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PubMed1993

Current topics of immunohistochemistry as applied to skin tumors.

Suppressor oncogene p53 is expressed more frequently in the nodular portion than the superficial spreading portion of the same melanoma. PCNA expression follows the same pattern but it is strongly expressed already in the superficial spreading portion. CD34 is found to label dermatofibrosarcoma protuberans. There is the mixture of negative strands but the immunostains are predominantly positive in the three cases studied. Neurogenic tumors are reactive but the intensity of staining is only moderate. Fibrous histiocytoma, dermatofibroma and other fibrohistiocytic tumors are non-reactive. CD34 is expressed in the outer root sheath of hair follicle below the sebaceous gland level. A case of piloepidermal cyst is CD34 positive. CD34 is expressed in vascular endothelial cells; not only hemangiomas but also lymphangiosarcoma is CD34 positive. A case of indeterminate cell histiocytosis following scabies and superficial variant of clear cell sarcoma are discussed as examples of new entities.

Antigens, CD↗
PubMed1985

Non-Hodgkin's lymphoma of the skin associated with chronic limb lymphoedema.

Cutaneous non-Hodgkin's lymphoma developed within a leg affected by chronic lymphoedema. The lymphoedema had followed radiotherapy to bony metastases from a carcinoma of the prostate. Eighteen months after the development of the cutaneous tumours, extracutaneous involvement by the lymphoma became apparent. This is the second report of a non-Hodgkin's lymphoma appearing within a lymphoedematous limb. The possible reasons for such an unusual localization are discussed. Our case report illustrates that cutaneous tumours other than lymphangiosarcomas may localize to a lymphoedematous limb and clinically simulate the Stewart-Treves syndrome.

Aged↗
PubMed1998

Lymphedema: classification, diagnosis and therapy.

This review presents the diagnostic features, the pathophysiology and the available therapies for lymphedema. This disease is often able to be diagnosed by its characteristic clinical presentation, yet, in some cases, ancillary tests might be necessary to establish the diagnosis, particularly in the early stages of the disease and in edemas of mixed etiology. These diagnostic modalities are also useful in clinical studies. Available modalities include isotopic lymphoscintigraphy, indirect and direct lymphography, magnetic resonance imaging, computed tomography and ultrasonography. Lymphedema may be primary or secondary to the presence of other disease and/or to the consequences of surgery. Primary lymphedema may occur at any phase of life but it most commonly appears at puberty. Secondary lymphedema is encountered more often. The most prevalent worldwide cause of lymphedema is filariasis, which is particularly common in south-east Asia. In the USA, postsurgical lymphedema of the extremity prevails. Complications of chronic limb lymphedema include recurrent cellulitis and lymphangiosarcoma. Most patients are treated conservatively, by means of various forms of compression therapy, including complex physical therapy, pneumatic pumps and compressive garments. Volume reducing surgery is performed rarely. Lymphatic microsurgery is still in an experimental stage, although a few centers consistently report favorable outcomes.

Combined Modality Therapy↗
PubMed1999

Principles of surgical treatment of chronic lymphoedema.

Lymphoedema, refractory to non-operative management, may require surgical treatment. Potential indications include impaired limb function, recurrent episodes of cellulitis and lymphangitis, intractable pain, lymphangiosarcoma and cosmesis (patient unwilling to undergo more conservative treatment and willing to proceed even with experimental operations). The principle of excisional operations is to remove excess tissue to decrease volume of the extremity. Good reduction can be achieved with staged resection of the subcutaneous tissue, with resection of the excess skin and using the remainder for coverage. However, prolonged hospitalization, poor wound healing, long surgical scars, sensory nerve loss, residual oedema of the foot and ankle and poor cosmetic results can be significant problems and prevent offering such procedures short of a large and truly disabling lymphoedema, not responding to medical measures. Physiologic operations have been aimed at restoring lymphatic transport capacity, most frequently with lymphovenous anastomoses or lymphatic grafting. Chylous reflux due to valvular incompetence has been treated effectively by ligation and excision of retroperitoneal lymphatics, with or without lymphovenous anastomoses. Lymphovenous anastomoses operations for obstructive lymphoedema have been performed for several decades, but their use continues to be controversial. Such reconstructions can be indicated in a subset of patients who have proximal obstruction with preserved or dilated lymphatics distally. While few groups have reported good late clinical results, direct confirmation of long-term patency of lymphovenous anastomoses in patients is unavailable. Lymphatic grafting is a promising operation, but it requires true microsurgical expertise and commitment to treat this frequently frustrating and difficult disease. Long-term patency rates associated with documented clinical improvement have to be reported in larger number of patients, operated on in more than one centre before this operation can be recommended for treatment as an alternative to conservative measures. The large number of individual surgical techniques of physiological and excisional operations that are practiced today worldwide to treat lymphoedema continues to be testimony to our frustration in dealing with this difficult problem.

Chronic Disease↗
PubMed1991

Transformation of mouse skin endothelial cells in vivo by direct application of plasmid DNA encoding the human T24 H-ras oncogene.

Plasmid DNA containing the human T24 H-ras oncogene, with or without viral transcriptional enhancer sequences, was applied to scarified mouse skin, followed by multiple treatments with the tumour promoter 12-O-tetradecanoyl-phorbol-13-acetate. This resulted in the formation of vasoformative tumours histologically characterized as lymphangiosarcomas. All of the animals treated developed cystic fluid-filled swellings. Polymerase chain reaction analysis revealed the presence of human H-ras sequences within the cystic fluid from 3 out of 4 swellings. An endothelial cell line established from the cystic fluid removed from one of these swellings was found to contain human H-ras sequences and to express the mutant human p21ras. Injection of the cell line into nude mice, or adult syngeneic mice, resulted in the formation of aggressive angiosarcomas. Further experiments showed that 12-O-tetradecanol-phorbol-13-acetate promotion is not required for tumour formation and would appear to reduce the yield of tumours. These results indicate that a single application of the human H-ras oncogene is sufficient to induce endothelial cell transformation in vivo, even in the absence of any further promotional stimulus.

Animals↗
PubMed1985

[Kaposi's sarcoma: comparative immunohistochemical study and histogenic significance of endothelial markers].

The origin of spindle-shaped cells in Kaposi's sarcoma (KS) remains controversial. Non-specific histochemical reactions, electron microscopic examinations and immunostainings using antibody against factor VIII-related antigen (F VIII-RAG) and Ulex europaeus agglutinin I (UEAI) lectin as endothelial markers have given contradictory results. Immunohistochemical techniques were applied to 7 frozen skin biopsy specimen of KS from 5 elderly Mediterranean people and 1 renal allograft recipient, and a group of 27 other frozen cutaneous tumours including haemangio and lymphangiosarcomas, benign vascular lesions and various epithelial, melanocytic, fibrohistiocytic, fibrosarcomatous and muscular tumours. Using UEAI and antibodies against F VIII-RAG, HLA-DR and vimentin, a large proportion of positive KS spindle cells was found in all cases whereas cells were negative for keratin. Among the various immunoreactivity patterns observed in this study, a unique immunohistochemical profile was demonstrated for KS, angiosarcoma and endothelial cell, which strongly supports the endothelial origin of spindle cells in KS. Whereas F VIII-RAG, HLA-DR, vimentin and UEAI were sensitive endothelial markers, only F VIII-RAG appeared specific for endothelial cells since UEAI stained 2 squamous cell carcinomas and HLA-DR and vimentin were present in various mesenchymal and melanocytic tumours.

Adult↗
PubMed1987

[Stewart-Treves syndrome: hemangiosarcoma in chronic lymphedema. Ultrastructural analysis of various clinical developmental stages].

Ultrastructural studies of angiosarcoma in chronic lymphedema (Stewart-Treves syndrome) at various stages of development show that endothelial cell proliferation originates not in the lymphatic but in the blood capillary vessels. The results indicate that the term "lymphangiosarcoma" is no longer suitable to describe the histopathologic characteristics of Stewart-Treves syndrome.

Aged↗
PubMed1985

Second cancer following cancer of the breast in Connecticut, 1935-82.

Among 41,109 women diagnosed with breast cancer between 1935 and 1982 in Connecticut, 3,984 developed a second cancer, whereas 2,426 were expected [relative risk (RR) = 1.64; 95% CI = 1.6-1.7]. This increased risk persisted for 30 years and was highest in women under 55 years of age at the time of breast cancer diagnosis. Second primary breast cancers (RR = 3.0) accounted for almost one-half of all new neoplasms. However, if subsequent breast cancers were excluded, the risk for all other second cancers was only 1.15 (95% CI = 1.10-1.20), and no excess risk was seen among women over age 55 at initial breast cancer. Significant risks were found for cancers of the ovary (RR = 1.7) and uterine corpus (RR = 1.4), possibly linked with shared reproductive factors such as nulliparity or late age at menopause. Malignant melanoma (RR = 1.5), thyroid cancer (RR = 1.6), and colon cancer (RR = 1.2) were also significantly elevated; possible shared risk factors remain to be elucidated. Significant deficits of multiple myeloma and chronic lymphocytic leukemia were noted. Women who received initial radiotherapy compared with those who did not were at slightly higher risk of developing a second cancer, most notably acute nonlymphocytic leukemia, non-Hodgkin's lymphoma, and cancers of the esophagus, kidney, and connective tissue, although the nature of the associations was not always clear. Some of the soft tissue sarcomas were lymphangiosarcomas of the arm, a consequence of the lymphedema that may complicate radical mastectomy (Stewart-Treves syndrome). Women treated with radiation were at higher risk of developing a second breast neoplasm (RR = 3.9) than nonirradiated women (RR = 2.8). Further investigation should focus on the mechanisms underlying the relationships between breast, genital tract, and colon cancers, and on the effects of treatment modalities on the risk of subsequent neoplasms.

Breast Neoplasms↗
PubMed1984

Angiosarcoma in primary lymphedema of the lower extremity--Stewart-Treves syndrome.

After a 20-year latent period an angiosarcoma developed in the edematous leg of a 74-year-old woman with primary lymphedema. A deep venous thrombosis of the leg which further aggravated tissue swelling preceded the appearance of angiosarcoma. Histogenetic classification of the tumor as hemangiosarcoma rather than lymphangiosarcoma was favored by positive immunohistochemical staining for Factor VIII. Despite high amputation and isolated perfusion with hyperthermal cytostatic infusion, she developed local recurrence and distant metastases and died 16 months after operation. Patients with chronic primary or secondary lymphedema are susceptible to angiosarcoma although the overall risk is small.

Aged↗
PubMed1983

Angiosarcoma of serous membranes.

Three angiosarcomas of serous membrane are described. One originated in peritoneum, one in pleura, and one in pericardium. The tumor arising in peritoneum was a cystic lymphangiosarcoma and may have been caused by previous therapeutic irradiation for carcinoma of the endometrium. This tumor invaded the peritoneal and right pleural cavities extensively and thus resembled diffuse mesothelioma in its behavior. The tumors arising in pleura and pericardium were hemangiosarcomas.

Aged↗
PubMed1977

Cutaneous lymphangioma.

Cutaneous lymphangiomas from 158 patients were studied clinically and pathologically. Lymphangiomas show a predilection for the neck and axilla, breasts and chest, and buttocks and thighs, but may occur on almost any area of skin. They show highest incidence of onset in infancy, the majority are present by age 5 years, but they may appear spontaneously in adolescence or adult life. No correlation among cutaneous lymphangioma, mucous membrane lymphangioma, internal lymphangioma, or lymphangiosarcoma was found. No familial histories of lymphangioma were elicited. Single surgical excision cured 75% of cutaneous lymphangiomas and reexcision cured an additional 12%. The cutaneous lymphangiomas are divided into superficial "lymphangioma circumscriptum" and deep "lymphangioma cavernosum." No specific histologic criteria could be found to differentiate lymphangioma from "bloodless" hemangioma, primary from secondary lymphangioma (lymphangiectasia), or cystic cavernous lymphangoma from cystic hygroma.

Adolescent↗
PubMed1997

Squamous cell carcinoma arising in chronic lymphoedema.

Two patients are reported in whom a squamous cell carcinoma arose in chronic lymphoedematous skin on the lower legs. Although lymphangiosarcoma is a well recognized complication of chronic lymphoedema, squamous cell carcinoma has only been reported on seven previous occasions. The pathogenesis of malignant tumours in chronic lymphoedema is discussed.

Carcinoma, Squamous Cell↗
PubMed1980

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.

Blood Group Antigens↗