Solid Component Volume as a Proxy to Identify Distinct Hemangioblastoma Populations.

BACKGROUND: Posterior fossa hemangioblastomas usually consist of a small solid nodule with a large cyst, while more rarely they present as a large solid mass with a small or absent cyst, which can be surgically challenging. We sought to investigate the potential existence of multiple distinct hemangioblastoma populations using tumor volumetric data as an indicator. METHODS: We conducted a retrospective review of surgically treated hemangioblastomas between 2005 and 2019 in our unit, including clinical notes, preoperative magnetic resonance imaging volumetric analysis of the solid component of the tumor, and pathology. Finite Gaussian mixture modeling was applied on the solid component volume dataset to identify potential underlying Gaussian distributions with their associated characteristics. Nonparametric Mann-Whitney U tests were used to investigate significance of differences (P < 0.05) in solid component volume and different variables (Von Hippel-Lindau disease, extent of resection, outcome). RESULTS: A total of 68 consecutive patients were included. Solid component volumes followed a multimodal distribution (median = 1287 mm3, interquartile range of 3428 mm3). The best-fit finite Gaussian mixture modeling model identified 3 statistically significant different (P = 0.001) potential mixture components: X1 (219 ± 187 mm3), X2 (2686 ± 1299 mm3), and X3 (10,800 ± 5514 mm3). The second-best model detected 2 significantly different (P = 9.99e-08) mixture components Y1 (222 ± 189 mm3) and Y2 (5391 ± 5094 mm3). A significant difference in solid component volume was found between patients with favorable and unfavorable outcome (P = 0.002). CONCLUSIONS: This study has shown preliminary evidence that large solid hemangioblastomas may constitute a completely distinct population, rather than a variant of one large group of hemangioblastomas.

Diagnostic challenges of posterior fossa hemangioblastomas: Refining current radiological classification scheme.

Hemangioblastomas (HBMs) are known to exhibit very typical radiological features and thus classified by well-established radiological classification scheme. We reviewed our series of posterior fossa HBMs in order not only to evaluate the relevance of current classification scheme, but also to possibly refine it. Also, we added descriptions on several cases with unusual radiological magnetic resonance imaging (MRI) findings in which differential diagnosis was challenging. We retrospectively reviewed preoperative MRI of 118 patients with pathologically diagnosed posterior fossa HBMs at our institution between 2002 and 2015. Total 128 tumors were included to this study and classified into four categories based on the presence and nature of cystic components: extratumoral cystic (Type Ce, classical cystic with a mural nodule), intratumoral cystic (Type Ci), mixed cystic (Type Cm), and solid (Type S). The association with von Hippel-Lindau (VHL) disease was also investigated. In 118 patients (65 male and 53 female), 79 (66.9%) had solitary HBMs and 39 (33.1%) were diagnosed with VHL disease. Type Ce with typical radiological findings was the most prevalent type of HBM (63.3%), followed by Type S (21.1%). HBMs with intratumoral cysts were uncommon (Type Ci, 11.7%) and mixed extratumoral and intratumoral cysts (Type Cm) accounted for only 3.9%. No intergroup differences were observed in the proportions of each subtype between the solitary and VHL disease-associated HBMs. The blood loss was much lower in Type Ce than in other subtypes. In Type Cm, radical resection was often challenging as the differentiation between intratumoral and extratumoral cysts was difficult resulting in incomplete resection. Refined radiological classification scheme is more practical because it does not only help surgeons determine whether the cystic wall should be removed or not, but also covers cases with atypical radiological presentations. For solid and extraparenchymal HBMs, differential diagnosis is more difficult as well as very critical as surgical removal is often very challenging.

The relationship between angioblastoma (Nakagawa) and tufted angioma: report of four cases with angioblastoma and a literature-based comparison of the two conditions.

We report four recent cases of angioblastoma (Nakagawa). Histopathologic examinations of all cases revealed dispersed islets of clear marginal lobules of varying sizes in the dermis. Neoplastic endothelioid cells with moderate atypia and enlarged capillaries containing erythrocytes were found in the conglomerates. Recently, the features of this disease have been compared to the tufted angioma that has been reported in Europe and the U.S. Our evaluation suggests that these two diseases are very likely the same. We suggest that this disease should be called "angioblastoma" in agreement with the first report of this disease by Nakagawa.

Angiogenic histogenesis of stromal cells in hemangioblastoma: ultrastructural and immunohistochemical study.

Controversy regarding the origin of characteristic stromal cells (SC) is responsible for the placement of hemangioblastoma as a single entity in the category of "tumors of uncertain histogenesis" in the current WHO classification of brain tumors. This subclassification of hemangioblastoma is, to a large extent, a consequence of a remarkable antigenic heterogeneity of SC demonstrated in many, often contradictory immunohistochemical studies. In contrast, most of the electron microscopic studies demonstrated a number of features indicating angiogenic nature of SC and, therefore, hemangioblastoma. This study reevaluated the histogenesis of SC, applying immunohistochemistry as well as electron microscopy and immunoelectron microscopy. Immunohistochemical studies confirmed most of the previous results indicating a very frequent expression of vimentin, S-100 protein, neuron-specific enolase, and cytokeratins. SC were less commonly immunoreactive for desmin, factor XIIIa, and Ricinus communis lectin receptors, and only occasionally for factor VIII and Ulex europeus lectin. They were negative for other markers of endothelial, neuronal, glial, neuroendocrine, and smooth muscle differentiation. Approximately 1% of SC showed Ki67 immunoreactivity, indicating their slight proliferative activity, consistent with the benign nature of the tumor. In contrast to the inconclusive results of the immunohistochemistry, electron microscopy demonstrated a clear relationship of SC to endothelial cells, smooth muscle cells, and pericytes. Occasional SC were found within the vascular lumina. SC often showed intracellular caveolae consistent with the formation of early capillary lumina. Moreover, occasional SC contained small Weibel-Palade bodies positive for factor VIII in immunoelectron microscopy. SC represent a heterogeneous population of abnormally differentiating mesenchymal cells of angiogenic lineage, with some morphological features of endothelium, pericytes, and smooth muscle cells. Occurrence of SC in hemangioblastoma could be related to a limited ability of angioformative stromal cells to develop an architecture of capillary lumina integrated with the vascular network of the tumor. Hemangioblastoma should be reclassified and included together with other vascular tumors of the central nervous system.

Enfermedad de von Recklinghausen (neurofibromatosis) y embarazo: a propósito de un caso clínico / Von Recklinghausen's disease (neurofibromatosis) and pregnancy: apropos of a clinical case

Presentamos un caso clínico de una embarazada con neurofibromatosis de von Recklinghausen, cuyo embarazo terminó en óbito fetal en el tercer trimestre, determinado probablemente por insuficiencia placentaria. Pese a que ésta es una de las enfermedades genéticas más frecuente, el diagnóstico se realiza en raras ocasiones