Cellular and reticular variants of haemangioblastoma revisited: a clinicopathologic study of 88 cases

Abstract

The presence of histological variants of haemangioblastoma is well established, but data on the prognostic implications of histological subtyping are missing. We thus characterized clinical factors associated with histological subtypes, that is, of the cellular and reticular variant of haemangioblastoma, in a series of 88 consecutive primary haemangioblastomas of the central nervous system. Ten haemangioblastomas were classified as 'cellular' according to Cushing and Bailey. As compared to the more common 'reticular' variant (n = 78), the proportion of tumours containing glial fibrillary acidic protein-positive tumour cells (80% vs. 7%), as well as median Ki67 (MIB1) proliferation indices [4% (quartiles: 1-8%) vs. < 1% (<1-2%)], was significantly higher in cellular haemangioblastomas (P < 0.01). Recurrences were more frequent in the cellular variant [2/8 (25%) vs. 4/51 (8%)]. Kaplan-Meier analysis confirmed a significantly higher probability of recurrence in the cellular variant (Log-Rank test P < 0.01). Cox regression analysis not only confirmed the well established association of von Hippel-Lindau disease with tumour recurrence (P < 0.01), but also revealed an independent effect of histological subtype on the probability of recurrence (P < 0.05), whereas no significant influence of age, sex or tumour location was observed. To conclude, the results from this retrospective study suggest that histological subtyping of haemangioblastomas has prognostic implications and might contribute to identify patients at risk for recurrence.

Cellular and reticular variants of hemangioblastoma differ in their cytogenetic profiles

“…Histologic criteria for subclassifying a hemangioblastoma as cellular or reticular were those used by Hasselblatt et al [4]. Briefly, cellular hemangioblastomas were characterized by zellballen-like cellular clusters of uniform tumor cells with finely granular eosinophilic cytoplasm and endothelial hyperplasia, whereas the reticular subtype showed abundant capillaries and scattered stromal cells with highly vacuolated or clear cytoplasms (Fig.…”

“…They are characterized histologically by the 2 main components of large vacuolated stromal cells and a rich capillary network [1] and can be subclassified into 2 variants on the basis of the abundance of the stromal cell component: the rarer cellular hemangioblastomas defined by zellballen-like cellular clusters of uniform tumor cells, and the more common reticular subtype showing abundant capillaries and stromal cells [4,5]. A recent large clinicopathologic study of 88 hemangioblastomas found the cellular variant to comprise 11.4% of all hemangioblastomas and to be significantly associated with a greater probability of recurrence and a higher MIB-1 0046 proliferation index [4]. To investigate whether these 2 subtypes of capillary hemangioblastomas also differ in their cytogenetic profile and may thus provide biologically and diagnostically useful information, we carried out a comparative genomic hybridization (CGH) analysis of 10 cellular and 10 reticular hemangioblastomas.…”

Specific immunohistochemical pattern of carbonic anhydrase IX is helpful for the diagnosis of CNS hemangioblastoma

“…Primary glioblastomas, however, only rarely show these genetic alterations [9]. Especially cellular hemangioblastomas show morphological similarities with glioblastomas [6]. Strong carbonic anhydrase IX staining was found in all three cases included in our control group.…”

Outcomes of gamma knife treatment for solid intracranial hemangioblastomas

“…Cellular hemangioblastomas are less common than the reticular kind, and they recur more frequently. 3 Hemangioblastomas present in both sporadic forms and familial forms associated with von Hippel-Lindau (VHL) disease. VHL disease is an autosomal-dominant disorder characterized by benign and malignant tumors mostly seen in the retina, kidney, adrenal gland, pancreas, and epididymis, in addition to central nervous system hemangioblastomas.…”