical follow-up, available for 36 patients (range, 2-84 months; median, 17 months), revealed 4 patients who died of disease, 4 patients had systemic metastasis, and 12 patients with local recurrence. All patients with systemic relapse had an initial diagnosis of angiosarcoma. One patient with an AVL had a recurrence at the same site, 3 patients developed additional new lesions, and 1 patient developed multiple small papules on the chest wall, which progressed from an AVL to angiosarcoma.
This study outlines the morphologic spectrum of radiation-associated cutaneous AVLs. No adverse outcome has been observed so far in this more benign subset of cases, but longer-term follow-up is necessary.
Am J Dermatopathol. 2005 Oct;27(5):422-7. Abstract quote
A 55-year-old white female with a complex medical history including mixed connective tissue disease and peripheral vascular disease developed a group of red-purple papules on her proximal medial thigh that was followed, five months later, by the development of a large violaceous patch.
She reported a history of radiation to this site (for melanoma) during her childhood. She was admitted to the hospital with a presumptive diagnosis of cellulitis, but failed to respond to antibiotics.
A biopsy was performed and demonstrated a well-differentiated angiosarcoma arising in conjunction with reactive angioendotheliomatosis. Excision of the lesion was performed, and fifteen months of follow-up have shown no recurrence or metastasis.
VASCULAR GRAFT Arising with arteriovenous fistulae and vascular grafts Am J Surg Pathol 1998;22:1154-1159
CHARACTERIZATION ADRENAL GLAND
Primary epithelioid angiosarcoma of the adrenal gland.
Croitoru AG, Klausner AP, McWilliams G, Unger PD.
Department of Pathology, Mount Sinai Medical Center, New York, NY.
Ann Diagn Pathol 2001 Oct;5(5):300-3 Abstract quote
Primary angiosarcomas of the adrenal gland are exceptionally rare vascular tumors. We report a case of a 63-year-old man with an epithelioid angiosarcoma of the left adrenal gland. Visualized on computed tomography as a nonhomogeneous round mass, the tumor measured 3 cm in diameter. Histology showed a vascular tumor composed of epithelioid cells with vesicular nuclei and prominent nucleoli that lined irregular vascular spaces and also formed solid areas and showed pleomorphism and rare mitotic activity. Immunohistochemical stain confirmed the diagnosis of epithelioid angiosarcoma.
We report our findings and review previously described literature cases of this rare entity.
- Multicentric contiguous variant of epithelioid angiosarcoma of the bone. A rare variant showing angiotropic spread.
Mitsuhashi T, Shimizu Y, Ban S, Ogawa F, Hirose T, Tanaka J, Shimizu M.
Department of Pathology, Saitama Medical School, Saitama, 350-0495, Japan.
Ann Diagn Pathol. 2005 Feb;9(1):33-7. Abstract quote
Epithelioid angiosarcoma of the bone is a rare tumor and is a diagnostic challenge. Here we present an autopsy case of a 62-year-old man with multifocal osteolytic lesions in the extremities and the pelvis. The initial diagnosis of a tibial biopsy was poorly differentiated adenocarcinoma. On the occasion of autopsy, a fungating thrombotic nodule was found at the anterior wall of the right atrium, and small hemorrhagic infarcts with tumor thrombi were found in the lung.
Histologically, the above lesions were identical to the former tibial biopsy and they showed large eosinophilic epithelioid cells with irregular ovoid nuclei and prominent eosinophilic nucleoli. Rare intracytoplasmic lumina were identified. Immunohistochemically, the tumor cells were positive for cytokeratins (CAM5.2 and AE1/AE3), CD31, factor VIII-related antigen, and vimentin. This case showed angiotropic spread of the tumor only to the right atrium and the lung, with no solid mass in other organs. Multicentric epithelioid angiosarcoma of the bone is a pitfall in pathological diagnoses, especially if a strong radiological impression of metastatic carcinoma is provided.
Therefore, pathologists should be aware of this rare variant.
Vascular tumors of bone: A study of 17 cases other than ordinary hemangioma, with an evaluation of the relationship of hemangioendothelioma of bone to epithelioid hemangioma, epithelioid hemangioendothelioma, and high-grade angiosarcoma.
Evans HL, Raymond AK, Ayala AG.
Hum Pathol. 2003 Jul;34(7):680-9 Abstract quote
Cases filed as vascular tumor of bone other than ordinary hemangioma were reviewed. They were included in the study if there was adequate histologic material and clinical information, clear evidence of bone origin, and at least 5 years follow-up.
The study group comprised 17 cases, of which 13 were categorized as hemangioendothelioma of bone, 1 as epithelioid hemangioendothelioma, and 3 as high-grade angiosarcoma. Hemangioendothelioma of bone had growth patterns varying from vasoformative to solid, but well-formed vessels were present in at least some area in all cases. The cells generally had a rounded, epithelioid character, regular nuclei, and relatively few mitotic figures; occasional features included spindle cells and scattered enlarged, hyperchromatic or pleomorphic nuclei. Lymphoplasmacytic and eosinophilic inflammatory infiltrate ranged from prominent to slight or absent, and myxoid or hyaline stroma was never more than focal. Epithelioid hemangioma could not be separated from hemangioendothelioma of bone. The single epithelioid hemangioendothelioma for the most part had cords of relatively uniform epithelioid cells in a prominent myxoid stroma but focally demonstrated an angiosarcoma-like appearance, with irregular vascular spaces and marked nuclear pleomorphism. The high-grade angiosarcomas exhibited predominantly irregular vasoformation combined with solid areas, diffuse nuclear hyperchromatism and pleomorphism, and, in 2 cases, numerous mitotic figures (the third case had only a small biopsy and a postradiation amputation specimen).
Of the hemangioendotheliomas of bone, 7 were unicentric and 6 were regionally multicentric either concurrently or sequentially. Three patients had intraosseous local recurrence, 2 had discontinuous regional skin or soft tissue involvement (including the popliteal artery in 1), and 1 had a solitary lung metastasis, but none died of tumor. The patient with epithelioid hemangioendothelioma had multicentric tumors in widely separated bones and died with liver and lung metastases. Two of the high-grade angiosarcomas were unicentric, and the third was regionally multicentric, with a popliteal artery-soft tissue component as well. All 3 of these patients died with metastases in various sites.
Epithelioid angiosarcoma of the breast involving the skin: a highly aggressive neoplasm readily mistaken for mammary carcinoma.
Farina MC, Casado V, Renedo G, Estevez L, Martin L, Requena L.
Departments of Dermatology, Oncology, and Pathology, Fundacion Jimenez Diaz, Universidad Autonoma, Madrid, Spain.
J Cutan Pathol 2003 Feb;30(2):152-6 Abstract quote
BACKGROUND: Angiosarcomas are malignant neoplasms of endothelial cells. Angiosarcoma of the breast is a rare neoplasm that behaves in a highly malignant fashion. It must be differentiated from benign vascular proliferations and from mammary carcinoma.
METHODS: We report on a 49-year-old-woman who presented with a large mass involving the left breast.
RESULTS: The lesion had an erythematoviolaceous hue and livedoid pattern at the periphery. Histopathologic study showed an epithelioid malignant neoplasm, and immunohistochemical studies demonstrated that neoplastic cells expressed immunoreactivity for endothelial cell markers.
CONCLUSIONS: A diagnosis of epithelioid angiosarcoma of the breast was established. The patient was treated with radical mastectomy, but she refused any other additional therapy.
A rare case of angiosarcoma of the breast in a man: case report.
Mansouri H, Jalil A, Chouhou L, Benjaafar N, Souadka A, El Gueddari B.
Department of Medical Oncology, Rabat University School of Medicine, Marocco.
Eur J Gynaecol Oncol 2000;21(6):603-4 Abstract quote
This is a case report of a 57-year-old man who had primary angiosarcoma of the left breast. Five months after detecting a mass in his breast, he underwent mastectomy with biopsy of the ipsilateral axillary lymph nodes. Three years later, he is still alive without any recurrence. Angiosarcoma of the female breast is rare and exceptional in males.
It is a condition with a poor prognosis and there are as yet no established chemotherapeutic regimens.
Angiosarcoma of the breast: report of a case and its findings of mri.
Murakam S, Nagano H, Okubo K, Sakata H, Tsuji Y, Ishiguro T, Hirayama R, Amanuma M, Hirose T.
Second Department of Surgery, Saitama Medical School, 38 Morohongo, Moroyama-machi, Iruma-gunn, Saitama 350-0495, Japan.
Breast Cancer 2001;8(3):254-8 Abstract quote
A 67-year-old woman with angiosarcoma of the left breast is presented. Physical findings showed a hard mass in the left breast with skin discoloration and erythema.
Mammography showed a high density shadow in the mass without microcalcification and spicula. On ultrasonography, a hypoechoic mass with an ill-defined boundary was detected. On MRI, the tumor had low signal intensity on T1-weighted images, and higher signal intensity on T2-weighted images. MRI with Gd-DTPA images showed higher signal intensity on T1-weighted images with relatively lower intensity in the central area of the tumor. The artery supplying the tumor derived from the left inner thoracic artery and was visualized on three-dimensional dynamic MRI angiography. Initially misdiagnosed as inflammatory breast cancer, an arterial injection of CPA (100 mg) and 5-FU (500 mg) had been performed preoperatively. The definitive diagnosis of angiosarcoma was established by intraoperative frozen section examination. She underwent modified radical mastectomy and is now free of recurrence.
This case emphasizes the difficulties in the clinical diagnosis of angiosarcoma of the breast.
Angiosarcoma of the Breast: Report of Case and Autopsy Findings.
Kagawa Y, Saeki T, Takiyama W, Takashima S, Mandai K.
Department of Surgery, National Shikoku Cancer Center Hospital, 13 Horinouchi, Matsuyama 790, Japan
Breast Cancer 1997 Mar 25;4(1):33-37 Abstract quote
We report a case of angiosarcoma of the breast and the autopsy findings.
The patient was a 35-year-old premenopausal woman who complained of a tumor in her left breast. We found a tumor measuring 55 mm in diameter in the lower external quadrant. The tumor was elastic and soft, smooth surfaced, well-difined and mobile. Dimpling sign or change of skin color were not observed. Clinically it was diagnosed as phyllodes tumor, but tumorectomy revealed primary angiosarcoma of the breast. Further extended surgery was recommended, but the patient refused additional therapy.
Histological findings revealed a free surgical margin and neither lymph node metastasis nor distant metastasis were clinically observed. Seven months later, local recurrence in the same breast was recognized and finally radical mastectomy was carried out. Histological findings showed recurrence of angiosarcoma in the left breast but lymph node metastasis was not detected. Two months after mastectomy, metastases to the cervical and thoracic vertabrae were observed and radiatioon therapy was performed. Sixteen months from onset, she died due to multi-organ failure as general metastases of angiosarcome. At autopsy, metastases to many organs including the digestive system were observed. The incidence of primary angiosarcoma of the breast is low but its prognosis is poor.
This case emphasized the diffculties in clinical diagnosis and treatment for the angiosarcoma of breast.
Angiosarcoma Involving the Gastrointestinal Tract: A Series of Primary and Metastatic Cases
Allison, Kimberly H MD*; Yoder, Brian J MD†; Bronner, Mary P MD*; Goldblum, John R MD†; Rubin, Brian P MD, PHD*
From the *Department of Anatomic Pathology, University of Washington Medical Center, Seattle, WA and †Department of Pathology, Cleveland Clinic Foundation, Cleveland, OH.
The American Journal of Surgical Pathology : Volume 28(3) March 2004 pp 298-307 Abstract quote
Angiosarcoma occurs very rarely in the intestinal tract as either a primary or metastatic malignancy and can present great diagnostic difficulty, especially when it displays epithelioid cytomorphology. Since only isolated case reports have been published, the purpose of this study is to more fully delineate the histopathological and clinical features from a series of 8 angiosarcomas involving the gastrointestinal tract.
There were 5 male and 3 female patients whose ages ranged from 25-85 years (median 57). Presenting symptoms included intestinal bleeding, anemia and pain. Five cases involved the small bowel and 3 involved the colon/rectum. Four cases were primary to the intestinal tract, 2 patients initially presented with secondary involvement of the large bowel from occult retroperitoneal primaries, 1 patient presented with disseminated disease including small bowel involvement, and 1 case was metastatic from a breast primary. Seven cases were composed predominantly of sheets of malignant appearing epithelioid cells with subtle areas forming cleft-like spaces suggestive of vascular differentiation. Immunohistochemical studies revealed the lesional cells to be immunoreactive for CD31 (8/8), CD34 (8/8), Factor VIII (8/8), cytokeratins AE1/AE3 (7/8), cytokeratin 7 (2/8), Cam5.2/cytokeratin 8 (5/8), and cytokeratin 19 (5/8).
Cytokeratin 20 was negative in all eight cases, which contrasts sharply with the characteristic positivity for cytokeratin 20 in virtually all intestinal carcinomas. One case was weakly and focally positive for EMA and all cases were negative for S-100 protein. Cytokeratin staining was variable and ranged from focal to extensive. Follow-up was available in eight cases and ranged from 1-33 months (median 12.5). Five patients died of disease, between 1 and 33 months (median 6) after diagnosis. One recently diagnosed patient is alive with disease 18 months after diagnosis, and one patient is free of disease 27 months after original diagnosis. Angiosarcomas of the gastrointestinal tract commonly display epithelioid cytomorphology, may be diffusely and strongly positive for cytokeratins and only show subtle signs of vascular differentiation, creating potential diagnostic confusion with primary or metastatic carcinoma. Given the clinically aggressive behavior of angiosarcoma, proper classification and treatment is important. Immunohistochemistry with vascular markers, CK20, and S-100 protein may be helpful in differentiating angiosarcoma from carcinoma and melanoma. Angiosarcoma classically presents with cutaneous involvement of the head and neck region in elderly patients or in the limbs of patients with lymphedema. A smaller, but increasingly recognized subset of angiosarcoma has been described in the deep soft tissues and in areas of prior irradiation, trauma or in association with foreign bodies such as ateriovenous shunts.
Deep-seated angiosarcoma frequently has an epithelioid cytomorphology. The epithelioid phenotype of angiosarcoma was first described in cases of cutaneous angiosarcoma by Rosai et al in 1976 and later documented in deep soft tissue by Weiss et al and Fletcher et al. Intra-abdominal angiosarcoma has been described previously, usually arising in the liver, spleen and rarely adrenal glands, ovaries or as diffuse angiosarcomatosis.
Angiosarcoma of the gastrointestinal tract is quite rare, with only individual case reports and very small series scattered throughout the literature. Intestinal angiosarcoma usually presents with gastrointestinal bleeding and anemia. This non-specific presentation often causes delay in diagnosis. In addition, the frequently solid growth pattern and epithelioid cytology can be easily confused with poorly differentiated carcinoma, melanoma, and mesothelioma, as well as sarcomas with epithelioid cytomorphology. Most importantly, the epithelioid variant of angiosarcoma is notorious for its tendency to react with antibodies to cytokeratin, which can lead to diagnostic confusion with poorly differentiated carcinoma.
To further understand this rare entity, we studied the clinical, pathologic, and immunohistochemical characteristics of eight cases of angiosarcoma involving the gastrointestinal tract.
Small intestinal angiosarcoma leading to perforation and acute abdomen: a case report and review of the literature.
Kelemen K, Yu QQ, Howard L.
Arkadi M. Rywlin Department of Pathology and Laboratory Medicine, Mount Sinai Medical Center, Miami Beach, FL 33140, USA.
Arch Pathol Lab Med. 2004 Jan;128(1):95-8. Abstract quote
A 76-year-old man presented to the emergency room with abdominal pain and fatigue. The patient had a history of gastrointestinal bleeding. An abdominal computed tomographic scan showed collections of free air in the abdomen with obstruction of the distal small intestine and multiple masses in the liver.
Laparotomy revealed a widespread malignant neoplasm in the abdomen, with multiple tumor nodules in the ileal wall, mesentery, and liver. The ileal wall was perforated within the area of one of the tumors. Pathologic examination of the lesion showed a neoplasm composed of solid sheets of spindle and undifferentiated cells, forming interlacing delicate vascular channels with atypical endothelial cells. The tumor cells were positive for the endothelial marker CD31, whereas reactivity for a broad panel of epithelial and other endothelial markers was negative.
This case demonstrates that although angiosarcomas of the gastrointestinal tract are rare, they should be considered in cases of intestinal perforation or severe bleeding, especially in the elderly. A broad panel of immunochemical markers might be necessary to establish the pathologic diagnosis.
Cardiac angiosarcoma: a case report.
Brown BC, Mason TE, Ballard WP, Wickliffe CW, Bone D.
Pathology Department, Piedmont Hospital, Atlanta, GA 30309.
J Med Assoc Ga 1991 Aug;80(8):435-8 Abstract quote
Primary neoplasms of the heart are rare and difficult to diagnose prior to surgery, even with modern imaging techniques. Often, the tumors are diagnosed only at autopsy.
Angiosarcoma is the most common malignant neoplasm. This disease is most commonly found in middle-aged men, and the tumor is most often located in the right atrium. It commonly causes blood flow abnormalities, extensively infiltrates cardiac structures, and may extend through the heart wall to involve adjacent structures. Metastatic spread at the time of diagnosis is common, and surgical mortality is high.
We present a case of primary angiosarcoma involving the right ventricle of the heart. This tumor developed 6 months after the patient had undergone coronary artery bypass surgery. The patient was initially thought to have a massive thrombus within the right ventricle but at surgery was found to have a malignant neoplasm invading the myocardium. Subsequently, he was found to have pulmonary metastases.
A debulking procedure was performed, and the patient was started on chemotherapy. Rather prompt improvement occurred after the debulking procedure, but subsequent studies have indicated progression of the pulmonary metastases despite ongoing chemotherapy.
Laryngeal angiosarcoma: a clinicopathologic study of five cases with a review of the literature.
Loos BM, Wieneke JA, Thompson LD.
Department of Otolaryngology-Head and Neck Surgery, Georgetown University Medical Center, Washington, DC, USA.
Laryngoscope 2001 Jul;111(7):1197-202 Abstract quote
OBJECTIVE: Primary laryngeal angiosarcoma (LA) is rare without a reported series evaluating these tumors.
STUDY DESIGN/METHODS: Five patients with LA were retrospectively retrieved from the Otorhinolaryngic Registry of the Armed Forces Institute of Pathology.
RESULTS: Three men and 2 women, aged 29 to 71 years, presented with hoarseness (n = 4) and hemoptysis (n = 1). Two patients had previous neck radiation. The tumors involved the supraglottis (n = 4) with a mean size of 3.1 cm. Histologically, all tumors had anastomosing vascular channels lined by remarkably atypical endothelial cells protruding into the lumen, frequent atypical mitotic figures, and hemorrhage. All cases tested (n = 4) demonstrated immunoreactivity with antibodies to Factor VIII-RA and CD34. All patients had surgery followed by postoperative radiation (n = 3 patients). Three patients died with disease (mean, 17 mo), whereas one patient is alive with no evidence of disease at 18 years.
CONCLUSIONS: LA is a rare tumor, frequently associated with previous radiation, usually involving the supraglottis with characteristic histomorphologic and immunophenotypic features. LA has a poor prognosis, making appropriate separation from other conditions important.
Extracutaneous Angiosarcomas Metastatic to the Lungs: Clinical and Pathologic Features of Twenty-One Cases
T. Bocklage, M.D., K. Leslie, M.D., S. Yousem, M.D. and T. Colby, M.D.
Department of Pathology, University of New Mexico School of Medicine (TB), Albuquerque, New Mexico; Department of Pathology, University of Pittsburgh School of Medicine (SY), Pittsburgh, Pennsylvania; and Department of Pathology, Mayo Clinic Scottsdale (KL, TC), Scottsdale, Arizona
Mod Pathol 2001;14:1216-1225 Abstract quote
Angiosarcomas are rare malignant vascular tumors with a high rate of metastasis involving lungs (most commonly), liver, regional lymph nodes, bone, and other sites.
In this study, we have reviewed the clinical presentation and histopathology of 21 cases of extracutaneous angiosarcoma metastatic to the lungs. Tumors with exclusively pleural involvement were excluded. Patients presented with dyspnea, chest pain, and/or hemoptysis lasting a few weeks to months. Radiologically, the most common finding comprised multiple peripheral lung nodules (57%), often accompanied by infiltrates. For 11 cases (52%), the primary tumor was not identified at the time of presentation. Vasoformative areas were identified in 15 cases (71%). Nine cases comprised spindle cells (43%), two contained epithelioid cells (9.5%), and 10 consisted of both spindle and epithelioid cells (48%). Nuclear pleomorphism was at least moderate in all cases. However, five tumors contained regions of minimal nuclear atypia. Hemorrhage, siderophages, and fibrosis were commonly present. Immunohistochemical staining (IHS) was performed on 14 cases. Thirteen tumors showed reactivity for vascular markers. Tumor cells reacted for Von Willebrand factor in 13 of 14 cases, and CD31 and CD34 were each positive in 2/2 cases. Two cases (of nine examined) also expressed cytokeratins. Because the tumor often first presented in the lungs before the primary sarcoma was identified, the clinical impression included both benign and malignant entities.
For patients with primary cardiac tumors, symptoms referable to the primary tumor complicated the clinical presentation, and radiologic evaluation supported a clinical diagnostic impression of non-neoplastic pericarditis. Thus, angiosarcoma in the lung may elude diagnosis until histopathologic evaluation of the lung biopsy.
Spindle cell angiosarcoma of the oropharynx.
Maheshwar A, Barnes MD, Douglas-Jones AG, Nind NR, Burroughs SH.
Department of Otolaryngology, University Hospital of Wales, Cardiff, UK.
J Laryngol Otol 2000 Feb;114(2):160-2 Abstract quote
Angiosarcomas are uncommon malignant tumours of vascular endothelium. In the head and neck, the scalp is the commonest site of origin. A rare case of spindle-cell angiosarcoma of the oropharynx, treated by surgery and post-operative radiotherapy, is reported. We discuss the clinical presentation and histopathological diagnosis of this lesion.
- Angiosarcomas arising in the viscera and soft tissue of children and young adults: a clinicopathologic study of 15 cases.
- Am J Surg Pathol. 2009 Feb;33(2):264-9. Abstract quote
Angiosarcomas are rare tumors that predominantly affect adult and elderly patients and pursue an aggressive clinical course with high mortality. Although angiosarcomas are well described in a variety of clinical settings, they have been incompletely characterized.
We identified 15 high-grade angiosarcomas arising from the viscera and soft tissue of patients 21 years old and younger from institutional and consultation files. Both clinical (patient age, tumor site, tumor size, tumor focality) and histologic features including growth pattern (vasoformative vs. solid), nuclear grade (high vs. low), mitotic rate (mitotic figures/10 high-power fields), necrosis (present vs. absent), and cell shape (epithelioid vs. nonepithelioid) were assessed. Tumors arose in both sexes (8 males; 7 females); age at diagnosis ranged from 3 months to 19 years (mean, 10 y, 5 mo; median, 11 y). Tumors were located in the mediastinum (7), visceral organs (2 in liver, 1 in spleen), breast (2), mesentery (1), pelvis (1), and deep soft tissue of upper extremity (1). Tumor size was documented for 8 patients (range 3.5 to 13 cm; mean 8.1 cm). Eight cases showed epithelioid morphology and 7 cases were primarily spindled. Of 8 cases assessed for podoplanin expression by immunohistochemistry, 7 were negative and 1 was positive.
Clinical follow-up was obtained for all patients: 10 (67%) died of disease (range, 27 mo to 11 y; mean, 6 y 8 mo) and 4 patients were alive without disease (range, 27 to 132 mo; mean, 79 mo).
Although extremely rare, angiosarcomas do affect children and young adults and this diagnosis should be considered in atypical vascular tumors occurring in the mediastinum and those with brisk mitotic activity and/or necrosis.
Malignant epithelioid vascular tumors of the pleura: report of a series and literature review.
Zhang PJ, Livolsi VA, Brooks JJ.
Department of Pathology, Roswell Park Cancer Institute, Buffalo, NY, USA.
Hum Pathol 2000 Jan;31(1):29-34 Abstract quote
Primary malignant vascular tumors of the pleura are rare. The significance and difficulty of distinction between pleural epithelioid hemangioendothelioma (EHE) and angiosarcoma have not yet been addressed.
A new series of pleural angiosarcoma is reported, and the relevant literature is reviewed. Five cases were identified from files of the authors' institutions and personal consultation cases (J.J.B.). Twenty-six cases of primary malignant vascular tumors of the pleura were identified in the literature. In a total of 31 cases, 22 were from the West and 9 from Japan. Patients were 22 to 79 years old (average, 57), and the male/female ratio was 9:1. Prior chronic pyothorax was identified only in cases reported from Japan. History of exposure to radiation or asbestos was noted in a few Western cases. The most common presentation was pleural thickening and effusion. Almost all of the patients died of disease shortly after diagnosis.
A spectrum of histology ranging from characteristic high-grade epithelioid to relatively low-grade EHE-like features was observed in our cases and can be found in previous reports. Most cases showed variable spotty cytokeratin immunoreactivity. Endothelial markers (factor 8, CD34, or CD31) were invariably positive.
Pleural angiosarcomas are often epithelioid and can be easily mistaken for mesothelioma or carcinoma clinically and histologically. Awareness of this rare tumor should prompt the use of endothelial markers when faced with a questionable mesothelioma. When cytokeratin is negative, or focal with strong vimentin reactivity, a vascular tumor should be suspected and confirmed with vascular markers. Because of their invariably aggressive behavior, all epithelioid vascular tumors of the pleura should be considered highly malignant regardless of the presence of EHE-like histological features.
Postirradiation angiosarcoma of the prostate.
Chandan VS, Wolsh L.
Department of Pathology, Upstate Medical University, State University of New York, Syracuse, NY 13210, USA
Arch Pathol Lab Med. 2003 Jul;127(7):876-8 Abstract quote
Angiosarcomas are high-grade sarcomas of vascular origin that rarely arise in the prostate.
We describe a unique case of angiosarcoma arising in the prostate 10 years after radiotherapy for adenocarcinoma of the prostate.
A review of literature regarding angiosarcomas of prostate is also discussed.
Angiosarcoma of the prostate: report of 2 cases and review of the literature.
Smith DM, Manivel C, Kapps D, Uecker J.
J Urol 1986 Feb;135(2):382-4 Abstract quote
We report 2 cases of angiosarcoma of the prostate gland.
The patients were 42 and 60 years old, which is in sharp contrast to the presentation of rhabdomyosarcoma, which occurs primarily in children.
Immunoperoxidase staining for factor VIII associated antigen was positive in both cases, and was particularly useful in confirming the diagnosis in 1 case that was otherwise poorly differentiated. One patient is alive without evidence of recurrence 2 years after surgical excision, while the other presented with unresectable tumor and died 6 months after presentation.
Angiosarcoma represents less than 2 per cent of sarcomas of the prostate but it should be considered in the differential diagnosis of poorly differentiated sarcomas, particularly those occurring in adults.
Ann Diagn Pathol. 2005 Aug;9(4):209-14 Abstract quote.
A 69-year-old man presented with cough, shortness of breath, and fatigue. He was initially treated for allergies and then for pulmonary embolism. Radiologically, a tumor mass was found to occlude the right pulmonary artery and involve the pulmonary trunk. A right pneumonectomy was performed.
Histologically, a cellular malignant spindle and epithelioid tumor with areas of necrosis and brisk mitotic activity was seen. In some areas, the tumor appeared to form vascular channels. Focal osteosarcomatous differentiation was present. Immunohistochemical studies were performed including vimentin, smooth muscle actin, desmin, CD31, CD34, S100, and pan-cytokeratin.
The tumor cells were positive for CD31 and vimentin and negative for pan-cytokeratin, CD34, and S100. Two months after surgery, the patient was alive and well.
Oral and salivary gland angiosarcoma: a clinicopathologic study of 29 cases.
Fanburg-Smith JC, Furlong MA, Childers EL.
Departments of Soft Tissue (JCFS and MAF) and Oral and Maxillofacial Pathology (ELBC), Armed Forces Institute of Pathology, Washington, D.C.
Mod Pathol 2003 Mar;16(3):263-71 Abstract quote
Angiosarcomas of the oral and salivary gland area are extremely rare, mostly presented as case reports.
We wanted to study the clinicopathologic features of a series of oral and salivary gland angiosarcomas. Cases coded as "angiosarcoma" were retrieved from the Oral and Maxillofacial Pathology Department of the Armed Forces Institute of Pathology. Patient folders and pathology were reviewed and recorded; immunohistochemistry and follow-up were obtained. Inclusion required oral or salivary gland location, vasoformative growth, cytologic atypia, mitoses, and vascular markers. Skin, bone, and subcutaneous angiosarcomas were excluded. Primary and secondary (metastatic) oral angiosarcomas were included.
The 22 primary angiosarcomas involved tongue (n = 9), parotid (n = 4), lip (n = 4), submandibular gland (n = 3), and 1 each of soft and hard palate. The 7 secondary angiosarcomas involved the gingiva (n = 4) and parotid gland (n = 3). Overall, patient ages ranged from 6-90 years (mean, 55 years). There were 15 males and 14 females. Symptoms included a mass with recent enlargement and bleeding. Tumor sizes ranged from 0.8-7.0 cm (mean, 2.6 cm).
Histologically, all tumors were vasoformative; 86% had solid and 17% had distinctive papillary areas. Eight (28%) were classified as the epithelioid subtype. Immunohistochemical stains showed that the tumor cells were positive for Factor VIIIrag in 19/21, CD31 in 16/19, CD34 in 7/12, and Ulex in 1/1. Primary tumors were classified as low grade (n = 7, in all locations except salivary gland), intermediate (n = 7), and high grade (n = 8); all secondary tumors were high grade.
Follow-up was available on 14/22 primary and 7/7 secondary angiosarcomas. Of primary tumors, two tongue angiosarcoma patients died at 1 and 9 years, but 4 were alive without disease over a mean of 7.3 years (range, 1-13 years). Four primary salivary gland angiosarcoma patients were alive without disease over a mean of 5.8 years (range, 1-14 years), and 1 had only a late (15 years) metastasis and death (at 20 years). Three primary lip angiosarcoma patients were without disease over a mean of 14.3 years (range, 13-16 years). Of secondary tumors, three salivary gland angiosarcoma patients died within 1 year, and all four secondary gingival angiosarcoma patients died of disease within 3 years. Assessing follow-up of primary oral and salivary gland angiosarcoma patients by grade, 5 patients with high-grade tumors had no evidence of disease over a mean of 7.6 years (range, 1-16 years), 3 patients with intermediate-grade tumors had no evidence of disease over a mean of 12.7 years (range, 11-14 years), 2 patients with intermediate-grade tumors died of disease at 9 and 20 years, 3 patients with low-grade tumors had no evidence of disease over a mean of 6.3 years (range, 1-14 years), and 1 patient with low-grade tumor died of disease at 1 year.
Primary oral and salivary gland angiosarcomas, albeit rare, mostly involve the tongue, parotid gland, and lip of adults, often with relatively good outcome. Although the most common angiosarcoma morphology in this area is spindled vasoformative and solid, almost one third of oral and salivary gland angiosarcomas are the rare epithelioid angiosarcoma variant. Most gingival and few parotid angiosarcomas appear to be metastases from other locations, with many patients succumbing to death within 3 years. Despite predominantly high- or intermediate-grade morphology, patients with primary angiosarcoma of the tongue, salivary gland, and lip have a better prognosis than do patients with primary cutaneous or deep soft tissue angiosarcoma, including those patients with secondary oral and salivary gland involvement.
SKIN AND SOFT TISSUE
- Sporadic Cutaneous Angiosarcomas: A Proposal for Risk Stratification Based on 69 Cases.
*Department of Pathology ‡Department of Biostatistics, Winship Cancer Institute, Emory University, Atlanta GA †Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR §Department of Pathology, The Mayo Clinic, Rochester, MN.
- Am J Surg Pathol. 2008 Jan;32(1):72-77. Abstract quote
Angiosarcomas have traditionally been considered high-grade lesions for which histologic features and grading have played no role in prognostication and, consequently, they have been excluded from the American Joint Committee on Cancer staging system.
We have, therefore, analyzed 69 cutaneous angiosarcomas seen in consultation and not associated with lymphedema or prior radiation therapy to determine if a combination of histologic and clinical parameters could be used to differentiate indolent from aggressive tumors.
The clinical features analyzed included patient age, location, size, depth, and focality of the lesion; the histologic features studied included pattern of growth (vasoformative vs. solid), nuclear grade (high vs. low), necrosis (present/absent), cell type (epithelioid or spindled), extent of inflammatory infiltrate (minimal vs. marked), and mitotic rate. Lesions occurred on the head/neck (49), extremities (15), and trunk (5) of adults (21 to 94 y) and predominated in males (41 males; 28 females). Tumors ranged in size from 0.3 to 15 cm (average 3.1 cm) and involved the papillary (n=9), reticular (n=16), or deep dermis/ subcutis (n=30). They could be predominantly vasoformative (n=28) to solid (greater than 50% solid, n=41). Most lesions were of high (n=65) as opposed to low (n=4) nuclear grade, were mitotically active (0 to 99/10 high power fields), and occasionally displayed necrosis (n=14) and epithelioid features (n=21). Inflammatory infiltrates were minimal in most cases.
Follow-up information was obtained for all patients. Recurrences developed in 18 patients (26%) and metastasis in 15 (22%) to the following sites: lung (6), lymph node (7), liver (2), bone (2), and parotid gland (1). Forty-seven patients died (30 of disease) and 22 were alive at last known follow-up (range, 16 to 158 mo; mean, 65; median, 36). Five-year disease-specific survival was 48%. By univariate analysis only older age, anatomic site, necrosis, and epithelioid features correlated with increased mortality. Tumors were stratified into low (n=41) or high (n=28) risk groups based on necrosis and/or epithelioid features.
By multivariable analysis, high-risk group (hazard ratio 4.07, P=0.0004) and age >70 (hazard ratio 2.79, P=0.012) were associated with increased mortality, and tumor depth (P=0.048) correlated with the risk of local recurrence. The high-risk group had a significantly worse prognosis than the low-risk group with 3-year survival of 24% and 77%, respectively. No patients with high-risk features survived 5 years.
In conclusion, we report that a combination of clinical and histologic features allows stratification of angiosarcoma patients into 2 risk groups that are strongly associated with marked differences in clinical course. These features seem to diminish in importance with increased tumor size and are probably most useful in tumors less than 5 cm in maximum dimension.
Cutaneous angiosarcoma: A case series with prognostic correlation.
Morgan MB, Swann M, Somach S, Eng W, Smoller B
J Am Acad Dermatol. 2004 Jun;50(6):867-74. Abstract quote
BACKGROUND: Cutaneous angiosarcoma (CA) is a rare and aggressive endothelial-derived sarcoma. Few large studies have examined the clinicopathologic and prognostic attributes of CA.
OBJECTIVES: We sought to discern the potential prognostic significance of a variety of demographic features (ie, age, sex, location), histologic attributes (ie, depth of invasion, tumor necrosis, tumor cell morphology, margin status, mitoses), and follow-up data (ie, tumor recurrence, metastases) in CA.
METHODS: The statistical influence of age, sex, anatomic location, tumor depth of invasion, tumor cell morphology, presence or absence of necrosis, number of mitoses, and margin status on time to tumor recurrence and metastases were examined in a series of 47 patients with CA. Angiosarcoma arising within the breast, in a previously irradiated anatomic site, and a pre-existing vascular malformation or one associated with a lymphedematous extremity were excluded from study.
RESULTS: Most of the patients were men (76%), with an average age of 75.1 years (range: 59-92 years). The most common location was the head and neck region (96%). The most common presentation was of a rapidly expanding erythematous patch, and the most common clinical impression was angiosarcoma. The average external diameter of the tumor was 5.3 cm (range: 1.1-8.9 cm). The most common histologic pattern was characterized by anastomosing dissecting sinusoids lined by atypical endothelial cells (64%) with 15% of cases showing a diffuse epithelioid or spindle cell proliferation and 21% showing a mixture of the 2 histologic patterns. The average depth of tumor invasion was 2.86 mm (range: 1.8->6.0 mm). Of the tumors, 78% had a mitotic rate that exceeded 3/mm(2). Follow-up was available in 37 of the patients and ranged from 6 to 65 months. The 5-year local recurrence rate was 84% and the overall 5-year survival was 34%. Most patients died as a result of their disease with widespread pulmonary, cardiac, and/or brain metastases.
CONCLUSIONS: Of the gross and histologic features, external diameter (>5 cm), depth of invasion (>3 mm), mitotic rate (>3 HPF), positive surgical margins, tumor recurrence, and metastases correlated with adverse outcome by univariate analysis and, with the exception of mitotic rate, by multivariate analysis. Of the foregoing, tumor diameter, depth of invasion, positive margins, metastases, and tumor recurrence were the most robust predictors of outcome. None of the demographic factors was associated with outcome. This study confirms the poor prognosis of patients with CA. Among all demographic and histologic patterns examined for prognostic significance, tumor diameter, tumor depth of invasion, margin status, tumor recurrence, and metastases emerged as the most important determinants of outcome.
Cutaneous angiosarcoma of the face: clinicopathologic and immunohistochemical study of a case resembling rosacea clinically.
Mentzel T, Kutzner H, Wollina U.
Institute of Pathology, University of Jena, Germany.
J Am Acad Dermatol 1998 May;38(5 Pt 2):837-40 Abstract quote
An unusual cutaneous angiosarcoma resembling rosacea clinically is described. A 66-year-old man presented with a red discoloration and a diffuse swelling on his nose over a 2-year period that was diagnosed as rosacea. Despite antiinflammatory treatment, the infiltration increased and, after repeated skin biopsies, the diagnosis of a well-differentiated cutaneous angiosarcoma associated with a prominent inflammatory infiltrate was considered. The neoplasm was treated by surgery.
The described case emphasizes that diffuse swelling and rosacea-like clinical features should be added to the variably clinical features of cutaneous angiosarcoma.
Gingival and cutaneous angiosarcoma.
Abdullah BH, Yahya HI, Talabani NA, Alash NI, Mirza KB.
Department of Oral Diagnosis, College of Dentistry, University of Baghdad, Iraq.
J Oral Pathol Med 2000 Sep;29(8):410-2 Abstract quote
Multiple oral and cutaneous nodular and papular reddish-blue lesions are described in the case of a 60-year-old woman. The duration of the lesions was more than 1 year, with the oral lesion preceding the skin lesions. Histopathological examination revealed malignant vascular tumour with changes consistent with angiosarcoma.
Angiosarcoma is an extremely rare malignant tumour of the oral cavity, and the present case describes oral and skin lesions with a unique clinical behaviour.
Ann Diagn Pathol. 2005 Oct;9(5):289-92. Abstract quote
Primary angiosarcomas of the spleen are rare and almost always fatal. With no more than 200 cases reported in the literature worldwide, no specific risk factors are strongly associated with the disease. The mean age of patients at presentation is 59 years and the major clinical findings include abdominal pain, splenic rupture, and splenomegaly.
Grossly, this neoplasm appears as hemorrhagic and/or cystic nodules, with a low-density signal seen on computed tomographic scans. Histologically, the tumor is characterized by neoplastic proliferation with diffuse or focal areas of a vasoformative component with cavernous and arborizing channels. The vascular spaces are lined by endothelial cells with variable degree of atypia.
The differential diagnosis includes a variety of benign and malignant vascular proliferations (littoral cell angioma and Kaposi's sarcoma) as well as metastatic tumors. The worst prognostic factor is splenic rupture with early metastasis. The liver is the most common site.
We report a case of the 43-year-old woman with a long-standing history of recurrent ovarian carcinoma treated with surgery and multiple courses of radiation therapy and chemotherapy who clinically appeared to have a metastatic ovarian cancer to the spleen and treated with partial resection of stomach and splenectomy. However, histopathologic examination of the specimen showed the tumor to be of a primary angiosarcoma.
We believe that the lengthy exposure to radiation may have played a role in the histopathogenesis of this neoplasm in this patient.
Splenic angiosarcoma: a clinicopathologic and immunophenotypic study of 28 cases.
Neuhauser TS, Derringer GA, Thompson LD, Fanburg-Smith JC, Miettinen M, Saaristo A, Abbondanzo SL.
Department of Hematopathology, Armed Forces Institute of Pathology, Washington, DC, USA.
Mod Pathol 2000 Sep;13(9):978-87 Abstract quote
Primary angiosarcoma of the spleen is a rare neoplasm that has not been well characterized. We describe the clinical, morphologic, and immunophenotypic findings of 28 cases of primary splenic angiosarcoma, including one case that shares features of lymphangioma/lymphangiosarcoma.
The patients included 16 men and 12 women, aged 29 to 85 years, with a mean of 59 years and median of 63 years. The majority of patients (75%) complained of abdominal pain, and 25% presented with splenic rupture. The most common physical finding was splenomegaly (71%). Seventeen of 21 patients were reported to have anemia. Macroscopic examination showed splenomegaly in 85% cases. Sectioning revealed discrete lesions in 88% of cases, ranging from well-circumscribed firm nodules to poorly delineated foci of necrosis and hemorrhage associated with cystic spaces.
Microscopically, the tumors were heterogenous; however, all cases demonstrated at least a focal vasoformative component lined by atypical endothelial cells. Solid sarcomatous, papillary, and epithelioid growth patterns were observed. The solid sarcomatous component resembled fibrosarcoma in two cases and malignant fibroushistiocytoma in one case. Hemorrhage, necrosis, hemosiderin, extramedullary hematopoiesis, and intracytoplasmic hyaline globules were frequently identified. A panel of immunohistochemical studies revealed that the majority of tumors were immunoreactive for at least two markers of vascular differentiation (CD34, FVIIIRAg, VEGFR3, and CD31) and at least one marker of histiocytic differentiation (CD68 and/or lysozyme). Metastases developed in 100% of patients during the course of their disease. Twenty-six patients died of disease despite aggressive therapy, whereas only two patients are alive at last follow-up, one with disease at 8 years and the other without disease at 10 years.
In conclusion, primary splenic angiosarcoma is an extremely aggressive neoplasm that is almost universally fatal. The majority of splenic angiosarcomas coexpress histiocytic and endothelial markers by immunohistochemical analysis, which suggest that some tumors may originate from splenic lining cells.
A Kaposi-like Variant of Splenic Angiosarcoma Lacking Association With Human Herpesvirus 8
Tetuo Mikami, MD, Makoto Saegusa, MD, Fumiyuki Akino, MD, Daisuke Machida, MT, Keiichi Iwabuchi, MD, Shotaro Hagiwara, MD, and Isao Okayasu, MD
From the Department of Pathology (Drs Mikami, Saegusa, Akino, Iwabuchi, and Okayasu), Kitasato University School of Medicine, Sagamihara, Japan; and the Departments of Pathology (Drs Mikami, Saegusa, Akino, Iwabuchi, and Okayasu, and Mr Machida) and Hematology (Dr Hagiwara), Kitasato University Hospital, Sagamihara, Japan
Arch Pathol Lab Med 2002;Vol. 126, No. 2, pp. 191194. Abstract quote
We report the case of a Kaposi-like variant of splenic angiosarcoma in a 28-year-old woman. The tumor featured a Kaposi sarcomalike spindle cell proliferation with slit formation and markedly dilated spongelike vascular channels filled with erythrocytes.
Thirteen months following the initial splenectomy, metastatic lesions were found in the patient's liver and bone marrow. The proliferating cells were positive for factor VIIIassociated antigen and CD34. The human herpesvirus 8 genome, which is regarded as a diagnostic feature of Kaposi sarcoma, was not detected by polymerase chain reaction analysis.
Although the histologic findings were similar, this Kaposi-like variant of splenic angiosarcoma must be considered distinct from Kaposi sarcoma.
HISTOPATHO-LOGICAL VARIANTS CHARACTERIZATION CAPILLARY LOBULE
- The Capillary Lobule: A Deceptively Benign Feature of Post-Radiation Angiosarcoma of the Skin: Report of Three Cases.
Di Tommaso L, Rosai J.
From the Department of Pathology, University of Milan Medical School and Humanitas Clinical Institute, Rozzano, Italy; and daggerDepartment of Pathology, National Cancer Institute, Milan, Italy.
Am J Dermatopathol. 2005 Aug;27(4):301-305. Abstract quote
Three cases are presented of a proliferative vascular lesion of the skin developing in the chest wall of women who had received radiation therapy for breast carcinoma.
All 3 lesions were characterized microscopically by the presence of the so-called capillary lobule, a formation generally regarded as a sign of benignancy but that in this setting proved to be a forerunner or indicator of angiosarcoma (malignant hemangioendothelioma).
Therefore, the detection of capillary lobules in irradiated skin ought to be regarded with great suspicion, and other morphologic signs suggestive of angiosarcoma should be sought in the specimen.
- Cutaneous epithelioid angiosarcoma: a neoplasm with potential pitfalls in diagnosis.
Department of Pathology, University of Nevada School of Medicine, Las Vegas, NV, USA.
- J Cutan Pathol. 2009 Mar;36(3):362-9. Abstract quote
Angiosarcoma (AS) is a rare neoplasm. Cutaneous AS is the most common form of AS. The epithelioid variant of the disease, however, is a rare entity. This subset can histologically mimic non-vascular neoplasms and impose serious challenges in reaching the correct diagnosis.
We present five patients with cutaneous epithelioid angiosarcoma (EAS); in none, the clinical diagnosis included a vascular lesion. Three patients had history of breast conservation surgery with/without radiation therapy. Other patients had no previous radiation, and there was no lymphedema in any of the cases.
The histopathological examination of the biopsy specimens by hematoxylin and eosin method was not suggestive of a malignant vascular neoplasm initially and the differential diagnoses included carcinoma, malignant melanoma and atypical lymphoid infiltrate. Only after performing immunohistochemical studies that included vascular markers, a definitive diagnosis was possible. Some cases showed unusual histopathological features.
Cutaneous EAS is a rare variant of cutaneous AS that can mimic a variety of more common, non-vascular neoplasms, creating a major pitfall in the diagnosis. A careful and thorough histopathological examination and a high index of suspicion, along with appropriate immunohistochemical evaluation, can help reach a correct diagnosis and provide optimal patient care.
Epithelioid angiosarcoma of the bone: a series of 10 cases.Deshpande V, Rosenberg AE, O'Connell JX, Nielsen GP.
Am J Surg Pathol. 2003 Jun;27(6):709-16 Abstract quote
The clinical and pathologic features of 10 epithelioid angiosarcomas of bone were analyzed. There were eight males and two females who ranged in age from 26 to 83 years (mean 62 years). Four tumors were solitary and six were multifocal. In two consultation cases, the submitted diagnosis was metastatic carcinoma.
Microscopically, the tumor cells were arranged in solid and infiltrative sheets, and in most cases vascular channels or cystically dilated spaces were present. The neoplastic cells had abundant eosinophilic cytoplasm and large nuclei with open chromatin and prominent eosinophilic nucleoli. Intratumoral hemorrhage, neutrophilic infiltrates, and intracytoplasmic lumina were frequently present.
All 10 tumors stained positive for one or more endothelial markers, with CD31 being the most sensitive marker. Seven cases stained positive for cytokeratin. Ultrastructural examination in three tumors confirmed their endothelial differentiation. In the absence of obvious vascular differentiation, abundant intratumoral hemorrhage and intratumoral neutrophils are useful ancillary morphologic features that may suggest a vascular origin. Six patients are dead of disease, one is alive with metastasis, and two patients are currently disease free.
Epithelioid angiosarcoma of bone should be included in the differential diagnosis of epithelioid neoplasms of bone, and endothelial markers should be a part of their immunohistochemical analysis to avoid the misdiagnosis of a metastatic carcinoma because of the significant differences in the treatment and clinical outcomes of these entities.
J Cutan Pathol. 1997 Jan;24(1):56-60 Abstract quote.
This report describes a patient with a poorly differentiated cutaneous angiosarcoma (CA) of the face superinfected with pseudomonas aeruginosa.
- Neoplastic cells were positive for CD-34, CD-31 and vimentin, whereas they failed to express other vascular markers such as Factor VIII and Ulex europeaus lectin. The tumor spread rapidly through the skin and the superficial soft tissue before metastasizing. The patient died of disease 6 months after histopathological diagnosis. An autopsy revealed widespread metastases in the lung and the liver.
- The aim of this report is to call attention to some circumstances in which CA may masquerade as an inflammatory process, delaying the right diagnosis with serious consequences for the patient.
Intravascular ("intimal") epithelioid angiosarcoma: clinicopathological and immunohistochemical analysis of three cases. Hottenrott G, Mentzel T, Peters A, Schroder A, Katenkamp D.
Department of Pathology, University of Jena, Ziegelmuhlenweg 1, D-07740 Germany.
Virchows Arch 1999 Nov;435(5):473-8 Abstract quote
Angiosarcomas are rare malignant mesenchymal tumours, characterized morphologically by anastomosing vascular channels lined by atypical and proliferative active endothelial cells. An epithelioid cytomorphology of tumour cells is often seen focally in angiosarcoma, whereas purely epithelioid angiosarcomas are rare. Although angiosarcomas show a vascular differentiation they are almost never confined to pre-existing blood vessels.
We describe three cases of intravascular epithelioid angiosarcoma arising in the carotid artery of a 60-year-old man, in the infrarenal part of the abdominal aorta and both renal arteries of a 69-year-old woman, and in the abdominal aorta of a 68-year-old man. In all cases malignant tumour tissue was found incidentally after disobliteration of thrombosed vessels.
Histologically, purely epithelioid angiosarcoma composed of solid sheets of epithelioid tumour cells was seen; immunohistochemistry confirmed the endothelial differentiation of neoplastic cells.
The reported cases show that angiosarcoma can occasionally arise within a pre-existing vessel.
J Cutan Pathol. 2006 Jan;33(1):38-42. Abstract quote
Background: Cutaneous epithelioid angiosarcoma is a type of cutaneous angiosarcoma and usually arise both on the head or neck of the elderly.
Case report: An 86-year-old male with an epithelioid angiosarcoma of the scalp that mimicked malignant melanoma.
Results: A large irregular dark grey-blue plaque with an adjacent speckled tan nodule was suggestive of a primary cutaneous malignant melanoma with adjacent in-transit metastasis. Both had a well-circumscribed growth pattern and were composed of numerous large epithelioid cells with scattered severe atypia and mitoses. The tumor was positive for S-100 protein and vimentin and negative for low- and high-molecular weight cytokeratins. However, at high power, the epithelioid cells with severe atypia were negative for S-100 protein, and abundant large epithelioid macrophages were responsible for the S-100 protein positivity. The malignant tumor cells were negative for HMB-45, positive for CD31 and Factor VIII-related antigen, and focally positive for CD34. A focus of infiltrative, classical angiosarcoma with irregular vascular channels lined with plump, anaplastic endothelial cells was then found deep to the epithelioid tumor.
Conclusions: Macrophage-rich epithelioid angiosarcoma demonstrates abundant S-100 protein-positive epithelioid macrophages. This subset of epithelioid angiosarcoma may mimic malignant melanoma and may present as a pitfall in diagnosis.
Spindle cell angiosarcoma following irradiation therapy for cervical carcinoma
Takahiro Kiyohara,1 Masanobu Kumakiri,1 Hitoshi Kobayashi,2 Kei Itoh,2 Li-Min Lao,1 Akira Ohkawara2 and Hideki Nakamura2
J Cutan Pathol 2002;29:96-100 Abstract quote
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 10years 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 2months. 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 19months after diagnosis.
Conclusions:Radiation-induced lymphedema may be a factor in angiosarcoma associated with radiotherapy.
Cutaneous angiosarcomas with a starry-sky pattern. Smith KJ, Lupton GP, Skelton HG.
National Naval Medical Center, Bethesda, Md 20814-6000, USA.
Arch Pathol Lab Med 1997 Sep;121(9):980-4 Abstract quote OBJECTIVE: A subgroup of epithelioid angiosarcomas, which we have identified, has a prominent starry-sky histologic pattern. All these neoplasms were evaluated with routine histopathology and with immunohistochemical stains. Clinical follow-up was also obtained to determine whether these angiosarcomas' had any other distinctive properties. DESIGN: Histopathologic features and immunohistochemical stains, including cytokeratin, epithelial membrane antigen, CD34, LCA, factor VIII-related antigen, KP-1, vimentin, HMB-45, and S100 protein were performed on all four neoplasms. PATIENTS: These angiosarcomas occurred on the extremities of patients with chronic edema as well as on the scalp of elderly patients. MAIN OUTCOME: All patients were dead within 5 years of diagnosis. Of the three patients where angiosarcoma was listed as the cause of death, all were dead within 30 months. RESULTS: All tumors showed a similar immunohistochemical staining pattern. Vimentin, factor VIII-related antigen, and CD34 were positive in all tumors. The remaining immunohistochemical stains including cytokeratin, which may be positive in other epithelioid angiosarcomas, were negative.
CONCLUSIONS: We present a distinctive starry-sky histologic pattern in epithelioid angiosarcomas. Knowledge of this pattern may be important in the early diagnosis of this rapidly fatal neoplasm.
- Undifferentiated Intimal Sarcoma of Large Systemic Blood Vessels: Report of 14 Cases With Immunohistochemical Profile and Review of the Literature.
Sebenik M, Ricci A Jr, Dipasquale B, Mody K, Pytel P, Jee KJ, Knuutila S, Scholes J.
From the *Department of Pathology, Staten Island University Hospital, Staten Island, NY; daggerDepartment of Pathology, Hartford Hospital, Hartford, CT; double daggerDepartment of Pathology, Cleveland Clinic, Naples, FL; section signNew York University Medical Center, New York, NY; parallelUniversity of Chicago Medical Center, Chicago, IL; and paragraph signDepartments of Pathology and Medical Genetics, Haartman Institute and HUSLAB, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
Am J Surg Pathol. 2005 Sep;29(9):1184-1193. Abstract quote
Intimal sarcoma (IS) is defined as a malignant tumor arising in the tunica intima of large blood vessels. In systemic circulation, the majority of IS develop in the aorta, where close to three fourths of published cases lack specific differentiation and are called undifferentiated intimal sarcomas (UIS). The remaining cases are intima-associated sarcomas of recognized types, also called differentiated intimal sarcomas (DIS).
In this report, we further characterize UIS, including its immunohistochemical profile and results of comparative genomic hybridization. A total of 14 cases of UIS were collected from 17 medical institutions, including slides, blocks, electron photomicrographs, clinical abstracts, and reports of surgical pathology specimens and autopsies. The patients, 7 women and 7 men, were 41 to 85 years of age (median, 65.6 years). Twelve tumors arose from the aorta, one from the left external iliac and femoral arteries, and one in a large systemic vein (the venous tumor was included due to histologic similarity with the arterial lesions). Tumors ranged from 1 cm to over 10 cm in diameter.
Histopathology was that of a largely necrotic, poorly differentiated epithelioid and pleomorphic malignant neoplasm relating to the tunica intima. Usually there was only a thin layer of viable tumor cells overlying a large thrombus. All tumors stained at least focally with the endothelial markers CD31 and Fli-1; however, there was otherwise considerable variability in immunophenotype. The distinctive histopathologic appearance of the primary luminal lesion was lost whenever tumor invaded outside the vessel wall (into adventitia and beyond) or in metastatic sites. Such extravascular tumors assumed a variety of patterns reminiscent of undifferentiated pleomorphic sarcoma (UPS; in older literature also known as pleomorphic malignant fibrous histiocytoma, MFH) or other distinct types of sarcomas, including osteosarcoma, angiosarcoma, and rhabdomyosarcoma. The results of comparative genomic hybridization were nonspecific. Eleven patients died of the disease, in an average of 11 months after diagnosis. Three patients are still alive and free of disease at 4, 16, and 27 years. UIS of large systemic vessels represents a distinct clinical entity where intraluminal sarcoma presents with thrombosis and occlusion of large vessels. It is associated with a highly characteristic, although not entirely specific, histology and immunohistochemical phenotype.
The histogenesis of UIS is not certain; however, it seems that the cell of origin must leave the confines of the vessel wall to show altered morphology. Although there are rare long-term survivors, UIS behaves as a fully malignant neoplasm that is almost uniformly associated with metastases and tumor-related death.
Verrucous angiosarcoma of the skin: a distinct variant of cutaneous angiosarcoma.Diaz-Cascajo C, Weyers W, Borghi S, Reichel M.
Centre for Dermatopathology, Freiburg, Germany.
Histopathology 1998 Jun;32(6):556-61 Abstract quoteAIMS: Cutaneous angiosarcoma is a malignant vascular neoplasm with well established clinical and histopathological features. Epidermal changes in cutaneous angiosarcoma other than atrophy and necrosis have not been described. In this study, we report three cases of a peculiar variant of angiosarcoma with striking verrucous changes of the overlying epidermis. METHODS AND RESULTS: On light microscopy, verrucous changes characterized by marked pseudocarcinomatous epithelial hyperplasia with hypergranulosis, compact orthokeratosis, and papillomatosis were present overlying an angiosarcoma in the dermis. Clinically the lesions presented as violaceous to brown scaly verrucous nodules or plaques. All lesions developed on an extremity.
CONCLUSIONS: Verrucous epidermal changes seem to be a manifestation of pseudocarcinomatous hyperplasia, presumably caused by lymphoedema and the superficial setting of the tumour in the papillary dermis. It is important to be aware of this presentation of angiosarcoma because verrucous epidermal changes may be seen in a wide variety of skin diseases. Furthermore, a biopsy that includes the dermis is necessary to ensure that the angiosarcoma underlying the hyperplastic epidermis is correctly identified. The descriptive appellation verrucous angiosarcoma of the skin is proposed to designate a newly recognized variant of angiosarcoma.
- Arch Pathol Lab Med. 2007 Feb;131(2):288-92. Abstract quote
CONTEXT: Expression of epithelial cell markers can occur in mesenchymal tumors and has been reported in angiosarcomas with variable frequency. In these situations, establishing the diagnosis becomes problematic.
OBJECTIVE: To determine the expression of cytokeratin and epithelial membrane antigen in angiosarcoma.
DESIGN: To address this issue, 33 well-documented cases of angiosarcomas were retrieved from the archival material of Shands Hospital at the University of Florida, Gainesville, and Jackson Memorial Hospital at the University of Miami, Miami, Florida. These cases were all reviewed and studied using a cytokeratin cocktail (CAM 5.2 and AE1/AE3) and epithelial membrane antigen using standard immunohistochemical techniques. All 33 cases had available material for cytokeratin analysis; however, only 20 cases had enough material for epithelial membrane antigen staining.
RESULTS: In the 33 cases studied, the age range of the patients was 2 to 88 years (mean, 63 years). There were 23 (70%) men and 10 (30%) women. One (3%) of 33 was cytokeratin-immunoreactive and 2 (10%) of 20 were epithelial membrane antigen-immunoreactive.
CONCLUSION: Cytokeratin and epithelial membrane antigen immunoreactivity in angiosarcomas is infrequent but may be encountered. Interpretation of such expression should be done with caution and in conjunction with the characteristic clinical and morphologic features of the tumor as well as the expression of endothelial cell antigens.
Monoclonal antibody D2-40, a new marker of lymphatic endothelium, reacts with Kaposi's sarcoma and a subset of angiosarcomas.Kahn HJ, Bailey D, Marks A.
Department of Pathology, Women's College Campus, Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario, Canada.
Mod Pathol 2002 Apr;15(4):434-40 Abstract quote
There is controversy over the histogenesis of Kaposi's sarcoma (KS) from lymphatic or blood vessel endothelium. D2-40 is a novel monoclonal antibody to an Mr 40,000 O-linked sialoglycoprotein that reacts with a fixation-resistant epitope on lymphatic endothelium. We sought to establish the selectivity of D2-40 for lymphatic endothelium in normal tissues and compare its reactivity with the expression of the widely used vascular endothelial marker CD31 in a series of 62 formalin-fixed and paraffin-embedded vascular lesions including KS. In normal tissues, D2-40 stained the endothelium of lymphatic channels but not of blood vessels, including arteries and capillaries defined by reactivity with the blood vessel endothelial marker PAL-E. In our series of vascular lesions, D2-40 stained lymphangiomas (10/10), benign tumors of undisputed lymphatic origin, but not benign neoplasms or tumorlike lesions of blood vessel origin, including hemangiomas (0/10), glomus tumors (0/3), angiolipomas (0/2), pyogenic granulomas (0/2), vascular malformations (0/2), hemangiopericytoma (0/1), or hemangioendothelioma (0/1). D2-40 stained all cases of cutaneous KS (24/24) at all stages of progression, including patch, plaque, and nodular stages, supporting the concept that this disease originates from a cell type capable of undergoing lymphatic differentiation. D2-40 also stained three of seven angiosarcomas, indicating that a subset of these tumors can undergo at least partial differentiation along the lymphatic endothelial lineage and could be classified as lymphangiosarcomas. In comparison, CD31 was expressed in all benign and malignant vascular lesions, except for glomus tumors (0/3) and 5/10 lymphangiomas, in which staining was absent.
We conclude that D2-40 is a new selective marker of lymphatic endothelium in normal tissues and vascular lesions and is valuable for studying benign and malignant vascular disorders in routinely processed tissue specimens.
- Estrogen receptor beta expression in vascular neoplasia: an analysis of 53 benign and malignant cases.
Deyrup AT, Tretiakova M, Khramtsov A, Montag AG.
1Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Mod Pathol. 2004 Nov;17(11):1372-7 Abstract quote.
The importance of estrogen in vascular neoplasia is suggested by a predilection for women and a tendency for rapid growth during pregnancy. Although early experiments using radioligand assays demonstrated estrogen receptor (ER) expression, these findings were not confirmed by subsequent immunohistochemical studies which were performed with antibodies raised against ERalpha.
A newly discovered estrogen receptor subtype, ERbeta, has not been previously characterized in vascular lesions. In order to verify the expression of estrogen receptors in vascular neoplasms as well as to clarify the inconsistency between radioligand and early immunohistochemical studies, we examined a series of 53 benign and malignant vascular neoplasms for ERbeta expression. All of the subtypes of vascular neoplasia examined had nuclear expression of ERbeta. The majority of cases (94%) displayed 2+ to 3+ staining. The discrepancy between radioligand studies and previous immunohistochemical studies is attributable to the use of antibodies raised against ERalpha, which is not expressed in vascular lesions, and not ERbeta, which is broadly expressed in both benign and malignant vascular neoplasms.
Although ERbeta may be of limited diagnostic use in vascular neoplasia due to its broad expression, the potential exists for a therapeutic approach using ER agonists.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIAL FEATURES CUTANEOUS
Cutaneous epithelioid angiomatous nodule: a distinct lesion in the morphologic spectrum of epithelioid vascular tumors.
Brenn T, Fletcher CD.
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Am J Dermatopathol. 2004 Feb;26(1):14-21. Abstract quote
Cutaneous epithelioid vascular proliferations comprise a morphologic spectrum ranging from benign, reactive to frankly malignant conditions. We present a group of morphologically distinct epithelioid vascular lesions in the skin that defy classification according to current criteria.
Clinically, the lesions presented as single (14/15) or multiple (1/15) small (< 1.5 cm, median = 0.5 cm) erythematous to bluish nodules or papules of short duration (weeks to months) without gender predilection (M:F = 1:1). Age distribution ranged from 15 to 79 years (median: 37). Lesions were predominantly located on the trunk (8/15) but also involved the extremities (5/15), face (1/15), and nasal mucosa (1/15). No patient was immunocompromised. Treatment was simple surgical excision.
Histologically, the lesions were located superficially in dermis (or submucosa) and consisted of a circumscribed, unilobular, mainly solid proliferation of large polygonal epithelioid endothelial cells with vesicular nuclei and conspicuous nucleoli. Cytoplasm was abundant and contained frequent intracytoplasmic vacuoles. Nuclear atypia was absent. Mitotic figures (up to 5/10HPF) were observed in 8 lesions. Formation of endothelial-lined channels was a focal but constant feature. Also noted were adjacent dilated dermal vessels (8/15), hemosiderin deposition (6/15), and mild fibrosis (9/15). The lesion was accompanied by a chronic inflammatory infiltrate with a lymphoplasmacytic component (14/15), most pronounced at the periphery of the lesion, and varying numbers of eosinophils scattered throughout the lesion (12/15). Eosinophils were conspicuous in only 4 cases. Epidermal hyperplasia was present in 11 cases. By immunohistochemistry, lesional cells stained positively for at least one endothelial marker. Clinical follow-up (median = 30 months) showed no recurrence or metastases.
Epithelioid angiomatous nodule is a benign, likely reactive cutaneous lesion in the clinical and morphologic spectrum of epithelioid vascular proliferations. It differs from conventional epithelioid hemangioma both in its clinical presentation with predominant involvement of trunk and extremities as well as its histologic features, which more closely resemble epithelioid angiosarcoma.
OF THE BONE
Epithelioid hemangioma of bone. A tumor often mistaken for low-grade angiosarcoma or malignant hemangioendothelioma. O'Connell JX, Kattapuram SV, Mankin HJ, Bhan AK, Rosenberg AE.
Department of Pathology, Massachusetts General Hospital, Boston 02114.
Am J Surg Pathol 1993 Jun;17(6):610-7 Abstract quoteEpithelioid hemangiomas are benign vascular tumors that usually occur in the skin and subcutis. They have been infrequently recognized in bone. Because of their unusual cytologic appearance and growth patterns, they are commonly confused with malignant tumors. We report a series of 12 epithelioid hemangiomas of bone occurring in adult patients, including five males and seven females whose ages at presentation ranged from 24 to 74 years, with a mean of 46 years. Five tumors were associated with involvement of the adjacent soft tissue. A single patient had multifocal bone disease. The most common presenting symptom was localized pain. Treatment of the patients varied widely; however, none of the tumors behaved aggressively. In 11 cases, adequate tissue was available for immunohistochemical analysis, which revealed positive staining for the epithelial markers cytokeratin and epithelial membrane antigen in nine cases. All 11 tumors stained for factor VIII-related antigen and Ulex europeus agglutinin. We believe that many of the vascular tumors of bone that have been reported as low-grade malignant hemangioendotheliomas probably represent examples of epithelioid hemangiomas.
We recommend that the criteria for diagnosing vascular tumors of bone conform to those used for morphologically similar tumors that arise in the soft tissues.
Florid vascular proliferation of the colon related to intussusception and mucosal prolapse: potential diagnostic confusion with angiosarcoma. Bavikatty NR, Goldblum JR, Abdul-Karim FW, Nielsen SL, Greenson JK.
Department of Pathology, University of Michigan Hospitals, 1500 E. Medical Center Dr., Ann Arbor, MI 48109-0054, USA.
Mod Pathol 2001 Nov;14(11):1114-8 Abstract quote With the exception of angiodysplasia, vascular abnormalities of the intestines are unusual. We describe a florid benign vascular proliferation of the colon in five adult patients, three of whom presented with idiopathic intussusception. In all cases, the proliferation was sufficiently exuberant to raise the possibility of angiosarcoma as a diagnostic consideration. The group included 2 males and 3 females with a median age of 43 years. Two patients were HIV positive. Four patients presented with a colonic mass; other symptoms at presentation included abdominal pain, diarrhea, bleeding, and bowel obstruction. In all cases, a florid lobular proliferation of small vascular channels lined by plump endothelial cells extended from the submucosa through the entire thickness of the bowel wall. The endothelial cells showed minimal nuclear atypia, and mitotic figures were infrequent. The overlying mucosa showed ulceration with ischemic-type changes, and had features of mucosal prolapse. A possible underlying arteriovenous malformation was identified in two cases. All patients were alive and well at last follow-up (interval, 6 months to 5 years).
The presence of intussusception or mucosal prolapse in all of the cases suggests repeated mechanical forces applied to the bowel wall as a possible etiologic factor. The role of HIV infection in the pathogenesis of these lesions remains to be determined.
Intravascular papillary endothelial hyperplasia. A benign lesion mimicking angiosarcoma.
Barr RJ, Graham JH, Sherwin LA.
Arch Dermatol 1978 May;114(5):723-6 Abstract quoteObservations were made of three cases of intravascular papillary endothelial hyperplasia (IPEH). Lesions of IPEH usually occur on the head and neck area as a subcutaneous red or blue nodule. This papillary proliferation of endothelial and stromal tissue occurs de novo in organizing venous thrombi or in preexisting hemangiomas or phlebectasias.
An adequate understanding of this benign vascular disorder is important, since the lesion may be clinically and histologically mistaken for low grade angiosarcoma.
Cutaneous intravascular papillary endothelial hyperplasia: a benign lesion that may simulate angiosarcoma.
Schwartz IS, Parris A.
Cutis 1982 Jan;29(1):66-9, 72-4 Abstract quote
An example of intravascular papillary endothelial hyperplasia (Masson's pseudoangiosarcoma) of the skin of the forearm is presented. The clinical and pathologic features of the unusual lesion are described. Its benign, self-limited nature is emphasized, despite histopathologic features which may suggest the diagnosis of angiosarcoma. Appropriate therapy should therefore be directed to local excision rather than radical surgery.
LIP VASCULAR PROLIFERATIONS
Benign atypical vascular lesions of the lip. A study of 12 cases. Renshaw AA, Rosai J.
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Am J Surg Pathol 1993 Jun;17(6):557-65 Abstract quoteWe present 12 cases of benign atypical vascular lesions of the lip with cytologic or architectural features that raised microscopically the possibility of angiosarcoma.
The patterns encountered in these lesions, sometimes in combination, were the following: lobular capillary hemangioma in five cases; intravascular papillary endothelial hyperplasia in five cases; epithelioid hemangioma in four cases; and acquired progressive lymphangioma in one case.
Benign lymphangioendothelioma of the thigh simulating a low-grade angiosarcoma. Sevila A, Botella-Estrada R, Sanmartin O, Serra V, Cabadas P, Aliaga A, Guillen C.
Dermatology Service, Instituto Valenciano de Oncologia, Valencia, Spain.
Am J Dermatopathol 2000 Apr;22(2):151-4 Abstract quoteBenign lymphangioendothelioma (BL) is a rare vascular neoplasm that can histopathologically mimic a low-grade angiosarcoma or the patch stage of Kaposi sarcoma. We report on the case of a 49-year-old man with a benign lymphangioendothelioma on the right thigh that evolved on a vascular birthmark after a trauma. Because of constant pain and the slow but progressive growth of the lesion, we decided to excise the tumor. Three stages of surgery were needed to obtain negative margins.
We review the reports of BL to date, with special attention to those that developed after trauma and those that had a preexistent vascular lesion, and expound on the histopathologic differential diagnosis with low-grade angiosarcoma.
Benign Lymphangioendothelioma (Acquired Progressive Lymphangioma): A Lesion Not to Be Confused With Well-Differentiated Angiosarcoma and Patch Stage Kaposi's Sarcoma Clinicopathologic Analysis of a Series Louis Guillou, M.D.; Christopher D. M. Fletcher, M.D., F.R.C.Path.
From the University Institute of Pathology (L.G.), Lausanne, Switzerland; and the Department of Pathology (C.D.M.F.), Brigham and Women's Hospital, Boston, Massachusetts
Am J Surg Pathol 2000;24:1047-1057 Abstract quoteThe clinicopathologic features of 12 cases of benign lymphangioendothelioma (acquired progressive lymphangioma) are reported. There were five male and seven female patients. Age at diagnosis ranged from 17 to 90 years (median age, 54 yrs). Development of a single macular/papular hemangiomatous or pigmented lesion was the main presenting symptom. Symptom duration before diagnosis ranged from 2 months to 20 years (median, 5.5 yrs). Tumor size ranged from 0.3 cm to 10 cm (median, 1.5 cm). Location included skin of the head and neck (n = 5), back (n = 1), breast (n = 1), shoulder (n = 1), forearm (n = 1), plantar aspect of the foot (n = 2), and oral mucosa (n = 1). No patient had any other concomitant vascular anomaly (for example, lymphangiomatosis) or was suspected to have acquired immunodeficiency syndrome. Treatment consisted of excisional biopsy in nine patients, incisional biopsy in two, and wide excision in one. Follow-up information on nine patients (range, 4–40 mos; median, 12 mos) showed two local recurrences in one patient. Microscopically, the lesions consisted of anastomosing, often widely dilated vascular structures developing in the superficial dermis. As the lesion grew within deeper dermis, the vascular spaces collapsed and dissected the dermal collagen in an angiosarcoma-like pattern. The lining endothelium was flat and monolayered, with little or no cytologic atypia and no evident mitoses. Some vascular structures contained stromal papillary projections resembling papillary endothelial hyperplasia, and intravascular red blood cells were present occasionally. Immunohistochemistry performed in eight specimens showed variable endothelial cell reactivity for CD31 (7 of 8), CD34 (7 of 7), and factor VIII-related antigen (4 of 6). A smooth muscle cell layer was observed focally around the vascular spaces in six lesions.
Benign lymphangioendothelioma (acquired progressive lymphangioma) is an uncommon benign lesion that, in view of major differences in treatment and prognosis, should be distinguished from well-differentiated angiosarcoma and Kaposi's sarcoma, especially the patch stage and lymphangioma-like variants of the latter.
RADIATION INDUCED Benign Vascular Proliferations in Irradiated Skin
Luis Requena, M.D.; Heinz Kutzner, M.D.; Thomas Mentzel, M.D.; Rafael Durán, M.D.; José Luis Rodríguez-Peralto, M.D.From the Department of Dermatology (L.R.), Fundación Jiménez Díaz, Universidad Autónoma, Madrid, Spain; Dermatohistopathologisches Gemeinschaftslabor (H.K., T.M.), Friedrichshafen, Germany; the Department of Pathology (R.D.), Hospital de Elda, Alicante, and the Department of Pathology (J.L.R.-P.), Hospital 12 de Octubre, Universidad Complutense, Madrid, Spain.
Am J Surg Pathol 2002;26:328-337 Abstract quote
Several types of cutaneous vascular proliferations have been described in areas of irradiated skin, including both benign lesions, such as benign lymphangiomatous papules, atypical vascular lesions, or benign lymphangioendothelioma, and malignant neoplasms such as high-grade angiosarcomas. This report describes the clinicopathologic features of 15 cases of different types of benign cutaneous vascular proliferations arisen within irradiated skin. All patients were female ranging in age from 33 to 72 years, and they had received postoperative external radiotherapy for treatment of breast carcinoma (14 cases) or ovarian carcinoma (one case). In those cases in which the latency interval period between radiotherapy and the development of the vascular lesion was known from the clinical records, the latency interval period elapsed between radiotherapy and diagnosis of the vascular lesion ranged from 3 to 20 years. The most common clinical presentation of the cutaneous lesions consisted of papules, small vesicles, or erythematous plaques on the irradiated field. Histopathologically, most lesions consisted of irregular dilated vascular spaces, with a branching and anastomosing pattern, thin walls, and lymphatic appearance involving the superficial dermis. A discontinuous single layer of endothelial cells with flattened nuclei lined these vascular channels, and numerous small stromal papillary formations also lined by endothelial cells projected into the lumina of the dilated lymphatic vessels. These cases were classified as benign lymphangiomatous papules or plaques. Two cases showed different histopathologic findings because they consisted of poorly circumscribed and focally infiltrating irregular jagged vascular spaces involving the entire dermis and lined by inconspicuous endothelial cells. In some areas these irregular slit-like vascular spaces dissected collagen bundles of the dermis. These cases were classified as atypical vascular proliferations mimicking benign lymphangioendothelioma or patch-stage Kaposi's sarcoma. All cases showed similar immunohistochemical findings and the endothelial cells lining the vascular spaces expressed immunoreactivity for CD31, but they stained only focally positive for CD34 or were negative for this marker. Immunohistochemical investigations for -smooth muscle actin failed to demonstrate a complete peripheral ring of actin-positive pericytes in most of the neoformed vascular structures.
This immunohistochemical profile also supported the lymphatic nature of these vascular proliferations developed in irradiated skin. Although some of these lesions may mimic histopathologically patch-stage Kaposi's sarcoma or well-differentiated angiosarcoma, the follow-up of the patients of this series demonstrated that the vascular proliferations arisen in irradiated skin invariably showed a benign biologic behavior.
Reactive angioendotheliomatosis. Case report and review of the literature. Lazova R, Slater C, Scott G.
Department of Pathology, University of Rochester School of Medicine and Dentistry, NY 14642, USA.
Am J Dermatopathol 1996 Feb;18(1):63-9 Abstract quoteAngioendotheliomatosis is an uncommon disease characterized histologically by proliferation of cells within vascular lumina with secondary intravascular thrombi resulting in obliteration of the involved vessels. While angioendotheliomatosis was initially thought to be a single disease entity, recent studies show that the disease may be divided into benign (reactive) and malignant variants, with the malignant variant representing intravascular malignant lymphoma. The reactive variant is rare, with only 16 cases reported in the literature, and is characterized histologically by proliferating endothelial cells within vessel lumina.
In this report we present a case of reactive angioendotheliomatosis and review the literature on this rare entity.
PROGNOSIS AND TREATMENT CHARACTERIZATION
Cutaneous angiosarcoma of the head and neck. A therapeutic dilemma. Morrison WH, Byers RM, Garden AS, Evans HL, Ang KK, Peters LJ.
Department of Radiotherapy, University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA.
Cancer 1995 Jul 15;76(2):319-27 Abstract quoteBACKGROUND. Because of a tendency for diffuse, clinically undetectable local spread, cutaneous angiosarcoma is difficult to treat with surgery alone. Radiation is a rational treatment modality for this disease, because a wide region of dermis can be treated, whereas the underlying normal tissues are spared. METHODS. The authors retrospectively studied 14 patients with dermal angiosarcoma of the head and neck who were treated with electron-beam radiation from 1970 to 1989. Primary tumors were located in the scalp and forehead (11 patients) and in the upper face (3 patients). Eleven patients presented with multiple foci of disease. Three patients were treated with radiotherapy alone; the other 11 were treated with chemotherapy (10 patients) and/or surgery (7 patients). Surgical excisions were limited procedures for patients whose disease readily could be encompassed; total scalp resections were not performed. Patients were irradiated with a multiple-field electron-beam technique. Six patients presented postoperatively for radiotherapy with no macroscopic disease in the treatment field and were given a median dose of 60 Gy (range, 50-66 Gy) over a median of 40 days (range, 37-43 days). Eight patients were irradiated with clinically evident disease; doses ranged from 55 to 75 Gy over a median of 44 days (range, 33-66 days). RESULTS. Five of the six patients irradiated without clinically detectable disease were controlled in the treatment field, but only two are currently disease free. Of the eight patients irradiated with macroscopic tumor, initial disease recurrence occurred in the radiation field in two patients and at the radiation field margin in three patients. The actuarial 5-year control rates above the clavicles for patients irradiated with and without clinical disease were 24% and 40%, respectively (P = 0.03). The 5-year actuarial incidence of distant metastases for all patients was 63%. The 5-year actuarial survival rate for patients irradiated with and without clinical disease was 13% and 50%, respectively (P = .04).
CONCLUSIONS. Radiation is an effective modality for treating local disease, especially when used after surgical resection of macroscopic tumor. Our current strategy is to resect clinically evident tumor in patients presenting with focal, limited disease, and to follow this resection with moderate dose, very wide-field radiation. The survival outcome for patients presenting with diffuse multifocal disease is bleak, but some patients can be controlled infield with radiation. There must be continued efforts to develop effective systemic therapy.
Combined surgical and X-ray treatment for angiosarcoma of the scalp: report of a case with a favourable outcome. Brand CU, Yawalkar N, von Briel C, Hunziker T.
Dermatological and Radio-oncological Clinic, University of Berne, Switzerland.
Br J Dermatol 1996 Apr;134(4):763-5 Abstract quoteClassic angiosarcoma is an uncommon malignant neoplasm of vascular differentiation which is highly aggressive. The diagnosis is often delayed and, since the response to treatment mainly depends on the size of the tumour, the prognosis is usually poor. Here we report a 76-year-old man in whom an extensive angiosarcoma of the scalp was treated by excision followed by wide-field radiotherapy.
More than 4 years later there are no signs of local recurrence or of metastasis.
Successful treatment of angiosarcoma of the scalp by intralesional cytokine therapy and surface irradiation. Ulrich L, Krause M, Brachmann A, Franke I, Gollnick H.
Department of Dermatology and Venereology, Otto von Guericke University, Magdeburg, Germany.
J Eur Acad Dermatol Venereol 2000 Sep;14(5):412-5 Abstract quoteAn 88-year-old woman presented to us with angiosarcoma of the scalp that had developed over a 6-month period following previous trauma. Despite explicit information concerning the extremely malignant potential of the tumour the patient refused any surgical intervention. However, she agreed to receive local, intralesional interferon alpha-2b and interleukin-2 therapy. After partial remission of the tumour, the intralesional cytokine injections were combined with surface radiotherapy. This combination therapy led to a 2-year remission of both the tumour and sonographically suspicious cervical lymph nodes. Apart from the typical, moderate side-effects of interferon alpha-2b and interleukin-2 the therapy was well tolerated.
In conclusion, in our limited experience intralesional cytokine therapy--alone as well as in combination with surface irradiation--seems to be an alternative therapeutic option for patients who is not a candidate for surgery.
Angiosarcoma of the scalp: treatment with liposomal doxorubicin and radiotherapy. Wollina U, Fuller J, Graefe T, Kaatz M, Lopatta E.
Department of Dermatology and Allergology, School of Medicine, Friedrich Schiller University of Jena, Erfurter Strasse 35, 07740 Jena, Germany
J Cancer Res Clin Oncol 2001;127(6):396-9 Abstract quotePURPOSE: Angiosarcoma of the scalp and face is a rare malignant endothelial tumor arising mainly in elderly people. The prognosis is poor. Effective and safe treatments are warranted. METHODS: A 79-year-old woman with an angiosarcoma of the scalp larger than 5 cm in diameter was treated with intravenous liposomal doxorubicin, 20 mg per square meter body surface (i.e., 30 mg) once per month followed by radiotherapy. RESULTS: After 12 infusions of liposomal doxorubicin, we observed a partial remission with a > 50% decrease of affected area and disappearance of ulceration. After 21 infusions, however, there was no further improvement. We decided to discontinue chemotherapy but move on with radiotherapy with an electron beam using fractionated doses of 2 Gy five times per week for up to a total of 40 Gy. To ensure a maximum dose in the upper layer of the dermis a bolus technique was used. Radiotherapy was terminated due to a temporary circumscribed epidermolysis. At the end of treatment a remarkable regression of the cutaneous lesion was noted. During the subsequent 24 months she has not developed any metastatic spread.
CONCLUSION: Sequential therapy of bad prognosis angiosarcoma with liposomal doxorubicin followed by radiotherapy showed a marked clinical improvement and prolonged relapse-free survival in this patient.
Macpherson and Pincus. Clinical Diagnosis and Management by Laboratory Methods. Twentyfirst Edition. WB Saunders. 2006.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fifth Edition. Mosby Elesevier 2008
Learn how a pathologist makes a diagnosis using a microscope
Surgical Pathology Report
Examine an actual biopsy report to understand what each section means
Understand the tools the pathologist utilizes to aid in the diagnosis
How Accurate is My Report?
Pathologists actively oversee every area of the laboratory to ensure your report is accurate
Recent teaching cases and lectures presented in conferences
Last Updated March 13, 2009