Brazil ranks second globally in leprosy burden, with approximately 25 000 cases reported in 2022. This study aimed to analyse the 26-year experience (1997-2023) in nerve biopsies at a specialized leprosy outpatient clinic, focusing on their usefulness in diagnosing peripheral neuropathy in patients with clinical and neurophysiological features suggestive of leprosy but lacking dermatological lesions. Tissue samples were preserved in glutaraldehyde, buffered formalin and liquid nitrogen, with histopathological analysis using various staining techniques and molecular testing on frozen material. In 819 cases, 529 were diagnosed with leprosy (64.6% overall leprosy diagnosis rate), and 207 pure neural leprosy cases were confirmed. Other conditions identified included vasculitis, diabetic neuropathy and amyloidosis, while 16.5% of cases yielded inconclusive results. The predominant clinical symptoms included sensory disorders (85.7%), localized paraesthesia (70.3%) and muscle weakness (59.4%), with multiple mononeuropathies frequently observed on electroneuromyography. The most biopsied nerves were the ulnar cutaneous branch (50.6%), sural (37.2%) and superficial peroneal (6.8%). Nerve biopsy proved valuable for confirming leprosy and distinguishing differential diagnoses in complex cases, particularly when clinical findings alone were insufficient. Integrating clinical-pathological correlation optimized diagnostic accuracy, underscoring the importance of this tool in managing suspected neural leprosy and guiding treatment in challenging cases.

Primary TTF1-positive posterior pituitary tumors (PPT) are uncommon and frequently misdiagnosed preoperatively. This study aims to describe our experience with PPT, examining clinical, radiological and histopathological data, as well as surgical and clinical outcomes. We conducted a retrospective review of medical records from patients treated at a single neurosurgical center between 2013 and 2023. Immunohistochemistry for TTF-1 was performed using AB_1158934. Nine PPT were included: 6 spindle cell oncocytomas (SCO), 2 granular cell tumor (GCT) and 1 pituicytoma. The median age was 53 years (range 34–70), with six (66.7

IntroductionLiquid biopsy is a non-invasive method used to detect cancer and monitor treatment responses by analyzing blood or other bodily fluids for cancer biomarkers. Meningiomas are the most common primary central nervous system tumors, and biomarkers play a crucial role in their diagnosis, prognosis, and treatment monitoring. The World Health Organization (WHO) classifies meningiomas based on tumor grades and molecular alterations in genes such as in NF2, AKT1, TRAF7, SMO, PIK3CA, KLF4, SMARCE1, BAP1, H3K27me3, TERT promoter, and CDKN2A/B. Liquid biopsy, specifically cell-free DNA (cfDNA) analysis, has shown potential for monitoring meningiomas as it can detect ctDNA release in the blood, unaffected by the blood-brain barrier. MicroRNAs (miRNAs) have also been found to be deregulated in various cancers, including meningiomas, presenting potential as diagnostic biomarkers. Additionally, studying cytokines in the tumor microenvironment may aid in establishing prognostic or diagnostic panels for meningiomas.MethodsIn the present study we analyzed the DNA coming from both the plasma and tumor samples, in addition to analyze miRNA-21 and cytokines in the plasma of 28 meningioma patients.Discussion and ConclusionOur findings indicate that the detection of ctDNA in the plasma of meningioma patients is feasible. However, it's important to note that certain challenges persist when comparing plasma DNA analysis to that of tumor tissues. In our study, we observed a paired identification of mutations in only one patient, highlighting the complexities involved. Furthermore, we successfully identified miR-21 and cytokines in the plasma samples. Notably, our analysis of Interleukin 6 (IL-6) unveiled higher expression in the clear cell subtype compared to the other types. Despite the ongoing research, the clinical implementation of liquid biopsy in meningiomas remains somewhat limited. Nevertheless, our promising results underscore the need for further investigation.

Pituitary gigantism is a rare pediatric disorder caused by excess growth hormone (GH) secretion. In almost 50% of cases, a genetic cause can be identified, with pathogenic variants in the aryl hydrocarbon receptor-interacting protein (AIP) gene being the most common. We present a case of an 11-year-old boy who exhibited progressive vision loss, associated with accelerated linear growth, and weight gain. On physical examination, he had enlarged hands, right eye amaurosis, and was already above his target height. Increased GH and IGF-I concentrations confirmed the diagnosis of pituitary gigantism. Magnetic resonance imaging showed a giant sellar lesion with supra- and para-sellar extensions. He underwent two surgeries which did not achieve a cure or visual improvement. Histopathological analysis revealed a sparsely granulated tumor, negative for somatostatin receptor type 2 (SST2) and an immunoreactivity score of 6 for somatostatin receptor type 5 (SST5). Our published artificial intelligence prediction model predicted an 83% chance of not responding to first-generation somatostatin receptor ligands. Pasireotide was therefore prescribed, and afterward cabergoline was added on. IGF-I concentrations decreased but did not normalize. We discovered a novel germline single nucleotide variant in the splicing donor region of intron 2 of the AIP gene (NM_003977.4:c.279+1 G>A), classified as likely pathogenic according to the American College of Medical Genetics and Genomics guidelines.

To prospectively evaluate the usefulness of T1-weighted imaging (T1WI) and diffusion-weighted imaging (DWI) sequences in predicting the consistency of macroadenomas. In addition, to determine their values ​​as prognostic factors of surgical outcomes. Patients with pituitary macroadenoma and surgical indication were included. All patients underwent pre-surgical magnetic resonance imaging (MRI) that included the sequences T1WI before and after contrast administration and DWI with the apparent diffusion coefficient (ADC) map. Post-surgical MRI was performed at least 3 months after surgery. The consistency of the macroadenomas was evaluated at surgery, and they were grouped into soft and intermediate/hard adenomas. Mean ADC values, signal on T1WI and the ratio of tumor ADC values ​​to pons (ADCR) were compared with tumor consistency and grade of surgical resection. A total of 80 patients were included. A softened consistency was found at surgery in 53 patients and hardened in 27 patients. The median ADC in the soft consistency group was 0.532 × 10–3 mm2/sec (0.306 – 1.096 × 10–3 mm2/sec), and in the intermediate/hard consistency group was 0.509 × 10–3 mm2/sec (0.308 − 0.818 × 10–3 mm2/sec). There was no significant difference between the median values ​​of ADC, ADCR and signal on T1W between the soft and hard tumor groups, or between patients with and without tumor residue. Our results did not show usefulness of the DWI and T1WI for assessing the consistency of pituitary macroadenomas, nor as a predictor of the degree of surgical resection.

Pituitary tumours (PT) are formed in the pituitary gland, a small gland situated at the base of the brain. These tumours can be categorized according to their histological origin and hormone production. In surgical series, non-functioning PT are the commonest subtype, followed by functioning somatotroph and corticotroph tumours. Different somatic alterations have been implicated in the pathogenesis of these tumours and the objective of our study was to expand our previous new finding of KRAS pathogenic genetic variants in pituitary tumours. We conducted a digital polymerase chain reaction (PCR) analysis on formalin-fixed paraffin-embedded tissue blocks belonging to 189 patients. The results showed that, from the 184 pituitary tumours with good quality samples, 13 tumours (7.1%) presented mutant KRAS. The median age of the mutated group was 47 years old (range 19-77) and most patients with mutant KRAS tumours were from the female gender (61.5%, 8/13) and non-functioning subtype. For the first-time, mutant KRAS in corticotroph and somatotroph tumours were detected, and the variants showed low allele frequencies. In conclusion, we demonstrated that pituitary tumours might have mutant KRAS, and these data were not previously described probably due to lack of sensitivity of previous technologies. By identifying these variants, even at minimal levels, we open doors to a deeper understanding of the tumour microenvironment, clonal evolution and potential therapeutic targets.

Neurocytomas are neuronal tumors that are usually intraventricular. Rare cases can arise from extraventricular sites. To our knowledge, only 29 cases of extraventricular neurocytoma of the sellar region (EVNSR) have been reported in the literature. We describe a case of a 39-year-old woman who presented with a one-month history of refractory headache, nausea and vomiting. Magnetic resonance imaging (MRI) showed a 5.1 × 3.1 × 2.2 cm sellar and suprasellar mass, suggestive of a pituitary adenoma (PA). She had hyponatremia, obstructive hydrocephalus, and panhypopituitarism at presentation (hypogonadism, adrenal insufficiency). After glucocorticoid replacement therapy and ventriculoperitoneal shunt, the vomiting and headache resolved, but she remained with nausea and hyponatremia. She was submitted to surgery, and histopathological analysis revealed a neurocytoma with positive immunostaining for arginine vasopressin. Syndrome of inappropriate antidiuresis (SIAD) was diagnosed but did not resolve after surgery due to residual tumor, despite fluid restriction and saline replacement. SIAD later resolved with empagliflozin. In conclusion, EVNSR is extremely rare and can be misdiagnosed as PA on MRI. In the context of SIAD and extraventricular neurocytoma, a secreting arginine vasopressin tumor must be considered. SIAD can be challenging to treat, with excision of the EVNSR the treatment choice and, alternatively, empagliflozin associated with fluid restriction.

Nonfunctioning pituitary adenomas (NFPAs) are benign tumors growing in the sellar region. Total surgical excision of the lesion is recommended as the preferred treatment choice with preservation of adjacent structures. The objective is to establish a radiological score to predict the feasibility of NFPA total surgical excision. Patients with treatment-naïve NFPA who underwent a transsphenoidal approach and sellar magnetic resonance imaging (MRI) in the preoperative period and 3 months after surgery were included. Data on age, sex, tumor diameter, extrasellar extension, postoperative cure rates, and hormone and transcription factor expression were collected. A combined score was proposed based on Knosp and SIPAP classifications. We proposed 3 classification groups depending on the tumoral extension to the suprasellar, infrasellar, anterior and posterior directions of the sellar region. A total of 164 patients were included in the study, and 85 (52

Somatic alpha thalassemia/mental retardation syndrome X-linked (ATRX) pathogenic variants have been shown to predict a malignant phenotype in neuroendocrine tumors. They were recently identified in aggressive pituitary tumors and carcinomas, mainly of corticotrophic origin. To our knowledge, these tumors are rare in a general cohort of pituitary tumors, with no cases described in null cell tumors. These variants can lead to loss of protein expression as revealed by immunohistochemistry. We describe a case of an aggressive null cell pituitary tumor with loss of ATRX expression. The patient underwent two transsphenoidal surgeries and radiotherapy and exhibited tumor growth despite conventional therapy. Analysis of the tumor samples revealed loss of ATRX expression in both surgical specimens, suggesting that ATRX may be a useful biomarker for the early identification of aggressive pituitary tumors.

Acromegaly is a chronic systemic disease caused in the vast majority of cases by growth hormone (GH)-secreting adenoma, with surgery being the first-line treatment. When a cure is not attained with surgery, first-generation somatostatin receptor ligands (fg-SRLs) are the most common medication prescribed. Predictors of response to fg-SRLs have been studied; however, they cannot fully predict the response to fg-SRL. MicroRNAs are small RNAs, the main role of which is messenger RNA (mRNA) post-transcriptional regulation. This study aimed to identify the microRNAs involved in resistance to treatment with fg-SRLs in acromegaly. Ten patients with acromegaly undergoing treatment with fg-SRLs were selected to undergo miRNA sequencing: five controlled and five uncontrolled with treatment. Bioinformatic analysis was performed to detect differentially expressed miRNAs. Then, the same 10 samples were used for validation by qPCR and an additional 22 samples were analyzed, totaling 32 samples. e We found 59 differentially expressed miRNAs in the first analysis. miR-181a-5p and miR-181b-5p were downregulated, and miR-383-5p was upregulated in the uncontrolled group. Receiver operating characteristic (ROC) curve analysis of miR-383-5p showed an NPV of 84.3% and a PPV of 84.5%. In summary, miR-181a-5p, miR-181b-5p, and miR-383-5p are biomarkers of response to fg-SRLs, and they can be used individually or included in prediction models as tools to guide clinical decisions.

A 19-year-old student developed hypoventilation and cyanosis at the end of a cosmetic liposuction procedure. She was awake, but severely abulic, disoriented, and unable to stand and walk due to severe locomotor ataxia. Neuropsychological evaluation showed psychomotor slowness, and deficits in memory encoding and retrieval, and on executive, and visuospatial and visuoperceptual tests; oral comprehension and constructional praxis were spared. ¹H-MRS showed a reduction of NAA. A year later, her cognitive and neurological exam, and NAA returned to normal, and she resumed her normal life. The severity of the acute manifestations of hypoxic encephalopathy not always entail a poor prognosis.

Glioblastoma is the most frequent and aggressive primary brain cancer. In preclinical studies, Zika virus, a flavivirus that triggers the death of glioblastoma stem-like cells. However, the flavivirus oncolytic activity has not been demonstrated in human patients. Here we report a glioblastoma patient who received the standard of care therapy, including surgical resection, radiotherapy and temozolomide. However, shortly after the tumor mass resection, the patient was clinically diagnosed with a typical arbovirus-like infection, during a Zika virus outbreak in Brazil. Following the infection resolution, the glioblastoma regressed, and no recurrence was observed. This clinical response continues 6 years after the glioblastoma initial diagnosis.

To analyze the expression of glucose-dependent insulinotropic polypeptide receptor (GIPR) in somatotropinomas specimens and compare clinical, biochemical, radiological, therapeutic, molecular, and pathological data among those who overexpressed (GIPR +) and those who did not overexpress (GIPR − ) GIPR. Clinical, biochemical, radiological, molecular, and pathological data were collected. GNAS1 sequencing was performed with the Sanger method. Protein expression of somatostatin receptor subtypes 2 and 5 and CAM 5.2 were analyzed by immunohistochemistry. Quantitative real-time PCR was performed to analyze the mRNA expression of GIPR with the TaqMan® method. Positive expression was considered when the fold change (FC) was above 17.2 (GIPR +). A total of 74 patients (54

To evaluate the efficacy and safety of oral estrogen therapy in female patients of childbearing age with uncontrolled acromegaly and to verify the significance of the presence of estrogen receptor α (ER-α) in somatotropinomas. Prospective study in which biochemical and radiological evaluations were performed at baseline and after six months of treatment with an oral formulation of ethinyl-estradiol 0.03 mg and levonorgestrel 0.15 mg. ER-α was assessed by immunohistochemistry and immunopositivity was considered when it was present in ≥ 1% of cells. Eight patients with uncontrolled acromegaly were selected. All patients underwent surgery. Four patients were on octreotide LAR 30 mg, two patients were on lanreotide autogel 120 mg, and two patients had active disease after surgery. At the end of follow-up, IGF-I normalized in 3/8 (37%), 2/8 (25%) patients presented with mean IGF-I reduction of 25% but without IGF-I normalization, and 2/8 (25%) did not respond—one had a 13% increase in IGF-I and IGF-I level remained unchanged after treatment in the other. In one patient, treatment was discontinued after 3 months due to side effects (headache), with an IGF-I reduction of 28% but without normalization. Tumor volume increase (41%) was observed in only one patient (the only tumor with positive ER-α expression). In uncontrolled patients with acromegaly, a trial with oral estrogen can be an option for young women. Oral estrogen was well tolerated, but the somatotropinoma that presented ER-α expression was the only somatotropinoma that presented growth during treatment.

Craniopharyngiomas are histological and cytological benign epithelial tumors of the central nervous system which may be aggressive and tend to recur after excision. Malignant transformation in craniopharyngiomas is extremely rare; only around 15 reports are found in literature. In this report, we describe a case of squamous cell carcinoma, in a 58-year-old woman, developing from a previous benign craniopharyngioma. The patient was diagnosed with a recurrent craniopharyngioma in 2011. During the subsequent months, she experienced evolution of the recurrent tumor and then was submitted to a partial resection plus radiotherapy in another Institution. In 2012, the tumor recurred with involvement of sellar, suprasselar region, basal cisterna, and medial fossa, with midbrain compression and central skull base destruction. Histologic evaluation revealed cellular anaplasia and a high mitotic activity in a lesion with foci of craniopharyngioma. Radiation might have been a contributing factor to the malignant transformation in this case.

O diagnóstico dos tumores cerebrais deve ser integrado, compreendendo o fenótipo das células neoplásicas (histologia), os marcadores imuno-histoquímicos e o perfil molecular, sempre em correlação com os dados clínicos e de imagem. Os gliomas difusos (astrocitoma ou oligodendroglioma) partem do grau II e tendem a progredir para III ou IV. Do ponto de vista molecular, a mutação de IDH (ausente no glioblastoma – grau IV) e a co-deleção 1p 19q (no oligodendroglioma) são sinais de melhor prognóstico. Os gliomas difusos pediátricos hemisféricos de baixo grau relacionados com epilepsia, não tem a mutação do IDH1, são em geral estáveis e podem apresentar alterações do BRAF, MYB, MYBL1 ou FGFR1. No grupo dos malignos, os de linha média (ponte, tálamo e medula espinhal), de prognóstico muito ruim, têm mutação da histona H3.3K27M. Mutações de outras histonas, como a H3. 3G34R/V, relacionam-se com gliomas difusos da infância, mas em outras topografias, como nos hemisférios cerebrais. Os circunscritos (neuronais, gliais ou mistos), em geral em pacientes mais jovens, têm prognóstico melhor, podem ser grau I ou II, sendo os anaplásicos, grau III, devendo ser pesquisada alteração no gene do BRAF, importante também como alvo terapêutico. Outros tumores acometem o tecido nervoso, os ependimomas, os tumores embrionários, os extraparenquimatosos (meningiomas, schwannomas), outros menos comuns e as metástases. Apesar dos avanços nos métodos diagnósticos, continua nas mãos do patologista a interpretação correta do aspecto histológico, o direcionamento da análise molecular, sendo sempre o responsável pela seleção da amostra a ser investigada.

Context: Artificial intelligence (AI), in particular machine learning (ML), may be used to deeply analyze biomarkers of response to first-generation somatostatin receptor ligands (fg-SRLs) in the treatment of acromegaly. Objective: To develop a prediction model of therapeutic response of acromegaly to fg-SRL. Methods: Patients with acromegaly not cured by primary surgical treatment and who had adjuvant therapy with fg-SRL for at least 6 months after surgery were included. Patients were considered controlled if they presented growth hormone (GH) <1.0 ng/mL and normal age-adjusted insulin-like growth factor (IGF)-I levels. Six AI models were evaluated: logistic regression, k-nearest neighbor classifier, support vector machine, gradient-boosted classifier, random forest, and multilayer perceptron. The features included in the analysis were age at diagnosis, sex, GH, and IGF-I levels at diagnosis and at pretreatment, somatostatin receptor subtype 2 and 5 (SST2 and SST5) protein expression and cytokeratin granulation pattern (GP). Results: A total of 153 patients were analyzed. Controlled patients were older (P = .002), had lower GH at diagnosis (P = .01), had lower pretreatment GH and IGF-I (P < .001), and more frequently harbored tumors that were densely granulated (P=.014) or highly expressed SST2 (P < .001). The model that performed best was the support vector machine with the features SST2, SST5, GP, sex, age, and pretreatment GH and IGF-I levels. It had an accuracy of 86.3%, positive predictive value of 83.3% and negative predictive value of 87.5%. Conclusion: We developed a ML-based prediction model with high accuracy that has the potential to improve medical management of acromegaly, optimize biochemical control, decrease long-term morbidities and mortality, and reduce health services costs.