Lower Extremity Angiosarcoma: A Life-Threatening Complication of Lymphedema.

ABSTRACT: When angiosarcoma, a rare and aggressive tumor of the soft tissue, develops in the setting of chronic lymphedema, it is referred to as Stewart-Treves syndrome. It is usually seen in chronic lymphedema of the upper limbs postmastectomy. Angiosarcoma developing in the lower limb in the setting of chronic lymphedema is rare and has a poor outcome. The presentation of angiosarcoma can vary, ranging from a bleeding papule to a plaque or a subcutaneous mass, which can later progress to ulceration or necrosis. Treatment for Stewart-Treves syndrome is aggressive because of its poor prognosis and usually requires a multidisciplinary approach of surgery, radiation, and chemotherapy. Several theories have been put forth to explain the mechanism of Stewart-Treves syndrome, but it remains ambiguous. The current literature regarding angiosarcoma developing in the setting of chronic lymphedema in the lower limb is limited to single case reports. Herein, the authors report a series of six cases of biopsy-proven angiosarcoma in the setting of lower extremity lymphedema. Providers should include angiosarcoma in the differential diagnosis of ulcerative or vascular tumors arising in the context of lower extremity lymphedema.

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.

Angiosarcoma arising from congenital primary lymphedema.

We herein report the case of a 3-year-old girl with atypical congenital right upper limb lymphedema who developed an angiosarcoma. Only a few cases have been reported following congenital form of lymphedema and only 4 in such a young child. We also summarize all cases of angiosarcoma associated with congenital lymphedema reported in the literature.

Presumed primary ocular lymphangiosarcoma with metastasis in a miniature horse.

A 7-year-old, 153.0-kg American Miniature mare presented for evaluation of keratoconjunctivitis of the right eye (OD). A superior palpebral conjunctival mass and stromal keratitis were diagnosed. The incisional biopsy diagnosis was a presumptive corneal hemangiosarcoma. Transpalpebral enucleation was performed, and histopathologic evaluation confirmed angiosarcoma of the conjunctiva, cornea, and extraocular muscles. The horse developed progressive epistaxis and orbital swelling following surgery. A systemic workup was performed 3 months after enucleation, revealing regrowth within the orbit and marked cranial cervical lymphomegaly, suggestive of metastasis. Humane euthanasia was performed, and necropsy confirmed a locally invasive periorbital tumor with metastasis to the submandibular tissue, submandibular lymph node, and thoracic inlet. Histopathologic evaluation of necropsy specimens revealed polygonal to spindle neoplastic cells lining neoplastic vascular channels lacking erythrocytes. Immunohistochemically, the neoplastic cells labeled strongly positive for PROX-1, vimentin, CD-31, VEGF, weakly positive for factor VIII-related antigen, and negative for collagen IV. Based on the clinical, histological, and immunohistochemical features of this tumor, a primary ocular lymphangiosarcoma with metastasis was diagnosed.

Remarkable response to radiation therapy with concurrent chemotherapy in Stewart-Treves syndrome.

Stewart-Treves syndrome (STS) is a rare, cutaneous angiosarcoma associated with chronic lymphedema. The prognosis of this syndrome is extremely poor, with a median survival time of 5-8 months, if untreated. An 82-year-old Asian woman noticed a painless elastic mass with partial discoloration (purplish discoloration) on the left thigh. She had lower lymphedema for 15 years. Lesion biopsy and immunohistochemistry analysis led to the diagnosis of angiosarcoma, which was considered to be STS. She was referred to our department for concurrent chemoradiotherapy. Radiation therapy consisted of 25 daily fractions of 2 Gy each (prescription dose: 50 Gy). Concurrent chemotherapy consisted of 2 monthly cycles of docetaxel (75 mg/body on day 1) and recombinant interleukin-2 (700,000 units/body on days 1-5). She experienced acute adverse events such as Grade 2 dermatitis, Grade 2 anemia, and Grade 4 leukopenia. Posttreatment computed tomography images revealed that lesions had disappeared. Moreover, the accumulation patterns on positron emission tomography images were markedly weakened after the treatment. She exhibited no signs of recurrence for 4 years.

Stewart-Treves syndrome and other cutaneous malignancies in the context of chronic lymphedema: a systematic review.

INTRODUCTION: Angiosarcoma developing in chronically lymphedematous tissue, or Stewart-Treves syndrome (STS), is a rare and lethal complication of lymphedema. This systematic review summarizes characteristics and outcomes of STS and other cutaneous malignancies arising in chronic lymphedema. METHODS: MEDLINE and EMBASE databases were searched on February 19th, 2021, to identify 200 articles included in the analysis. RESULTS: Of 369 included patients, 89.7% (n = 331/369) had STS and 10.3% (n = 38/369) had other associated malignancies. Mean age of onset was 61.2 years, and 85.9% (n = 317/369) of cases were female. Common risk factors were previous cancer history (69.8%, n = 258/369) and radiation history (53.7%, n = 198/369). Lymphedema was most commonly attributed to surgical causes (68.3%, n = 252/369). STS begins on average 14.9 years after lymphedema with mortality of 53.9% (n = 178/331) and remission rate of 16.1% (n = 53/331). Other malignancies begin on average 23.7 years after lymphedema, with mortality of 10.5% (n = 4/38) and remission rate of 31.6% (n = 12/38). STS and other malignancies had 5-year survivals of 22.4% and 65.2%, respectively (P = 0.00145). For all patients, patients initially treated with excision had the best survival (median: 48 months, 5-year survival: 43.3%) and radiotherapy had the worst survival (median: 10 months, 5-year survival: 6.5%) (P = 0.0141). CONCLUSION: Malignancy can appear in lymphedematous tissue many years after lymphedema onset. STS has poorer prognosis compared to other malignancies. Further research should be conducted to better understand the causes, risk factors, and management of this phenomenon.

[Angiosarcoma in chronic lymphoedema: a case of Stewart-Treves syndrome]. / Angiosarcome sur lymphoedème chronique: un cas de syndrome de Stewart-Treves.

The Stewart-Treves Syndrome is defined as an angiosarcoma (very aggressive malignant tumor originating from endothelial cells) appearing in a specific clinical setting. This tumor develops in patients suffering from chronic lymphedema of the upper limb following mastectomy and axillary lymph node dissection for breast cancer. The diagnosis relies on medical history, clinical examination and a histological assesment (biopsy or resection). This syndrome represents a rare clinical entity. Unfortunately, the prognosis is poor. A large surgical resection is the treatment of choice if the patient is a candidate for a surgical resection with a curative intent Radiotherapy is sometimes used as a palliative local treatment. Chemotherapy is only used in more advanced cases, not curable by surgery alone.

Kaposi Sarcoma and Cutaneous Angiosarcoma: Guidelines for Diagnosis and Treatment. / Sarcoma de Kaposi y angiosarcoma cutáneo: directrices para el diagnóstico y tratamiento.

Kaposi sarcoma is a vascular sarcoma with 4 clinical variants: classic Kaposi sarcoma, which mainly affect the extremities of elderly patients and follows a chronic, generally indolent course; African Kaposi sarcoma; immunosuppression-associated Kaposi sarcoma; and AIDS-associated Kaposi sarcoma. Type8 human herpesvirus is the etiologic agent in all 4variants. Cutaneous angiosarcoma is a cutaneous neoplasm with a very poor prognosis. It carries a high probability of local relapse and has a 10% to 15% survival rate at 5years. There are 3 main variants of cutaneous angiosarcoma: idiopathic angiosarcoma of the face and scalp; Stewart-Treves syndrome; and postradiation angiosarcoma. The only potentially curative treatment is surgery with or without radiotherapy. However, its indistinct borders and multicentric nature mean that treatment is often palliative with chemotherapy, radiotherapy, or both.

Lymphangiosarcoma in 12 dogs: a case series (1998-2013).

Lymphangiosarcoma (LAS) is an uncommon malignant neoplasia arising from lymphatic endothelium; little information exists regarding therapy. Single institutional retrospective review for canine LAS histopathology diagnoses over a 15-year period yielded 12 dogs. Ten dogs were presented for a mass and/or swelling at cervical, trunk or limb regions. Prior to diagnosis, 10 dogs received empiric wound therapy. Cytology performed in 10 consisted of mild inflammation. Survival ranged from 60, 168 and 876 days for three dogs with palliation; 90 days with prednisone in one; 182 days with chemotherapy in one; 240, 267, 487, 630 and 941 days for five receiving surgery; and 574 days for one receiving surgery, radiation and chemotherapy. One dog is alive with recurrence at 243 days following surgery and carboplatin chemotherapy. Clinical improvement existed in LAS dogs receiving multimodal therapies. Early tissue biopsies are recommended for progressive oedematous lesions of unknown origin.

Lymphangiosarcoma of dogs: a review.

Lymphangiosarcoma in dogs, an extremely rare tumour with only 16 cases reported in the literature, is reviewed. Lymphangiosarcoma in humans, also very rare, and known in post-mastectomy, chronically-lymphoedematous patients as 'Stewart-Treves' syndrome, is briefly outlined, as well as the various other causes of lymphoedema, both primary and secondary, which usually precede malignancy. Comparisons between human and canine lymphoedema are made when such references were found. The genetic links to primary lymphoedema and the manifestation thereof in humans are mentioned. Lymphangiosarcoma in the majority of human and canine patients is an aggressively malignant tumour with few patients surviving despite various attempted treatments. The tumour most commonly arises in the subcutaneous tissues and rapidly invades underlying tissues and may spread widely internally via haematogenous and lymphatic routes, with frequent pleural and chest involvement. The tumour has been reported mostly in medium- to large-breed dogs, in slightly more males than females, and in an age-range of 8 weeks to 13 years, with more cases aged 5 years and older. Methods of diagnosis, with the variations encountered, including routine histopathology, immunohistochemistry, electron microscopy, tissue culture characteristics and endothelial expression of glycocongugates, are discussed.

Angiosarcoma (Stewart-Treves syndrome) in postmastectomy patients: report of 10 cases and review of literature.

AIMS: To study the clinicopathologic features of Stewart-Treves syndrome (STS) in postmastectomy patients including the epidemiology, presentation, morphology, differentiation, pathogenesis and therapeutic options. METHODS AND RESULTS: Ten cases of STS in postmastectomy patients were retrospectively identified in our archives, and immunohistochemistry for CD34, CD31, D2-40, HHV-8, CK, EMA and Ki-67 was performed. All ten patients presented with lymphedema after mastectomy as the first sign. Physical examination revealed multiple raised, pinkish-red papulo-vesicular lesions or ulceration as the early evidence of tumor in the field where radiation therapy was introduced. Microscopic examination revealed infiltrative proliferation of vessels and the heteromorphic tumor cells expressed CD34, CD31 and D2-40. Despite the various treatment modalities, 5 patients died in an average of 19 months, 4 patients survived to the last follow-up (9-31 months), and 1 patient got lost. CONCLUSIONS: STS is a fatal complication of postmastectomy lymphedema. Patients with STS have very poor prognosis. The key to improve patient's survival is the early diagnosis through a high alert of this disease by primary care physicians and comprehensive physical examination of patients with pertinent history and suspicious clinical presentations followed by prompt biopsy for definitive diagnosis.

Stewart-Treves syndrome. A lethal complication of postmastectomy lymphedema and regional immune deficiency.

Lymphangiosarcoma is a fatal complication of postmastectomy lymphedema. The pathogenesis of lymphangiosarcoma in chronic lymphedema is a combination of two factors. First, the edematous region responds in a manner similar to "immunologically privileged sites." Second, because of its anatomic and physiologic properties, it is a favorable site for the development of mutant cell populations for reasons that are not fully understood. As a result, these mutant cells, with their genetically nonidentical antigens, escape recognition by the host's impaired immune surveillance mechanism. The failure to promote a sufficient immune response allows unrestricted tumor growth to take place, resulting in the ultimate death of the patient. Available therapeutic measures are equally unsatisfactory. Emphasis is placed on periodic examination of the lymphedematous extremity, aggressive treatment of established lymphedema and infections, and surgical preservation of lymphatic channels during breast cancer surgery.

Vascular soft-tissue sarcomas. An analysis of tumor-related mortality.

Between 1982 and 1990, 69 adult patients were admitted to Memorial Sloan-Kettering Cancer Center with a diagnosis of angiosarcoma, lymphangiosarcoma, or malignant hemangiopericytoma. The existing literature regarding sarcomas focuses on individual histologic conditions or site-specific activity and includes pediatric patients, which makes estimates of survival difficult. We describe the clinical course of all vascular sarcomas, the survival without distant recurrence of patients with vascular sarcomas, and the overall survival of patients with vascular sarcomas. Using Cox's stepwise regression model, histologic characteristics of the tumors, tumor grade, tumor size, and other factors were assessed to determine their prognostic significance. Noncurative treatment and the presence of metastases were the only two factors influencing survival. Tumor grade approached significance. Disease recurrence was common among curatively treated patients (37% of such patients), and more than half of these recurrences involved distant sites. The survival of these patients depends on complete surgical resection and is independent of individual histologic characteristics of the tumor.

Lymphangiosarcoma. Reports of 3 cases and review of the literature.

Three cases of lymphangiosarcoma have been followed recently. All were finally treated by amputation. Only one is actually disease-free. The other two developed local recurrence at the thoracic cage. An extensive review of the literature follows the case presentation.

Lymphedema-induced lymphangiosarcoma.

A series of eight patients with chronic lymphedema-related lymphangiosarcoma is presented. All but one case showed a typical rapid progression and fatal outcome, as has been reported in other series. In one patient the lymphangiosarcoma developed on the chest wall, the axilla and the arm where persisting lymphedema and fibrosis occurred after bilateral mastectomy and bilateral postoperative radiotherapy. In this patient an asymptomatic course and slow locoregional progression of lesions was seen. The clinical picture, the etiological considerations and the therapeutic options of the lymphedema-induced lymphangiosarcoma with regard to the literature are discussed.

Vascular and lymphatic tumors in infancy, childhood and adulthood: challenge of diagnosis and treatment.

The essential features of the major benign and malignant vascular tumors affecting infants, children and adults have been presented. Major emphasis has been placed upon the classification and treatment of hemangiomas, although malignant vascular tumors are discussed, and extensive and selected references are cited. The classification system of hemangiomas presented in this monograph is based upon the clinical prognosis of the angioma. The principles of treatment for hemangiomas based upon our clinical classification are discussed and may be summarized as follows: 1. The diagnostic features and prognosis vary with the variety of the angioma. 2. Spontaneous regression occurs only with juvenile hemangiomas, and the major involution occurs before age 5. 3. Patients with rapidly growing capillary cavernous hemangiomas should be treated with steroids. 4. Treatment modalities that increase scarring of the surface epithelium are contraindicated. 5. Intradermal and cirsoid angiomas do not spontaneously regress. 6. Congenital A-V fistulas require aggressive surgery. 7. The ultimate deformity resulting from angiomas may be greatly reduced by plastic surgical techniques. 8. Radiation therapy is never indicated for the treatment of hemangiomas. 9. The psychologic impact of the congenital deformity on patients is generally more detrimental than comparable postsurgical or traumatic deformities.

[Surgical treatment of irradiation-induced sarcoma after treatment for breast carcinoma, personal experience: 4 case reports] ]. / Kirursko lijecenje sarkoma induciranih iradijacijom poslije lijecenja karcinoma dojke, nase iskustvo: prikaz cetiriju bolesnica.

In the Department of Plastic Surgery of "Dubrava" University Hospital from 1993 to 1999 four patients were treated for radiation induced sarcoma. All of the patients were formerly operated for breast cancer and irradiated postoperatively. The mean time span between radiotherapy and development of sarcoma was 4.75 years. Four patients were treated with wide excision and immediate reconstruction with local flaps. One of the patients had fibrosarcoma, two patients had lymphangiosarcoma, and one patient had osteosarcoma. Two patients died within two years. Radiation induced sarcomas are therapy resistant, and the review of literature did not show large controlled investigations which would offer the most optimal treatment. Most frequently a rapid progression of the disease is seen.