Clinical Neuropathology最新文献

Objective: The risk of meningioma recurrence depends mainly on the extent of resection and tumor grade. In a series of 196 meningiomas, we investigated the influence of clinical and histopathological criteria and sought to identify simple and reproducible criteria associated with meningioma recurrence.

Materials and methods: Clinical data (age, sex, location), preoperative embolization (POE), presence of peritumoral edema, Simpson grade, histological grade and histopathological parameters (Ki-67 index labeling index (LI), mitotic index, hypercellularity, small cells, prominent nucleoli, sheeting pattern, necrosis, nuclear atypia, microvascular proliferation as well as infiltration of the dura mater, bone and brain), and dura mater were collected. The prognostic value of each parameter for recurrence-free survival (RFS) was assessed using the Kaplan-Meier method and log-rank test. Multivariate analysis was carried out using a Cox regression model on single features identified by univariate analysis.

Results: The Ki-67 LI was the factor most strongly associated with recurrence. In multivariate analysis, independent factors for shorter RFS were male sex, subtotal resection, and a Ki-67 LI > 5%, which was the most significant factor. In addition, a Ki-67 LI > 5% was strongly associated with shorter RFS (p = 9.79e-05) for grade 1 meningiomas in multivariate analysis. Ki-67 LI assessment and POE did not modify the Ki-67 LI evaluation.

Conclusion: Importantly, for grade 1 meningiomas, which are tumors that lack histological criteria for aggressiveness, a Ki-67 > 5% is a predictive factor for recurrence. These data, which are easy to collect and reproduce, could be used in practice to select patients who would benefit from closer clinical follow-up or to identify tumors requiring further molecular analysis at the time of first surgery.

Anaplastic lymphoma kinase (ALK)-positive histiocytosis is a novel and rare entity commonly described as a systemic disease affecting infants, while isolated systemic involvement including the central nervous system (CNS) have been reported in older children and young adults. We report 2 cases of CNS ALK-positive histiocytosis, with detailed histopathological and radiological information, and provide a review of literature. Two patients, a child and a young adult, presented with extra-axial mass lesion. The radiological differentials considered were meningioma and schwannoma. The histopathological examination of both cases showed sheets of cells resembling histiocytes admixed with scattered Touton-type and foreign body giant cells. These tumors do not have any distinct diagnostic radiological, features and hence histopathological examination is crucial in the diagnosis of these tumors. The cells were immunopositive for CD68, CD163, and ALK. Understanding the histopathological spectrum of ALK-positive histiocytosis is important as targeted therapy (ALK inhibitor therapy) exists and the prognosis is better.

Toxoplasmosis is a common opportunistic infection in immunocompromised patients. Cerebral toxoplasmosis can be the initial manifestation of acquired immunodeficiency syndrome (AIDS). We report a case diagnosed at autopsy as the primary presentation of an undiagnosed human immunodeficiency virus (HIV)-positive patient. Histological examination revealed a prominent rim of periventricular necrosis involving the frontal, temporal, and occipital horns of the lateral ventricle, third and fourth ventricle. The ependymal lining was denuded with numerous encysted bradyzoites and scattered tachyzoites of Toxoplasma dispersed in the necro-inflammatory areas. Hydrocephalus due to cerebral toxoplasmic ventriculitis is very rare in adults. Mortality was significantly higher in cases with ventriculitis as compared to patients with only hydrocephalus due to mass lesions. Choroid plexus involvement in toxoplasmic ventriculitis could indicate a hematogenous spread from reactivation of latent systemic infection rather than reactivation of latent brain lesion. This case report emphasizes the importance of evaluation of HIV status in the presence of complex periventricular enhancement and the importance of a high degree of clinical suspicion for toxoplasmic ventriculitis in HIV patients with hydrocephalus, as an early institution of empirical anti-toxoplasma treatment could play a crucial role in cure.

Introduction: Since progression from grade 2 to grade 4 occurs in the evolution of IDH-mutant astrocytoma (A, IDH-mut), it is crucial to identify the key factors that define the different grades.

Aims: To evaluate the impact on overall survival (OS) of molecular alterations traditionally associated with high-grade gliomas within the grading scheme.

Materials and methods: We retrospectively analyzed the role of 10q loss, CDKN2A deletions, EGFR amplification (Amp), and trisomy of chromosome 7 (trisomy 7) in 189 A, IDH-mut, reclassified according to the WHO 2021 criteria (grade 2, n = 133; grade 3, n = 18; grade 4, n = 38).

Results: Among the 189 cases, 29 presented with CDKN2A hemizygous deletion (hemidel), 17 with CDKN2A homozygous deletion, 18 showed trisomy 7, and 2 showed EGFR Amp. A multivariate test revealed that WHO grade 4 and trisomy 7 significantly impacted OS. CDKN2A hemidel and 10q loss did not influence OS in our cohort. Given that 11 out of 18 cases with trisomy 7 were IDH-mutant grade 2 (G2), we compared G2 cases with and without trisomy 7 and found worse OS in cases with trisomy (p = 0.0034), similar to WHO grade 4.

Conclusion: Our results suggest that trisomy 7 plays a significant role in the OS of A, IDH-mut. Further research is needed to determine whether trisomy 7 is an independent marker or if it is associated with other molecular alterations that affect OS.

Intracranial mesenchymal tumors with female expressed transcript::cyclic AMP responsive element binding protein (FET::CREB) fusion, characterized by Ewing sarcoma breakpoint region 1/EWS RNA binding protein 1 (EWSR1) rearrangements, represent a rare and complex category of neoplasms with varied morphologies and significant diagnostic challenges. These tumors commonly occur in young adults, presenting as dural-based masses with solid and cystic components on radiological imaging, often mimicking meningioma. Histopathologically, they exhibit a spectrum of features, including spindle, stellate, and epithelioid cells within myxoid or collagenous stroma, occasionally with hemangioma-like vasculature or chronic inflammatory infiltrates. Immunohistochemistry typically reveals strong positivity for cluster of differentiation 99 (CD99) and epithelial membrane antigen (EMA), with variable expression of Desmin, S100, and MUCIN 4 (MUC4). Molecular studies confirm EWSR1 rearrangements via fluorescence in situ hybridization (FISH), while RNA sequencing further elucidates specific fusion partners, such as cyclic AMP response element binding protein (CREB)1 or ATF1. Differential diagnosis includes solitary fibrous tumors, inflammatory myofibroblastic tumors, and chordoid meningiomas, necessitating thorough morphological and immunohistochemical analysis. Emerging genomic profiling divides these tumors into two epigenetic subgroups with distinct molecular and clinical profiles, influencing prognosis and progression-free survival. This case series highlights five instances of such tumors, underscoring the importance of recognizing their unique histopathological and molecular characteristics for accurate diagnosis. While the study employed FISH for cost-effective analysis, the absence of RNA sequencing limits identification of fusion partners. Overall, the study contributes valuable insights into these rare tumors, advancing understanding of their pathology and potential clinical implications.

Our purpose was to provide a clinical-pathological overview, evaluate the prognostic value of Ki-67 and p53 in pediatric-juvenile pituitary neuroendocrine tumors (PitNETs) and explore the incidence of somatic variants in SF3B1 in pediatric-juvenile lactotroph PitNET. We present a clinical, morphological, immunohistochemical, and molecular study of 30 patients aged 8 - 20 years (16 females, 53%; 14 males, 47%). Clinical data were available for 21 patients (70%). Nine patients (43%) had mass effect symptoms. Imaging was available for 25 cases (83%). 21 patients (84%) had macro-PitNET or giant PitNET. Most tumors were lactotroph PitNETs (22 cases, 73%). Nine patients out of 22 lactotroph PitNET (41%) were male. Ki-67 and p53 immunostaining were performed in 27 cases. 15 tumors (56%) were p53 positive and exhibited a high Ki-67 index. Of these, 12 tumors (80%) were macro-PitNETs or giant PitNETs. Eight tumors (30%) were p53 negative and had low Ki-67 index, with 5 of these classified as macro-PitNETs (100% of the cases for which this data was available). Genetic analysis of the recurrent SF3B1 c.1874G>A p.Arg625His was negative in all 15 tested tumors. In conclusion, pediatric-juvenile PitNETs are often large lesions causing mass effects in almost half of the cases. In our cohort, lactotroph PitNETs were the most frequent PitNETs and present without sex predilection. SF3B1 mutations, documented in a proportion of adult lactotroph PitNETs, were not observed in our cohort, potentially hinting at a different molecular background. Our results did not reveal any association between Ki-67 and p53 status and tumor size or invasiveness in pediatric-juvenile PitNETs.

Orbital neurofibromas are benign tumors originating from the peripheral nerve sheath, often linked to neurofibromatosis type 1 (NF1) [1], although they account for less than 1% of all orbital tumors [2, 3]. These tumors can cause symptoms such as proptosis, vision impairment, and ocular misalignment [4]. While typically linked to NF1, multiple isolated orbital neurofibromas in the absence of a definitive NF1 diagnosis remain exceedingly rare, warranting clinical attention. A 56-year-old female presented with ptosis and dystopia on the right side. MRI revealed multiple intraorbital and extraconal masses, with the largest being excised via anterior orbitotomy. Histopathological analysis confirmed the diagnosis of neurofibroma. The patient had no cutaneous or systemic signs suggestive of NF1. In adults, multiple orbital tumors should prompt suspicion for neurofibromas, even when NF1 is not confirmed. Furthermore, recurrence is possible, emphasizing the importance of long-term follow-up. This case highlights the diagnostic challenge posed by orbital neurofibromas without NF1 and the need for comprehensive systemic evaluation in such presentations.

Primary intracranial smooth muscle tumors are rare and range from benign to malignant. We report 2 patients with primary intracranial smooth muscle neoplasms in immunocompromised host, 1 patient each with primary intracranial leiomyoma and primary intracranial leiomyosarcoma, both of whom clinically and radiologically mimicked meningioma. Both patients were human immunodeficiency virus (HIV) positive. Hence, smooth muscle neoplasms should be considered in the differential diagnosis of well-circumscribed intracranial lesion, especially in immunocompromised patients.