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.

Feline ventral abdominal wall angiosarcoma: haemangiosarcoma or lymphangiosarcoma? Clinical and pathological characteristics in nine cases.

OBJECTIVES: Angiosarcomas are rare malignant mesenchymal neoplasms of endothelial cell origin with a predilection to the ventral abdominal wall in cats. Larger case series describing this entity are lacking. METHODS: Two referral centre laboratory databases were searched for angiosarcoma of the ventral abdominal wall. Nine cases with a histological diagnosis were included. Immunohistochemistry (factor VIII and PROX-1 antibodies) was used to phenotype them as haemangiosarcoma or lymphangiosarcoma. RESULTS: All cats presented with a ventral abdominal mass, five of which were producing a serosanguinous discharge. Eight underwent tumour staging and pulmonary metastases were suspected in one cat (but not histologically confirmed). With histopathology alone, a diagnosis of angiosarcoma and lymphangiosarcoma was made in four and five cases, respectively. After immunohistochemistry, five cases had a haemangiosarcoma phenotype and four had a lymphangiosarcoma phenotype, including two cases of lymphangiosarcoma that were reclassified as hemangiosarcoma. Eight cats received treatment (either surgery with or without adjuvant therapies or medical management alone). Six cats were euthanased due to local disease progression. The median survival time for haemangiosarcoma was 166 days (range 137-381), and for lymphangiosarcoma it was 197 days (range 67-208). Two cats with haemangiosarcoma remained alive for a follow-up period of 329 and 580 days, respectively. CONCLUSIONS AND RELEVANCE: Feline ventral abdominal angiosarcomas are rare locally aggressive neoplasms. While histology often provides a diagnosis of angiosarcoma, immunohistochemistry is ultimately required to differentiate between haemangiosarcoma and lymphangiosarcoma phenotypes. Further studies are required to evaluate whether the different phenotypes have an impact on treatment response and outcome.

Primary small intestinal lymphangiosarcoma in a dog presenting with a segmental partial mesenteric volvulus.

A 3-year-old Great Dane presented with a history of chronic vomiting and diarrhoea. Abdominal computed tomography followed by exploratory laparotomy revealed a perforated, segmental partial mesenteric volvulus, affecting an abnormal section of distal jejunum, which was resected. Histopathology and immunohistochemistry results were consistent with jejunal lymphangiosarcoma. This case represents the first report of primary small intestinal lymphangiosarcoma in dogs and the importance of immunohistochemistry for definitive diagnosis.

Patient with composite haemangioendothelioma containing angiosarcoma-like areas in the setting of congenital lymphoedema mimicking Stewart-Treves syndrome: a case report.

BACKGROUND: Composite haemangioendothelioma is a rare vascular neoplasm with indolent to intermediate malignant potential. Diagnosis of this disease relays on histopathological identification of at least two different morphologically distinctive vascular components in proper clinical settings. Exceedingly rare cases of this neoplasm can exhibit areas resembling high-grade angiosarcoma, which does not change the biological behaviour. Such lesions tend to occur in the setting of chronic lymphoedema and thus, can mimic Stewart-Treves syndrome, which has a much worse clinical outcome and prognosis. CASE PRESENTATION: We present a case of 49 years old male suffering from chronic lymphoedema of the left lower extremity who had developed a composite haemangioendothelioma with high grade angiosarcoma-like areas mimicking the Stewart-Treves syndrome. Given the multifocality of the disease, the only potentially curable surgical treatment would be hemipelvectomy, which was refused by the patient. The patient has been followed-up, with no signs of local progression of the remaining disease, nor a distant spread outside the involved extremity for two years. CONCLUSIONS: Composite haemangioendothelioma represents a rare malignant vascular tumour, with significantly more favourable biological behaviour than angiosarcoma, even in cases where angiosarcoma-like areas are present. For that reason, composite haemangioendothelioma can be easily misdiagnosed as true angiosarcoma. The rarity of this disease unfortunately hampers the development of clinical practice guidelines and the implementation of treatment recommendations. Most of the patients with localized tumour are treated by wide surgical resection, without neo- or adjuvant radiotherapy or chemotherapy. However, in the case of this diagnosis, the watch-and-wait approach is better than mutilating procedure, highlighting the necessity of establishing of the correct diagnosis.

A retrospective analysis of Stewart-Treves syndrome in the context of chronic lymphedema.

BACKGROUND: stewart-treves syndrome (STS) is an angiosarcoma associated with chronic lymphedema. OBJECTIVES: This article analyses the characteristics of twenty-two patients and proposes active intervention in lymphedema and the early diagnosis of STS. METHODS: Twenty-two patients with STS were diagnosed at the centre over an 11-year period. Clinical manifestations, a series of conventional analyses, and histopathology were used to study these cases retrospectively. RESULTS: The age range of 22 patients with STS was 15 to 78 years. The main clinical manifestations included multiple skin and subcutaneous nodules and scattered red or purplish-red rashes in the lymphoedematous limbs. These patients often showed clinical symptoms such as lymphedema, weakness, emaciation, pain, mass, lymphadenopathy and so on. The positive rates of ultrasonography, MRI and radionuclide imaging were 66.7% (6/9), 92.3% (12/13) and 18.2% (2/11), respectively. The main points regarding active intervention in lymphedema and early diagnosis of STS were summarized. STUDY LIMITATIONS: Since this was a retrospective study, the main points summarized by the author need to be further quantified in clinical work to guide the diagnosis of this kind of disease more conveniently. In addition, further clinical trials are needed to evaluate the role of lymphedema in the occurrence and development of malignant tumors. CONCLUSIONS: STS can appear in lymphoedematous tissue many years after lymphedema onset. To avoid delays in the diagnosis and therapy of STS, physicians should actively look for signs or symptoms of malignant lymphedema during the follow-up period and promptly manage patients developing problems.

Autophagy inhibition prevents lymphatic malformation progression to lymphangiosarcoma by decreasing osteopontin and Stat3 signaling.

Lymphatic malformation (LM) is a vascular anomaly originating from lymphatic endothelial cells (ECs). While it mostly remains a benign disease, a fraction of LM patients progresses to malignant lymphangiosarcoma (LAS). However, very little is known about underlying mechanisms regulating LM malignant transformation to LAS. Here, we investigate the role of autophagy in LAS development by generating EC-specific conditional knockout of an essential autophagy gene Rb1cc1/FIP200 in Tsc1iΔEC mouse model for human LAS. We find that Fip200 deletion blocked LM progression to LAS without affecting LM development. We further show that inhibiting autophagy by genetical ablation of FIP200, Atg5 or Atg7, significantly inhibited LAS tumor cell proliferation in vitro and tumorigenicity in vivo. Transcriptional profiling of autophagy-deficient tumor cells and additional mechanistic analysis determine that autophagy plays a role in regulating Osteopontin expression and its down-stream Jak/Stat3 signaling in tumor cell proliferation and tumorigenicity. Lastly, we show that specifically disrupting FIP200 canonical autophagy function by knocking-in FIP200-4A mutant allele in Tsc1iΔEC mice blocked LM progression to LAS. These results demonstrate a role for autophagy in LAS development, suggesting new strategies for preventing and treating LAS.

Unusual coexistence of Stewart-Treves syndrome and sickle cell anaemia: a case of dual pathology.

Chronic lymphoedema can rarely be complicated by an angiosarcoma. This combination called Stewart-Treves syndrome usually observed in upper limb in patients of post-mastectomy with axillary lymph node resection. Here, we report a male patient who had a 10-year history of right leg elephantiasis. Later on, he developed two large ulceronodular masses in the same leg with few satellite nodules in the surrounding skin. With the clinical suspicion of malignancy, a wedge biopsy was performed which revealed histological features of angiosarcoma with sickled red cells. The above knee amputation specimen received further confirmed the histological diagnosis. The investigation for haemoglobinopathy also suggested the presence of sickle cell trait. This report describes a multifocal tumour as a rare manifestation of Stewart-Treves syndrome in a post-filariasis case with sickle cell trait, which is an extremely uncommon combination.

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 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.

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.

Síndrome de Stewart-Treves no membro inferior com apresentação exuberante: relato de caso / Profuse Stewart-Treves syndrome in the right leg: a case report

A Síndrome de Stewart-Treves é uma rara condição onde um angiossarcoma se desenvolve sobre área de linfedema crônico. Afeta mais frequentemente os membros superiores e representa 5% dos casos de angiossarcoma. Apesar de ser mais comum em mulheres submetidas a mastectomia radical e esvaziamento axilar por neoplasia de mama, pode ocorrer a partir de linfedema de outras etiologias. Clinicamente as lesões são caracterizadas por nódulos únicos ou múltiplos de cor avermelhada ou azulada no estágio inicial e, em estágio avançado, podem evoluir para massas hemorrágicas e até gangrena. O prognóstico é ruim e a conduta cirúrgica com excisão ampla ou amputação oferecem uma maior chance de sobrevida. Relata-se um caso de Síndrome de Stewart-Treves na perna direita, apresentando-se de forma exuberante e com acometimento de linfonodos pélvicos e abdominais.

Stewart-Treves syndrome is a rare condition characterized by the development of an angiosarcoma at sites of chronic lymphedema. It most often affects the upper limbs and accounts for 5% of cases of angiosarcoma. Although the syndrome is more common in women undergoing radical mastectomy and axillary dissection for breast cancer, it may result from lymphedema of other etiologies. Clinically, the lesions are characterized by single or multiple bluish-red nodules in the early stage and may progress to hemorrhagic masses and even gangrene in advanced stages. The prognosis is poor, and surgical management with wide excision or amputation offers a greater chance of survival. We report a case of profuse Stewart-Treves syndrome in the right leg, with involvement of pelvic and abdominal lymph nodes.

[Stewart-Treves syndrome]. / Syndrome de Stewart-Treves.

Détention d'armes et permis de chasser. Les armes à feu sont la cause de plus d'un millier de décès chaque année, représentant ainsi un objectif de santé publique conséquent. Pour les armes à feu de type B et C, le tir sportif et le permis de chasse, le médecin traitant joue un rôle crucial, délivrant à chaque fois un certificat selon des modalités bien particulières.