CDKN2A is a tumor suppressor gene encoding the p16 protein, a key regulator of the cell cycle. CDKN2A homozygous deletion is a central prognostic factor for numerous tumors and can be detected by several techniques. This study aims to evaluate the extent to which immunohistochemical levels of p16 expression may provide information about CDKN2A deletion. A retrospective study was conducted in 173 gliomas of all types, using p16 IHC and CDKN2A fluorescent in situ hybridization. Survival analyses were performed to assess the prognostic impact of p16 expression and CDKN2A deletion on patient outcomes. Three patterns of p16 expression were observed: absence of expression, focal expression, and overexpression. Absence of p16 expression was correlated with worse outcomes. p16 overexpression was associated with better prognoses in MAPK-induced tumors, but with worse survival in IDH-wt glioblastomas. CDKN2A homozygous deletion predicted worse outcomes in the overall patient population, particularly in IDH-mutant 1p/19q oligodendrogliomas (grade 3). Finally, we observed a significant correlation between p16 immunohistochemical loss of expression and CDKN2A homozygosity. IHC has strong sensitivity and high negative predictive value, suggesting that p16 IHC might be a pertinent test to detect cases most likely harboring CDKN2A homozygous deletion.

Over the last few decades, deciphering the alteration of molecular pathways in brain tumors has led to impressive changes in diagnostic refinement. Among the molecular abnormalities triggering and/or driving gliomas, alterations in the MAPK pathway reign supreme in the pediatric population, as it is encountered in almost all low-grade pediatric gliomas. Activating abnormalities in the MAPK pathway are also present in both pediatric and adult high-grade gliomas. Across those alterations, BRAF p.V600E mutations seem to define homogeneous groups of tumors in terms of prognosis. The recent development of small molecules inhibiting this pathway retains the attention of neurooncologists on BRAF-altered tumors, as conventional therapies showed no significant effect, nor prolonged efficiency on the high-grade or low-grade unresectable forms. Nevertheless, tumoral heterogeneity and especially molecular alteration(s) associated with MAPK-pathway abnormalities are not fully understood with respect to how they might lead to the specific dismal prognosis of those gliomas and/or affect their response to targeted therapies. This review is an attempt to provide comprehensive information regarding molecular alterations related to the aggressiveness modulation in BRAF-mutated gliomas and the current knowledge on how to use those targeted therapies in such situations.

Pseudoangiomatous stromal hyperplasia (PASH) is a benign breast lesion frequently discovered incidentally during imaging or biopsy for other conditions. We present two cases of PASH associated with fibroadenomas in premenopausal women, both presenting as palpable, symptomatic breast masses. In the first case, a 26-year-old woman exhibited a 5.2 cm hypoechoic lesion, initially diagnosed as PASH on core biopsy, later confirmed as fibroadenoma with PASH components post-excision. The second case involved a 37-year-old woman with a painful 5.6 cm mass, diagnosed similarly via biopsy, and later confirmed as fibroadenoma fully colonized by PASH after surgical removal. Both cases highlight the diagnostic challenge in distinguishing PASH from fibroadenomas, given overlapping clinical and imaging features. Hormonal factors, particularly contraceptive use, may contribute to PASH development. Management remains controversial, with surgery indicated for symptomatic lesions, while conservative approaches may suffice for smaller, asymptomatic cases. Based on our findings and current literature, we propose a management algorithm to guide clinicians in differentiating cases warranting surgical intervention from those suitable for monitoring. Further studies are needed to validate this approach.

The online version contains supplementary material available at 10.1186/s40478-025-02089-7.