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Introduction: Myeloid sarcoma (MS) is a mass-forming proliferation of myeloid blasts. Frequently, it arises as blast phase of pre-existing myeloproliferative, myelodysplastic disorders or consequent to bone marrow transplant. Its molecular characterization has become an increasingly important requirement for the diagnostic definition of this solid leukemia. Case Presentation: Our case report concerns an MS arising in the breast of a woman with a previous diagnosis of JAK2-mutated essential thrombocythemia (Val617Phe exon 14p) mimicking, on histology, a lobular carcinoma of the breast. The immunohistochemical study of the neoplasm provided the key that solved the diagnostic doubt and the immunohistochemical evaluation of NPM protein expression, which turn out to be negative, provided a clear indication on the molecular status and prognosis of the disease. A year later, the neoplasm relapsed in the pelvic area. Discussion: This diagnostic challenge led us to review the literature of the past 10 years concerning MS of the breast. To the best of our knowledge, this was the first case of MS of the breast occurring in a patient with a history of essential thrombocythemia and recurred in the pelvic region.

Unresectable neuroendocrine neoplasms (NENs) often poorly respond to standard therapeutic approaches. Alkylating agents, in particular temozolomide, commonly used to treat high-grade brain tumors including glioblastomas, have recently been tested in advanced or metastatic NENs, where they showed promising response rates. In glioblastomas, prediction of response to temozolomide is based on the assessment of the methylation status of the MGMT gene, as its product, O 6-methylguanine-DNA methyltransferase, may counteract the damaging effects of the alkylating agent. However, in NENs, such a biomarker has not been validated yet. Thus, we have investigated MGMT methylation in 42 NENs of different grades and from various sites of origin by two different approaches: in contrast to methylation-specific PCR (MSP), which is commonly used in glioblastoma management, amplicon bisulfite sequencing (ABS) is based on high-resolution, next-generation sequencing and interrogates several additional CpG sites compared to those covered by MSP. Overall, we found MGMT methylation in 74% (31/42) of the NENs investigated. A higher methylation degree was observed in well-differentiated tumors and in tumors originating in the gastrointestinal tract. Comparing MSP and ABS results, we demonstrate that the region analyzed by the MSP test is sufficiently informative of the MGMT methylation status in NENs, suggesting that this predictive parameter could routinely be interrogated also in NENs.

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.

Purpose To assess a radiomic machine learning (ML) model in classifying solid adrenal lesions (ALs) without fat signal drop on chemical shift (CS) as benign or malignant. Method 55 indeterminate ALs (21 lipid poor adenomas, 15 benign pheocromocytomas, 1 oncocytoma, 12 metastases, 6 primary tumors) showing no fat signal drop on CS were retrospectively included. Manual 3D segmentation on T2-weighted and CS images was performed for subsequent radiomic feature extraction. After feature stability testing and an 80–20% train-test split, the train set was balanced via oversampling. Following a multi-step feature selection, an Extra Trees model was tuned with 5-fold stratified cross-validation in the train set and then tested on the hold-out test set. Results A total of 3396 features were extracted from each AL, of which 133 resulted unstable while none had low variance (< 0.01). Highly correlated (r > 0.8) features were also excluded, leaving 440 parameters. Among these, Support Vector Machine 5-fold stratified cross-validated recursive feature elimination selected a subset of 6 features. ML obtained a cross-validation accuracy of 0.94 on the train and 0.91 on the test sets. Precision, recall and F1 score were respectively 0.92, 0.91 and 0.91. Conclusions Our MRI handcrafted radiomics and ML pipeline proved useful to characterize benign and malignant solid indeterminate adrenal lesions.

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 We report an extremely unusual case of anterior clinoid process (ACP) metastasis as the first presentation of a signet ring cell carcinoma. Case Description A 54-year-old female patient presented with right-sided visual disturbances due to optic nerve compression from a computed tomography (CT)-identified right anterior clinoid bone lesion. Contrast-enhanced magnetic resonance imaging showed an extra-axial, well-bordered enhancing mass extending from the right ACP toward the inner lumen of the optic canal. Pterional approach was adopted to remove the lesion and decompress the optic canal. Histological examination demonstrated a metastasis from a signet ring cell carcinoma. Postoperative CT showed near-total resection of the tumor and decompression of the optic canal. Visual defect remained unchanged. Conclusion Metastasis should be considered in the differential diagnosis of the ACP lesions. The early suspicion and identification of this extremely rare pathological entity can be helpful for the prompt management of patients, especially in the absence of any other signs of oncological diseases.

In 2010, serrated polyps (SP) of the colon have been included in the WHO classification of digestive tumors. Since then a large corpus of evidence focusing on these lesions are available in the literature. This review aims to analyze the present data on the epidemiological and molecular aspects of SP. Hyperplastic polyps (HPs) are the most common subtype of SP (70–90%), with a minimal or null risk of malignant transformation, contrarily to sessile serrated lesions (SSLs) and traditional serrated adenomas (TSAs), which represent 10–20% and 1% of adenomas, respectively. The malignant transformation, when occurs, is supported by a specific genetic pathway, known as the serrated-neoplasia pathway. The time needed for malignant transformation is not known, but it may occur rapidly in some lesions. Current evidence suggests that a detection rate of SP ≥15% should be expected in a population undergoing screening colonoscopy. There are no differences between primary colonoscopies and those carried out after positive occult fecal blood tests, as this screening test fails to identify SP, which rarely bleed. Genetic similarities between SP and interval cancers suggest that these cancers could arise from missed SP. Hence, the detection rate of serrated-lesions should be evaluated as a quality indicator of colonoscopy. There is a lack of high-quality longitudinal studies analyzing the long-term risk of developing colorectal cancer (CRC), as well as the cancer risk factors and molecular tissue biomarkers. Further studies are needed to define an evidence-based surveillance program after the removal of SP, which is currently suggested based on experts’ opinions.

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.

Lateral periodontal cyst (LPC) and odontogenic keratocystic (OK) are two osteolytic lesions of the jaw with different local invasiveness and percentage of recurrence. The aim of this study was to highlight the attention on the differential diagnosis of these lesions that sometimes can have unexpected location and can lead doubts on diagnosis, therapy, and follow-up. A 34-year-old man presented to our department with a complaint of soft pain in the vestibular aspect of left mandibular second premolar and left mandibular first molar. Vital teeth in the left mandible, no mucosal swelling, and no drainage were observed. The CBCT showed a well circumscribed hypodensity area, extending between 3.5 and the apex of mesial root of 3.6. No displacement and no resorption of the roots were notified. Upon clinical and radiographical examination, a provisional diagnosis of LPC was made and enucleation of the lesion and histological examination were planned. Histologically, a cystic wall partially lined by a keratinizing squamous epithelium was observed. Surrounding and within the lesion, there was a chronic inflammatory infiltrate also of granulomatous type and with cholesterol clefts. Based on these findings, the diagnosis of odontogenic keratocystic was done. Radiolucent lesions in the premolar and canine region are frequently clinically and radiographically misdiagnosed. The identification of keratocyst in a location preoperatively favoring a lateral periodontal cyst should be suspected and biopsy must be considered in all cases to establish the nature of the lesion, the best surgical treatment, and the follow-up appointments.

This report shows a rare case of gastric heterotopia in the duodenum presented as a large polypoid lesion, differently from data reported in literature, which enters into differential diagnosis with other duodenal lesions that are not always benign.

CONTEXT. The 5th edition of the World Health Organization classification of digestive system tumors discusses several advancements and developments in understanding the etiology, pathogenesis, and diagnosis of several digestive tract tumors. OBJECTIVE. To provide a summary of the updates with a focus on neuroendocrine neoplasms, appendiceal tumors, and the molecular advances in tumors of the digestive system. DATA SOURCES. English literature and personal experiences. CONCLUSIONS. Some of the particularly important updates in the 5th edition are the alterations made in the classification of neuroendocrine neoplasms, understanding of pathogenesis of appendiceal tumors and their precursor lesions, and the expanded role of molecular pathology in establishing an accurate diagnosis or predicting prognosis and response to treatment.

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

Meningiomas recur with a rate of 10–32% at ten years. Several features influence the risk of recurrence. Our aim is to define the pathological and surgical features at risk of diffuse-multicentric versus local-peripheral recurrence. Thirty-three cases of multicentric-diffuse recurrence of intracranial meningiomas were retrospectively analyzed and compared with 50 cases who experienced local-peripheral recurrence. The analyzed factors included age and sex, tumor location and shape, brain-tumor interface, entity of resection, WHO grade, Ki67 MIB1, progesterone receptor (PR) expression, number of reoperations, progression of WHO grade, and outcome. The multicentric-diffuse recurrences were mainly related to flat-shaped and Ki67 Li greater than 4% features at first surgery. Among patients with multicentric-diffuse recurrences, 25 underwent one to three reoperations; among them, 17 are alive with local tumor control or slow progression 2 to 25 years after the initial surgery versus only 2 out of 8 who did not undergo surgery. We conclude that flat-shaped meningiomas and those with Ki67 Li greater than 4% are at higher risk to recur in multicentric-diffuse pattern. Even multiple reoperations over a period of several years may obtain rather long survivals in selected patients with prevalent intradural not anaplastic tumors and not too extensive dural infiltration.

Growing evidence supports the pivotal role played by periprostatic adipose tissue (PPAT) in prostate cancer (PCa) microenvironment. We investigated whether PPAT can affect response to Docetaxel (DCTX) and the mechanisms associated. Conditioned medium was collected from the in vitro differentiated adipocytes isolated from PPAT which was isolated from PCa patients, during radical prostatectomy. Drug efficacy was studied by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide citotoxicity assay. Culture with CM of human PPAT (AdipoCM) promotes DCTX resistance in two different human prostate cancer cell lines (DU145 and PC3) and upregulated the expression of BCL‐xL, BCL‐2, and TUBB2B. AG1024, a well‐known IGF‐1 receptor inhibitor, counteracts the decreased response to DCTX observed in presence of AdipoCM and decreased TUBB2B expression, suggesting that a paracrine secretion of IGF‐1 by PPAT affect DCTX response of PCa cell. Collectively, our study showed that factors secreted by PPAT elicits DCTX resistance through antiapoptotic proteins and TUBB2B upregulation in androgen independent PCa cell lines. These findings reveal the potential of novel therapeutic strategies targeting adipocyte‐released factors and IGF‐1 axis to overcome DCTX resistance in patients with PCa.

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.

Pheochromocytomas may show atypical imaging findings leading to diagnostic pitfalls. We correlated the results of magnetic resonance imaging (MRI) with those of radionuclide studies in patients with pheochromocytomas. T2-weighted (-w), T1-w chemical-shift and T1-w dynamic contrast enhanced (DCE) MRI sequences were evaluated to assess tumor structure. 131Iodine metaiodobenzylguanidine (MIBG) scintigraphy, 18fluoro (F) deoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) or FDG PET/MRI were evaluated for direct comparison. Of a total of 80 adrenal lesions in 73 patients, 20 in 18 patients were pheochromocytomas. More than half (55%) of the pheochromocytomas (n = 11) had the typical increased signal intensity on T2-w and T1-w DCE, while the remaining (n = 9) lesions showed atypical findings, of these nine latter atypical lesions, seven (35%) were cystic (two totally, three predominantly and two partially) and two (10%) were hemorrhagic on MRI. In these atypical lesions, MIBG scintigraphy (n = 5), FDG PET/CT (n = 6) or FDG PET/MRI (n = 2) showed inhomogeneous tracer uptake in the residual viable tissue providing tumor characterization, however, one predominantly cystic pheochromocytoma showed false negative MIBG scan. Our preliminary results show that cystic degeneration may be frequent in pheochromocytoma being so marked that only a thin rim of viable cells may residue to disclose the true nature of the tumor. MRI findings together with those of correlative planar/hybrid radionuclide images are helpful to characterize these atypical pheochromocytomas. In particular, tumor accumulation of MIBG and/or FDG is able to classify these lesions as not simple cysts, in detail, the presence of partial MIBG uptake allows the diagnosis of pheochromocytomas, while the presence of partial FDG uptake generically reflects the presence of viable solid tissue of such cystic tumors.

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).

Pleomorphic adenoma accounts for the majority of benign tumors of the salivary gland. It is also called mixed tumor because it is composed by ductal epithelial and myoepithelial cells, variably intermixed within a chondromyxoid stroma. The recurrence rate is around 3.4% and 6.3%, respectively at 5 and 10 years and, to date, there are no valuable predictive factors. Aim of our study was to assess the role of Ki67 proliferative index in our cases and through meta-analysis.Immunohistochemistry with Ki67 antibody was performed on 28 cases. A manual count of the signal was performed, to establish the proliferative activity. Statistical tests were applied to assess the correlation between the score and clinico-pathologic parameters. Further data were extrapolated from studies published on Pubmed, Cochrane and Web of Science database.Higher values of Ki67 were found among cases with larger size (p value = 0.0061) and showing greater cellularity (p value=0.0004). 19 papers were selected from the bibliographic search, concerning a total of 1187 patients affected by pleomorphic adenoma. In most of them, a higher Ki67 was detected among relapsing forms but results were controversial. In each study, several count methods were applied.The role of Ki67 in pleomorphic adenoma of the salivary glands remains unclear. The lack of homogeneity of the data makes it very difficult to standardize them in order to draw a conclusion. It would therefore be desirable to carry out a comparison study of the various possible methods of Ki67 counting.

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.

Gut microbiota is represented by different microorganisms that colonize the intestinal tract, mostly the large intestine, such as bacteria, fungi, archaea and viruses. The gut microbial balance has a key role in several functions. It modulates the host’s metabolism, maintains the gut barrier integrity, participates in the xenobiotics and drug metabolism, and acts as protection against gastro-intestinal pathogens through the host’s immune system modulation. The impaired gut microbiota, called dysbiosis, may be the result of an imbalance in this equilibrium and is linked with different diseases, including cancer. While most of the studies have focused on the association between microbiota and gastrointestinal adenocarcinomas, very little is known about gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs). In this review, we provide an overview concerning the complex interplay between gut microbiota and GEP NENs, focusing on the potential role in tumorigenesis and progression in these tumors.

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.

Fractional COA single-center observational prospective cohort study was performed enrolling all GSM patients from July 2017 to October 2018. Patients underwent three outpatient vulvovaginal applications of fractional COOf 20 enrolled patients, 18 underwent all laser applications, and 15 underwent both vulvar biopsies. 93.3% of patients showed remodeling of vulvar connective tissue; 80% showed improvement in vulvar epithelium trophism and 86.7% showed neovascularization. Differences in means between before and after treatment were significant for VuHI, VHI, and all GSM symptoms. Means ± standard deviation of the degree of pain at each laser application were 4.4 ± 0.9, 3.7 ± 1.6, and 2.9 ± 1.9. The rate of overall satisfaction with the treatment was 72.2%.Fractional CO

Extraovarian germ cell tumors are very rare and their occurrence during pregnancy is exceptional. In this case report an abdominal mass was shown by ultrasonography, during a routine monitoring of a 26-year-old pregnant woman. The patient was left under radiological control in the following months in order to bring the pregnancy to term. A few months after the delivery, the patient underwent surgery and a diagnosis of extraovarian (abdominal) dysgerminoma was made. To the best of our knowledge, there are only 3 other case reports describing an extra-gonadal dysgerminoma occurring during pregnancy. The aim of this study was to report an extremely rare tumor, whose management can be challenging first because this neoplasm has some differences from its ovarian and testicular counterparts. Furthermore, the occurrence during pregnancy makes the multidisciplinary approach mandatory since 3 distinct but not independent entities are involved (tumor, mother and fetus).

The first step leading to metastasis, or for the acquisition of local invasiveness, involves changes in the phenotype of neoplastic cells in the primary tumor. The epithelial&ndash, mesenchymal transition (EMT) is a process that determines the acquisition of a form and a transcriptional program that are characteristic of mesenchymal cells, in epithelial cells. The factors involved in this process are E-cadherin and N-cadherin adhesion proteins and some transcription factors such as Slug and Twist. EMT is a site-specific mechanism that is also active in embryogenesis&mdash, embryonic cells are affected if invested in certain points, probably due to the signals emanating from the cells or groups of surrounding cells. It is known that neuroendocrine neoplasms have a biological behavior that differs in grading, staging, and site. The aim of our study was to investigate the immunohistochemical expression of EMT factors (Twist, Slug, and E-cadherin) in the neuroendocrine neoplasms of the gastrointestinal tract, the pancreas, and lungs, in 65 cases retrieved from the archives of the Department of Pathology, of three hospitals. The immunoscores were compared in each site and correlated with the clinico-pathological parameters. Statistical evaluation revealed an association between the higher Twist immunoscore and higher grading (p value &lt, 0.0001) and staging (p value = 0.0055). Slug was detected only in pancreatic cases where its reduced expression was associated with a higher grading (p value = 0.0033). This data could be of diagnostic utility in the case of metastases from neuroendocrine neoplasm, to define the site of the primitive tumor when the traditional immunohistochemical panel is not sufficient. In summary, our results indicated, first that the EMT is also an active process in neuroendocrine neoplasms. To the best of our knowledge, this was the first study that evaluated the expression of EMT factors in neuroendocrine neoplasms of different districts.

Background: Meningiomas recur with a rate of 10–32% at 10 years. Several features influence the risk of recurrence. Objective: To define the pathological and surgical features at risk of multicentric-diffuse versus local–peripheral recurrence. Methods: Thirty-three patients operated on for intracranial meningiomas who experienced multicentric-diffuse recurrence were retrospectively analyzed. The data of these patients were compared to those of 50 patients who experienced local–peripheral recurrence. The analyzed factors included age and sex, tumor location and shape, brain-tumor interface, entity of resection, WHO grade, Ki67 MIB1, progesterone receptor (PR) expression, number of reoperations, progression of WHO grade, and outcome. Results: Meningiomas which recurred in multicentric-diffuse pattern showed at initial surgery a significantly higher rate of flat-shaped tumors (p =.0008) and of cases with Ki67 Li ≥ 4% (p =.037) than those which recurred in localized-peripheral pattern, whereas other factors did not significantly differ. Among patients with multicentric-diffuse recurrences, 25 underwent one to three reoperations; 17 among them (66%) are alive with local tumor control or slow progression 2–25 years after the initial surgery versus only 2 out of 8 who did not undergo surgery. Conclusions: Flat-shaped meningiomas and those with Ki67 Li ≥ 4% are at higher risk of multicentric-diffuse recurrence. Multiple reoperations over a period of several years may obtain rather long survivals in selected patients with prevalent intradural, not anaplastic tumors and not too extensive dural infiltration.

Angiomyolipomas (AMLs) are among the most common benign renal tumors, typically consisting of varying proportions of 3 components: blood vessels (angio), smooth muscle cells (myo), and fatty tissue (lipoma), and are thus called triphasic. Occasionally, AMLs may present atypical histologic features consisting almost exclusively of one component (monophasic) or containing numerous epithelioid muscle cells with small amount of fat, as in the rare epithelioid variant (E-AMLs). AMLs occur as a sporadic entity in 80% of cases; more rarely, they are related to hereditary diseases such as tuberous sclerosis complex (TSC). Hereditary AMLs can reach huge dimensions and may present unusual imaging features determining diagnostic pitfalls. Few cases of giant sporadic AMLs are reported in literature, and even fewer regarding the epithelioid variant. We present a case of a 36-year-old man suffering from anemia and fever, whose contrast-enhanced computed tomography (CT) depicted the presence of a huge (14 x 21 x 30 cm) retroperitoneal fat-containing mass.

An increased calcitonin serum level is suggestive of a medullary thyroid cancer (MTC), but is not pathognomonic. The possibility of false positives or other calcitonin-secreting neuroendocrine neoplasms (NENs) should be considered. Serum calcitonin levels are generally assessed by immunoradiometric and chemiluminescent assays with high sensitivity and specificity; however, slightly moderately elevated levels could be attributable to various confounding factors. Calcitonin values >100 pg/mL are strongly suspicious of malignancy, whereas in patients with moderately elevated values (10–100 pg/mL) a stimulation test may be applied to improve diagnostic accuracy. Although the standard protocol and the best gender-specific cut-offs for calcium-stimulated calcitonin are still controversial, the fold of the calcitonin increase after stimulation seems to be more reliable. Patients with MTC show stimulated calcitonin values at least three to four times higher than the basal values, whereas calcitonin-secreting NENs can be distinguished from a C-cell disease by the absence of or

Neuroendocrine neoplasms (NENs) are a group of tumors originating from the neuroendocrine system. They mainly occur in the digestive system and the respiratory tract. It is well-know a strict interaction between neuroendocrine system and inflammation, which can play an important role in NEN carcinogenesis. Inflammatory mediators, which are produced by the tumor microenvironment, can favor cancer induction and progression, and can promote immune editing. On the other hand, a balanced immune system represents a relevant step in cancer prevention through the elimination of dysplastic and cancer cells. Therefore, an inflammatory response may be both pro- and anti-tumorigenic. In this review, we provide an overview concerning the complex interplay between inflammation and gastroenteropancreatic NENs, focusing on the tumorigenesis and clinical implications in these tumors.

Background: Endocrine neoplasms are generally slow-growing tumors that can show hormonal activity and give metastases. In most cases they are benign and clearly malignant forms are easy to diagnose. However, borderline forms may occur and be, for the pathologists, very difficult to classify. In these cases, there is a strong need to identify factors that may aid. Official classification systems for endocrine neoplasms are based on the evaluation of proliferation and, in most cases, they rely on mitotic count. In support, the study of Ki67 is carried out which, however, has not yet been included in any official classification system, except for neuroendocrine neoplasms of the gastro-entero-pancreatic tract. Purpose: The aim of the present study was to investigate the proven or unproven role of Ki67 in endocrine neoplasms, in different districts, in order to bring to light the substantial differences, in terms of proliferation, existing between neoplasms so similar, but at the same time, so different. Methods: A thorough search of English language literature was performed, looking for articles concerning Ki67 in five endocrine neoplasms (pituitary adenomas, thyroid neoplasms, adrenocortical neoplasms, pheochromocytomas and paragangliomas). Results: From 2170, 236 articles were selected and it was seen that the endocrine neoplasm in which Ki67 was most studied was the pituitary, where it still shows a controversial role. In other neoplasms different roles were identified. Conclusion: The pathologist should be aware of the contribution that this proliferative marker can give to the diagnosis and, sometimes, to the therapy selection, for the clinician.