Stewart-Treves syndrome in an older woman successfully treated by metronomic chemotherapy: case report and literature survey.

The authors present the case of a 94-year-old woman suffering from a right arm angiosarcoma developed after primary breast cancer and treated with success by oral metronomic chemotherapy based on daily low doses of cyclophosphamide and prednisone. The case description is followed by a short review of actual knowledge on the subject.

Secondary angiosarcoma: A fatal complication of chronic lymphedema.

Secondary Angiosarcoma (Stewart-Treves Syndrome) is a rare malignant cutaneous lesion, which arises in chronic lymphedema of the extremity, often observed after breast cancer treatment. We reviewed the history and the oncological outcome of two patients with this disease. Multimodal therapy including hyperthermic isolated limb perfusion with TNF-alpha and Melphalan, combined with radical resection of the affected skin and subcutaneous tissue including the fascia, with large safety margins may probably lead to better survival.

Successful management of lymphangiosarcoma in a puppy using a tyrosine kinase inhibitor.

A puppy was diagnosed with lymphangiosarcoma associated with lymphedema based on lymphography and histopathology. The lesions resolved after toceranib therapy, and the dog remains in remission 1 year later. This is the first report of a successful outcome following oral toceranib as first-line therapy for lymphangiosarcoma in a dog.

Gestion réussie d'un lymphangiosarcome chez un chiot à l'aide d'un inhibiteur de la tyrosinekinase. Un chiot a été diagnostiqué avec un lymphangiosarcome associé à un lymphoedème en se basant sur une lymphographie et l'histopathologie. Les lésions se sont résorbées après un traitement au tocéranib et le chien demeurait en rémission un an plus tard. Il s'agit du premier rapport d'un résultat favorable après le recours au tocéranib oral comme traitement de premier recours pour le lymphangiosarcome chez un chien.(Traduit par Isabelle Vallières).

Constitutive Activation of mTORC1 in Endothelial Cells Leads to the Development and Progression of Lymphangiosarcoma through VEGF Autocrine Signaling.

Angiosarcoma/lymphangiosarcoma is a rare malignancy with poor prognosis. We generated a mouse model with inducible endothelial-cell-specific deletion of Tsc1 to examine mTORC1 signaling in lymphangiosarcoma. Tsc1 loss increased retinal angiogenesis in neonates and led to endothelial proliferative lesions from vascular malformations to vascular tumors in adult mice. Sustained mTORC1 signaling was required for lymphangiosarcoma development and maintenance. Increased VEGF expression in tumor cells was seen, and blocking autocrine VEGF signaling abolished vascular tumor development and growth. We also found significant correlations between mTORC1 activation and VEGF, HIF1α, and c-Myc expression in human angiosarcoma samples. These studies demonstrated critical mechanisms of aberrant mTORC1 activation in lymphangiosarcoma and validate the mice as a valuable model for further study.

A novel approach to treatment of lymphangiosarcoma in a boxer dog.

A five-year-old female boxer presented with a swelling in the area of the caudal mammary gland. The mass was surgically excised and histopathological examination revealed a poorly demarcated lesion, extending into mammary tissue and infiltrating the sinuses of adjacent lymph nodes. The diagnosis was lymphangiosarcoma. Full blood work, thoracic radiographs, abdominal and scar ultrasound were unremarkable, apart from possible inflammatory reactions in the latter and reactive/metastatic changes in inguinal lymph nodes. Doxorubicin treatment resulted in a 6-month recurrence free interval. At relapse, the dog was treated with metronomic chemotherapy using chlorambucil and meloxicam, which failed to adequately control the disease. Toceranib phosphate was introduced and resulted in almost complete regression of the mass, leaving just a skin plaque. To the authors' knowledge this is the first report describing the use of two novel therapeutic approaches to treat canine lymphangiosarcoma that resulted in a higher than previously described survival time.

Stewart-Treves syndrome angiosarcoma expresses phenotypes of both blood and lymphatic capillaries.

BACKGROUND: The development of angiosarcoma in oedematous tissue is referred to as Stewart-Treves syndrome (STS). This rare and fatal complication is associated with chronic post mastectomy lymphoedema and radiotherapy for breast cancer. Angiosarcoma spread is facilitated by the formation of blood vessels (angiogenesis) and lymph vessels (lymphangiogenesis). In the future antiangiogenic therapy may improve the poor outcome of current treatments. There was evidence that blocking the angiogenenesis would inhibit progression of angiosarcoma. It seems reasonable to hypothesize that blocking the lymphangiogenesis may yield similar results. Although angiosarcomas commonly derive from blood vessels, in case of STS angiosarcomas chronic lymphoedema may suggest its lymphatic origin. The goal of this study was to visualize interstitial space and lymphatics in the central and peripheral regions of STS angiosarcoma. METHODS: On tissue samples obtained from STS angiosarcoma we have performed: first colour stereoscopic lymphography to visualise the morphology of lymphatic vessels and extracellular spaces, second immunohistochemical staining specific for lymphatic vessels endothelium (LYVE-1) and blood endothelial cells (CD31, factor VIII) and prolymphangiogenic vascular endothelial growth factor (VEGF-C) for precise identification of lymphatic endothelia. STS angiosarcoma morphology was assessed by comparison of pictures obtained on lymphography, microscopy and confocal microscopy. RESULTS: STS angiosarcomas present heterogenous morphology with areas dominated by hemangiosarcoma and lymphangiosarcoma structures. STS angiosarcoma expressed phenotypes of both blood and lymphatic endothelia. LYVE-1 and VEGF-C is expressed by STS angiosarcoma and may be used to discriminate tumour differentiation. Morphology of lymphatic vessels and spaces in the tumour suggest absence of their normal lymphatic function. CONCLUSIONS: Our results confirmed both hemangio- and lymphangiogenic origin of STS angiosarcoma. Expression of VEGF-C makes STS angiosarcoma a good candidate for targeted antilymphangiogenic therapy. However, morphology of intratumoral lymphatics on colour lymphography suggested their impaired function, which can hamper drug distribution.

Use of surgery and mitoxantrone chemotherapy in a dog with disseminated lymphangiosarcoma.

CASE DESCRIPTION: A 5-year-old sexually intact male Giant Schnauzer was evaluated because of difficulty breathing and left pelvic limb swelling. Eighteen months previously, the patient had had intermittent left pelvic limb swelling, but the owner declined further testing at that time. CLINICAL FINDINGS: Physical examination revealed severe pitting edema of the left pelvic limb and prepuce and muffled heart sounds on thoracic auscultation. Results of thoracic radiography and thoracocentesis were consistent with chylothorax, and CT imaging of the thorax and abdomen revealed a mass involving the whole left sublumbar area. TREATMENT AND OUTCOME: In an attempt to treat the chylothorax, pleural omentalization and pericardectomy were performed. Histologic evaluation of several biopsy specimens harvested in the abdominal and thoracic cavities revealed disseminated lymphangiosarcoma. The patient recovered well from surgery, and mitoxantrone chemotherapy was administered. As of 10 months after surgery, the dog was clinically normal except for mild pelvic limb edema. CLINICAL RELEVANCE: The combination of clinical signs, multiple imaging features, surgical findings, and histologic examination findings enabled the final diagnosis of lymphangiosarcoma. Clinical management that included medical and surgical treatments and chemotherapy resulted in improved quality of life and extended survival time in a dog with metastatic lymphangiosarcoma.

Lymphangiosarcoma complicating extensive congenital mixed vascular malformations.

Pediatric hepatic angiosarcoma is a very rare malignant vascular tumor. A few cases have shown pediatric hepatic angiosarcoma occurring on a background of preexisting vascular lesions. We report the case of a newborn girl who presented extensive limbs and upper trunk cutaneous mixed vascular malformations at birth. These malformations were associated with thrombocytopenia. Cutaneous biopsies revealed complex vascular malformations with a significant lymphatic component. Compressive body suit therapy led to regression of the limbs' cutaneous vascular malformations. At the age of 9 months, the patient presented multiple heterogeneous hepatosplenic nodules. Aggressive treatment with prednisone, vincristine, and hepatosplenic embolizations resulted in initial improvement of the hepatosplenic lesions for few months, followed by an increase of the lesions with failure of response to treatment despite adding alpha-interferon-2b to treatment. The patient died at the age of 19 months. The autopsy's pathological examination revealed a hepatic-based angiosarcoma with plurimetastatic dissemination to the spleen, lungs, peritoneum, pleura, mesenteric linings as well as the serosa of the stomach and small intestine. Multiple cutaneous and visceral complex capillaro-lymphatico-venous malformations were also identified. We hypothesize that these multiple extensive mixed vascular malformations were associated with chronic lymphedema which probably predisposed to the development of the angiosarcoma in our patient.

[Lymphangiosarcoma treated with liposomal doxorubicin (Caelyx)]. / Lymphangiosarcome traité par doxorubicine liposomale (Caelyx).

BACKGROUND: Lymphangiosarcoma is a highly malignant tumor with a poor prognosis. Anthracyclines constitute the form of chemotherapy most commonly used in these patients. Unfortunately, they are poorly tolerated. We report a case of lymphangiosarcoma in an elderly woman with good response to liposomal doxorubicin, an anthracycline with lower toxicity. CASE REPORT: A 70 year-old-woman with a previous history of post-mastectomy lymphedema presented a painful and bleeding lymphangiosarcoma on the arm and the chest. Because of the wide extent of the tumor, surgery was not performed. The patient was treated with liposomal doxorubicin 50 mg/m2. Marked tumor regression was observed after the first course of chemotherapy. After 5 courses, 90% regression of tumor mass was seen. Pain and bleeding also stopped. Two months after the final course of liposomal doxorubicin, relapse occurred and the patient died. DISCUSSION: A dramatic response to liposomal doxorubicin was noted in the present case, as previously reported in a patient with an angiosarcoma of the scalp. Liposomal doxorubicin could be considered for the treatment of lymphangiosarcoma, particularly in elderly patients.

Lymphangiosarcoma in a dog treated with surgery and chemotherapy.

A large subcutaneous mass at the left cervical site in a 9-year-old male Siberian husky was removed surgically. Histopathologically, the mass was mainly consisted of a proliferation of spindle-shaped neoplastic cells arranging in solid sheath and partially vascular channels containing few blood cells. The tumor cells exhibited highly invasive activity to the surrounding tissues. In addition, the tumor cells were immunopositive for Factor VIII-related antigen. On the basis of these findings, the tumor was diagnosed as lymphangiosarcoma. Recurrent mass was noticed 3 weeks after surgery but completely disappeared after the doxorubicin treatment. Neither recurrence nor metastasis was observed for 9 months after the remission.

Isolated limb perfusion with tumor necrosis factor and melphalan for nonresectable sSewart-Treves lymphangiosarcoma.

BACKGROUND: Cutaneous Stewart-Treves lymphangiosarcomas represent a rare group of tumors characterized by a high grade of vascularization and by localization in an extremity with lymphedema. The multifocality and the localization makes these tumors eligible for treatment with isolated limb perfusion (ILP). ILP with tumor necrosis factor (TNF) and melphalan is a safe and highly effective procedure that can achieve limb salvage in >or=80% of all patients with nonresectable extremity soft tissue sarcoma or melanoma. METHODS: In 10 patients with multifocal Stewart-Treves lymphangiosarcoma of the extremities, 16 ILPs with TNF plus melphalan were performed. All patients would have been candidates for exarticulation of the extremity. RESULTS: We observed an 87% overall response rate (complete and partial responses); one patient had a mixed response, and one patient did not respond to the therapy. In nine perfusions (56%), a complete response was achieved, and five perfusions (31%) resulted in a partial response. Limb salvage was achieved in eight patients (80%), with a mean follow-up duration of 34.8 months (range, 3 to >or=115 months). Regional toxicity was limited and systemic toxicity minimal to moderate, with no toxic deaths. CONCLUSIONS: Multifocal Stewart-Treves lymphangiosarcomas in extremities with chronic lymphedema can be successfully treated by ILP with TNF and melphalan.

Intra-arterial mitoxantrone and paclitaxel in a patient with Stewart-Treves syndrome: selection of chemotherapy by an ex vivo ATP-based chemosensitivity assay.

We report on a 72-year-old patient developing Stewart-Treves syndrome (STS) of the right arm 9 years after curative irradiation for ipsilateral stage III breast cancer. Facing the poor track record of both irradiation and chemotherapy in this highly malignant lymphangiosarcoma, amputation was recommended but refused by the patient. Therefore, limb conserving-therapy using three courses of intra-arterial mitoxantrone (MX) and paclitaxel (PTX) was attempted. This novel chemotherapy protocol was selected by pretherapeutic ex vivo ATP-based chemosensitivity testing of autologous tumor tissue. The patient experienced complete response, which was subsequent histologically confirmed by compartment resection. When developing recurrent STS outside of the perfused area 6 months after primary therapy, the patient was retested and reinduced with three other courses of intraarterial MX/PTX which again produced durable complete remission. This case demonstrates the benefit of indivdualized therapy in this prognostically desperate disease allowing both limb conservation and maintained quality of life.

Stewart-Treves syndrome: lymphangiosarcoma following mastectomy.

Lymphangiosarcoma (LAS) is an aggressive, malignant vascular tumor following long-lasting chronic lymphedema. Patients with LAS demonstrate a history of breast cancer treated by radical mastectomy in the majority of patients. In the 1960s the incidence of LAS in patients with a 5-year survival after radical mastectomy varied from 0.07 to 0.45%. Today, due to changes in the operative techniques of breast cancer, less chronic lymphedema is seen with only a scant number of LAS patients. The etiology of this enigmatic tumor is not yet completely understood. Histologically, LAS arises from vascular endotheliocytes, and all vascular sarcomas originating in the setting of a chronic lymphedema are categorized as LAS. There is no standard treatment of LAS. The treatment options include radical ablative surgery, radiation therapy, and chemotherapy. The prognosis of LAS is poor; long-term survival is the exception. Only early recognition and radical surgery offer a chance of cure.