Elevated coagulation factor VIII plasma activity in a patient with lymphangiosarcoma.

A 72-year-old woman was referred to our hospital for palliative care. Fifteen years earlier, she had undergone total hysterectomy and radiotherapy for cervical cancer. One year before her referral, she visited a hospital due to a gait disturbance and was diagnosed with lymphangiosarcoma. The level of coagulation factor VIII plasma activity was >201% (normal range: 62-145%) and the immunohistochemical results were positive for factor VIII-related antigen in a tumor specimen. To the best of our knowledge, this is the first report of high coagulation factor VIII plasma activity in a patient with lymphangiosarcoma.

Establishment and characterization of a novel lymphangiosarcoma cell line (MO-LAS) compared with the hemangiosarcoma cell line (ISO-HAS).

The concept of "lymphangiosarcoma" remains obscure. Therefore, we reported a patient with lymphangiosarcoma, resistant to immunotherapy. The patient presented with impressive and discriminative features: clinically an ill-defined edematous lesion with lymphorrhea and pathologically atypical vascular channel formation without extravasation of blood, clearly distinguished from common angiosarcoma with hemorrhage. From this case, a lymphangiosarcoma cell line, MO-LAS, was established and its characteristics were compared with the hemangiosarcoma cell line, ISO-HAS. Flow cytometric analysis revealed that MO-LAS was negative for factor VIII-related antigen, but positive for CD31, D2-40, NZ-1, and vascular endothelial growth factor receptor-3 (VEGFR-3), similar to ISO-HAS. However, MO-LAS expressed a much higher level of homeobox gene PROX1, indicating a lymphatic phenotype, compared with ISO-HAS. Furthermore, MO-LAS showed a much lesser expression of oncogenes and much lower sensitivity against lymphokine-activated killer (LAK) cells. Lymphangiosarcoma may be difficult to recognize by the immune system. Conclusively, the establishment of MO-LAS, a novel angiosarcoma cell line bearing lymphatic characters, strongly suggests the entity of lymphangiosarcoma.

Metastatic lymphangiosarcoma in a horse.

A lymphangiosarcoma with metastases was found in a horse that presented with respiratory distress and edema in the ventral thorax and abdomen. The necropsy revealed diffuse edema in the subcutaneous connective tissue. Mediastinal, mesenteric, iliac, and renal lymph nodes were enlarged and white with soft, yellowish necrotic areas. Histologic examination revealed numerous channels and disorganized vessels lined by large polyhedral, polymorphic cells. Tumor metastases were observed in the spleen, lungs, and kidneys. Immunohistochemical evaluation of the tumor cells demonstrated positive staining for factor VIII, vimentin, and keratin. Laminin was scarce, and collagen IV staining was negative, consistent with a discontinuous or absent basement membrane.

[A case of Stewart-Treves syndrome--treatment with recombinant interleukin 2 and a review of Japanese literature].

A 76-year-old woman developed angiosarcoma 11 years after a radical mastectomy in the chronic lymphedema of the ipsilateral arm, referred to as Stewart-Treves syndrome. The patient was treated by intravenous and intralesional injection of recombinant interleukin 2 (rIL-2; TGP-3, Takeda Chemical Industries, LTD, Osaka). Intralesional injection was more effective than systemic administration. After a month, the lesion where the local injection was done showed little tumor cells with a dense infiltrate composed of lymphoid cells. It was observed that NK activity, LAK activity and IL-2 receptor positive T-cells in the peripheral blood increased during the administration of rIL-2. As the lesion was too large to be treated with rIL-2 alone, radiotherapy was performed. But the patient had no remarkably improvement and died 16 months later from the onset. Immunotherapy with rIL-2 can be useful for angiosarcoma and more effective regimen of rIL-2 is a important problem.

Malignant angioendotheliomatosis: an angiotropic lymphoma.

Malignant angioendotheliomatosis is a rare, systemic, usually fatal disease characterized by massive proliferation of large, neoplastic, mononuclear cells within the lumen of small blood vessels. Recent studies suggested that the tumor cells are of lymphoid origin. We studied two cases of malignant angioendotheliomatosis by Southern blot hybridization analysis that showed rearrangements of the immunoglobulin heavy chain and kappa light chain (case 2), indicating the presence of a monoclonal B cell lymphoma. Our results provide further evidence that malignant angioendotheliomatosis is an angiotropic lymphoma.

Stewart-Treves syndrome: an histogenetic (ultrastructural and immunohistological) study.

One case of the so-called "Stewart-Treves syndrome" (STS), appearing on a lymphoedematous arm complicating radical mastectomy for breast cancer, was characterized electronmicroscopically and immunohistologically, in order to elucidate its disputed (epithelial vs endothelial) histogenesis. Epithelial and endothelial differentiation markers used comprised: antibodies against keratin, vimentin, factor VIII-related antigen (F VIII-RA), HLA-DR antigens and the lectin Ulex europeaus agglutinin I (UEA I). At the ultrastructural level, neoplastic cells were found to contain typical Weibel-Palade bodies, whereas by immunohistological techniques they proved to be keratin-negative/vimentin+, F VIII-RA+, UEAI+, HLA-DR+. These results rule out a possible epithelial differentiation and strongly favour an endothelial one for STS.

Immunohistochemical identification of factor VIII-related antigen in endothelial cells of cutaneous lesions of alleged vascular nature.

Immunohistochemical staining for factor VIII-related antigen (FVIII-RAG) with the peroxidase-antiperoxidase technic was used as a marker for endothelial cells in a variety of nevoid, reactive, and malignant vascular cutaneous proliferations. The endothelial cells of small normal cutaneous vessels gave the strongest reaction. The cells of hemangioma and angiokeratoma generally were stained, but with less consistency. In lymphangioma, pyogenic granuloma, and pigmented purpuric dermatosis, positivity was either patchy or of lesser intensity. Numerous strongly positive endothelial cells lining well-formed blood vessels were present in lesions of Kaposi's sarcoma, but the proliferating spindle cells forming "vascular slits" were uniformly negative. The cells of angiosarcoma were essentially negative, except for isolated elements in the better-differentiated areas. Plasma was also strongly positive; this may aid in distinguishing vascular from lymphatic channels. Anti-FVIII-RAG immunoperoxidase staining is a helpful aid in evaluating cutaneous vascular proliferations.

Blood group antigens in vascular tumours. Evaluation of the immunoperoxidase technique.

Determination of blood group isoantigens A, B and H, was performed in benign and malignant vascular tumours of the skin and subcutaneous tissue, using the immunoperoxidase technique. No differences were noted between benign haemagioendotheliomas from children or adults: neither tumour showed the presence of antigens in intercapillary cells. Reactive conditions such as angiolymphoid hyperplasia with eosinophilia showed an intense positive reaction to blood group substances of the endothelial proliferative cells. In malignant tumours no relationship between tumour differentiation and loss of blood group isoantigens was seen. Cases of Kaposi's sarcoma did not show antigens in spindle cells or capillaries but in medium sized vessels variable preservation or loss of blood group isoantigens was found.