Hemangioblastoma of the hypothalamus.
Hemangioblastoma is one of the less common neoplasms of the central nervous system accounting for around 3% of all CNS tumors. It is a highly vascularized benign lesion possessing a number of characteristic features. It is typically encountered within the posterior fossa and the spinal cord, primarily within its cervical or lower thoracic segments. Being clearly demarcated from the surrounding neural tissue it becomes symptomatic due to the local mass effect resulting both in compression of the neighboring structures as well as in obstructive hydrocephalus. Risk of spontaneous bleeding and presentation as an intracerebral hemorrhage is estimated to be low. Rarely a hemangioblastoma is detected owing to a clinically symptomatic polycythemia induced by the production of erythropoietin by the tumor cells (4).
Most hemangioblastomas occur sporadically, however in approximately 30% of cases they are associated with von Hippel-Lindau disease, a genetic disorder related to inactivation of a tumor suppresor gene on chromosome 3p25 whose principal function is negative regulation of VEGF and stimulation of secretion of erythropoietin. Solitary lesions tend to present later, most often during the 4th and 5th decades of life (2), and if succesfully removed they yield excellent prognosis with very low risk of recurrence. Those associated with VHL disease are often multicentric and most often detected in early adulthood. Surgery is not curative for these patients as new tumors may arise de novo and close surveillance with serial MRI imaging of the whole neuraxis is mandatory. Suspicion of VHL disease warrants a thorough search for other neoplasms associated with the disease, notably with hemangioblastomas of the retina (retinal angiomas), renal clear cell carcinomas, pheochromocytomas, pancreatic tumors, epidydymis cysts and endolymphatic sac tumors (1). Owing to the lifelong course of the disease timing of surgery plays an important role and decision about operative treatment should be taken after careful analysis of patients' history (3) including current neurological status, symptomatology of existing lesions, documented growth of known asymptomatic tumors and the relation of the neoplastic foci to the nearby critical structures to ensure that they would not be rendered inoperable in case of their further growth.
MRI imaging shows characteristic findings consisting of a cystic, well-circumscribed cerebellar mass with a contrast enhancing mural nodule in about two-thirds of cases of infratentorial hemangioblastoma. In the remaining one third the tumor is solid and contains no cyst. These radiologic features combined with the clinical picture usually allow the correct diagnosis to be made however a number of other lesions must be considered (metastases and high-grade gliomas, pilocytic astrocytoma, AVM, cavernoma). In case of location of the tumor within the spinal cord it is often accompanied by a syrinx extending cranially, or less commonly in both directions. Supratentorial hemangioblastomas are exceedingly rare and would not usually be considered in the differential diagnosis of a lesion in this location.
Microscopic investigation showed typical pattern for a hemangioblastoma as detailed in the case description.The tumor was composed mostly of clusters and solid areas of large stromal cells with delicate to faint reticulin nerwork, which corresponds to the so-called 'cellular' variant of hemangioblastoma. These tumor areas merged with other parts where foci of smaller stromal cells were embedded in reticulin and capillary-rich zones corresponding to the 'reticular' variant of the neoplasm (Figs. 1D, 1E, 1F).
Several entities should be included in the differential diagnosis. The most challenging and prognostically important task is distinguishing hemangioblastoma from clear cell renal cell carcinoma (ccRCC), which can be both associated with von Hippel-Lindau disease (VHL). The architecture of hemangioblastoma with foci of clear and vacuolated stromal cells accompanied by numerous capillaries and thin-wallled vessels resembles that of metastatic renal malignancy. In contrast to a RCC metastasis stromal cells of hemangioblastoma are immunonegative to markers of epithelial differentiation, i.e. EMA and cytokeratins, and positive to NSE and inhibin, which in turn are not expressed by renal cell carcinoma. Another entity of similar morphology and immunophenotype to hemangioblastoma is paraganglioma, however it seldom occurs in extra-axial localizations, mainly in the cauda equina region and filum terminale. In contrast to hemangioblastoma, paraganglioma cells are usually strongly immunopositive to chromogranin. From the clinical point of view the differential diagnosis must also include a pilocytic astrocytoma, most often a cerebellar one due to the infratentorial location. Both tumors often present as cystic lesions with a mural nodule. The pathologic examination of mural nodule in those cases warrants the correct diagnosis, whereas the morphology of cystic walls can be misleading as it proves to be very similar in significant proportion of cases.
Among other neoplasmes to be taken into account one should think of meningeal neoplasms, including meningiomas and solitary fibrous tumors (SFT) with hemangiopericytoma phenotype. Immunopositivity to NSE and lack of EMA expression by stromal cells differentiates hemangioblastoma from angiomatous meningioma. Neither of the above-mentioned meningeal neoplasms expresses NSE nor inhibin.
There are no universally accepted guidelines for further management of patients diagnosed with a hemangioblastoma however a repeat MRI scan of the neuraxis at 12 to 24 months is often suggested. Careful search for other tumors associated with VHL disease including ophtalmologic assessment and abdominal imaging as well as genetic testing help to establish or exclude its diagnosis. MRI imaging of the entire neuraxis allows exclusion of clinically asymptomatic foci. VHL patients require multiple MRI examinations as well as abdominal ultrasound or CT imaging and laboratory check-ups to control the course of the disease and growth of new lesions.
Contributed by Podgórski Andrzej, Zielinski Grzegorz, Grala Bartlomiej, Koziarski Andrzej