Thrombomodulin as a marker for vascular tumors. Comparative study with factor VIII and Ulex europaeus I lectin

Thrombomodulin (TM) is a newly described endothelial cell-associated protein that functions as a potent natural anticoagulant by converting thrombin from a procoagulant protease to an anticoagulant. Various vascular tumors were characterized with immunoperoxidase staining with the use of a polyclonal anti-TM serum. The staining patterns of TM were compared with those of Factor VIII-related antigen (FVIII-RAG) and Ulex europaeus agglutinin-I (UEA-I), which have been used as markers for endothelial cells. The results showed that TM is a specific and a highly sensitive marker for angiosarcomas in comparison with FVIII-RAG or UEA-I. In contrast, UEA-I is more sensitive for benign vascular tumors than TM or FVIII-RAG. The other mesenchymal tumors of nonvascular origin showed negative staining for three endothelial markers. These results indicate that TM is a new specific and sensitive tool for the diagnosis of angiosarcomas.     

D2-40 and podoplanin are highly specific and sensitive immunohistochemical markers of epithelioid malignant mesothelioma

Recent investigations have shown that podoplanin and the D2-40 monoclonal antibody, which reacts with an oncofetal antigen present in fetal germ cells, are highly reliable lymphatic endothelial markers. The observation that both of these markers are also expressed in normal and reactive mesothelial cells prompted an investigation into their potential value in the diagnosis of mesotheliomas. To determine whether podoplanin and D2-40 had any use in the diagnosis of these tumors, 40 mesotheliomas (29 epithelioid, 5 biphasic, and 6 sarcomatoid), 34 carcinomas of the lung (24 adenocarcinomas, 10 squamous carcinomas), 80 nonpulmonary adenocarcinomas (17 ovary, 10 breast, 10 colon, 10 kidney, 5 endometrium, 5 stomach, 5 pancreas, 5 prostate, 3 thyroid), 12 synovial sarcomas (6 biphasic and 6 monophasic), 5 angiosarcomas, and 2 adenomatoid tumors were immunostained with a monoclonal antibody to podoplanin and with the D2-40 antibody. Reactivity for both D2-40 and podoplanin was obtained in 25 (86%) of the 29 epithelioid mesotheliomas but in none of the carcinomas or sarcomatoid mesotheliomas. Positivity for D2-40 and podoplanin was also seen in the epithelioid components of 4 of 5 biphasic mesotheliomas and 4 of 6 synovial sarcomas, whereas the spindle cell components of these tumors were negative as were the monophasic synovial sarcomas. Two (40%) of the 5 angiosarcomas expressed these markers, thus confirming previous reports suggesting that some angiosarcomas may have lymphatic endothelial differentiation. Both of the adenomatoid tumors were also positive for D2-40 and podoplanin, a finding which provides further support for the mesothelial derivation of these tumors. It is concluded that, because of their high specificity and sensitivity for epithelioid mesotheliomas, D2-40 and podoplanin are very useful markers for the diagnosis of these tumors. When compared with the other markers that are currently available, in my opinion, they appear to be the best.     

Comparison of Ulex europaeus I lectin and factor VIII-related antigen in vascular lesions

Factor VIII-related antigen (FVIIIR:Ag) has been widely used as a marker for endothelial cells. Recent studies have shown that Ulex europaeus agglutinin I lectin (UEAI) also binds specific endothelial cells. To determine the relative utility of the two endothelial cell markers, a group of vascular and nonvascular tumors were studied with both markers, using an immunoperoxidase method. Our results indicate that UEAI is a more sensitive marker for endothelial cells than FVIIIR:Ag, and that it should be used as an additional diagnostic marker for endothelial cell-derivated tumors.     

Ulex europaeus I lectin as a marker for tumors derived from endothelial cells

Some skin and soft tumors, which generally are assumed to be derived from endothelial cells or blood vessels, were characterized with fluorochrome-labeled Ulex europaeus I agglutinin (UEA I), recently shown to bind specifically to endothelial cells in various normal human tissues. The staining pattern was compared with that obtained with immunostaining using antibodies against factor-VIII-related antigen (FVIII-RAG), a known marker for endothelial cells. The results showed that UEA-I is a specific and a more sensitive marker for the endothelial cells in benign vascular lesions as compared with anti-FVIII-RAG. UEA-I also stained many neoplastic cells of endothelial sarcomas, which generally were negative for FVIII-RAG. Melanomas, anaplastic carcinomas, and other types of sarcomas were negative for both UEA-I and FVIII-RAG. The results suggest that UEA-I lectin is a specific and sensitive adjunct tool in demonstrating endothelial cells and endothelial derivation of human tumors.     

Angiosarcomas express mixed endothelial phenotypes of blood and lymphatic capillaries: podoplanin as a specific marker for lymphatic endothelium

Angiosarcomas apparently derive from blood vessel endothelial cells; however, occasionally their histological features suggest mixed origin from blood and lymphatic endothelia. In the absence of specific positive markers for lymphatic endothelia the precise distinction between these components has not been possible. Here we provide evidence by light and electron microscopic immunohistochemistry that podoplanin, a approximately 38-kd membrane glycoprotein of podocytes, is specifically expressed in the endothelium of lymphatic capillaries, but not in the blood vasculature. In normal skin and kidney, podoplanin colocalized with vascular endothelial growth factor receptor-3, the only other lymphatic marker presently available. Complementary immunostaining of blood vessels was obtained with established endothelial markers (CD31, CD34, factor VIII-related antigen, and Ulex europaeus I lectin) as well as podocalyxin, another podocytic protein that is also localized in endothelia of blood vessels. Podoplanin specifically immunolabeled endothelia of benign tumorous lesions of undisputed lymphatic origin (lymphangiomas, hygromas) and was detected there as a 38-kd protein by immunoblotting. As paradigms of malignant vascular tumors, poorly differentiated (G3) common angiosarcomas (n = 8), epitheloid angiosarcomas (n = 3), and intestinal Kaposi's sarcomas (n = 5) were examined for their podoplanin content in relation to conventional endothelial markers. The relative number of tumor cells expressing podoplanin was estimated and, although the number of cases in this preliminary study was limited to 16, an apparent spectrum of podoplanin expression emerged that can be divided into a low-expression group in which 0-10% of tumor cells contained podoplanin, a moderate-expression group with 30-60% and a high-expression group with 70-100%. Ten of eleven angiosarcomas and all Kaposi's sarcomas showed mixed expression of both lymphatic and blood vascular endothelial phenotypes. By double labeling, most podoplanin-positive tumor cells coexpressed endothelial markers of blood vessels, whereas few tumor cells were positive for individual markers only. From these results we conclude that (1) podoplanin is a selective marker of lymphatic endothelium; (2) G3 angiosarcomas display a quantitative spectrum of podoplanin-expressing tumor cells; (3) in most angiosarcomas, a varying subset of tumor cells coexpresses podoplanin and endothelial markers of blood vessels; and (4) all endothelial cells of Kaposi's sarcomas expressed the lymphatic marker podoplanin.     

Hepatic sinusoidal endothelium: Ulex lectin binding

The sinusoidal endothelial cells of human liver can be identified by light and electron microscopy, but there appear to be no specific immunocytochemical markers of these cells. Among specific markers available for vascular endothelial cells in general, Ulex europaeus I lectin (UEA I) is the most sensitive. In the present study, 37 liver biopsies were examined for UEA I binding and for Factor VIII related antigen (F VIII RAg) to determine if sinusoidal endothelial cells were positive. The material included normal liver, biopsies from patients with cirrhosis and biopsies in a variety of other liver diseases. Three embryonal human livers were also included in the immunocytochemical analysis. Eleven oesophageal rings obtained at mechanical transection for variceal bleeding in cirrhotic patients were used as control tissue. Sinusoidal endothelial cells of normal liver did not stain with UEA I, but six of seven with alcoholic cirrhosis and only one of 25 non-cirrhotic liver specimens (a case of acute hepatitis with bridging necrosis) were positive. In two of the six cirrhoses the sinusoidal endothelial cells were stained for F VIII RAg as well. Embryonal sinusoidal endothelial cells were stained with UEA I but were negative for F VIII RAg. The results of the study confirm that sinusoidal endothelial cells of normal adult human liver are phenotypically different from those lining blood vessels in other sites. In cirrhosis, positive staining may be related to the transformation of hepatic sinusoids into true capillaries and thus be a marker of the severity of physiological disturbance in the liver.     

Expression of D2-40 in lymphatic endothelium of normal tissues and in vascular tumours

AIMS: To evaluate the expression of D2-40 in normal lymphatic endothelium and vascular tumours or tumour-like lesions of the skin and soft tissue. D2-40 is a novel monoclonal antibody to a Mr 40 000 O-linked sialoglycoprotein that reacts with a fixation-resistant epitope in lymphatic endothelium. METHODS AND RESULTS: Formalin-fixed paraffin-embedded sections from 30 normal tissue samples, including skin, soft tissue, stomach, and colon, and 84 vascular tumours or vascular tumour-like lesions were immunostained with monoclonal antibodies to D2-40 and CD31. Normal lymphatic endothelial cells in all normal tissues expressed D2-40. Its positive staining delineated flattened channels or open spaces lined by a single layer of endothelial cells whose lumena were sometimes filled with lymphocytes. Ten of 10 cases of lymphangioma, nine of 10 Kaposi's sarcomas (KSs), one of five spindle cell haemangiomas, one of one reactive angioenodotheliomatosis, one of one vascular transformation of lymph node sinuses, three of three Dabska tumours, one of 10 epithelioid haemangioendotheliomas (HEs) and seven of 15 angiosarcomas were positive for D2-40. Positively staining angiosarcomas were characterized by epithelioid or papillary endothelial cells. Twenty-two non-spindle cell haemangiomas, one retiform HE and one Kaposiform HE, and five glomus tumours were negative for D2-40. In comparison, CD31 was expressed in five of 10 lymphangiomas, nine of 10 KSs, 27 of 27 haemangiomas, three of three Dabska tumours, 10 of 10 epithelioid HEs, 15 of 15 angiosarcomas and one of one each of retiform HE, Kaposiform HE, reactive angioendotheliomatosis, and vascular transformation of node sinuses. Five glomus tumours were negative for CD31. CONCLUSIONS: The monoclonal antibody D2-40 is a highly sensitive and specific marker of lymphatic endothelium in normal tissue and a subset of vascular lesions, including KS, Dabska tumour, and lymphangioma. The findings support the concept that these tumours show at least partial lymphatic endothelial differentiation. Subsets of angiosarcomas and HEs show both vascular and lymphatic endothelial differentiation. D2-40 can be used in a panel of markers to classify vascular tumours. There is no requirement for epitope retrieval. This novel monoclonal antibody also has the potential for increasing the accuracy of detection of lymphatic invasion in primary tumours and could be widely applied for this purpose in surgical pathology.     

Epithelioid sarcoma and epithelioid hemangioendothelioma: an immunocytochemical and lectin-histochemical comparison

Summary Epithelioid sarcoma (ES) and epithelioid hemangioendothelioma (EH) both occur preferentially in the soft tissues, and may be confused with one another microscopically. We compared 8 examples of each tumor immunohistochemically, using formalin-fixed tissue, the ABC method, unconjugatedUlex europaeus I agglutinin (UEA), rabbit antibody to UEA, and monoclonal antibodies to epithelial membrane antigen (EMA), cytokeratin (CK), factor VIII-related antigen (FVIIIRAG), and blood group isoantigens A, B, and H (BGI). Six of 8 cases of ES, and 7 of 8 epithelioid hemangioendotheliomas bound UEA; similarly, 6 of 8 ES cases were reactive for BGI, as were 4 of 8 examples of EH. All epithelioid sarcomas were positive for CK, and 7 displayed EMA, whereas these antigens were lacking in EH. Conversely, 5 of 8 cases of EH contained FVIIIRAG, which was absent in all examples of ES. These findings underscore the nonspecificity of UEA-binding and BGI-expression as markers of endothelial differentiation. Moreover, they suggest that sole reliance upon these immunohistologic reactants for the identification of vascular tumors may result in diagnostic error. Inasmuch as ES and EH differ in biological behavior, such a mistake would be significant. Thus, we advocate the inclusion of immunostains for EMA, CK, and FVIIIRAG in the evaluation of histologically-similar cases of epithelioid sarcoma and epithelioid hemangioendothelioma.Presented at the Seventy-fifth Annual Meeting of the International Academy of Pathology (United States-Canadian Division), New Orleans, Louisiana, USA, March 11, 1986Dr. Wick is a recipient of a Career Development Award in Oncology from the American Cancer Society     

Different immunoreactivity of endothelial markers in well and poorly differentiated areas of angiosarcomas

This study evaluated the immunohistochemical staining of four endothelial cell markers in well differentiated and poorly differentiated areas of angiosarcomas. Formaldehyde-fixed, paraffin-embedded sections from eight angiosarcomas were studied using the antibodies anti-factor VIII-related antigen (FVIII-RA), Ulex europaeus I agglutinin, anti-CD34 (QBEND/10) and anti-CD31 (JC70). The immunostaining of the angiomatous (well differentiated) and solid (poorly differentiated) areas was separately analysed and specificity was evaluated in 20 non-vascular tumours. The antibody anti-CD31 and Ulex europaeus were the most sensitive markers staining well differentiated vasoformative structures and poorly differentiated solid areas. Anti-FVIII-RA and anti-CD34 did not stain undifferentiated malignant endothelial cells from solid areas. Ulex europaeus and anti-CD34 showed very low specificity; in contrast, none of the non-vascular tumours expressed CD31 or FVIII-RA. JC70 (anti-CD31) appears to be the most useful marker in elucidating the vascular nature of angiosarcomas. Is important to emphasize the lack of specificity of Ulex europaeus and the low sensitivity of anti-CD34 and anti-FVIII-RA for poorly differentiated lesions.     

JC70: a new monoclonal antibody that detects vascular endothelium associated antigen on routinely processed tissue sections.

A new monoclonal antibody, JC70, raised against a membrane preparation from a spleen affected by hairy cell leukaemia, recognises a membrane bound glycoprotein identical with that of the CD31 group of monoclonal antibodies. The antibody stains a fixation resistant epitope on endothelial cells in benign and malignant conditions in a wide variety of paraffin wax embedded tissue. JC70 stained malignant endothelial cells in 10 angiosarcomas with more consistency than monoclonal or polyclonal antibodies to factor VIII related antigen (FVIII-Rag). In four cases of Kaposi's sarcoma the antibody stained malignant endothelial cells but not spindle cells. It is concluded that antibody JC70 is of value for studying benign and malignant human vascular disorders in routinely processed tissue.     

Monoclonal antibodies to detect markers specific for tumors

Monoclonal antibodies to different markers can facilitate the diagnosis of T and B cell lymphomas, histiocytic lymphomas, malignant histiocytosis, and Hodgkin's disease. The B-cell lymphomas can be identified specifically by monoclonal anti-idiotype antibodies. Monoclonal antibodies are produced to defined markers like carcinoembryonic antigen (CEA) in colon carcinomas and other antigens especially of breast and ovarian carcinomas. When conjugated with 123I, monoclonal antibodies can be used to detect tumors by emission computerized tomography. Chromogranins are markers for neuroendocrine tumors, and they can be identified by monoclonal antibodies. More recently monoclonal antibodies have been produced to ras gene product p21, present in breast and colon carcinoma cells.     

Cytokeratin expression in epithelioid vascular neoplasms.

Seven epithelioid and eight non-epithelioid vascular tumors were studied by the avidin-biotin-peroxidase method for the presence of endothelial- and epithelial-associated markers, using Ulex europaeus agglutinin-1 (UEA-1) lectin, and antibodies directed against factor VIII-related antigen, (FVIII-RA), vimentin, keratin, carcinoembryonic antigen, and epithelial membrane antigen. The cases included four epithelioid hemangiomas, two epithelioid hemangioendotheliomas (EHE), one epithelioid angiosarcoma (EAS), four common non-epithelioid capillary hemangiomas, and four non-epithelioid angiosarcomas. Staining for FVIII-RA, UEA-1, and vimentin were observed in all cases. The EAS showed staining for keratin in formalin-fixed, paraffin-embedded sections and in frozen sections. Staining for keratin was also observed in frozen sections of one EHE. Both keratin-positive vascular tumors were confirmed with electron microscopy. Carcinoembryonic antigen and epithelial membrane antigen stains were negative in all cases. Our results show that the epithelioid vascular tumors EHE and EAS, in addition to staining for the endothelial markers and vimentin, may also express the epithelial marker keratin. This is important since these tumors may closely resemble carcinomas by routine light microscopy. This study further underscores the importance of using a broad panel of immunohistochemical markers in the diagnostic workup of soft-tissue neoplasms.     

AN IMMUNOCYTOCHEMICAL ASSESSMENT OF 19 CASES OF CUTANEOUS ANGIOSARCOMA

Four endothelial cell markers, two selective cytokeratin markers and a monoclonal smooth muscle antibody (SMA) were employed in the assessment of 19 cases of cutaneous angiosarcoma classified according to their degree of tumour differentiation. No labelling was seen for SMA or with cytokeratin markers MNF116 and CBL170. Expression of factor VIII-related antigen was seen in two tumours and positivity for CD34 (QBend 10 antibody) was found in four tumours. By contrast the pan-endothelial cell marker Ulex europeaus agglutinin 1 (UEA-1) and the CD31 marker JC70A labelled all cases of cutaneous angiosarcoma with the exception of one poorly differentiated tumour. These data confirm the endothelial cell origin of angiosarcoma, they demonstrate that CD31 and UEA1 are reliable markers in routinely processed tissue, and they suggest a lymphatic derivation for the tumour. This finding is in marked contrast to Kaposi's sarcoma where CD34 is the most reliable marker.     

Distribution of keratins in normal endothelial cells and a spectrum of vascular tumors: implications in tumor diagnosis

Vascular endothelial cells are specialized mesenchyme-derived epithelial-like lining cells which are the essential participants in benign and malignant vascular tumors. Although endothelia in lower animals often express keratins (K), human endothelia are generally K negative and vimentin-positive. However, K expression has been noted in some endothelia and in some epithelioid vascular tumors. In this study, we systematically examined normal human vascular endothelia and a spectrum of human vascular tumors (n = minimum of 137 tumors with each marker) for simple epithelial keratin polypeptides of the Moll catalogue (K7, K8, K18, and K19). Selected vascular tumors were also evaluated with antibodies to K14 and the monoclonal antibody 34betaE12 that recognizes several keratins of stratified epithelia. Endothelia of normal veins, venules, and lymphatics commonly exhibited focal positivity for K7 and K18, whereas K8, K14, and K19 were not seen in non-neoplastic endothelia with the antibodies used. Lymphangiomas (6 of 7) and venous hemangiomas (6 of 13) often showed K7-positive endothelial cells; K18 was detected less commonly, whereas K8 and K19 were not detected. Epithelioid hemangioendotheliomas (EHEs) showed K7 and K18 expression in the majority of cases (50% and 100%, respectively), while K8 was seen in 10% cases and K14 and K19 in none. In contrast, epithelioid angiosarcomas (EAs) were often positive for K8 and K18 (approximately 50%), whereas they less commonly showed K7 and only occasionally K19; all tumors were negative for K14 and with the antibody 34betaE12. Nonepithelioid angiosarcomas (AS) less commonly showed keratin expression with K7, K8, and K18 being positive in 20% of cases, and K14 and K19 in none of the cases. Epithelial membrane antigen (EMA) was occasionally detectable in EHE (2/19) but was present in 4 of 16 (25%) EAs and 17 of 48 (35%) nonepithelioid AS. These findings document the common presence of focal reactivity for K7 and K18 in subsets of normal endothelia and also the frequent presence of simple epithelial keratins in malignant vascular tumors, while such expression is uncommon in nonepithelioid angiosarcomas. K- and EMA-positivity in neoplastic endothelia needs to be considered in the evaluation of human tumors. K antibodies such as those specific to K19 or AE1 that do not react with K8 and K18 should be used in the differential diagnosis of epithelioid vascular tumors and carcinomas.     

Small Bleeding Hemangiosarcoma of the Jejunum: Case Report and Immunocytochemical Findings

Abstract

A case of a 68-year old man with intestinal bleeding caused by a small hemangiosarcoma in the jejunum is reported. Tissue specimens were examined by light microscopy with classical histochemical techniques and the immunogold-silver staining method in combination with silver acetate autometallography. Monoclonal and polyclonal antibodies to various tissue type markers and lymphocyte associated antigens were employed. Factor VIII-related antigen was negative in the neoplastic cells but positive in most endothelial cells of veins and some capillaries of the adherent tissue. However, antibodies to vimentin, the endothelial marker BMA 120, and Ulex europeus I agglutinin (UEA I) lectins gave strongly positive reactions throughout the lesion and in endothelial cells of all vessels. T lymphocytes as well as neuronal and glial structures were detected between the proliferating cells. (The J Histotechnol 13:141, 1990)     

Differential expression of markers for endothelial cells, pericytes, and basal lamina in the microvasculature of tumors and granulation tissue.

The structure and function of the tumor microvasculature is of great interest for cancer biology, diagnosis, and therapy. The distribution of endothelial cells, pericytes, and basal lamina in tumors is not well documented. In this study, the authors investigated the distribution of markers for these different components in a series of malignant human tumors and in human granulation tissue, both situations with extensive angiogenesis. Their results show a striking heterogeneity in the expression of markers for pericytes and endothelial cells between different tumors, but also within a single tumor lesion. To be able to distinguish between these two adjacent cell types decisively, all marker studies were carried out both on the light and the electron microscopical level and compared with staining results in granulation tissue of cutaneous wounds in healthy volunteers and of decubitus lesions. In granulation tissue of decubitus lesions, well-defined zones with increasing levels of maturation can be delineated. It was found that antibodies recognizing von Willebrand factor often failed to stain the tumor capillaries. Of the pericyte markers, alpha-smooth muscle actin was only locally expressed by pericytes in the tumor vasculature, whereas the high-molecular-weight melanoma-associated antigen, a chondroitin sulfate proteoglycan, stained the microvasculature broadly. Staining of the basal lamina components collagen type IV and laminin was, within the tumor, not restricted to the microvasculature. From their findings the authors conclude that 1) for the visualization of the tumor vasculature, antibodies recognizing endothelial markers, especially monoclonal antibodies PAL-E and BMA 120, are preferable to those recognizing pericytes or basal lamina; 2) within the microvasculature of tumors and granulation tissue, a heterogeneity of expression of endothelial and pericyte markers is observed; 3) during the formation of granulation tissue, all three microvascular components can be demonstrated already in the histologically earliest stage, suggesting not only an involvement of endothelial cells but also of pericytes and basal lamina in the initial steps of angiogenesis in wound healing.     

Expression of a lymphatic endothelial cell marker in benign and malignant vascular tumors

Tumors of endothelial cell origin are relatively common. Soft tissue tumors and numerous subtypes of benign and malignant vascular tumors have been described; the histogenesis of many of these tumors is uncertain, and distinguishing between benign and malignant vascular tumors, some of which express lymphatic endothelial cell markers, can be problematic. In the present study, immunophenotypic expression of a novel hyaluronan receptor (LYVE-1), which is expressed by endothelial cells of normal lymphatic vessels but not blood vessels, was determined in benign and malignant vascular tumors. It was found that, except in lymphangiomas, intramuscular hemangiomas, and Masson's hemangiomas, endothelial cells in benign blood vessel tumors (including capillary and cavernous hemangiomas, glomus tumors, pyogenic granulomas, and epithelioid hemangiomas) were negative for LYVE-1, and that all angiosarcomas and Kaposi's sarcomas were positive for LYVE-1. Expression of LYVE-1 and other lymphatic endothelial cell markers in relatively few vascular neoplasms has implications for the histogenesis of these lesions, and may prove useful in distinguishing angiosarcoma and Kaposi's sarcoma from most common benign vascular tumors.     

The histogenesis of angiosarcoma of the face and scalp: an immunohistochemical and ultrastructural study

Thirteen cases of angiosarcoma of the face and scalp have been examined using immunohistochemistry and electron microscopy. Endothelial cell markers have been employed in an immunoperoxidase technique on tissue that has either been routinely processed, periodate-lysine paraformaldehyde fixed (PLP) and cold processed, or fixed in methacarn. A consistent pattern of endothelial cell labeling was only achieved in the PLP fixed tissue. In this fixative the angiosarcomas were factor VIII related antigen negative, Ulex europaeus lectin positive, laminin positive, unlabelled by the monoclonal antibody PAL-E, and positively labelled by the monoclonal antibody EN4. Ultrastructural examination of four cases showed evidence of vascular lumina in all tumours. Weibel-Palade bodies were seen in only one case but three tumours showed some evidence of tight junction formation and marginal folding. Thus, our cell marker studies can be interpreted as consistent with a lymphatic derivation for this type of angiosarcoma but in contra-distinction the ultrastructural studies showed tumour channels with features suggestive of blood vessel differentiation.     

Heterogenous expression of endothelial cell markers in infantile hemangioendothelioma. Immunohistochemical study of two solitary cases and one multiple one

Three cases of infantile hemangioendothelioma were immunohistochemically studied with the use of antibodies against von Willebrand factor (vWF), Ulex europaeus I lectin (UEA I), vimentin, thrombomodulin (TM), and actin, as endothelial cell (EC) markers. Because of a broad variety of histologic features, the growth pattern of the tumor cells was subclassified into the following four subtypes: capillary, sinusoidal, cavernous, and myxomatous parts. The solitary tumor from patients 1 and 2 was composed of these four components, but the multiple tumor in the patient 3 consisted of capillary and sinusoidal parts. Immunohistochemically, vWF and vimentin were dominantly expressed in the ECs of the cavernous and myxomatous parts. UEA I had strongly positive results in all histologic types, except the myxomatous part. Expression of vWF and vimentin in neoplastic EC suggests that functional differentiation of the tumor tissue occurs in the myxomatous and cavernous parts and may be related to the spontaneous regression of the infantile hemangioendothelioma.