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.

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.

Targeted therapy for mTORC1-driven tumours through HDAC inhibition by exploiting innate vulnerability of mTORC1 hyper-activation.

BACKGOUND: The mechanistic target of rapamycin complex 1 (mTORC1) is important in the development and progression of many cancers. Targeted cancer therapy using mTORC1 inhibitors is used for treatment of cancers; however, their clinical efficacies are still limited. METHODS: We recently created a new mouse model for human lymphangiosarcoma by deleting Tsc1 in endothelial cells and consequent hyper-activation of mTORC1. Using Tsc1iΔEC tumour cells from this mouse model, we assessed the efficacies of histone deacetylase (HDAC) inhibitors as anti-tumour agents for mTORC1-driven tumours. RESULTS: Unlike the cytostatic effect of mTORC1 inhibitors, HDAC inhibitors induced Tsc1iΔEC tumour cell death in vitro and their growth in vivo. Analysis of several HDAC inhibitors suggested stronger anti-tumour activity of class I HDAC inhibitor than class IIa or class IIb inhibitors, but these or pan HDAC inhibitor SAHA did not affect mTORC1 activation in these cells. Moreover, HDAC inhibitor-induced cell death required elevated autophagy, but was not affected by disrupting caspase-dependent apoptosis pathways. We also observed increased reactive oxygen species and endoplasmic reticulum stress in SAHA-treated tumour cells, suggesting their contribution to autophagic cell death, which were dependent on mTORC1 hyper-activation. CONCLUSION: These studies suggest a potential new treatment strategy for mTORC1-driven cancers like lymphangiosarcoma through an alternative mechanism.

Pathologic and flow cytometric features of a case of canine ventral cervical lymphangiosarcoma.

An 11-y-old spayed female German Shepherd was presented for a second opinion of ventral cervical swelling of 3-mo duration. On examination, the dog had significant dependent ventral cervical swelling. Enlarged lymph nodes with cystic changes and severe edematous facial swelling were noted on computed tomography. Fine-needle aspiration of the ventral cervical swelling revealed yellow-tinged fluid, with a predominance of lymphoid cells noted on cytologic examination. On cervical exploratory surgery, the left mandibular lymph node was surrounded by a large fluid pocket; biopsies of the lymph node were obtained. Impression smear cytology, flow cytometry, PCR for antigen receptor gene rearrangements, and histopathology were performed on samples from the left mandibular lymph node. Impression smear cytology revealed a population of atypical discrete cells. Flow cytometry identified a population of CD34+/CD45- large cells. A tumor of endothelial origin within the medulla of the lymph node was identified by histopathology, and lymphangiosarcoma was confirmed based on prospero-related homeobox gene 1 (PROX1) immunoreactivity. Our study describes the challenges in the diagnosis of a rarely reported entity and highlights that neoplastic endothelial cells should be considered as a differential when high proportions of CD34+/CD45- cells are present in flow cytometry.

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.

Lymphatic-type "Angiosarcoma" With Prominent Lymphocytic Infiltrate.

We report 21 cases of a distinctive and unique vascular tumor which we propose to be a pure lymphatic-type angiosarcoma characterized by architectural and growth characteristics of angiosarcoma, cytologic, and immunohistochemical features of lymphatic differentiation, a prominent lymphocytic infiltrate, and variable nuclear grade. Patients included 12 males and 9 females with a median age of 65 years (range: 32 to 95 y). Tumors involved the head and neck (n=11), lower extremities (n=5), trunk (n=4), and upper extremity (n=1) and were located superficially in the dermis and/or subcutis. Tumors were designated "low grade" (n=10) when the nuclear grade was low, and vascular channel formation was evident throughout but with multilayering of endothelium within the vessels. Cases were designated "high grade" (n=11) when nuclei appeared higher grade with more rounded contours and prominent nucleoli and when solid areas predominated over vascular channel formation. A striking feature of both groups was the presence of a dense, lymphocytic infiltrate with occasional germinal center formation. All cases strongly and diffusely expressed at least 1 lymphatic marker (21/21) with podoplanin (17/19) and Prox-1 (11/11) more commonly expressed than LYVE-1 (5/10). No consistent molecular alteration was identified. Follow-up on 17 patients (median: 41 mo, mean: 54 mo) showed 10 patients were alive without disease, 5 were alive with disease, 1 died of other cause, and 1 died of disease. Local recurrence developed in 9 cases and metastasis in 2 cases, although neither correlated with grade as defined. On the basis of clinical follow-up to date, the natural history of lymphatic-type angiosarcoma appears to be more favorable than other forms of cutaneous angiosarcoma.

Unsuspected Stewart-Treves syndrome clinically mimicked by apparent bullous erysipelas and a systematic review of dermatological presentations of the classical Stewart-Treves syndrome.

BACKGROUND: Stewart Treves-Syndrome (STS) was first characterized as angiosarcoma in the homolateral limb of a patient with breast cancer and lymphedema. Now, other conditions represent STS. It's a rare condition. The diagnosis is easier in the presence of single or multiple purple nodules. Even though other dermatological aspects have been reported, no study has grouped its characteristics. AIM: Evaluate the dermatological characteristics of classical STS (c-STS). METHODS AND RESULTS: We report a patient with chronic lymphedema with a history of recurrent erysipelas that rapidly developed multiple papules in the superior limb. It was initially diagnosed as bullous erysipelas, but unsatisfactory evolution led to biopsy, which demonstrated an unsuspected epithelioid angiosarcoma. We have also performed a review of dermatologic aspects of c-STS using PubMed and Lilacs databases. PICTOS methodology and PRISMA flow chart were considered. The main dermatological aspects associated with c-CTS were summarized. Using a systematic evaluation from 109 articles, 29 were selected and 44 patients were described to whom we added one case. The mean time with lymphedema was 10 years. Of the patients analyzed, 97.2% were female; 95.6% were submitted to radical mastectomy; 81.2% presented with multiple lesions, 67.4% of the lesions were reported as nodules or tumors, 53.4% were purple, 33.4% were associated with an ecchymotic halo, and 33.4% were ulcerated lesions. CONCLUSION: When evaluating patients with chronic lymphedema with new dermatological abnormalities, clinical suspicion, or unfavorable evolution, the knowledge of clinical signs is important for diagnosis, and a biopsy must be considered. Papules associated with erythematous-wine color and bluish hematoma aspect must raise clinical suspicion.

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.

Pancreatic metastasis of angiosarcoma (Stewart-Treves syndrome) diagnosed using endoscopic ultrasound-guided fine needle aspiration: A case report.

BACKGROUND: Pancreatic involvement of angiosarcoma is extremely rare. METHODS: We herein report a rare case of angiosarcoma associated with chronic lymphedema (Stewart-Treves syndrome) with pancreatic metastasis that was diagnosed using endoscopic ultrasound (EUS)/fine needle aspiration (FNA). RESULTS: A 43-year-old woman with a history of radical hysterectomy with bilateral inguinal lymphadenectomy and chemoradiotherapy for cervical cancer 15 years prior noticed the presence of erythematous indurative plaques on her right femoral region, where chronic lymphedema had developed. Contrast-enhanced computed tomography (CT) revealed not only multiple nodules in the subcutaneous tissue of the right femoral region but also a 25 mm × 20 mm solid mass in the region of the pancreatic tail. A histological analysis of the specimens obtained using EUS/FNA revealed angiosarcoma that was immunohistochemically positive for platelet/endothelial cell adhesion molecule-1 but negative for cytokeratin. The patient was diagnosed as Stewart-Treves syndrome that had metastasized to the pancreas. Chemotherapy was performed, but the patient died 14 months after her diagnosis. CONCLUSION: Unfortunately, this patient was not followed up, even though she had chronic lymphedema of the right femoral region due to the repeated occurrence of phlegmon. To improve the survival rate of this fatal secondary malignant complication of radical lymphadenectomy, an early diagnosis with consecutive and long-term clinical follow-up and close monitoring for Stewart-Treves syndrome is therefore important.

Clinicopathological features of breast angiosarcoma.

BACKGROUND: Breast angiosarcomas are rare neoplasm. Due to its rarity, our therapeutic strategy is extremely limited. Therefore, we investigated the clinicopathologic features and examined the treatment for angiosarcoma compared with some literatures. METHODS: We conducted a retrospective chart and slide review of all patients in our division seen from 1997 to 2012 with a diagnosis of primary or secondary breast angiosarcoma at the National Cancer Center Hospital (Tokyo, Japan). RESULTS: Nine patients were diagnosed with breast angiosarcoma (six primary and three secondary cases). The median age of patients with primary angiosarcoma was 39 years (range 27-65 years). The median tumor size was 6.78 cm (range 3.0-8.8 cm). In the primary tumor, 4 patients had total mastectomy and 2 had a breast conserving surgery. 3- and 5-year disease-free survival (DFS) of the patients with primary angiosarcoma was 20 and 0 %. 5-year surviving rate of primary angiosarcoma was 50 %. In all patients with secondary angiosarcoma, recurrence was observed in all cases. But one case obtained long-term survival in local control therapy. CONCLUSIONS: Our study demonstrates breast angiosarcoma exhibits high recurrence rates. Tumor size and surgical margin may be important factor to obtain long-term survival. In this point of view, total mastectomy with adequate tumor margin with early detection is desired. In case of recurrence, if it is local, surgery may be potentially curative.