Clinical Neuropathology最新文献

Cerebellar liponeurocytoma (cLNC) is a rare tumor. It affects adults with no sex predilection. It appears as a heterogeneously enhancing mass, most commonly unifocal. Histologically, it is a biphasic neurocytic tumor with lipomatous component, with minimal atypia, and low proliferative index, corresponding to central nervous system (CNS) World Health Organization (WHO) grade 2. TP53 missense mutation is reported in 20% of cases. Gross total resection, with or without radiotherapy, is considered an adequate treatment. Bifocality and features of anaplasia are rarely reported. We are reporting a 41-year-old lady with bilateral cerebellar contrast-enhancing masses who underwent gross total resection 3 months apart. Pathology revealed features consistent with cLNC. However, the tumor resected from the right cerebellar hemisphere demonstrated atypical morphological features, including microvascular proliferation and necrosis. Ki-67 proliferative marker was estimated at 10% in the most active areas. Next-generation sequencing (NGS) revealed 2 pathogenic mutations within exonic regions of ERBB2, and PIK3CA genes, and a variant mutation of unknown significance (VUS) involving the PDGFRA gene. DNA methylation profiling confirmed the diagnosis of cLNC. The patient has been under observation without any further intervention for 70 months since diagnosis, with no evidence of disease recurrence. In addition to the rarity of cLNC, this is a unique case in terms of bifocality, anaplastic histology, and the described genetic abnormalities.

The "Azzopardi phenomenon" refers to the deposition of deeply basophilic, smudged material on the stromal blood vessels of highly cellular malignant tumors, and the material is considered to be derived from the nuclear chromatin liberated from necrotizing tumor cells. This phenomenon was observed in a case of high-grade astrocytoma with a primitive neuroectodermal tumor (PNET)-like component that arose in the frontal lobe of a 44-year-old man. The deeply basophilic material was deposited from the media to the adventitia of small or medium-sized blood vessels, and vascular smooth muscle cells largely disappeared. Endothelial cells were relatively preserved. The material was positive for the Feulgen reaction and immunoreactive for histone H3. The Azzopardi phenomenon is frequently seen in small cell lung carcinoma or retinoblastoma, but rare in tumors arising in the CNS. The present case is the first case of an astrocytic tumor that showed this phenomenon. This is also the first example in which histone protein was demonstrated to be co-deposited in the vascular walls in the Azzopardi phenomenon.

Repetitive head injury in athletes has been increasingly linked to the development of chronic traumatic encephalopathy (CTE), a progressive neurodegenerative disorder. However, its underlying pathobiology remains poorly understood, and definitive diagnosis requires post-mortem examination due to the absence of established in-life biomarkers. Here, we report the neuropathological findings in a retired elite rugby union player with a prolonged history of repetitive head impacts and progressive behavioral changes in the decade preceding his death at the age of 60. The clinical course was characterized by gradually progressive behavioral and affective disturbance in the absence of overt cognitive impairment. Neuropathological findings were consistent with stage IV CTE, with phosphorylated tau (p-Tau) deposition involving neocortical, hippocampal, and midbrain regions, and exhibiting a characteristic distribution in the sulcal depths and perivascular zones. No β-amyloid, α-synuclein, or TDP-43 pathology was identified, suggesting the absence of coexistent neurodegenerative tauopathies. Analysis of blood-brain barrier (BBB) integrity demonstrated reduced claudin-5 immunoreactivity and diffuse immunoglobulin G extravasation in the sulcal depths, overlapping with dense p-Tau deposition, suggestive of BBB dysfunction. To our knowledge, this is the first description of BBB alterations in a case of CTE without dementia or evidence of a coexisting neurodegenerative disease. While based on a single case, warranting cautious interpretation, these findings add to accumulating evidence suggesting that BBB alteration may represent a hallmark feature of CTE.

Spinal tumors are classified as extradural or intradural. The latter are further divided into intradural/extramedullary and intradural/intramedullary. The location, coupled with radiological assessment, intraoperative findings, size of biopsy, histological features, and molecular analysis serve to aid accurate diagnosis. We compiled a neuropathologic database of all adult (over 18 years) brain and spinal cord tumors diagnosed at the National Neuroscience Centre in Beaumont Hospital from 2018 to 2023. In this retrospective audit we identified 3,987 tumors, of which 90% (3,596) were intracranial and 10% (391) were spinal. The majority of the spinal tumors were intradural (n = 198) with extradural (n = 122) and intramedullary (n = 71) being much less common. In this review we outline the commonest tumors encountered, by location and age group, unusual tumors that may come to light, and difficulties that may arise, specifically with sampling.

Posterior fossa ependymomas may be classified based on H3 p.K28Me3 (also called as H3K27Me3 or K27Me3) expression status, with group A characterized by loss of K27Me3 expression. We present a rare case of posterior fossa ependymoma with H3K27M mutation, typically associated with diffuse midline gliomas. A 5-year-old child presented with headache and vomiting. Magnetic resonance imaging (MRI) revealed a 4^th ventricular space-occupying lesion extending through the bilateral foramina of Luschka, radiologically consistent with ependymoma. Following maximal surgical resection and radiotherapy (60 Gy), the patient experienced recurrence after 1 year. Histopathological examination showed a moderately to highly cellular tumor with perivascular pseudorosettes and brisk mitotic activity. Immunohistochemistry demonstrated diffuse GFAP positivity, OLIG2 negativity, and characteristic dot-like EMA positivity. Notably, the tumor showed loss of K27Me3 expression and strong diffuse nuclear expression of H3K27M and EZH2. While H3K27M mutations are hallmark features of diffuse midline gliomas, rare cases of posterior fossa ependymomas harboring these mutations have been reported. Recent studies suggest molecular similarities between diffuse midline gliomas and posterior fossa ependymomas expressing H3K27M and EZHIP, potentially reflecting shared hindbrain developmental programs in their biological origins.

Oligodendrogliomas (ODG) account for ~ 5 - 7% of neuroepithelial tumors. Since the 2016 World Health Organization classification, ODG have been defined by IDH mutation and 1p/19q co-deletion, a genetic profile typically linked with classic oligodendroglial morphology and better survival compared with astrocytic gliomas. Although this genotype is considered a favorable prognostic marker, a subset of ODGs shows early recurrence and aggressive behavior, highlighting the need for additional prognostic indicators. Capicua (CIC), located on chromosome 19q13.2, is a transcriptional repressor downstream of receptor tyrosine kinase signaling. Loss of CIC function increases neural stem cell proliferation, promotes oligodendrocyte progenitor specification, and activates proliferative pathways. Somatic CIC alterations have been reported in up to 70% of ODGs, nearly always in the setting of 1p/19q co-deletion. In this study, we investigated the prognostic value of CIC immunohistochemical (IHC) expression in a homogeneous cohort of IDH-mutant, 1p/19q-codeleted ODGs. Our results demonstrated that complete CIC expression loss and 19q polysomy greater than 22.5%, together with mitotic counts ≥ 6 per 10 high-power fields, were significantly associated with early disease recurrence. Although the absence of molecular confirmation of CIC alterations limits interpretation, the findings suggest that CIC IHC can serve as a surrogate marker to identify patients who may benefit from additional molecular analysis. Conclusion: CIC; loss, 19q polysomy, and elevated mitotic activity may function as valuable prognostic indicators in ODGs. These features could improve risk stratification and guide personalized therapeutic strategies in otherwise favorable cases.

Lissencephaly is a migrational disorder that results in abnormal gyration and cortical lamination. Type 1 lissencephaly is characterized by absent or reduced number of gyri giving the brain a smooth appearance, while type 2 lissencephaly (cobblestone lissencephaly) is described as over-migration of neurons or neuronal precursors beyond the glia-pial limitans giving rise to a cobblestone appearance of the cerebral hemispheres. Both types of lissencephaly are typically thought of as congenital anomalies secondary to genetic defects while cases of lissencephaly due to acquired injury is rare. The few examples that do exist in the literature mainly describe changes in keeping with type 1 lissencephaly. We present here an unusual case of a fetus with brain structural changes consistent with cobblestone lissencephaly with concurrent CMV (cytomegalovirus) meningoencephalitis. Our patient is a 23-week-old stillborn fetus of a 28-year-old G1P0 mother who underwent elective termination of this pregnancy after ultrasound and fetal MRI revealed multiple brain anomalies. Post-mortem examination of the fetus revealed evidence of CMV infection involving multiple systemic organs and the brain. Evidence of malformative lesions included cobblestone appearance of the cerebral hemispheres, enlarged lateral ventricles, and focal polymicrogyria. Normal diploid complement for chromosomes 13, 18, and 21 was revealed by rapid aneuploidy testing. While single case reports of CMV with features in keeping with type 1 lissencephaly have been described in the literature, to the authors' knowledge this is the first example of cobblestone lissencephaly observed in the context of congenital CMV infection.