Lymphangioma-like Kaposi Sarcoma in Transplant-Associated Iatrogenic Immunosuppression: A Case Report.

Lymphangioma-like Kaposi sarcoma (LLKS) is a rare histologic presentation of Kaposi sarcoma (KS), with only 28 cases reported in the literature. LLKS has been described in acquired immunodeficiency syndrome and in endemic African-type as well as classic indolent KS. We present the 1st reported case of LLKS in a transplant-associated iatrogenic immunosuppressed patient.

Lymphatic differentiation in classic Kaposi's sarcoma: patterns of D2-40 immunoexpression in the course of tumor progression.

The recent development of lymphatic endothelium-specific immuno-indicators has given rise to research on the histogenesis of Kaposi sarcoma (KS), specifically focusing on its lymphatic root and differentiation. D2-40 is a new lymphatic marker that recognizes podoplanin and is easily applied to formalin-fixed paraffin-embedded human tissues. This study examined D2-40 immunoexpression in 178 classical KS lesions using immunohistochemical methods. D2-40 immunoexpression was also examined in 63 non-KS soft tissue lesions to test the reliability of D2-40 monoclonal antibody in the pathological diagnosis of KS. D2-40 immunoreactivity was detected at all of the KS lesions and in lymphangioma and nonneoplastic lymphatic endothelium. There was no significant relationship between the extent of D2-40 staining and histopathological stage; however, there was a positive correlation between the staining intensity and histopathological stage in KS cases. D2-40 immunoreactivity was detected at all histopathological stages of KS and may be added to the routine immunohistochemical panel used for the differential diagnosis of KS. Widespread D2-40 protein expression is evidence of a lymphatic origin or the differentiation of neoplastic cells in KS, and D2-40 expression increases with tumor progression.

Identification of equine cutaneous lymphangioma by application of a lymphatic endothelial cell marker.

An adult horse was presented with a mass located within the dermis and subcutis of the right forelimb. At post-mortem examination there was a marked increase in thickness of the subcutis of the right forelimb extending from the fetlock to the pectoral muscles. Microscopically, the dermis and subcutis were diffusely infiltrated by endothelial-like cells forming irregular channels and cavernous spaces. Immunohistochemical examination revealed the endothelial-like cells to express vimentin, factor VIII-related antigen and PROX-1, confirming the identity of the tumour as a lymphangioma. Ultrastructural analysis showed that the cavernous spaces were lined by a discontinuous endothelium lacking any basement membrane.

D2-40 immunohistochemistry--so far!

D2-40 is a commercially available monoclonal antibody directed against human podoplanin, a transmembrane mucoprotein that is expressed in lymphatic endothelial cells. Since its introduction, D2-40 immunoexpression has been described in a variety of lymphovascular neoplasms including lymphangioma, Kaposi sarcoma, and hemangioendothelioma, as well as nonvascular neoplasms such as epithelioid mesothelioma, seminoma, and hemangioblastoma. More recently, D2-40 immunoexpression has been reported in primary adrenal cortical tumors, schwannomas, and adnexal tumors of the skin. This brief review provides an update on the ever-expanding proposed applications of D2-40 immunohistochemistry in surgical pathology.

Immune response: A possible role in the pathophysiology of hemangioma.

Hemangioma is a distinct category of benign vascular tumors characterized by presentation within the first weeks of life, rapid growth during the first year and variable degree of spontaneous involution over a period of several years. Recent research reported that CD8+ T cells in hemangiomas, and the endothelia of hemangioma uniquely expressed leukocyte marker FCgammaRII and myeloid cell marker. Presence of high levels of indoleamine 2,3-dioxygenase in proliferating hemangiomas and significantly decreasing during involution was also confirmed. Topical application of imiquimod cream, an immune regulator, to proliferating hemangiomas apparently accelerated regression of the lesions. These findings suggest immune response may be involved in the pathogenesis of hemangioma. The endothelia of hemangioma may express various markers to escape the immune surveillance. An immune response may be one of the mechanisms for hemangioma regression. Strategies with systemically or locally applying immune regulator into the tumor may be an applicable way in accelerating the involution of hemangioma.

Benign lymphangioendothelioma (acquired progressive lymphangioma): a lesion not to be confused with well-differentiated angiosarcoma and patch stage Kaposi's sarcoma: clinicopathologic analysis of a series.

The clinicopathologic features of 12 cases of benign lymphangioendothelioma (acquired progressive lymphangioma) are reported. There were five male and seven female patients. Age at diagnosis ranged from 17 to 90 years (median age, 54 yrs). Development of a single macular/papular hemangiomatous or pigmented lesion was the main presenting symptom. Symptom duration before diagnosis ranged from 2 months to 20 years (median, 5.5 yrs). Tumor size ranged from 0.3 cm to 10 cm (median. 1.5 cm). Location included skin of the head and neck (n = 5), back (n = 1), breast (n = 1), shoulder (n = 1), forearm (n = 1), plantar aspect of the foot (n = 2), and oral mucosa (n = 1). No patient had any other concomitant vascular anomaly (for example, lymphangiomatosis) or was suspected to have acquired immunodeficiency syndrome. Treatment consisted of excisional biopsy in nine patients, incisional biopsy in two, and wide excision in one. Follow-up information on nine patients (range, 4-40 mos; median, 12 mos) showed two local recurrences in one patient. Microscopically, the lesions consisted of anastomosing, often widely dilated vascular structures developing in the superficial dermis. As the lesion grew within deeper dermis, the vascular spaces collapsed and dissected the dermal collagen in an angiosarcoma-like pattern. The lining endothelium was flat and monolayered, with little or no cytologic atypia and no evident mitoses. Some vascular structures contained stromal papillary projections resembling papillary endothelial hyperplasia, and intravascular red blood cells were present occasionally. Immunohistochemistry performed in eight specimens showed variable endothelial cell reactivity for CD31 (7 of 8), CD34 (7 of 7), and factor VIII-related antigen (4 of 6). A smooth muscle cell layer was observed focally around the vascular spaces in six lesions. Benign lymphangioendothelioma (acquired progressive lymphangioma) is an uncommon benign lesion that, in view of major differences in treatment and prognosis, should be distinguished from well-differentiated angiosarcoma and Kaposi's sarcoma, especially the patch stage and lymphangioma-like variants of the latter.

Benign lymphangioendothelioma.

We describe a 40-year-old white man with a red-brown, indurated plaque on the proximal aspect of his right thigh. The lesion had been present since birth, and the patient had a 20-year clinical history of recurrent cellulitis in the same area. The histopathologic features of the lesion included permeation of the dermis by flattened, endothelium-lined channels without cellular atypia, hemorrhage, or inflammation. The endothelial cells were stained intensely with monoclonal antibody anti-CD34 (clone MY10). In addition, antibodies to factor VIII antigen, HLA-DR, smooth muscle actin, ICAM-1, and the lectin Ulex europaeus labeled the luminal cells. The basement membrane of the channels stained with anti-type IV collagen and laminin. Desmin-positive cells were abundant adjacent to the channels. Factor XIIIa stained both mononuclear cells and occasional dendritic cells in the perivascular area. Ki-67 immunolabeling could not be demonstrated on fresh or frozen tissue. Electron microscopy revealed the presence of both tight junctions and a well-formed, continuous basement membrane but the absence of Weibel-Palade bodies.

Hepatic lymphangiomatosis: report of two cases, with an immunohistochemical study.

Two cases of hepatic lymphangiomatosis were examined. One tumor was noted incidentally at autopsy, and the other tumor was removed by operation. These liver tumors could not be detected by the naked eye, but ill-defined lace-like areas were seen. Microscopically, small cystic spaces were irregularly aggregated in the hepatic parenchyma and, in part, in the portal tracts. Faintly stained lymph-like material without any erythrocytes was found in the spaces. The silver impregnation method confirmed that most of the cystic lumina were dilated Disse's spaces. Also, some of them were directly connected with lymph vessels in the portal tracts. Thin lining cells along the internal surface of these cystic channels could not be positively stained by Ulex europaens 1 or factor 8-related antigen, both of which were present in the endothelium of the blood vessels in the portal tracts. We describe herein this rare lymphangiomatosis of the liver, with special reference to its immunohistochemistry.

Linfangiomiomatosis pulmonar y Linfangiomiomas: presentación de 8 casos y revisión de la literatura / Lymphangiomyomatosis and lymphangiomyomas: a study of 8 cases and review of the literature

Se presenta un estiduo clinicopatológico de 3 casos de linfangiomiomatosis pulmonar y mediastinal y de 5 linfangiomiomas de mediastino, retroperitoneo, mesenterio (2) y hombro. Seis pacientes fueron del sexo femenino y 2 del masculino, sus edades variaron de 19 meses a 47 años. Todos los pacientes presentaron grandes tumores por períodos que variaron de meses a muchos años, los cuales no afectaron su estado general. Cinco linfangiomiomas y un pulmón con linfangiomiomatosis se extirparon quirúrgicamente, a dos pacientes con linfangiomiomatosis solamente se les pudo biopsiar. Las lesiones midieron entre 12 y 32 cm de eje mayor, frecuentemente eran de aspecto multiquístico con pequeñas áreas sólidas. Microscópicamente, se observaron innumerables espacios quísticos, separados por septos tapizados con revestimiento endotelial y/o epitelial y dotados de músculo liso en haces. Un estudio inmunohistoquímico demostró que los quistes de la linfangiomiomatosis pulmonar tiene su orígen principalmente en conductos aéreos, mientras que los de los linfangiomiomas son exclusivamente de naturaleza vascular. Se informan 3 casos excepcionales en edad pediátrica (1 7/12, 9 y 11 años ) 2 localizaciones no descritas antes (mesenterio y hombro). Se presenta una revisión de las características clinicopatológicas de las dos formas de la enfermedad y su probale asociación con esclerosis tuberosa. Se discuten algunas ideas sobre la histogénesis y la etiopatogenia en estas lesiones de probable naturaleza hamartomatosa o corsistomatosa.

Clinical manifestations of brucellosis in cattle of the southern Darfur Province, western Sudan.

Ninety-seven adult Zebu cattle with hygromas, 32 with arthritis and two showing long calving intervals were investigated for brucellosis. 92 per cent of hygromatous cattle, 62 per cent of arthritic cattle and both animals having long calving intervals were serologically positive and 65 per cent of milk samples were positive by the Milk Ring Test. Hygromas were found on the jaw, bursa, thigh, flank, hip, shoulder, neck and joints. Hygroma aspirates gave higher titres than sera in the serum agglutination test. IgG1, IgG2 and IgA were detected in all the aspirates and all but one contained IgM. Cattle with hygromas are a potential source of infection to other animals and a serious public health problem.

Factor VIII-associated antigen in human lymphatic endothelium.

Lymphatic vascular endothelium both on tissue section and in culture exhibits positivity for Factor VIII-associated antigen although staining is generally less intense and more spotty than in comparable blood vascular endothelium. Lymphatic endothelium also exhibits Weibel-Palade bodies. Neither marker, therefore, reliably distinguishes blood vascular endothelium from lymphatic endothelium.

Peritoneal cystic mesothelioma: an electron microscopic and immunohistochemical study of two male patients.

The clinical, pathological, and ultrastructural features of two cases of peritoneal cystic mesothelioma occurring in men were studied. The results of immunohistochemical staining for CAM 5.2, epithelial membrane antigen, carcinoembryonic antigen, and Factor VIII related antigen are reported for the first time and compared with the staining results of two peritoneal cystic lymphangiomas. Although resembling cystic lymphangioma by light microscopy, cystic mesothelioma may have a greater tendency for local recurrence. Staining for CAM 5.2 or epithelial membrane antigen may facilitate the differentiation of these two entities.

Monoclonal antibodies to blood group isoantigens: an alternative marker to factor VIII related antigen for benign and malignant vascular endothelial cells.

Monoclonal antibodies to A, B and H blood group isoantigens (BGI) were used in an indirect immunoperoxidase technique to compare the distribution of BGI expression as a marker of vascular endothelial cells with that of coagulation factor VIII related antigen (F VIII-RAg), a well established marker for vascular endothelium. Formalin-fixed and paraffin-embedded material from 70 specimens representing a wide range of reactive and benign or malignant neoplastic states of the vascular endothelium was used to provide adjacent serial tissue sections to compare directly the tissue expression of BGI and of F VIII-RAg. In reactive and benign neoplastic conditions of the vascular endothelium, cell membrane expression of the BGI appropriate to the patient's blood group was readily detected. In the more cellular and proliferative areas of some haemangiomas, pyogenic granulomas and cases of angiolymphoid hyperplasia with eosinophilia, BGI proved a superior marker of the endothelial cells compared with F VIII-RAg. The malignant endothelial cells of 27 specimens of angiosarcoma showed deletion of BGI expression in 24 and of F VIII-RAg in 19. Expression of neither antigen showed any significant correlation with the degree of tumour differentiation. Some cases of lymphangioma, uniformly negative for F VIII-RAg staining, showed strong expression of BGI. The possible use of BGI expression as a marker of vascular endothelium is discussed in the light of the known tissue expression of F VIII-RAg.

Demostración inmunohistoquímica del factor VIII en tumores de posible origen endotelial / Inmunohistochemical demonstration of factor VIII in tumors presumably of endothelial origin

Se estudiaron 46 tumores de presunto origen vascular, los que fueron divididos en 4 grupos. 1) Tumores vasculares en los que se incluyeron 5 angiomas cavernosos, 5 capilares, 5 linfangiomas y 2 hemangioendoteliomas, 2) Tumores con un conspicuo componente vascular; 5 angiomas, 5 angiofibromas nasofaríngeos, 5 tumores glómicos y 1 hemangiopericitoma. 3) Mixomas cardíacos, 3 casos. 4) Sarcoma de Kaposi, 10 casos. Todos los casos estaban fijados en formal e incluidos en parafina y se intentó la demostración del antígeno relacionado con el factor VIII (F VIIIR: Ag) mediante el método de peroxidasa-antiperoxidasa. Todos los tumores de los dos primeros grupos presentaron positividad de las células endoteliales de intensidad variable. Los elementos musculares, pericíticos y fibroblásticos fueron negativos. Los vasos de 2 de los 3 mixomas cardíacos eran positivos pero las células tumorales del estroma negativos. En los sarcomas de Kaposi los vasos neoplásicos eran fuertemente positivos y en 3 de los casos se tiñeron las células fusiformes del estroma. Este trabajo demuestra que la marcación con F VIIIR: Ag es un método sensible y reproducible para la demostración del origen endotelial de un tumor. En los sarcomass de Kaposi confirma la controvertida diferenciación en sentido endotelial de las células fusiformes. El presunto origen endotelial de los mixomas cardíacos no ha podido ser confirmado

Immunoperoxidase localization of factor VIII in angiosarcomas.

Factor VIII-related antigen was studied in 28 cases of angiosarcoma from different sites by means of the immunoperoxidase technique. Positive immunostaining was observed in 23 cases. Five cases composed preponderantly of solid areas, with little vasoformative activity, showed negative immunostaining. This technique is of value in diagnosing tumors of endothelial origin.

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.

Pulmonary lymphangiomyomatosis. Demonstration of smooth muscle antigens by immunofluorescence technique.

A case is reported of pulmonary lymphangiomyomatosis in 44-year-old woman presenting with progressive exertional dyspnoea, unproductive cough and haemoptysis. The patient showed no symptoms or signs of tuberous sclerosis, a condition often found in association with pulmonary lymphangiomyomatosis. A pulmonary biopsy specimen showed disruption of alveolar septa and fibrosis. Subpleural lymph vessels and pulmonary venules showed cuffs of spindle-shaped cells. The leiomyomatous nature of these cells was evident from their appearance and staining reactions with light microscopy, and the presence of smooth muscle antigens as demonstrated by immunofluorescence technique. Since the lesion is not restricted to lymphatics, but can also be present in blood vessels, the condition may more appropriately be designated as pulmonary angiomyomatosis.