A case of Stewart-Treves syndrome. An immunohistochemical and electron-microscopic study

A case of so-called postmastectomy lymphangiosarcoma occurring 14 years after radical mastectomy and radiation therapy for the left mammary carcinoma was studied histologically, electron-microscopically and immunohistochemically. The tumor cells formed cellular areas in the deeper dermis and vascular areas in the upper dermis. The tumor cells had round to spindle-shaped hyperchromatic nuclei and poorly delineated eosinophilic cytoplasm. In an immunohistochemical study for factor VIII relating antigen (F VIII RAG), positive staining was observed in the cytoplasm of some atypical tumor cells lining vascular channels and in that of a few tumor cells in cellular areas. Electron-microscopically, the tumor cells were similar to vascular endothelial cells. In these studies, this tumor appeared to mimic not only lymphatic vessels, but also blood vessels. For these reasons, the authors propose that the term “angiosarcoma” would be better suited than “lymphangiosarcoma”.     

Lymphangiosarcoma arising after 33 years within a background of chronic filariasis: a case report with review of literature

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

Stewart-Treves syndrome: hemangiosarcoma in chronic lymphedema. Ultrastructural analysis of various clinical developmental stages

Ultrastructural studies of angiosarcoma in chronic lymphedema (Stewart-Treves syndrome) at various stages of development show that endothelial cell proliferation originates not in the lymphatic but in the blood capillary vessels. The results indicate that the term "lymphangiosarcoma" is no longer suitable to describe the histopathologic characteristics of Stewart-Treves syndrome.     

Pseudolymphomatous cutaneous angiosarcoma: a report of 2 new cases arising in an unusual setting

Pseudolymphomatous cutaneous angiosarcoma represents a rare, relatively new variant of cutaneous angiosarcoma exhibiting a prominent inflammatory lymphoid infiltrate that can mask the underlying vascular malignant proliferation and mimic a lymphomatous or pseudolymphomatous process. We describe the clinicopathologic characteristics of two new cases of pseudolymphomatous cutaneous angiosarcoma whose originality lies in the unusual setting from which they have arisen. In fact, the first case was an exceedingly lymphocyte‐rich recurrence of a typical epithelioid cutaneous angiosarcoma whose primary lesion that was almost devoid of inflammatory infiltrate underwent surgical excision and radiotherapy while the second one was an unexpected histopathological finding associated with a basal cell carcinoma. Immunohistochemically, most of the lymphocytes expressed immunoreactivity for T‐cell markers, while the neoplastic endothelial lymphatic cells expressed CD31 and CD34. D2‐40 immunoreactivity was observed lining some channels and some neoplastic cells. In the first case a possible relationship between radiotherapy and the pseudolymphomatous reactive pattern is discussed while the second case has been considered as a rare example of collision tumor.     

Angiosarcoma with pseudoepidermotropism in a patient with breast cancer: a mimic of epidermotropic metastatic adenocarcinoma

We report a case of cutaneous postradiation angiosarcoma of the breast exhibiting pseudoepidermotropism that resembled metastatic adenocarcinoma on hematoxylin and eosin. The patient is a 74-year-old woman with history of breast carcinoma treated with mastectomy, chemotherapy, and radiotherapy who complained of an erythematous "rash" along the central portion of the mastectomy scar. Radiography showed widespread osseous metastasis. Biopsy revealed an infiltrative tumor with single file growth and tumor cells obscuring the dermal--epidermal junction in multiple foci, imparting an appearance of epidermotropism. The tumor cells were positive for CD31, CD34, and D2-40 and negative for Cam 5.2. This novel case of pseudoepidermotropic angiosarcoma highlights a potential pitfall in the histomorphologic assessment of poorly differentiated angiosarcoma.     

Retiform hemangioendotheliomas usually do not express D2-40 and VEGFR-3

Retiform hemangioendothelioma (RH) is a rare vascular neoplasm most often occurring in the limbs of middle-aged females. This entity is characterized by infiltrative vascular spaces arranged in a pattern similar to the rete testis. RH differs from angiosarcoma by lacking cytologic atypia and high mitotic rates. This neoplasm frequently recurs but rarely metastasizes. RH tumor cells react with vascular endothelial markers CD31, CD34, and factor VIII-related antigen. A review of the English literature provides only one attempt at staining RH with D2-40, a marker of endothelium of lymphatic vessels, which was negative, and one reported staining of RH with lymphatic endothelial marker VEGFR-3, which was positive. The etiology of RH is unknown. RH has previously been considered closely related to Dabska tumors, which are positive for lymphatic endothelial marker D2-40. We stained 4 RHs with mouse monoclonal antibodies against D2-40 and CD31 and 3 of the 4 RHs with vascular endothelial growth factor receptor 3 (VEGFR-3), to further evaluate whether RH had lymphatic differentiation, in addition to vascular differentiation. Three of the 4 RH biopsies failed to demonstrate D2-40, none expressed VEGFR-3, whereas CD31 was strongly positive, suggesting that RH is a vascular entity which usually does not have lymphatic differentiation, but may rarely express D2-40.     

Immunohistological distribution of stem cell factor and kit receptor in angiosarcoma

Angiosarcoma is a rare neoplasm, originating in the endothelium, which has a poor prognosis because of a high potential for metastasis. Although little is known about the pathogenesis of angiosarcoma, angiogenic cytokines are suggested to play an important role in tumor progression in a paracrine/autocrine fashion. Mast cells contain several mediators or cytokines influencing vascularization. To clarify the role of mast cells in angiosarcoma, mast cells were counted in primary lesions of angiosarcoma (n=7). The results showed that the number of mast cells in the lesional skin of angiosarcoma (91.2+/-14.6/mm2) was significantly increased compared to that in normal skin (30.1+/-4.6/mm2) (p < 0.001). Immunohistological localization of stem cell factor, a mast cell growth factor, demonstrated that stem cell factor-positive cells occurred in the tumors forming the vascular lumen in nodular-type angiosarcoma. In macular angiosarcoma, stem cell factor was also detected in the tumor vascular endothelial cells. Infiltrating mast cells were positive for the kit receptor in both types of angiosarcoma. These results suggest that tumor cell-derived stem cell factor may play a role in the increased number of mast cells, via the kit receptor, which may contribute to the proliferation of tumor cells, leading to the progression of angiosarcoma.     

Pseudolymphomatous cutaneous angiosarcoma: a rare variant of cutaneous angiosarcoma readily mistaken for cutaneous lymphoma

Cutaneous angiosarcoma is probably the most malignant neoplasm involving the skin. Three clinical variants of cutaneous angiosarcoma are recognized, including angiosarcoma of the scalp and face of elderly patients, angiosarcoma associated with chronic lymphedema, and postirradiation angiosarcoma. Histopathologically, these three variants of angiosarcoma show similar features, which consist of poorly circumscribed, irregularly dilated, and anastomosing vascular channels lined by prominent endothelial cells that dissect through the dermis. Focally, neoplastic endothelial cells show large, hyperchromatic, and pleomorphic nuclei, protruding within vascular lumina and creating small papillations. Usually, inflammatory infiltrate is sparse and consists of a patchy, perivascular lymphoid infiltrate around the neoformed vessels. In rare instances, cutaneous angiosarcomas may exhibit prominent inflammatory infiltrate, and the neoplasm may be mistaken for an inflammatory process, both from clinical and histopathologic points of view. We describe four examples of cutaneous angiosarcomas with dense lymphocytic infiltrates involving the neoplasm. Immunohistochemically, lymphocytes expressed immunoreactivity for CD3, CD5, and CD45 markers, whereas the germinal centers were positive for CD20, CD79a, and Bcl-6. The neoplastic endothelial cells expressed immunoreactivity for the CD31, CD34, podoplanin, Prox-1, Lyve-1, and D2-40. We discuss the possible relationship between neoplastic endothelial lymphatic cells and reactive lymphocytes. Cutaneous angiosarcoma with prominent lymphocytic infiltrate may be readily mistaken for cutaneous follicle center cell lymphoma or cutaneous pseudolymphoma.     

Successful radiotherapy of facial angiosarcoma

Cutaneous angiosarcoma of the face and scalp is a rare malignant vascular tumor that affects mostly Caucasian elderly males. At present, connections concerning the etiology of this neoplasm with radiation therapy, exposure to environmental carcinogens and chronic lymphedema have been described. Due to the difficult histologic evaluation, high local recurrence and tendency to early metastasing, angiosarcoma poses generally a very poor prognosis. We report the case of an 80-year-old patient who experienced successful removal of large, exophytic growing angiosarcoma of the face achieved with radiotherapy with long-term relapse-free survival.     

Prognostic value of Ki-67, CD31 and epidermal growth factor receptor expression in basal cell carcinoma

Recurrence of basal cell carcinoma following treatment is common, and the majority of recurrences appear in the first 3 years. We examined the original tumors of 26 basal cell carcinoma cases, 14 of whom had a recurrence after an average of 3.7 years, and 12 of whom had no recurrence during an average of 4.4 years follow-up. Using immunohistochemistry, we tested for Ki-67, CD31 and epidermal growth factor receptor expressions in the tumor tissue. The percentages of expression for Ki-67, CD31 and epidermal growth factor receptor were significantly higher in the recurrent tumors than in the non-recurrent ones. Expression of Ki-67 and CD31 was 271.57 +/- 17.91 and 58.1 +/- 9.37 for the recurrent group and 187.08 +/- 21.48 and 23.9 +/- 5.45 for non-recurrent group respectively (p<0.0001; p<0.0001). Expression of epidermal growth factor receptor was positive in all basal cell carcinoma cells. The staining intensity was strong in 57% of recurrent and 8.3% of non-recurrent tumors (p=0.014). These results show that Ki-67, CD31 and epidermal growth factor receptor expression differ between basal cell carcinomas which later recur and those that do not recur.     

Cutaneous granular cell angiosarcoma

The majority of cutaneous angiosarcomas display typical architectural features of irregular anastomosing vascular channels in the dermis and subcutis. Nuclei are usually hyperchromatic and pleomorphic but die volume of cytoplasm of the neoplastic cells is often small. Diagnosis can be made readily on an adequate biopsy. We recently experienced difficulty diagnosing an angiosarcoma composed predominantly of cells with abundant granular cytoplasm. We were able to compare the present case with sections obtained from the only other reported example. The architectural expression of an anastomosing vascular pattern in areas of tumor, combined with the positive staining for Factor VIII-related antigen (FVIIIRAg) and Ulex europaeus agglutinin-1 (UEA1) enabled us to make a diagnosis of angiosarcoma. The tumor failed to stain for the other endothelial markers (CD31 and CD34) which were positive in the original case. A marker for lysosomes (CD68) stained the granules in both cases. The granular cell variant of cutaneous angiosarcoma is very rare. Diagnosis is possible by recognizing the typical anastomosing neoplastic vascular channels at the periphery of the lesion, and by use of a combination of lectin (UEA1) and immunohistochemical (FVIIIRAg, CD34 and CD31) endothelial markers.     

皮肤血管肉瘤

皮肤血管肉瘤是一种来源于血管或淋巴管内皮细胞的恶性软组织肉瘤.该病罕见,常发生于老年人头面部,其他部位则多与放疗或慢性淋巴水肿有关.该病临床表现和组织学形态多变,容易误诊.治疗方面,该病具有高度侵袭性,容易复发和转移,且发病机制不清,目前尚缺乏有效的治疗方式.对于早期患者,手术联合放疗为主要的治疗方式.对于局部进展和发生转移的患者,目前多采用细胞毒化疗.然而,患者的长期预后依然不理想.近年来,有部分学者开始研究该病的分子机制,并探索相关的靶向治疗.     

老年人头面部血管肉瘤七例分析

【摘要】 目的 探讨血管肉瘤的临床特点及疗效。 方法 回顾性分析2004年1月至2012年3月收治的血管肉瘤患者的临床资料,对肿瘤的临床表现、治疗方法和结果进行观察。结果 7例患者,男4例,女3例,中位年龄67岁（37 ~ 77岁）。7例患者中,不规则结节样肿块伴破溃4例,局部溃疡1例,红色不规则结节2例。入院后均予手术治疗,部分患者予术后辅助治疗。术后组织病理见肿瘤细胞分化程度不同,有异形,内皮细胞明显增生,均诊断为头皮原发的血管肉瘤。免疫组化：CD31、CD34均阳性。术后4例复发,首次复发中位时间为3.5个月（1 ~ 6个月）,1例5个月后发现脑组织转移,2例死亡。结论 血管肉瘤是少见的恶性肿瘤,临床表现多变,局部广泛切除为治疗的基础,辅助治疗对改善其预后起到积极的作用。     

Primary cutaneous anaplastic large cell lymphoma with intralymphatic involvement associated with chronic lymphedema

Chronic lymphedema predisposes to develop malignant cutaneous tumors, including angiosarcoma, Kaposi's sarcoma and B‐cell lymphoma. T‐cell malignancy has rarely been associated with chronic lymph stasis. Here, we report a case of primary cutaneous anaplastic large cell lymphoma (pcALCL) with lymphatic spread associated with chronic lymphedema. The patient is a 56‐year‐old man who received orchiectomy and right inguinal lymphadenectomy for malignant seminoma 10 years ago, which led to prominent lymphedema of the right leg. He developed extensive skin nodules on the lymphedematous area for 3 months. Histopathology findings confirmed a diagnosis of pcALCL, which is a subtype of cutaneous T‐cell lymphoma characterized by the presence of CD30+ T cells. Intralymphatic infiltration of malignant cells is prominent. The pathogenesis of intralymphatic cutaneous anaplastic large cell lymphoma is largely unknown. Our case suggests that chronic lymphedema resulted in persistent CD4+ T‐cell inflammation, which then may contribute to the development of pcALCL.     

Cardiac epithelioid angiosarcoma presenting as cutaneous metastases

BACKGROUND: Cardiac angiosarcoma is a rare tumor that has a predilection for middle-aged males and a marked predominance in the right atrium. The tumor may present abruptly with a fulminant clinical course. Initial presentation with metastatic disease is rare. Only one case has been reported of a patient who presented with cutaneous metastases. METHODS AND RESULTS: We here report the case of a 51-year-old man who initially presented with cutaneous metastases in the absence of cardiac symptoms. The skin biopsy was diagnosed as metastatic undifferentiated sarcoma. The patient died 26 days later with widely disseminated disease. At autopsy a tumor arising in the wall of the left atrium and in the interatrial septum was found. After an immunohistochemical study including CD31 and CD34 stains the diagnosis of cardiac pure epithelioid angiosarcoma was made. To the best of our knowledge this tumor variant has not been documented in the heart until now. CONCLUSION: Although cardiac angiosarcoma is a rare neoplasm, its presence should be suspected in patients with cutaneous metastatic angiosarcoma without an evident source of the tumor, even in absence of cardiac symptoms.     

老年人足部血管肉瘤

报告1例老年人足部血管肉瘤.患者男,73岁.双足部出现多发性紫红色丘疹、结节和斑块2个月.组织病理检查示肿瘤位于真皮全层,瘤组织内有大量增生的血管,管腔不规则,免疫组化染色示瘤细胞CD31(+),CD34(+),Ⅷ因子相关抗原(一).诊断为血管肉瘤.     

Cutaneous angiosarcoma of the leg showing radiation sensitivity

We report a case of cutaneous angiosarcoma occurring on the leg of a 97-year-old Japanese woman. Considering the patient's age and general condition, she was treated with electron beam irradiation, which led to the almost complete disappearance of the tumour. Because cutaneous angiosarcoma is an aggressive tumour with a high propensity for local recurrence and distant metastases, therapy preferably involves a multimodal approach. However, monotherapy with radiation may be effective in some cases of cutaneous angiosarcoma.     

The antiangiogenic agents TNP-470 and 2-methoxyestradiol inhibit the growth of angiosarcoma in mice

Background: Endothelial malignancies, such as angiosarcoma and hemangioendothelioma, are often resistant to chemotherapy and surgery, and may result in death. Improved means of therapy are needed for these disorders. Objective: We wanted to determine whether angiosarcoma can be treated with angiogenesis inhibitors in mice. Methods: Mice were inoculated with a cell line that gives rise to angiosarcoma and were treated with the angiogenesis inhibitors 2-methoxyestradiol and TNP-470. Response to therapy was monitored by measurement of tumors. Results: TNP-470 caused an 84% reduction in tumor size, and 2-methoxyestradiol caused a 68% reduction in tumor size. Conclusion: Angiogenesis inhibitors are highly effective in treatment of angiosarcoma in mice. Clinical trials of these agents in humans with angiosarcoma and hemangioendothelioma are warranted. (J Am Acad Dermatol 1999;40:925-9.)     

Cutaneous angiosarcoma: a case series with prognostic correlation

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 (i.e., age, sex, location), histologic attributes (i.e., depth of invasion, tumor necrosis, tumor cell morphology, margin status, mitoses), and follow-up data (i.e., 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.     

Pseudoangiosarcomatous squamous cell carcinoma of skin arising adjacent to decubitus ulcers

Pseudoangiosarcomatous, or pseudovascular, squamous cell carcinoma of skin is an unusual form of acantholytic (adenoid, pseudoglandular) squamous cell carcinoma that mimics the histolopathologic appearance of angiosarcoma. We report a case of pseudoangiosarcomatous squamous cell carcinoma arising adjacent to decubitus ulcers. The histopathologic examination of a wedge biopsy specimen revealed infiltrative cords of neoplastic cells that formed interanastomosing channels imitating angiosarcoma. Immunohistochemical staining was negative for the endothelial markers (CD31, CD34, and factor VIII-related antigen) and positive using cytokeratin antibodies (AE1/AE3 and 34 betaE12). Because of metastatic disease, palliative measures were undertaken and the patient died four months later. To our knowledge, our patient is the first with pseudoangiosarcomatous squamous cell carcinoma of skin developing within decubitus ulcer.