Search

Diagnoses of primary malignant mesenchymal brain tumors are a challenge for pathologists. Here, we report the case of a 52-year-old man with a primary brain tumor, histologically diagnosed as a high-grade glioma, not otherwise specified (NOS). The patient underwent two neurosurgeries in several months, followed by radiotherapy and chemotherapy. We re-examined the tumor samples by methylome profiling. Methylome analysis revealed an epi-signature typical of a primary intracranial sarcoma, DICER1-mutant, an extremely rare tumor. The diagnosis was confirmed by DNA sequencing that revealed a mutation in DICER1 exon 25. DICER1 mutations were not found in the patient's blood cells, thus excluding an inherited DICER1 syndrome. The methylome profile of the DICER1 mutant sarcoma was then compared with that of a high-grade glioma, a morphologically similar tumor type. We found that several relevant regions were differentially methylated. Taken together, we report the morphological, epigenetic, and genetic characterization of the sixth described case of an adult primary intracranial sarcoma, DICER1-mutant to-date. Furthermore, this case report underscores the importance of methylome analysis to refine primary brain tumor diagnosis and to avoid misdiagnosis among morphologically similar subtypes.

Objective: Spinal meningiomas are slow-growing tumors with low recurrence rate after complete resection. The aim of this study is to investigate the risk factors correlated to the recurrence. Material and Methods: Six patients with spinal WHO grade I meningiomas which recurred after complete resection were reviewed and compared to 50 patients with no recurrence; the data were also compared with those of 50 intracranial meningiomas which recurred and 50 which did not recur after complete resection. The investigated factors included age and sex, tumor location and size, type of arachnoid interface, entity of resection (Simpson I or II), tumor consistency and vascularity, histological type, Ki-67 MIB-1, progesterone receptor (PR) and estrogen receptor (ER) expression. The data were statistically analyzed with the Kaplan-Meier method. Results: The statistical analysis showed that the presence of arachnoidal invasion (p = 0.023) and higher Ki-67 LI (p

Meningiomas may show a different WHO grade and variable biological and clinical behaviors. The aim of the present study is to assess whether WHO grade, proliferation index, progesterone receptor (PR) expression, histological subtype, neuroradiological features, and the recurrence rate differ depending on the tumor location. Three hundred meningiomas operated on from 2006 to 2016 were reviewed. The WHO grade (2007 classification), Ki67-MIB1, progesterone receptor expression, and histological subtype were reexamined and correlated to the meningioma location, classified as medial skull base, lateral skull base, non-skull base, and spinal. Non-skull base and lateral skull base meningiomas showed significantly higher rates of atypical WHO II forms (34% and 25.5% respectively) than medial skull base (12.5%) and spinal ones (7%) (p = 0.0003) and also higher rates of tumors with Ki67-Li > 4% (42% and 38% vs 22% and 14%) (p = 0.0031). The rate of meningiomas with PR expression ≤ 50% was significantly lower in medial skull base (25%) than in non-skull base (48%) (p = 0.009). Meningothelial and transitional meningiomas were more frequent at the skull base (68.5% and 54.5%, respectively), the fibroblastic subtype at the non-skull base (48.5%), and the psammomatous at the spinal canal (50%) (p < 0.00001). Medial skull base and spinal meningiomas showed significantly lower size (p < 0.00001), lower rates of cases with lost arachnoid interface (p = 0.0022), and significantly lower recurrence rates (p = 0.0035) than lateral skull base and non-skull base meningiomas. Medial skull base meningiomas show lower size, lower rate of atypical forms, lower Ki67-Li values, and significantly higher PR expression than those at the lateral skull base and non-skull base. This corresponds to lesser aggressiveness and lower recurrence rates.

Here we review the pathologic features of a specialized tumor subset, collectively referred to as neuroendocrine tumors. These tumors arise almost anywhere in the body but many issues regarding their diagnosis and classification remain to be settled. Recent technical improvements, have increased the rate of detection, and have contributed to better diagnosis and classification of these tumors.

Two cases of the rare cellular variant of the solitary capillary haemangioblastoma are reported. On MR study both tumors appeared as cerebellar contrast-enhancing masses, without evidence of intra- or perilesional blood vessels. Histologically, they showed compact groups of polygonal or rectangular cells separated by compressed small capillaries. There were no reticulin fibres among cell clusters. The stromal cells were found to be immunopositive for neuron-specific enolase (NSE), factor VIII-related antigen (von Wille-brand factor), Ulex europaeus lectin, and glial frillary acidic protein (GFAP). The findings are discussed in light of the pertinent literature.

The aim of this study was to calculate MRI quantitative parameters extracted from chemical-shift (CS) and dynamic contrast-enhanced (DCE) T1-weighted (T1-WS) images of adrenal lesions (AL) with qualitative heterogeneous signal drop on CS T1-WS and compare them to those of AL with homogeneous or no signal drop on CS T1-WS. On 3 T MRI, 65 patients with a total of 72 AL were studied. CS images were qualitatively assessed for grouping AL as showing homogeneous (Group 1, n = 19), heterogeneous (Group 2, n = 23), and no (Group 3, n = 30) signal drop. Histopathology or follow-up data served as reference standard to classify AL. ROIs were drawn both on CS and DCE images to obtain adrenal CS signal intensity index (ASII), absolute (AWO), and relative washout (RWO) values. Quantitative parameters (QP) were compared with ANOVA analysis and post hoc Dunn’s test. The performance of QP to classify AL was assessed with receiver operating characteristic analysis. CS ASII values were significantly different among the three groups (p < 0.001) with median values of 71%, 53%, and 3%, respectively. AWO/RWO values were similar in Groups 1 (adenomas) and 2 (benign AL) but significantly (p < 0.001) lower in Group 3 (20 benign AL and 10 malignant AL). With cut-offs, respectively, of 60% (Group 1 vs. 2), 20% (Group 2 vs. 3), and 37% (Group 1 vs. 3), CS ASII showed areas under the curve of 0.85, 0.96, and 0.93 for the classification of AL, overall higher than AWO/RWO. In conclusion, AL with qualitative heterogeneous signal drop at CS represent benign AL with QP by DCE sequence similar to those of AL with homogeneous signal drop at CS, but different to those of AL with no signal drop at CS; ASII seems to be the only quantitative parameter able to differentiate AL among the three different groups.

Background: Familial forms of cavernous malformations (CMs) often occur as multiple lesions. Nevertheless, the presence of a single CM does not exclude the familiarity. The aim of this study is to establish which patients who undergo surgery for a single cerebral cavernous malformation (CCM), with no family history at initial diagnosis, should be investigated for familiarity through genetic testing and counseling. Methods: Eight families with 2 or more members affected by CCM have been studied. A control group of sporadic cases operated on, with no family history and followed up 10 years or more, was also included. Analyzed factors were patient age and sex, location, number and size of the lesions, associated developmental venous anomaly, presence of epileptic seizures, symptomatic hemorrhage, focal neurological deficits, and documented growth of the malformation and Ki67 MIB1 proliferation index. Results: The familial group of CCMs showed higher incidence of pediatric patients (P = 0.01), more frequent occurrence of multiple lesions (P = 0.0004), higher rate of large CCMs, and symptomatic hemorrhage; besides, all 3 cases with documented growth belonged to the familial group (14%). The expression of Ki67 MIB1 was positive in 79% of the familial cases versus 0% in the sporadic ones (P < 0.00001). Conclusions: Patients with CCM and no known family history at the time of the initial diagnosis who present specific features should be studied by genetic screening. The Ki67 MIB1 is a useful biomarker in favor of familial occurrence and may be studied in all patients with CMs to define the indication to the genetic tests.

The nature of endometrial morular metaplasia (MorM) is still unknown. The nuclear β-catenin accumulation and the not rare ghost cell keratinization suggest a similarity with hard keratin-producing odontogenic and hair matrix tumors rather than with squamous differentiation. We aimed to compare MorM to hard keratin-producing tumors. Forty-one hard keratin-producing tumors, including 26 hair matrix tumors (20 pilomatrixomas and 6 pilomatrix carcinomas) and 15 odontogenic tumors (adamantinomatous craniopharyngiomas), were compared to 15 endometrioid carcinomas with MorM with or without squamous/keratinizing features. Immunohistochemistry for β-catenin, CD10, CDX2, ki67, p63, CK5/6, CK7, CK8/18, CK19, and pan-hard keratin was performed; 10 cases of endometrioid carcinomas with conventional squamous differentiation were used as controls. In adamantinomatous craniopharyngiomas, the β-catenin-accumulating cell clusters (whorl-like structures) were morphologically similar to MorM (round syncytial aggregates of bland cells with round-to-spindled nuclei and profuse cytoplasm), with overlapping squamous/keratinizing features (clear cells with prominent membrane, rounded squamous formations, ghost cells). Both MorM and whorl-like structures consistently showed positivity for CD10 and CDX2, with low ki67; cytokeratins pattern was also overlapping, although more variable. Hard keratin was focally/multifocally positive in 8 MorM cases and focally in one conventional squamous differentiation case. Hair matrix tumors showed no morphological or immunophenotypical overlap with MorM. MorM shows wide morphological and immunophenotypical overlap with the whorl-like structures of adamantinomatous craniopharyngiomas, which are analogous to enamel knots of tooth development. This suggests that MorM might be an aberrant mimic of odontogenic differentiation. Supplementary Information The online version contains supplementary material available at 10.1007/s00428-021-03060-2.

Background Intradural metastases to the cauda equina from renal cell carcinoma are exceptional, with only 14 reported cases in the literature. This article reports a further case and discusses the indications and limits of the surgery and the best management. Case report: A 64-year-old man was observed because of sudden onset of intense radicular pain in the left L5 territory. Fourteen years before he underwent right nephrectomy for a clear renal cell carcinoma. MRI revealed two intradural metastatic lesions at L1-L2 and L4-L5 levels, respectively. Surgical resection of the symptomatic L4-L5 lesion, radiotherapy and chemotherapy were performed. The histological and immunohistochemical studies confirmed the diagnosis of metastatic renal cell carcinoma. The treatment resulted in remission of the radicular pain with no neurological deficits. The patient was symptom-free at one year follow-up. Conclusion Intradural metastases to the cauda from renal cell carcinoma are exceptional. Surgery is the first option in selected patients with stable neoplastic disease, good Karnofsky Performance Status (KPS > 70), intense radicular pain and progressive neurological symptoms. The tumor resection, even incomplete, results in clinical improvement.

Pituitary adenomas are among the most frequent intracranial tumors. They may exhibit clinically aggressive behavior, with recurrent disease and resistance to multimodal therapy. The ki-67 labeling index represents a proliferative marker which correlates with pituitary adenoma aggressiveness. Aim of our study was to assess the accuracy of machine learning analysis of texture-derived parameters from pituitary adenomas preoperative MRI for the prediction of ki-67 proliferation index class. A total of 89 patients who underwent an endoscopic endonasal procedure for pituitary adenoma removal with available ki-67 labeling index were included. From T2w MR images, 1128 quantitative imaging features were extracted. To select the most informative features, different supervised feature selection methods were employed. Subsequently, a k-nearest neighbors (k-NN) classifier was employed to predict macroadenoma high or low proliferation index. Algorithm validation was performed with a train-test approach. Of the 12 subsets derived from feature selection, the best performing one was constituted by the 4 highest correlating parameters at Pearson’s test. These all showed very good (ICC ≥ 0.85) inter-observer reproducibility. The overall accuracy of the k-NN in the test group was of 91.67% (33/36) of correctly classified patients. Machine learning analysis of texture-derived parameters from preoperative T2 MRI has proven to be effective for the prediction of pituitary macroadenomas ki-67 proliferation index class. This might aid the surgical strategy making a more accurate preoperative lesion classification and allow for a more focused and cost-effective follow-up and long-term management.

Pituitary tumors are a heterogeneous group of lesions (usually benign) and proper understanding of the anatomy, physiology, and pathology of the hypothalamic/pituitary region is essential to make an accurate diagnosis and define the essential treatment options (i.e., surgery, medical therapies, and radiotherapy, alone or in combination). Surgery is the primary treatment for acromegaly, Cushing disease, thyroid-stimulating hormone-secreting adenomas, resistant prolactinomas, and nonfunctioning pituitary adenomas causing mass effect. Medical and radiation therapy are reserved in cases in which surgery is not possible or does not provide a complete cure. In the last decades, tremendous innovations (i.e., targeted drugs and refined surgical tools and techniques) have expanded the treatment strategies for pituitary adenomas. We herein report the current indications for and depiction of the surgical techniques in pituitary surgery, review current medical treatments, and provide a glimpse of future possibilities.

Meningioangiomatosis is a rare congenital hamartomatous malformation of the leptomeninges that can also involve the adjacent cerebral tissue, sometime arising in association with neurofibromatosis. Here we report the case of a 55-year-old man with neuroradiological evidence of meningioangiomatosis, known to be a well-defined malformative-dysplastic lesion, preceding the onset of central nervous system B-cell lymphoma. We describe for the first time this unusual association, highlighting how meningioangiomatosis could accompany different pathologies more frequently than thought. Keywords: Meningioangiomatosis, Neurofibromatosis, Lymphoma, Magnetic resonance imaging

Cushing's syndrome is a pathological clinical condition caused by an exposure of elevated cortisol levels over a long period of time. It is therefore essential to establish what the cause of hypercortisolism is. In most cases (about 80%) the pathological process is due to adrenocorticotropic hormone (ACTH), while in a minor part of the cases (about 20%) the cause is represented by a pathology of the adrenal glands and therefore not related to ACTH. Most patients with ACTH dependent Cushing's syndrome have a pituitary microadenoma; in the remaining cases (30%), the high level of cortisol is linked to an ectopic secretion of ACTH. Surgical removal of the pituitary adenoma represents the treatment of choice in Cushing's disease (CD) patients; it is therefore necessary to identify and precisely locate the pituitary tumour responsible for the secretion of ACTH. Adequate diagnostic information is very often, even with magnetic resonance imaging (MRI), and in these cases we rely on bilateral inferior petrosal sinuses sampling (BIPSS). This procedure is considered the gold standard method for the diagnosis, but like any other diagnostic method it is not free from erroneous results such as false positives or false negatives.

BackgroundThe progesterone receptor (PR) is variably expressed in most meningiomas and was found to have prognostic significance. However, the correlation with patient age, tumor location, time to recurrence, and pattern of regrowth has scarcely been discussed.MethodsA surgical series of 300 patients with meningiomas is reviewed. The PR expression was classified as: 0. absent; 1. low (versus multicentric diffuse), and time to recurrence.ResultsThe PR expression has shown lower rate of high expression in the elderly group (p = 0.032) and no sex difference (including premenopausal versus postmenopausal women), higher expression in medial skull base and spinal versus other locations (p = 0.0036), inverse correlation with WHO grade and Ki67-MIB1 (p < 0.0001). Meningiomas which recurred showed at initial surgery higher rates of low or moderately low PR expression than the non-recurrent ones (p = 0.0004), whereas the pattern of regrowth was not significant. Higher rates of PR values ≥80% were found in cases with time to recurrence >5 years (p = 0.036).ConclusionThe higher PR expression in medial skull base meningiomas, the significant correlation with the time to recurrence, the lack of difference of PR expression between premenopausal and postmenopausal women and between local-peripheral versus multicentric-diffuse recurrences are the most relevant unreported findings of this study. The rate of PR expression must be included in the routine pathological diagnosis of meningiomas because of its prognostic significance.

Malignant intraventricular meningiomas (IVMs) are very rare with only a few reported cases. A midline search up to December 2020 selected 40 articles for a total of 65 patients. The inclusion criteria were series and case reports in English language, as well as papers written in other languages, but with abstracts written in English. Malignant IVMs at the first diagnosis (group A, 50 patients) and those with anaplastic transformation from previous WHO grades I and II tumors (group B, 15 patients) were separately analyzed. The unique personal case among 1285 meningiomas (0.078%) is also added. Malignant IVMs mainly occur in women (61%) with a median age of 45 years and are mainly located in the lateral ventricle (93%) and trigonal region (74%), with no cases in the fourth ventricle. Irregular borders (80%), heterogeneous enhancement (83%), and perilesional edema (76%) are the most frequent radiological findings. The histology was mainly pure anaplastic (85%), whereas papillary (7%), rhabdoid (5%), and mixed forms (3%) are very rare. The CSF spread was found in 60% of the cases. The prognosis is very dismal, with an overall median survival of 17.5 months after surgery for the anaplastic forms. Malignant IVMs at initial diagnosis (group A) show better overall survival (25 months) than those occurring from anaplastic transformation of lower grade tumors (group B) (10.1 months).

BackgroundSeveral epidemiological and pathological findings suggest that the female sex hormones may influence the development of meningiomas. However, the role of pregnancy, oral contraceptives, and fertilization therapies is still controversial.MethodsFrom the surgical series of 354 patients with meningiomas operated between 2006 and 2019, the group of 72 premenopausal women was separately considered. The tumor location, WHO grade, Ki67-labeling index (LI), progesterone receptor (PR) expression, and histological types were studied in premenopausal women with and without hormone-related conditions were compared.ResultsIn this premenopausal group, 24 patients had hormone-related conditions, including use of oral contraceptives in 16, intrauterine fertilization in one, pregnancy in three, and tumors of the female reproductive system in four. The group of patients with hormone-related conditions, as compared to that with no hormone related conditions, showed slightly lower median age (38 versus 43 years) and no significant difference of meningioma location WHO grade, Ki 67-Li, PR expression and histological type. The clinical onset during pregnancy in three patients and tumor growth during contraceptive progesterone therapy in two others were evidenced.ConclusionThe biological behavior of meningiomas and their pathological findings, including PR expression, are not correlated with the different hormone related conditions in premenopausal female patients. Contraceptives and fertilization therapies, mainly with progesterone, should be avoided in patients with meningiomas.

Coronaviridae family includes pathogen viruses for humans, that lead to clinical conditions with main respiratory involvement; many of these viruses have notoriously a neuroinvasive potential, as demonstrated by published data on SARS-CoV and MERS-CoV epidemics, as well by results obtained in experimental models. During pandemic of coronavirus disease 2019 (COVID-19), it is noticed that the central nervous system involvement represented a truly significant moment in the history of some COVID-19 patients; indeed, clinical and radiological features published in literature regarding COVID-19 disease are consistent with a neurological involvement. It is also known that histopathological data related to SARS-CoV2 infection have been published with considerable delay, which was even greater for neuropathological information. Moreover, many published data are incomplete, and often the lesions described are not directly related to the action of the virus. In this review, we collected the available radiological and neuropathological information, in order to delineate a more complete picture of the relationship between SARS-Cov2 and brain, focusing our attention on the two most important neuroinvasion routes for the virus. We also highlighted what we consider methodological mistakes both in the autopsy procedures and brain study in COVID-19 deaths. We emphasize the need for a complete study of all the organs in case of autopsy. It is important that through this experience, we no longer do the mistake of neglecting the brain.