Cerebellar Mass in a 31-Year-old Woman

Access at https://isn-slidearchive.org/?col=ISN&fol=Archive&file=BPA-23-08-CI-238-HE.svs. A 31-year-old woman presented to the emergency department with a one-month history of headache, dizziness, and phosphenes. Magnetic resonance imaging (MRI) revealed a 5 cm, well-circumscribed mass with small cystic areas, in the left cerebellar hemisphere. It was isointense, with focal hyperintensity and heterogeneous contrast enhancement, on T1-weigheted images, and hyperintense, with focal accentuation of hyperintensity, on T2-weigheted images (Figure 1). Intra-operative cytological smear showed uniform neurocytic cells without mitoses or pleomorphism. Histological examination of formalin-fixed paraffin-embedded (FFPE) surgical specimens revealed a tumor composed of small monomorphic cells with round to oval nuclei (Figure 2A) and rare mitoses (two in 50 high-power fields) arranged in sheets or lobules. In some areas, the tumor cells exhibited a clear cytoplasm and an oligodendroglial-like appearance (Figure 2A, Box 1). In others, the presence of fibrillary matrix around the vessels was reminiscent of perivascular pseudorosettes (Figure 2B). Lipidized cells, scattered or in small foci, were focally identified (Figure 2A, circles). Necrosis and microvascular proliferation were absent. By immunohistochemistry, the tumor was extensively positive for synaptophysin (Figure 2C) and NeuN (Figure 2D) and negative for OLIG2, EMA, and IDH1 p. R132H. GFAP immunostaining was restricted to reactive astrocytes. Ki-67 labelling index was 2% (Figure 2E). Next-generation sequencing revealed the lack of mutations or copy number variations in APC, PTCH1, CTNNB1, IDH1/2, and TP53. DNA methylation profiling indicated a match with cerebellar liponeurocytoma (calibrated score, 0.99; v. 12.5 Heidelberg Classifier). Copy number analysis using DNA methylation array revealed a flat profile. In t-distributed stochastic neighbor embedding (t-SNE) analysis, the tumor was positioned separately from medulloblastoma and central or extraventricular neurocytoma methylation classes (Figure 2F). Cerebellar liponeurocytoma, CNS WHO grade 2 (2021 WHO CNS tumor classification). Cerebellar liponeurocytoma is a rare, slow-growing tumor, with approximately 70 cases reported to date [1]. By definition, it occurs in the cerebellum, mostly in the cerebellar hemispheres of adults between the third and fifth decades of life [1], and displays neuronal or neurocytic differentiation and lipoma-like changes [2], caused by lipid accumulation in neuroepithelial tumor cells. The diagnosis of cerebellar liponeurocytoma is relatively straightforward when extensive lipomatous foci are present but it can be challenging if lipomatous foci are limited, as in the present case. On MRI, cerebellar liponeurocytoma is well-circumscribed, with fat deposits appearing as hyperintense in T1 and as accentuated hyperintensity in T2. In this case, the areas of hyperintensity in T1 and accentuation of hyperintensity in T2 were only focal, caused by the limited fat deposits. In intraoperative cytological smears, monomorphic neurocytic cells that lack significant atypia or mitoses represent a valuable diagnostic clue. Oil Red-O staining can be used to detect lipid accumulation in frozen sections. Given its morphological features, cerebellar localization, and synaptophysin positivity, the most challenging differential diagnosis of cerebellar liponeurocytoma is medulloblastoma. This is clinically relevant because the latter is classified as CNS WHO grade 4 and requires adjuvant treatment, whereas cerebellar liponeurocytoma is CNS WHO grade 2 and rarely recurs after gross total resection [1]. The relatively monomorphic aspect, low mitotic and Ki-67 labelling indices, and absence of necrosis or apoptotic bodies help to exclude medulloblastoma, which is a highly proliferative tumor composed of cells with moderately pleomorphic nuclei. The well-circumscribed aspect of cerebellar liponeurocytoma on imaging is an additional diagnostic clue. The presence of a neuropil matrix around the vessels, as we observed focally in this case, might recall the perivascular pseudorosettes of ependymomas. However, extensive synaptophysin immunostaining, limited GFAP expression and negative EMA staining are against this diagnosis. While oligodendroglial-like monomorphic cells could suggest oligodendroglioma, which is uncommon in the cerebellum, the absence of OLIG2 immunolabeling rules out this diagnosis. The identification of lipomatous foci, even when focal, allows the diagnosis of cerebellar liponeurocytoma. Although some reports have described supratentorial liponeurocytoma-like tumors, these likely represent central or extraventricular neurocytomas with lipomatous changes, which have epigenetic and genetic features distinct from those of cerebellar liponeurocytoma. As demonstrated in the present case, cerebellar liponeurocytoma does not harbor mutations in PTCH1, APC, CTNNB1 or isochromosome 17, unlike medulloblastoma [3]. In 70% and 50% of patients, it features recurrent 2p and 14p focal deletions, which were not found in this case. TP53 mutations have been reported in 4 of 20 previous cases [3]. The unique DNA methylation profile of cerebellar liponeurocytoma can be useful for the diagnosis of unresolved cases. However, a thorough search for lipomatous foci in cerebellar tumors with oligodendroglioma-like monomorphic cells, extensive synaptophysin immunostaining, and low mitotic index resolves the differential diagnosis without the need for additional genetic or epigenetic testing. Davide Mulone analyzed the data and wrote the draft. Rita Polati, Evelina Miele, Sara Patrizi, and Andrea Mafficini analyzed the data and reviewed the manuscript. Valeria Barresi co-wrote and reviewed the manuscript. All authors approved the final version of the manuscript. This study received was supported from the University of Verona, Italy (FUR 2023) to Valeria Barresi. The authors declare no conflicts of interest. All data related to this case are deidentified. The data that support the findings of this study are available from the corresponding author upon reasonable request.