Incidental simultaneous finding of intravascular histiocytosis and reactive angioendotheliomatosis: a case report.

Reactive angioendotheliomatosis (RAE) is a rare cutaneous vascular disorder characterized by intravascular hyperplasia of endothelial cells, sometimes with a vascular proliferation. Intravascular histiocytosis (IH) is a similar vascular disorder characterized by the presence of dilated vessels containing aggregates of mononuclear histiocytes (macrophages) within their lumina. Although their pathogenesis remains uncertain, there has been speculation about the possible relationship between IH and RAE. We report a case of coexistence of RAE and IH in a patient who underwent a wide reexcision of a metastatic malignant melanoma. The excision specimen did not show any residual melanoma but exhibited an intravascular collection of CD-68-positive histiocytes admixed with CD-31-positive endothelial cells and fibrin surrounded by D2-40-positive vascular wall. The presence of intravascular cells initially raised concern of intravascular invasion by melanoma. As there was no clinical lesion and immunohistochemical stains for melanocytic makers were negative, we interpret this as an incidental finding. Knowledge of this benign vascular disorder is important because the histologic changes may be mistaken for intravascular invasion of a malignant neoplasm.

A rare case of cutaneous kaposiform haemangioendothelioma.

Kaposiform haemangioendothelioma is a rare vascular neoplasm with a wide anatomical distribution. We describe an unusual case arising in the post-auricular skin of a male infant overlying a ventriculoperitoneal shunt.

Infantile hemangioendothelioma of the liver in a neonate. Immunohistochemical observations.

The study documents the immunohistochemical features of a case of infantile hemangioendothelioma (IHE) of the liver, which was found incidentally at autopsy in a 44-day-old girl. A precardial apical systolic murmur and hepatomegaly were found on day 4 of life. The tumor was multifocal and histologically composed of vascular channels lined by endothelial cells that were positive for von Willebrand factor, CD31, vimentin, and Ulex europaeus agglutinin 1, and that were invested in a continuous basement membrane (BM) on the antiluminal border. The endothelial cells, especially in the region of intravascular buds, showed intracytoplasmic synthesis of BM components (laminin and collagen IV). Underlying the endothelial cells were cells with cytoplasm that was positive for alpha-smooth muscle actin and antimuscle actin and negative for desmin, and that were enveloped with BM. The immunophenotype, appearance, and location of these cells are characteristic of pericytes. We found neither signs of endocrine secretion nor hepatitis B virus in the tumor tissue. The appearance of this tumor in the neonatal period supports a fetal origin of IHE.

Retiform haemangioendothelioma.

A case of retiform haemangioendothelioma (RH), a recently described rare cutaneous low-grade angiosarcoma, is presented. A 75-year-old female had a 3.5 cm cutaneous nodule in her right lower thigh with 10 year preoperative duration. Microscopically, the dermis and subcutis contained a diffuse and infiltrative neoplasm which was characterized by long arborizing blood vessels arranged in a retiform pattern lined by cuboidal and flattened cells, occasional hobnail appearance of endothelial cells, and a prominent small lymphocytic infiltrate. Small solid areas were also found. Neither significant cellular atypia nor mitotic activity was observed. Immunohistochemically, the tumour cells reacted with endothelial markers (CD31, CD34, factor-VIII-related antigen) and bound Ulex europaeus agglutinin 1. There was no pericytic component within the tumour. The tumour was diploid by flow cytometry. The patient had a local recurrence 27 months after the excision. These findings support the view that RH is a low-grade angiosarcoma and indicate that RH must be distinguished from conventional angiosarcoma.

A novel soluble form of mouse VCAM-1 is generated from a glycolipid-anchored splicing variant.

VCAM-1 is a cytokine-induced endothelial adhesion molecule which belongs to the immunoglobulin (Ig) superfamily and mediates the binding of various leukocytes. In addition to the 110-kDa form of VCAM-1, we have found four additional glycoproteins on mouse brain-derived endothelioma cells after stimulation with tumor necrosis factor-alpha (TNF-alpha), which are recognized by several monoclonal antibodies against VCAM-1. Biochemical analysis revealed that the two smaller proteins (35 kDa and 37 kDa) are intracellular precursors of the two larger forms (44 kDa and 45 kDa), that the 44 kDa and 45 kDa proteins are glycolipid-anchored at the cell surface and that they differ in their N-glycosylation. Most likely they are identical to the recently identified glycolipid-anchored splice variant of VCAM-1, since they are recognized by the M3 antiserum which we raised against a peptide from the unique protein domain of this splicing variant. With the help of this antiserum we could show by immunohistology that the corresponding VCAM-1 protein variant is induced in vivo by lipopolysaccharide (LPS) on endothelium of the mouse. In addition, we found a 42-kDa soluble form of VCAM-1 in the serum of LPS-stimulated mice, which was recognized by the M3 antiserum. This soluble form was undetectable in the serum of unstimulated mice in contrast to the soluble 100-kDa form of VCAM-1 which was clearly detected in serum of unstimulated mice and only increased 2-3-fold upon stimulation with LPS. Thus, only the expression of the 42-kDa shredded form and not of the 100-kDa soluble form of VCAM-1 is strictly dependent on stimulation by LPS.

Neoplastic angioendotheliomatosis: a treatable "vascular dementia" occurring in an immunosuppressed transplant patient.

A 53-year-old right-handed woman presented with headaches and dizziness. She had been well for ten years following successful cadaveric renal transplantation and was taking prednisolone and azathioprine. Two months later she had more headaches with transient dominant hemisphere disturbances and then suffered a completed right hemisphere deficit. As this was recovering, she developed an ischemic optic neuropathy, Computerized tomography (CT) was then normal although CSF analysis showed lymphocytosis and high protein. Steroid trial led to dramatic symptomatic and clinical recovery. On tailing off steroids, progressive bilateral hemisphere disturbance occurred. She was bedbound, with fever, headache, incontinence and disturbed consciousness. New evidence of infarction in watershed territories on CT led to temporal lobe biopsy. Cortical arterioles and venules showed proliferation of lymphoid cells staining for leucocyte common antigen and B-cell markers characteristic of Neoplastic Angioendotheliomatosis (NAE). After chemotherapy she regained independence and mobility and CSF protein fell. This is the first case of NAE to our knowledge in association with immunosuppression for renal transplant and is further evidence that NAE is malignant lymphoma. Cerebrovascular disease is common in such patients, the simultaneous events in differing territories is typical of NAE. Response to chemotherapeutic agents occurred although the typical natural history was unchanged.

Protein kinase C activation in murine endothelioma cell lines containing middle T antigen stimulated by platelet-activating factor.

Murine endothelial cell lines containing middle T antigen provide a good model to study the biology of capillary cells of different anatomical districts. These cell lines obtained from skin (sEnd.1), brain (bEnd.4), thymus (tEnd-1) and embryo tissue (eEnd.1) are activated by platelet-activating factor (PAF). PAF, but not lyso-PAF or the enantiomer (S)-PAF, induces the rapid translocation of protein kinase C (PKC) from the cytosol to the membrane. Maximal translocation of the enzyme is achieved after 5 min in all cell lines tested. The ED50 of PAF able to promote PKC translocation has a value of 5 nM in sEnd.1, bEnd.4 and eEnd.1, and 20 nM in tEnd.1, suggesting a different sensitivity between these cell lines. The data indicate that PAF activates capillary cells, thus explaining its activation of microvascular beds.

Intravascular lymphomatosis: report of an unusual case with T cell phenotype occurring in an adolescent male.

Intravascular lymphomatosis is a rare disorder which most often occurs in the elderly. The overwhelming majority of the cases studied immunophenotypically have expressed a B cell phenotype. We report an unusual case of T cell intravascular lymphomatosis occurring in an adolescent male.

A case of intravascular malignant lymphomatosis (angiotropic large-cell lymphoma) presenting memory T cell phenotype and its expression of adhesion molecules.

A case of intravascular malignant lymphomatosis (angiotropic large cell lymphoma), T cell type was reported. The patient, a 59-year-old woman, had reddish or violaceous indurated macules scattered over the entire body surface. Neither lymphadenopathy nor hepatosplenomegaly was recognized. A chest Roentgenogram, whole body CT scan, and 67Ga-citrate scintigraphy yielded normal findings. Serum anti-HTLV-1 antibody was negative. Histopathologically, lesions showed intravascular large mononuclear cell proliferation associated with occasional fibrin thrombi formation in the dermis to subcutis. Immunohistochemically, the large mononuclear cell immuno-phenotype had a memory T cell character. Also, both lymphocyte function-associated antigen-1s, CD11a and CD18, and intercellular adhesion molecule-1 were demonstrated on the tumor cells and vascular walls in the lesions. To our knowledge, the present case is the fourth case of intravascular malignant lymphomatosis in the T cell lineage.

Malignant proliferative angioendotheliomatosis or angiotropic lymphoma associated with a soft-tissue lymphoma.

We report a 63-year-old man with violaceous nummular patches on the trunk. Histopathologic studies were consistent with a diagnosis of malignant angioendotheliomatosis or angiotropic lymphoma. Immunohistochemical study of skin was positive for UCHL-1 antigen and leukocyte common antigen and negative for L-26, Ulex europaeus lectin I, vimentin, cytokeratin, and epithelial membrane antigen. Ultrastructural study ruled out an endothelial origin of the neoplastic cells. These data confirmed the diagnosis of malignant proliferative angioendotheliomatosis. Five years before, a soft tissue lymphoma had been excised. This is an unusual case of malignant angioendotheliomatosis for the following two reasons: (1) a previous association with a soft tissue lymphoma and (2) the rarely described T immunophenotype of neoplastic lymphoid cells.

Antitumor effect of recombinant human interleukin-2 on the growth of murine hemangioendothelioma D14 in nude mice: occurrence of large granular cells in the tumor.

The antitumor effect of recombinant human interleukin-2 (rIL-2) on murine hemangioendothelioma D14 (D14) in female BALB/c-nu/nu mice was examined histologically. D14 cells which had been maintained in vitro were transplanted subcutaneously into nude mice on day 0 (1 x 10(7) cells/mouse). The mice with established tumor on day 28 received rIL-2 subcutaneously at a dose of 20 micrograms/mouse/day for 35 days. On day 63, the mice were killed, and the tumor, spleen and bone marrow were examined histologically. In the mice that had received rIL-2, tumor growth was significantly suppressed. Histologically, there was marked infiltration of large granular cells (about 15-30 microns in diameter) in the tumors. In the adjacent areas, there was a significant increase in the number of tumor cells showing karyorrhexis. The large granular cells (LGC) contained periodic acid Schiff-positive round granules in the cytoplasm and were stained positively for Thy-1.2 surface antigen. The LGC were also positive for asialo GM1 surface antigen but not for Lyt-1, Lyt-2 or IgG surface antigens. This evidence suggests that the LGC are lymphokine-activated killer-like cells which were derived from a natural killer cell lineage. The concomitant increases in the number of LGC and the number of cells showing karyorrhexis in the tumors of the mice treated with rIL-2 suggest that LGC play an important role in the destruction of tumor cells.

[A case of malignant hemangioendothelioma effectively treated with intra-arterial continuous infusion of interleukin-2].

An 82-year-old female presented with a tumor in the right-frontal region and was diagnosed as MHE, based on the clinical and pathological findings. Increased LAK (lymphokine-activated killer cell) activity was observed during treatment with intraarterial continuous infusion of rIL-2. In addition, the decrease in tumor size was started when LAK activity became high. Treatments for MHE and mechanism of these therapies were discussed using data from this case and other authors' reports.

Endothelial markers in malignant vascular tumours of the liver: superiority of QB-END/10 over von Willebrand factor and Ulex europaeus agglutinin 1.

A new monoclonal antibody, QB-END/10, raised against the CD34 antigen in human endothelial cell membranes and haemopoietic progenitor cells, was studied for its usefulness as a marker of neoplastic vascular cells in 21 angiosarcomas and seven malignant haemangioendotheliomas of the liver. QB-END/10 was both more sensitive and more specific than Von Willebrand factor (VWF) and Ulex europaeus 1 agglutinin (UEA-1) in labelling endothelial cells and it did not cross react with epithelia as UEA-1 often does. Staining was uniformly strong and clear in all histological variants of these two tumours. QB-END/10 should prove particularly useful in the differential diagnosis of malignant vascular tumours of the liver.

Angiotropic lymphoma with histologic features of neoplastic angioendotheliomatosis presenting with predominant respiratory and hematologic manifestations. Report of a case and review of the literature [corrected].

Neoplastic angioendotheliomatosis (NAE) is a rare fatal disease characterized by widespread intravascular proliferations of neoplastic mononuclear cells. Clinically, dermatologic and bizarre neurologic manifestations usually predominate. The origin of the neoplastic cells remains still undetermined. The authors report a patient with NAE peculiar with respect to the following points: (1) the patient predominantly manifested respiratory symptoms and hematologic findings and lacked cutaneous or neurologic manifestations; and (2) immunohistochemical and molecular genetic studies showed the B-cell nature of the neoplastic cells, although previous cases with predominant respiratory or hematologic manifestations were reported to be of endothelial origin. Despite the rarity, this type of NAE or angiotropic [corrected] lymphoma should be recognized because it is easily confused with other disorders, particularly vasculitis or thrombotic thrombocytopenic purpura.

"Intravascular lymphomatosis" (angioendotheliomatosis): evidence for a T-cell origin in two cases.

Intravascular lymphomatosis (IL) is a rare and potentially fatal multifocal intravascular proliferative disorder, most often involving the skin and the central nervous system. Originally considered an endothelial disorder, IL has recently been reclassified as an angiotropic lymphoma, most often of B-cell origin. We report immunocytochemical and ultrastructural findings in two patients with IL, both representing angiotropic T-cell lymphomas. In one patient, lesional tissue was examined by Southern blot analysis and monoclonal T-cell receptor rearrangement was found. As an additional feature in one patient, a myelosuppressive serum factor was demonstrated in peripheral blood progenitor cell cultures as the cause of underlying chronic anemia and leukopenia; this factor is thought to be a cytokine product of the lymphoma cells.

Malignant haemangioendothelioma of the thyroid, immunohistochemical evidence of heterogeneity.

26 cases of malignant haemangioendothelioma (MHE) of the thyroid gland were investigated immunohistochemically with the endothelial marker UEA-1 lectin and the panepithelial marker Lu-5. The results were compared with the results of staining for factor VIII-related antigen in the same cases observed in a previous study of Pfaltz et al. The 26 cases were classified on light microscopic grounds without reference to the immunohistochemical results as classical MHE (15 cases) and borderline cases intermediate between MHE and undifferentiated carcinoma (11 cases). 7 of the 15 classical MHE revealed one or both of the vascular markers, but did not express the epithelial marker. One case showed no staining and another reacted only with Lu-5. Vascular and epithelial markers were found in 6 cases of the 15 classical MHE and in 2 of the 11 borderline cases. These findings indicate that MHE of the thyroid may represent a heterogeneous group of lesions. Tumours positive only for endothelial markers strongly support the hypothesis that MHE is of endothelial origin, whereas tumours which reacted only to the epithelial marker may be undifferentiated carcinomas. Cases with both epithelial and endothelial features on immunohistochemical investigation may represent either tumours in which the malignant cells are in transition from epithelial to mesenchymal differentiation as suggested by Eckert et al. or are tumours of malignant endothelial cells with epithelial differentiation particularly of their cytoskeleton.

[Intravascular malignant lymphoma (malignant angioendotheliomatosis). Apropos of a case with histologic, immunohistochemical and ultrastructural studies]. / Lymphome malin intravasculaire. (Angioendothéliomatose maligne) A propos d'une observation avec étude histologique, immunohistochimique et ultrastructurale.

We report a new case of intravascular malignant lymphoma that arose in an 81-year-old woman. The most prominent symptoms were impressive dermatologic anomalies including painful, diffuse edema over which arborescent telengiectasic lesions could be seen. This clinical picture was associated with the presence, in deep skin biopsy specimens, of mononucleate tumor cells located within the lumen of dermal vessels. Complementary immunohistochemical and ultrastructural studies confirmed that the intravascular tumor growth was lymphomatous in nature. Clinical manifestations of this disease are recalled, and histopathologic features as well as the characteristic location of this malignant lymphoma are analyzed and discussed. Thus, we agree with Félix [3] and Witschi [6] that the cords of cells that will give rise to the follicular cells surrounding the ovocytes originate only from the coelomic epithelium; the primary mesenchyma forms the cortical stroma, and this embryonic type tissue, characterized by enourmous physiologic plasticity, differentiates into endocrine tissue to form the inner theca. the mesonephros plays no part whatsoever in the formation of the ovary.