Combining Cadherin Expression with Molecular Markers Discriminates Invasiveness in Growth Hormone and Prolactin Pituitary Adenomas.

Although growth hormone (GH)- and prolactin (PRL)-secreting pituitary adenomas are considered benign, in many patients, tumour growth and/or invasion constitute a particular challenge. In other tumours, progression relies in part on dysfunction of intercellular adhesion mediated by the large family of cadherins. In the present study, we have explored the contribution of cadherins in GH and PRL adenoma pathogenesis, and evaluated whether this class of adherence molecules was related to tumour invasiveness. We have first established, by quantitative polymerase chain reaction and immunohistochemistry, the expression profile of classical cadherins in the normal human pituitary gland. We show that the cadherin repertoire is restricted and cell-type specific. Somatotrophs and lactotrophs express mainly E-cadherin and cadherin 18, whereas N-cadherin is present in the other endocrine cell types. This repertoire undergoes major differential modification in GH and PRL tumours: E-cadherin is significantly reduced in invasive GH adenomas, and this loss is associated with a cytoplasmic relocalisation of cadherin 18 and catenins. In invasive prolactinomas, E-cadherin distribution is altered and is accompanied by a mislocalisation of cadherin 18, ß-catenin and p120 catenin. Strikingly, de novo expression of N-cadherin is present in a subset of adenomas and cells exhibit a mesenchymal phenotype exclusively in invasive tumours. Binary tree analysis, performed by combining the cadherin repertoire with the expression of a subset of known molecular markers, shows that cadherin/catenin complexes play a significant role in discrimination of tumour invasion.

Hemangioblastoma of the corpus callosum: A case report and review of the literature on its origin.

A third case of corpus callosum hemangioblastoma (HB) is presented. With no preoperative embolization, surgery was uneventful and the postoperative course was excellent. Based on the literature, we attempted to clarify the histogenesis of HB and to explain why they are exceptional in the supratentorial region in contrast to the posterior cranial fossa. The VHL gene is expressed particularly in Purkinje cells of the cerebellum, but this expression is also possible in supratentorial structures. Its mutation leads to developmental arrest of angioblasts that become potentially neoplastic cells. These CD133-positive pluripotent neoplastic angioblasts, similar to stem cells, may be immature HB in the brain. They also express VEGF, coexpress Epo/EpoR, and are capable of differentiation into primitive vascular structures. This coexpression may not only mediate developmental stagnation, but may also induce HB proliferation. Therefore, HB tumorigenesis may be initiated during embryogenesis and may originate from angiomesenchyma because of the expression of three cell types (stromal cells, pericytes, and endothelial cells) in vimentin. Their capacity for proliferation and differentiation in HB depends on the microenvironment.

Subcutaneous tumoral seeding from a glioblastoma following stereotactic biopsy: case report and review of the literature.

Extracranial metastases from glioblastoma are uncommon, likely because short patient survival time prevent them to occur. Most of the few previously reported cases occurred after invasive surgical procedures. We describe a case of glioblastoma with concomitant seeding along the stereotactic biopsy trajectory and subcutaneous metastasis. A 60-year-old woman presented with severe headache. Neuroradiological work-up (including cranial computed tomographic scan and magnetic resonance imaging) showed a heterogeneous hyperdensity, suggestive of malignant glioma, in the left parietal region. A computed tomographic-guided stereotactic biopsy was performed and microscopic examination attested a diagnosis of glioblastoma. Radiotherapy and chemotherapy were administered. Eight months later, the patient presented with a subcutaneous tumor in the left occipital region. A cranial computed tomographic scan revealed a large enhancement of the initial tumor, intracranial tumor seeding along the stereotactic biopsy trajectory, and a subcutaneous tumor. Partial resection of the subcutaneous lesion was performed, and histological examination identified an extracranial metastasis from the glioblastoma. Although uncommon, this observation points to the risk of tumor seeding following stereotactic biopsy, and to the close connection between this intracranial seeding and subcutaneous metastasis.