Successful Treatment with Patisiran in Amyloid Polyneuropathy Harboring His90Asn Mutation in the TTR Gene.

Hereditary transthyretin amyloidosis (hATTR) is a multisystemic, rare, inherited, progressive and adult-onset disease, affecting the sensory-motor nerves, heart, autonomic function, and other organs. There are over 130 mutations known in the TTR gene. The His90Asn mutation has been previously reported in several reports, but its pathogenetic role is still debated. We report two sporadic cases of adult women with a heterozygous His90Asn mutation in TTR gene and neurological involvement extensively investigated. A typical Congo red-positive pathologic deposition of amyloid fibrils in the salivary glands was documented in one subject. Patients were successfully treated with patisiran with a good clinical outcome. These data support a pathogenetic role of His90Asn mutation in hATTR, and suggest early treatment in symptomatic carriers of His90Asn mutation.

Delayed Traumatic Rupture of the Spleen in a Patient with Mantle Cell Non-Hodgkin Lymphoma after an In-Hospital Fall: A Fatal Case.

Splenic rupture and hematoma are significant complications that can occur in patients with non-Hodgkin lymphoma (NHL). Understanding these associated complications is essential for optimal patient management and enhanced patient outcomes. Histopathological and immunohistochemical analyses are crucial in diagnosing NHL and assessing splenic involvement. In this study, a judicial autopsy had been requested by the Prosecutor's Office for a malpractice claim due to a fall in the hospital. In the Emergency Department, a 72-year-old man fell from a gurney and reported sustaining a wound to his forehead. No other symptoms were reported. A face and brain CT scan showed no abnormalities. Nine days after discharge, the patient presented with abdominal pain. An abdominal CT revealed splenic rupture and hemoperitoneum. The patient underwent open splenectomy but showed signs of hemodynamic shock and subsequently died. The evidence from the autopsy allowed us to diagnose mantle cell non-Hodgkin lymphoma with spleen involvement, previously unknown. Histopathological and immunohistochemical analyses were performed to assess the diagnosis of splenic rupture and estimate its timing. The findings strongly suggest that the splenic rupture was associated with the patient's fall and the pre-existing malignancy. This case highlights the importance of considering an underlying hematological malignancy when investigating delayed splenic rupture. An immunohistochemical study of spleen samples allowed the timing of splenic hematoma and rupture to be assessed, leading to the establishment of a causal relationship with trauma.

Infratentorial Relapsing Neuroglial Tumors in Adults: Management and Unsolved Issues-A Systematic Review.

(1) Background: Gangliogliomas are rare tumors accounting for about 0.4% of all central nervous system tumors. They are usually located in the temporal lobes of children and young adults, though such tumors in the infratentorial region and adult-age patients rarely reported. (2) Methods: A systematic review on ganglioglioma with infratentorial location in the adult population was conducted in accordance with the PRISMA guidelines. A total of 275 articles were found, and 23 were included. Demographic data, the location and histology of the lesion, pre-operative neurological status, the type of surgery, recurrence, radiotherapy/chemotherapy adjuvant treatments, neurological outcomes and follow-up information were collected. We also presented an illustrative case. (3) Results: A total of 27 patients were included. In 51%, the location was the cerebellum; in 40%, it was the fourth ventricle; in 11%, it was brainstem; and in 4%, it was the cerebellopontine angle. STR was performed in 44%, GTR in 26% and biopsy in 15% of the cases. Adjuvant radiotherapy was found in 22% of cases. Disease recurrence occurred in 15% of patients between 1 and 12 months after surgery with a diagnosis of high-grade ganglioglioma, while in six cases, no disease recurrence was documented. (4) Conclusions: Infratentorial glioneuronal tumors are rare findings in the adult population. Histopathological characterization does not seem to fully reflect their true behavior. Future studies are warranted for better characterizing histopathological findings and treatment.

Polymorphous Adenocarcinoma: A Systematic Review of the Literature and Presentation of Two Cases in a Less-Considered Anatomical Site.

BACKGROUND: Polymorphous adenocarcinoma (PAC) is the second-most common malignant tumour of the minor salivary glands. Although PAC predominantly affects the palate, it can also involve the buccal mucosa. This systematic review aims to investigate the literature data about PAC. Furthermore, we report two cases of patients affected by PAC in an infrequently considered anatomical site. METHODS: According to PRISMA guidelines, a systematic review search was conducted on PubMed, Scopus, and Web of Science. Observational studies conducted on patients with a histological diagnosis of PAC were selected and analysed. Furthermore, two cases of patients with PAC affecting the buccal mucosa were reported. RESULTS: Twenty-nine studies were included, and 143 patients affected by PAC were analysed (62 males, 75 females, and 6 undefined, with a mean age of 57.4 ± 14.5 years). The palate was the most affected site (99/143, 69.2%), followed by the buccal mucosa (12/143, 8.4%). Moreover, we report two cases of patients with PAC affecting the buccal mucosa (one male and one female, with a mean age of 70.5 ± 2.5 years). CONCLUSIONS: The present study underscores the importance of considering the buccal mucosa as a possible location of minor salivary gland tumours; although it is a less-considered affliction, it is not uncommon.

A Multicentric Castleman Disease Associated with Mixed Warm and Cold Antibody-Mediated AHA Responsive to Siltuximab.

Castleman disease is non-clonal lymphoproliferative disorders defined by hypertrophy of lymph nodes. The multicentric form (MCD), in which multiple lymph node stations are involved, is not associated with HHV8 infection, but considered idiopathic, although IL-6 appears to play a central role in its pathogenesis. Here, we report the case of a patient who presented with mixed autoimmune hemolytic anemia (AIHA) and adenopathy that was very challenging to diagnose due to very low values of hemoglobin and refractoriness of obtaining any improvement of AIHA with standard first and second lines of therapy (steroids, rituximab, immunoglobulin, erythropoietin, and cyclosporine). When we safely proceeded to lymph node biopsy, a diagnosis of MCD was established. This permitted the treatment with siltuximab, an anti-IL-6 monoclonal antibody. After only 1 week, hemoglobin raised and he was discharged. After 1 year, he was still in remission. This case underlines the challenges in diagnosis of MCD, and the first case of response to siltuximab after the failure of rituximab to relieve mixed AIHA.

Vascularized versus Free Nerve Grafts: An Experimental Study on Rats.

BACKGROUND: Vascularized nerve grafts (VNGs) have been proposed as a superior alternative to free nerve grafts (FNGs) for complex nerve defects. A greater regenerative potential has been suggested by clinical and experimental studies, but conclusive evidence is still lacking. METHODS: In this experimental study, 10 adult male Wistar rats received a non-vascularized orthotopic sciatic nerve graft on their right side, and a vascularized orthotopic sciatic nerve graft nerve on their left side. Functional outcome following nerve regeneration was evaluated through electrodiagnostic studies, target muscles weight and histomorphology, and data of VNGs and FNGs were compared. RESULTS: The results of this study showed a significant difference in the motor unit number of Gastrocnemius Medialis (GM) estimated by MUNE in the VNG side compared to the FNG side. No other significant differences in axonal regeneration and muscle reinnervation were evident at either electrodiagnostic, histomorphology studies or muscle weight. CONCLUSIONS: This experimental model showed slight differences in nerve regeneration between VNGs and FNGs, but cannot support a high clinical advantage for VNGs. The results of this study show that VNGs are not strongly superior to FNGs in the rat model, even in avascular beds. Clinical advantages of VNGs are likely to be limited to extensive and thick nerve defects and can only be assessed on experimental model with bigger animals. Also, we showed that the MUNE technique provided a reliable and reproducible evaluation of functional outcomes in the rat sciatic nerve and defined a reproducible protocol for functional evaluation of muscle reinnervation.

Severe case of rhabdomyolysis following jellyfish envenomation in the Mediterranean Sea.

Jellyfish envenomation is a common problem in coastal areas all over the world; usually symptoms are self-limited with no long-lasting complications. Despite that, some jellyfish species, mainly populating the Indian Ocean, are renown to be potentially lethal and in some cases may cause severe myopathy. We report the first case of rhabdomyolysis following a jellyfish sting in the Mediterranean Sea. A 17-year-old patient was admitted to the intensive care unit of our hospital in life-threatening conditions. He was dyspnoeic and dysphagic with pain and functional impairment of upper and lower limbs. The evidence of a red mark in his face and the clinical presentation, coupled with the diagnostic test performed, allowed the diagnosis of toxidrome from jellyfish venom. Treatment with hydration, ventilatory support and steroids led to a progressive improvement of patient conditions. Our case report stresses the importance of prompt identification and treatment of potential rhabdomyolysis determined by jellyfish and rises awareness on the presence of such venomous species in the Mediterranean Sea.

EBF1, MYO6 and CALR expression levels predict therapeutic response in diffuse large B-cell lymphomas.

Background: Diffuse large B-cell lymphoma (DLBCL) is a hematological malignancy representing one-third of non-Hodgkin's lymphoma cases. Notwithstanding immunotherapy in combination with chemotherapy (R-CHOP) is an effective therapeutic approach for DLBCL, a subset of patients encounters treatment resistance, leading to low survival rates. Thus, there is an urgent need to identify predictive biomarkers for DLBCL including the elderly population, which represents the fastest-growing segment of the population in Western countries. Methods: Gene expression profiles of n=414 DLBCL biopsies were retrieved from the public dataset GSE10846. Differentially expressed genes (DEGs) (fold change >1.4, p-value <0.05, n=387) have been clustered in responder and non-responder patient cohorts. An enrichment analysis has been performed on the top 30 up-regulated genes of responder and non-responder patients to identify the signatures involved in gene ontology (MSigDB). The more significantly up-regulated DEGs have been validated in our independent collection of formalin-fixed paraffin-embedded (FFPE) biopsy samples of elderly DLBCL patients, treated with R-CHOP as first-line therapy. Results: From the analysis of two independent cohorts of DLBCL patients emerged a gene signature able to predict the response to R-CHOP therapy. In detail, expression levels of EBF1, MYO6, CALR are associated with a significant worse overall survival. Conclusions: These results pave the way for a novel characterization of DLBCL biomarkers, aiding the stratification of responder versus non-responder patients.

Oral Secondary Syphilis in an HIV-Positive Transgender Patient: A Case Report and Review of the Literature.

BACKGROUND: Syphilis is a worldwide sexually transmitted infection caused by Treponema pallidum. In most cases, the oral manifestations of syphilis infection are associated with cutaneous involvement. However, the present case report is noteworthy since the oral lesions are the sole clinical sign in an HIV-positive transgender patient. CASE PRESENTATIONS: We reported an uncommon case of secondary syphilis in a 37-year-old seropositive transgender male, whose diagnostic suspect was based only on oral mucosal lesions. The patient was referred to the Oral Medicine Unit for the presence of multiple undiagnosed painful oral lesions. The intraoral examination revealed the presence of white and red plaques on the right and the left buccal mucosa and several painful lesions localized on the upper and lower labial mucosa. No cutaneous lesions were observed. Considering the sexual history of the patient and clinical findings, secondary syphilis infection was suspected. The serologic analysis was conducted, and the diagnosis of syphilis was confirmed. Moreover, to exclude the presence of oral epithelial dysplasia or malignant disease, an incisional biopsy was performed. DISCUSSION: Compared to the literature data, oral lesions as lone signs of secondary syphilis infection are uncommon, especially in HIV-positive patients. Syphilis and HIV coinfection create a concerning situation as they interact synergistically, leading to an increased risk of transmission and faster disease progression. CONCLUSIONS: This case report emphasizes the importance of considering syphilis as a diagnostic possibility, even when oral lesions are the only clinical manifestations, especially in HIV-positive patients. Comprehensive evaluation, including a detailed sexual history and careful oral examination, is essential for accurate diagnosis and appropriate management in such cases.

Hemophagocytic lymphohistiocytosis secondary to histoplasmosis: A case report in a patient with AIDS and recent SARS-CoV-2 infection and minireview.

Here, we describe the case of a naïve HIV late presenter female African patient with progressive disseminated histoplasmosis and a severe life-threatening clinical picture in a non-endemic area. She had not visited Africa in the past decade. She developed a reactive hemophagocytic lymphohistiocytosis and an acute psychiatric disorder. Histoplasmosis was diagnosed after two bone marrow biopsies. Therapy with liposomal amphotericin B resulted in rapid and progressive improvements in blood examinations and clinical conditions, including the disappearance of psychiatric disorders. The characteristics of our case were compared with those of all other cases of hemophagocytic syndrome secondary to histoplasmosis in HIV-positive patients reported in PubMed. In conclusion, clinicians outside endemic areas should evaluate histoplasmosis as a cause of severe clinical picture, especially in a patient with a travel history to an endemic area, even after many years, considering the possible reactivation of latent infection.

Body mass index and baseline platelet count as predictive factors in Merkel cell carcinoma patients treated with avelumab.

Background: Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer, associated with a worse prognosis. The Immune Checkpoint Inhibitors (ICIs) avelumab and pembrolizumab have been recently approved as first-line treatment in metastatic MCC (mMCC). The clinical observation of improved outcomes in obese patients following treatment with ICIs, known as the "obesity paradox", has been studied across many types of tumors. Probably due to the rarity of this tumor, data on mMMC patients are lacking. Patients and methods: This is an observational, hospital-based, study to investigate the role of Body Mass Index (BMI) as predictive biomarker of ICI response in mMCC patients treated with avelumab as first-line treatment. The study population included the patients treated from February 2019 to October 2022 in an Italian referral center for rare tumors. Clinico-pathological characteristics, BMI, laboratory parameters (NLR and platelet count), and response to avelumab were analyzed from a MCC System database prospectively collected. Results: Thirty-two (32) patients were included. Notably, the presence of pre-treatment BMI ≥ 30 was significantly associated with longer PFS [BMI < 30 Group: median PFS, 4 months (95% CI: 2.5-5.4); BMI ≥ 30 Group: median PFS, not reached; p<0.001)[. Additionally, the median PFS was significantly higher in patients with higher PLT (median PFS: 10 months in the "low PLT" Group (95% CI: 4.9, 16.1) vs 33 months (95% CI: 24.3, 43.2) in the "high PLT" Group (p=0.006). The multivariable Cox regression model confirmed these results. Conclusion: To our knowledge, this is the first study that investigates the predictive role of BMI in MCC patients. Our data were consistent with the clinical observation of improved outcomes in obese patients across other tumor types. Thus, advanced age, a weakened immune system, and the obesity-associated "inflammaging", are key factors that could impact the cancer immune responses of mMCC patients.

The Chaperone System in Salivary Glands: Hsp90 Prospects for Differential Diagnosis and Treatment of Malignant Tumors.

Salivary gland tumors represent a serious medical problem and new tools for differential diagnosis and patient monitoring are needed. Here, we present data and discuss the potential of molecular chaperones as biomarkers and therapeutic targets, focusing on Hsp10 and Hsp90. The salivary glands are key physiological elements but, unfortunately, the information and the means available for the management of their pathologies, including cancer, are scarce. Progress in the study of carcinogenesis has occurred on various fronts lately, one of which has been the identification of the chaperone system (CS) as a physiological system with presence in all cells and tissues (including the salivary glands) that plays a role in tumor-cell biology. The chief components of the CS are the molecular chaperones, some of which belong to families of evolutionarily related molecules named heat shock protein (Hsp). We are quantifying and mapping these molecular chaperones in salivary glands to determine their possible role in the carcinogenetic mechanisms in these glands and to assess their potential as diagnostic biomarkers and therapeutic targets. Here, we report recent findings on Hsp10 and Hsp90 and show that the quantitative and topographic patterns of tissue Hsp90 are distinctive of malignant tumors and differentiate benign from malignant lesions. The Hsp90 results show a correlation between quantity of chaperone and tumor progression, which in turn calls for negative chaperonotherapy, namely, elimination/inhibition of the chaperone to stop the tumor. We found that in vitro, the Hsp90 inhibitor Ganetespib is cytotoxic for the salivary gland UM-HACC-2A cell line. The drug, by interfering with the pro-survival NF-κB pathway, hampers cellular proliferation and migration, and favors apoptosis, and can, therefore, be considered a suitable candidate for future experimentation to develop a treatment for salivary gland tumors.

Thoracic dumbbell spinal metastasis secondary to neuroendocrine tumor of unknown origin: Case report and literature review.

Background: Dumbbell tumors are typically benign schwannomas, neurofibromas, and meningiomas and only rarely there are malignant variants of these lesions or other malignant histotypes. Here, a 34-year-old male presented with a thoracic spinal dumbbell metastatic neuroendocrine carcinoma of unknown primary origin. Case Description: A 34-year-old male presented with 2 months of thoracic pain and progressive mid thoracic sensory loss. A post contrast thoracic MRI showed a dumbbell tumor localized between the T7 and T9 levels with extension laterally into the T7-T8 and T8-T9 foramina. The patient underwent a laminectomy for tumor resection following which his pain and gait improved. Histopathologically, the tumor demonstrated multiple rounded small cells with a Ki67 level around 30%, suggesting a malignant metastatic neuroendocrine tumor of unknown etiology. Conclusion: We successfully treated a 34-year-old male with a T7-T9 malignant spinal dumbbell neuroendocrine tumor of unknown etiology utilizing a decompressive laminectomy.

Gluten Induces Subtle Histological Changes in Duodenal Mucosa of Patients with Non-Coeliac Gluten Sensitivity: A Multicentre Study.

Background: Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. Objectives: To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). Methods: Well-oriented biopsies of 262 control cases with normal gastroscopy and histologic findings, 261 CeD, and 175 NCGS biopsies from 9 contributing countries were examined. Villus height (VH, in µm), crypt depth (CrD, in µm), villus-to-crypt ratios (VCR), IELs (intraepithelial lymphocytes/100 enterocytes), and other relevant histological, serologic, and demographic parameters were quantified. Results: The median VH in NCGS was significantly shorter (600, IQR: 400−705) than controls (900, IQR: 667−1112) (p < 0.001). NCGS patients with Marsh I-II had similar VH and VCR to CeD [465 µm (IQR: 390−620) vs. 427 µm (IQR: 348−569, p = 0·176)]. The VCR in NCGS with Marsh 0 was lower than controls (p < 0.001). The median IEL in NCGS with Marsh 0 was higher than controls (23.0 vs. 13.7, p < 0.001). To distinguish Marsh 0 NCGS from controls, an IEL cut-off of 14 showed 79% sensitivity and 55% specificity. IEL densities in Marsh I-II NCGS and CeD groups were similar. Conclusion: NCGS duodenal mucosa exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture.

The chaperone system in glioblastoma multiforme and derived cell lines: diagnostic and mechanistic implications.

BACKGROUND: Glioblastoma multiforme (GBM) is the most common and malignant primary brain tumor in adults. Novel treatments are needed to counteract the molecular mechanisms of GBM growth and drug resistance. The chaperone system (CS) members are typically cytoprotective but some, termed Hsp, can become pathogenic and participate in carcinogenesis, along with the vascular endothelial growth factor (VEGF), and we investigated them in GBM biopsies and derived cell lines. The objectives were to identify diagnostic-prognostic biomarkers and gather information for developing chaperonotherapy. METHODS: Cell lines from GBMs were established, characterized (morphology, growth characteristics, and specific markers), and stored. Chaperones and angiogenic factors [Hsp10, Hsp27, Hsp60, Hsp70, Hsp90, FLT-1 (VEGFR-1), FLK1 (KDR, VEGFR-2), and FLT-4 (VEGFR-3)] were observed in cells by immunofluorescence while the chaperones were measured in tumor tissue by immunohistochemistry. RESULTS: Four cell lines were derived from four different GBMs; the cells were spindle shaped or polygonal and grew at high rates as adherent monolayers or clusters without evidence of contact inhibition. The astrocyte-specific glial fibrillary acidic protein (GFAP); and the neuronal NSE, malignancy VIM, and proliferation PCNA, markers were determined. The cells expressed GFAP but no NSE, indicating that they were primary glioblastoma cell lines, with high levels of Hsp10, Hsp27, Hsp60, Hsp90, and Flk1; and low levels of Hsp70, Flt1, and Flt4. CONCLUSIONS: Four cell lines were established derived from four out of ten GBM tumors studied. The cell lines showed intense positivity for chaperones studied and factors connected to malignancy and the tumors showed increased levels of chaperones, making them potential diagnostic-prognostic biomarkers and targets for anti-cancer compounds.

Whole Cow's Milk but Not Lactose Can Induce Symptoms in Patients with Self-Reported Milk Intolerance: Evidence of Cow's Milk Sensitivity in Adults.

BACKGROUND: Lactose intolerance is the most frequent food intolerance, but many subjects with self-reported milk intolerance (SRMI) are asymptomatic at lactose hydrogen breath test (LHBT). The aim of this study was to evaluate the frequency of lactose intolerance in SRMI patients and their clinical characteristics. METHODS: In a retrospective study, the clinical records of 314 SRMI patients (259 females, mean age: 39.1 ± 13.5 years) were reviewed; 102 patients with irritable bowel syndrome (IBS) served as controls. In a prospective study, 42 SRMI patients, negatives at the LHBT, underwent a double-blind, placebo-controlled (DBPC) whole cow's milk challenge. RESULTS: In the retrospective study, only 178 patients (56%) were lactose maldigesters and intolerant at LHBT; 68% of the subjects with SRMI were suffering from IBS; 74% reported dyspepsia (p = 0.0001 vs. IBS controls); and weight loss was recorded in 62 SRMI patients (20%) (p = 0.01 vs. IBS controls). Duodenal histology showed intra-epithelial lymphocytosis in about 60% of cases. In the prospective study, 36 patients (86%) experienced symptoms during the DBPC cow's milk challenge, and only 4 patients (9%) reacted to placebo (p = 0.0001). CONCLUSIONS: A percentage of SRMI patients were not suffering from lactose intolerance. DBPC revealed that SRMI patients had clinical reactions when exposed to whole cow's milk.

The tumor-agnostic treatment for patients with solid tumors: a position paper on behalf of the AIOM- SIAPEC/IAP-SIBioC-SIF Italian Scientific Societies.

The personalized medicine is in a rapidly evolving scenario. The identification of actionable mutations is revolutionizing the therapeutic landscape of tumors. The morphological and histological tumor features are enriched by the extensive genomic profiling, and the first tumor-agnostic drugs have been approved regardless of tumor histology, guided by predictive and druggable genetic alterations. This new paradigm of "mutational oncology", presents a great potential to change the oncologic therapeutic scenario, but also some critical aspects need to be underlined. A process governance is mandatory to ensure the genomic testing accuracy and homogeneity, the economic sustainability, and the regulatory issues, ultimately granting the possibility of translating this model in the "real world". In this position paper, based on experts' opinion, the AIOM-SIAPEC-IAP-SIBIOC-SIF Italian Scientific Societies revised the new agnostic biomarkers, the diagnostic technologies available, the current availability of agnostic drugs and their present indication.

Frequency and Clinical Aspects of Neurological and Psychiatric Symptoms in Patients with Non-Celiac Wheat Sensitivity.

BACKGROUND: Non-Celiac Wheat Sensitivity (NCWS) is characterized by both intestinal and extra-intestinal symptoms. The study aims to investigate the frequency of neuropsychiatric manifestations in NCWS patients and identify their clinical and demographic characteristics. METHODS: 278 clinical records of NCWS patients, diagnosed by a double-blind placebo-controlled wheat challenge between 2006 and 2020, were retrospectively revised. Fifty-two patients with Celiac Disease (CD) and 54 patients with Irritable Bowel Syndrome (IBS) served as controls. RESULTS: 87% of the NCWS patients had an IBS-like clinical presentation. The NCWS group showed a longer duration of symptoms, a higher frequency of positive serum anti-nuclear antibodies than CD and IBS patients, and a higher frequency of DQ2/DQ8 haplotypes and duodenal mucosa lymphocytosis than IBS controls. In addition, 50% of NCWS patients showed neuropsychiatric manifestations, while lower percentages were observed in CD (25%) and IBS (28%) controls. Neuropsychiatric symptoms in NCWS were more frequently associated with the male sex, longer duration of symptoms, and IBS-diarrhea-like clinical presentation. CONCLUSIONS: Our data suggest that in patients with IBS-like symptoms and neuropsychiatric manifestations of unknown cause, it could be useful to investigate a correlation of these symptoms with wheat ingestion to identify NCWS patients with this 'atypical' manifestation.

A Case of Follicular Tumor of Uncertain Malignant Potential (FT-UMP) with Glomeruloid Features Showing Capsular Mucinous Degeneration.

The most recent revision of the World Health Organization (WHO) Classification of Tumours of Endocrine Organs introduced a new variant of follicular thyroid carcinoma (FTC). It is characterized by a "glomeruloid" architectural pattern of growth. We present a case of follicular tumor with glomeruloid features, with Alcian Blue positive mucinous stromal degeneration in foci of questionable capsular microinvasion. At our knowledge, this the second case of glomeruloid follicular tumor in the literature and the first case in which Alcian Blue staining was used to investigate capsular invasion. Moreover, RAS mutation further supports that this is a variant of follicular tumor with uncertain malignant potential.

A rare diagnosis of an extraventricular neurocytoma.

BACKGROUND: Extraventricular neurocytoma (EVN) is an extremely rare neoplasm of the central nervous system. As reported, it arises in a variety of locations, but mainly within the cerebral hemispheres. Despite its histological similarity with central neurocytoma (CN), EVN occurs outside the ventricular system and, in 2007, was recognized by the World Health Organization as a separate entity. CASE DESCRIPTION: A 39-year-old man, with a ventriculoperitoneal shunt inserted for communicating hydrocephalus, was admitted at our Unit of Neurosurgery with a 1-month history of gait disturbance, postural instability, speech disorders, and occasional incontinence. Computed tomography scan and magnetic resonance imaging showed a mixed-density neoplasm in the left frontotemporal area, with anterior cerebral falx shift, and perilesional edema. The patient underwent surgical procedure; microsurgical excision of the lesion was performed through left pterional approach. Histopathological and immunohistochemical examination revealed monomorphic round cells of the neuronal lineage, with a percentage of Ki-67 positive nuclei <5% and no evidence of mitosis or necrotic areas. According to radiologic features, this pattern was compatible with the diagnosis of EVN. Patient had a favorable recovery and he is still in follow-up. CONCLUSION: Because of their rarity, clinical, radiologic, and histopathological characteristics of EVNs are not yet well defined, as well as the optimal therapeutic management. Whereas EVNs are rarely described in literature, we aimed to share and discuss our experience along with a review of the published literature.