Establishment and Characterization of Cell Lines from Primary Culture of Hemangioblastoma Stromal Cells.

CONTEXT: A well-established cell line of hemangioblastomas (HBs) is still lacking. AIM: This study aims to explore a stable way to establish primary cell lines of HB stromal cells and investigate the morphological and molecular features of these cells. PATIENTS AND METHODS: Specimens of HBs from 13 patients were collected for establishment of primary cell lines of stromal cells. The details on cell culture were described, and the characterizations of cultured cells were conducted by morphological observation, immunocytochemical staining of inhibin-α, brachyury, CD133, CD34, GFAP, CD31, NeuN, CD45, Oligo2, and transmission electron microscopy. RESULTS: Eleven cases were successfully cultured with a success rate of 84.6%. The cultured cells survived for 10 generations with an estimated doubling time of 77.2 ± 5.89 h. Light microscopy revealed that these cells showed vigorous growth status and presented as polygons or trigons with significant heterogeneity. The immunocytochemical staining showed that inhibin-α, brachyury, CD133, and CD34 were expressed in all the cultured cells, whereas the expression of GFAP, CD31, NeuN, CD45, and Oligo2 was all negative. Transmission electron microscopy confirmed that the cultured cells were stromal cells with typical lipid droplets. The phenomenon of lysosomal autophagy was commonly observed without apoptotic cells in late stage. CONCLUSION: Appropriate selection of tumor specimens, short duration of devascularization, ideal digestion time, and nutritious medium are critical points for establishment of primary cell line of HB stromal cells. Stromal cells from both von Hippel-Lindau disease-related HBs and sporadic HBs might originate from embryologically arrested hemangioblasts.

An ultrastructural study of the histogenesis of haemangioblastoma.

Seven cases of cerebellar haemangioblastoma, not associated with von Hippel-Lindau disease (sporadic haemangioblastomas), were studied by light and electron transmission microscopy. Morphological features that might provide information about the histogenesis of the tumour were examined. The ultrastructural data indicate both the common ancestry of the different cytotypes that make up the tumour, and the mesenchymal origin of the elements present, which were also documented by their capacity to synthesise lipid droplets in the cytoplasm (a process of lipidization similar to that of pre-adipocytes).

A report of supratentorial leptomeningeal hemangioblastoma and a literature review.

Hemangioblastomas of the CNS are solid or cystic vascular-rich tumors, most common in the cerebellum, less frequent in the brainstem or spinal cord, and rare in supratentorial locations with meningeal involvement. We document a case in a 58-year-old man who presented with about 2 months history of motor weakness and speech dysfunction. The tumor was a heterogeneously enhanced dural-based tumor with high vascularity and perifocal edema in the left frontal lobe. The tumor was completely removed followed by embolization and preoperative radiotherapy. Histologic examination revealed a hemangioblastoma with features resembling angiomatous meningioma. Immunohistochemistry for epithelial membrane antigen (EMA) and S100 may be helpful to make differential diagnosis. Electron microscopic investigation is essential to differentiate between meningiomas and other leptomeningeal tumors.

Histologic and histogenetic investigations of intracranial hemangioblastomas.

BACKGROUND: The aim of this study was to elucidate the histologic characteristics and the histogenesis of intracranial HBs. METHODS: Specimens from 40 patients with HBs were verified surgically and pathologically at the Huashan Hospital Department of Neurosurgery (Fudan University, Shanghai, China). All sections were immunohistochemically stained. In addition, fresh specimens were examined by electron microscopy in 3 cases and cells were cultured in 10. RESULTS: Hemangioblastomas were composed of endothelial cells, pericytes, and stromal cells. Vimentin was expressed in all 3 cell types of HB. CD34 was expressed in endothelial cells, and SMA was expressed in pericytes. Telomerase was expressed in stromal cells. Chromogranin A, CD68, and CD117 showed a negative reaction in HBs. Vascular endothelial growth factor showed a positive reaction in stromal cells, and Flt-1 showed a positive reaction in endothelial cells. There was no difference in immunohistochemical staining between specimens from cystic HBs and those from solid HBs. Three cell types had individual ultrastructural characteristics. Stromal cells represented a heterogeneity of abnormally differentiating mesenchymal cells in cell culture. CONCLUSIONS: Hemangioblastomas may originate from the mesenchyme. Stromal cells are the real tumor components of HBs although they represent a heterogeneity.

Capillary hemangioblastoma of soft tissue: report of a case and review of the literature.

Capillary hemangioblastoma (CH) is a tumor of unknown histogenesis that arises primarily in the posterior cranial fossa, either as a sporadic event or in association with von Hippel-Lindau disease. To date, only 6 examples of a tumor with morphological features of CH arising in the somatic soft tissues have been documented in case reports and small series, and 3 of these tumors were associated with a peripheral nerve. Herein, we report a case of CH arising in the gastrocnemius muscle and not associated with a peripheral nerve in a 53-year-old woman with no clinical stigmata or family history of von Hippel-Lindau disease.

Stromal cells in hemangioblastoma: neuroectodermal differentiation and morphological similarities to ependymoma.

The histogenesis of stromal cells in hemangioblastoma is inconclusive despite a long-term controversy. An immunohistochemical and ultrastructural study was conducted for 17 cases of cerebellar hemangioblastoma. A wide range of immunohistological markers, targeting epithelial, mesenchymal, endothelial and neuroectodermal tissues, was used. In all cases, the microscopic hallmark characterizing hemangioblastomas, that is, lipid-containing stromal cells and a fine capillary network, known as a reticular variant, was noted. Stromal cells showed a variable immunoreactivity for neuroectodermal markers, such as S-100 protein, CD56, CD57, CD99, and neuron-specific enolase. This result, in conjunction with the absence of immunoreactivity for epithelial, mesenchymal, and endothelial markers, likely suggests neuroectodermal differentiation of stromal cells. In three cases, another component, known as a cellular variant, where epithelioid tumor cells were arranged in nests encircled by capillaries and/or in pseudorosette-like structures, was noted. Glial fibrillary acidic protein-immunoreactivity, which was totally absent in cases only showing the reticular pattern, was noted in two of them, suggesting a distinctive sign of glial differentiation in a proportion of hemangioblastomas. Ultrastructurally, microvilli-like projections in intracytoplasmic vacuoles were demonstrated in stromal cells. This result, taken together with the neuroectodermal hypothesis of stromal cells, suggests that hemangioblastomas may occasionally exhibit morphological similarities to ependymomas.

Primary capillary hemangioblastoma of peripheral soft tissues.

A case of capillary hemangioblastoma located in the peripheral soft tissue of the inner ankle in a 74-year-old woman is presented. The tumor was an unencapsulated but sharply circumscribed nodule 2.5 cm in size, of a yellow-white color. It showed reddish-brown spots with small cysts up to 2 mm filled with blood. Grossly the tumor was not attached to any peripheral nerve. Signs of von Hippel-Lindau's disease were excluded by thorough clinical evaluation. No additional tumor or erythrocytosis was found in the patient clinically. Immunohistochemically, the tumor stromal cell reacted strongly with antibodies to S-100 protein, NSE, and calponin and they were negative with antibodies to GFAP, CD34, CD31, cytokeratins, actin, desmin, EMA, and HMB-45. Endothelium of the capillaries reacted positively with antibodies to CD31, CD34, and Factor VIII-related protein. Capillary pericytes were actin-positive. All cells of the tumor stained positively with antibody to vimentin. MIB1 antibody reacted only in very few cells (<1%). Ultrastructurally, the stromal cells contained electron-lucent cytoplasm with lipid droplets, a small amount of rough endoplasmic reticulum, and glycogen particles. No electron-dense structures typical of secretory granules were seen in the stromal cells. No mutation of coding sequence of VHL gene was found.

[Extramedullary erythropoiesis in cerebellar hemangioblastomas]. / Pozaszpikowa erytropoeza w naczyniakach plodowych mózdzku.

Three patients operated on for cerebellar haemangioblastoma are reported. Rarely observed extramedullary erythropoiesis was found in tumour tissue. One patient had erythrocytosis (solid form of the tumour), the remaining patients with cystic tumour had normal erythrocyte count.

["Tufted angioma". A benign vascular tumor to differentiate with Kaposi sarcoma]. / Le "tufted angioma" (angiome en touffes). Une tumeur vasculaire bénigne à différencier du sarcome de Kaposi.

Among recently characterized vascular tumors, tufted angioma or angioblastoma is a benign acquired slowly progressive cutaneous tumor, which most commonly arises in the neck and upper trunk in children and young adults. This case report emphasizes the clinical and histological features of tufted angioma. Light microscopic examination reveals numerous lobules of closely packed capillaries scattered throughout the dermis. Vascular lumina are difficult to define. There are no atypical cells. Familiarity with tufted angioma should prevent this lesion from being misdiagnosed as malignant vascular tumor arising in young persons, especially Kaposi's sarcoma.