Angiosarcoma. A rare secondary malignancy after breast cancer treatment

Life-saving mastectomy and radiation therapy are established in the treatment of early stage breast cancer. Angiosarcoma, i.e. malignant angioendothelioma, is a rare tumor which can develop after several years of such treatment. The number of post-operative and post-irradiation angiosarcomas has increased in recent years. We report four cases of angiosarcoma which occurred after treatment of breast cancer and review the literature. In two of these cases the angiosarcoma developed on the irradiated breast skin after partial mastectomy and radiation therapy, in the other two cases the angiosarcoma appeared on a chronically edematous arm after radical mastectomy and radiation therapy.     

Angiosarcoma in an irradiated breast: a case description

Post-radiotherapy cutaneous angiosarcomas have been described in different locations, including the breast. We present a case of cutaneous angiosarcoma of the breast, diagnosed 6 years after a carcinoma of the breast had been treated with radiation. The patient was a 44-year-old female with a history of ductal carcinoma (CA) of the right breast treated with tumorectomy, axillary lymphadenectomy, chemotherapy (FEC) and radiotherapy, who 6 years later presented with a violaceous, indurated plaque with a satellite nodule on the same breast. The histology of the skin biopsies showed angiomatous proliferation throughout the entire dermis, with no cellular atypia. Considering the patient's symptoms, history and the changes observed via mammography, it was decided to completely excise the lesion followed by a simple mastectomy, with the diagnosis of angiosarcoma being confirmed. The patient was later treated with paclitaxel, and the disease was apparently controlled. Despite this fact, two years and one month later, the angiosarcoma recurred on the internal area of the mastectomy scar. The patient was treated with paclitaxel, and surgical excision of the lesion area was once again performed. This complication usually appears 5-10 years after treatment with radiotherapy, so angiosarcoma should be ruled out if any angiomatous lesions later appear on skin that had been irradiated.     

Angiosarcoma in chronic lymphedema

Angiosarcoma that develops on a limb with chronic lymphedema is called Stewart-Treves syndrome. This typically appears as a complication of a long course lymphedema located on the arm, after mastectomy and/or radiotherapy due to breast cancer. There are cases of Stewart-Treves syndrome in chronic lymphedema in the upper limb contralateral to the breast treated for cancer and in chronic lymphedema of the leg. We present two cases of this syndrome. The first corresponds to a typical syndrome of Stewart-Treves in an 83-year-old woman who was diagnosed of angiosarcoma in a chronic lymphedema territory secondary to mastectomy and radiotherapy due to breast cancer. The second case is much rarer, since it is a case of diffuse angiosarcoma of the leg in a 42-year-old man with a history of lymphedema. Due to the aggressive nature of this syndrome, knowledge and research on its treatment are necessary.     

Cutaneous breast angiosarcoma after conserving treatment of breast cancer.

Cutaneous angiosarcoma is a rare malignancy that sometimes occurs as a late sequela of breast conservation therapy. We report on a 79-year-old female who developed well-differentiated angiosarcoma in a lymphedematous left breast 5.5 years after surgery and radiotherapy for early invasive ductal breast cancer. The initial appearance was very similar to late radiation dermatitis, and histologically interpreted as scar tissue with atypical vascular lesion. The lesion progressed further, and was clinically suspicious for angiosarcoma. Thus, a second biopsy was taken which confirmed the diagnosis. A complete mastectomy removed all the tumor with clear margins. However, within a period of 16 months she presented four local recurrences which were treated by wide local excision. At present, the patient is free of locally recurrent tumour for 7 months. The few cases of breast angiosarcoma after breast conservation therapy reported so far demonstrate that these lesions are difficult to diagnose due to their rarity and their highly variable and benign appearance, which sometimes may mimic radiation-induced cutaneous changes. Since chronic lymphedema possibly contributes to the development of angiosarcoma, long-term clinical surveillance of these patients is recommended. Biopsies should be taken if new skin lesions occur.     

Acquired progressive lymphangioma of the skin following radiotherapy for breast carcinoma

A case of a vascular tumor clinically and pathologically consistent with acquired progressive lymphangioma (benign lymphangioendothelioma) in a 48-year-old woman is reported. The lesion appeared in the skin close to a mastectomy scar 3 years after surgery and radiotherapy for invasive ductal carcinoma. On histologic examination, it mimicked an aggressive vascular neoplasm because of its infiltrative pattern. However, follow-up studies confirmed the benign nature of the lesion, clinically and histologically. This case indicates that acquired progressive lymphangioma may follow radiotherapy and must be considered in the differential diagnosis of other vascular proliferations occurring in the skin of the breast, especially of low-grade postradiation angiosarcoma, a recently described neoplastic entity.     

Radiotherapy in multilocalized lymphedema-associated angiosarcoma

We report an 80-year-old woman, suffering from a recurrence of a multilocalized lymphedema-associated angiosarcoma of the right arm. The tumor consisted of solid tumor cell formations and "classical" spongiform tumor complexes. In the tumor periphery, pathological endothelial cell proliferates on pre-existing dilated lymphatic capillaries were detectable, which, together with immunohistology (CD 31+/Desmoplakin-1-2.17+/CD 34-), supported the diagnosis of lymphangiosarcoma. Complete remission was achieved under radioimmunotherapy (54 Gy/Interferon beta). A further recurrence 3 months later outside the primary therapy fields was successfully treated with radiotherapy alone. During a follow-up observation period of 3 years, there was neither local recurrence nor metastasis. This case demonstrates for the first time the long-lasting efficacy of photon radiation in a case of histologically-defined lymphangiosarcoma. Further studies should elucidate the suitability of radio monotherapy as first-line therapy in lymphedema-associated angiosarcoma with lymphatic endothelium-like immunohistology.     

An "anaplastic" Kaposi's sarcoma mimicking a Stewart-Treves syndrome. A case report and a review of literature

Cutaneous angiosarcoma (AGS) developing in a lymphedematous arm, after lymphadenectomy in the context of breast cancer, is the definition of the classical Stewart-Treves syndrome. Like AGS, many tumors such as Kaposi's sarcoma (KS) could develop in chronic lymphedema. We describe the case of a 50-year-old woman who presented with several nodules on the left lymphedematous arm evocative of a Stewart-Treves syndrome, 2 years after a left mastectomy and a homolateral lymphadenectomy. The histological examination revealed an atypical vascular proliferation suggesting AGS, but endothelial atypical cells nuclei were strongly stained by herpes human virus 8 antibody. The final diagnosis was an "anaplastic" KS mimicking a Stewart-Treves syndrome. The total regression of the lesion was obtained by elastic contention and intradermic liposomal doxorubicin. "Anaplastic" KS is a rare histological form of nodular KS, which mimics a cutaneous AGS but classically expresses herpes human virus 8. It is essential to know about this entity, particularly in a lymphedematous arm, to avoid aggressive treatment such as amputation.     

Chronic lymphoedema and angiosarcoma

Angiosarcoma has frequently been described arising within chronic lymphoedema of the upper limb following mastectomy and radiotherapy for carcinoma of the breast. We report a case of angiosarcoma arising in a lymphoedematous leg that had been subjected to radiotherapy 20 years previously for Hodgkin's disease. The diagnosis was expedited once the patient noticed the development of bleeding nodules. Prognosis of angiosarcoma is poor with treatment options being wide-excision surgery, palliative radiotherapy or chemotherapy. Unusual bruised areas or bleeding nodules developing within chronic lymphoedematous limbs should be biopsied to exclude the diagnosis.     

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.     

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.     

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.     

Two cases of Kaposi's sarcoma mimicking Stewart-Treves syndrome found to be human herpesvirus-8 positive.

Although angiosarcoma is the most frequent tumor arising in the clinical setting of chronic lymphedema, as in Stewart-Treves syndrome, Kaposi's sarcoma has also been reported in this setting, although rarely. We describe two women who developed Kaposi's sarcoma in the lymphedematous arm many years after surgery for breast cancer. Case 1 is a 92-year-old and Case 2 is an 81-year-old; they underwent left total mastectomy and axillary node dissection for infiltrating breast carcinoma in 1981 and 1982 respectively. At that time, neither patient received further treatment. Except for persistent lymphedema, both women did well until over fourteen years later when each noted the development of several purple asymptomatic plaques on the edematous arm. In both, the clinical diagnosis at the time of biopsy was angiosarcoma. However, histologic findings in both cases were typical for Kaposi's sarcoma. In addition, a nested polymerase chain reaction (PCR) for the detection of a 233bp segment of KSHV/HHV8 was performed on DNA extracted from the paraffin-embedded specimens and both cases were positive for this sequence. Histologic sections of both cases were also tested for KSHV by in situ hybridization and demonstrated a positive signal in the lesional cells in each case.     

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.     

Stewart-Treves syndrome

A Stewart-Treves angiosarcoma (Stewart-Treves syndrome) developed 14 years after mastectomy (Halsted) and radiotherapy for breast cancer in a woman now 56 years old. Limited excision, graft and complementary radiotherapy have controlled the disease for 20 months. The microscopical and ultrastructural features of this angiosarcoma are presented and the last advances in immunopathology briefly commented.     

Epithelioid angiosarcoma of the breast involving the skin: a highly aggressive neoplasm readily mistaken for mammary carcinoma

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.     

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.     

Angiosarcoma of the abdominal wall after dermolipectomy in a morbidly obese man. A rare form of presentation of Stewart-Treves syndrome

Angiosarcoma is a rare malignant tumor, with a predilection for skin in the head and neck region, although it has been described in many other locations. Its association with chronic lymphedema is well known, mainly in the setting of postmastectomy lymphedema of the arm in breast cancer patients (termed Stewart-Treves syndrome). However, angiosarcoma can appear in lower limbs with chronic lymphedema and rarely in other locations such as the abdominal wall. Herein, we present a unique case of angiosarcoma developing in the abdominal wall of a morbidly obese patient after extensive dermolipectomy.     

Angiosarcoma after conservation treatment for breast carcinoma: our experience and a review of the literature

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.     

Intravascular histiocytosis: case report of a rare disease probably associated with silicone breast implant

Intravascular histiocytosis is a rare condition characterized by the aggregate of histiocytes within dilated dermal vessels. The diagnosis is mainly histophatological and immunohistochemical. We describe a case of a 55 year-old female patient presenting erythematous/purple patches on the breasts, back and limbs. She previously presented ductal carcinoma in the right breast in 2006 which was treated with mastectomy and proceeded to silicone breast implant in 2009. Clinical hypothesis was telangiectatic metastatic carcinoma. Histopathology showed vascular ectasia, thrombosis and recanalization of upper dermis small vessels. On immunohistochemistry, intravascular cells were CD 68+ and negative for estrogen and progesterone receptors, CK7, EMA and AE1/AE3 and endothelial cells were CD64+, leading to the diagnosis of intravascular histiocytosis.