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Pathology Oncology Research : POR 2024Gastric epithelial neoplasm of the fundic-gland mucosa lineages (GEN-FGMLs) are rare forms of gastric tumors that encompass oxyntic gland adenoma (OGA), gastric...
BACKGROUND
Gastric epithelial neoplasm of the fundic-gland mucosa lineages (GEN-FGMLs) are rare forms of gastric tumors that encompass oxyntic gland adenoma (OGA), gastric adenocarcinoma of the fundic-gland type (GA-FG), and gastric adenocarcinoma of the fundic-gland mucosa type (GA-FGM). There is no consensus on the cause, classification, and clinicopathological features of GEN-FGMLs, and misdiagnosis is common because of similarities in symptoms.
METHODS
37 cases diagnosed with GEN-FGMLs were included in this study. H&E-stained slides were reviewed and clinicopathological parameters were recorded. Immunohistochemical staining was conducted for MUC2, MUC5AC, MUC6, CD10, CD56, synaptophysin, chromograninA, p53, Ki67, pepsinogen-I, H/K-ATPase and Desmin.
RESULTS
The patients' ages ranged from 42 to 79 years, with a median age of 60. 17 were male and 20 were female. Morphologically, 19 OGAs, 16 GA-FGs, and two GA-FGMs were identified. Histopathological similarities exist between OGA, GA-FG, and GA-FGM. The tumors demonstrated well-formed glands, expanding with dense growth patterns comprising pale, blue-grey columnar cells with mild nuclear atypia. These cells resembled fundic gland cells. None of the OGA invaded the submucosal layer. The normal gastric pit epithelium covered the entire surface of the OGA and GA-FG, but the dysplasia pit epithelium covered the GA-FGM. Non-atrophic gastritis was observed in more than half of the background mucosa. All cases were diffusely positive for MUC6 and pepsinogen-I on immunohistochemistry. H/K-ATPase staining was negative or showed a scattered pattern in most cases. MUC5AC was expressed on the surface of GA-FGMs. p53 was focally expressed and the Ki67 index was low (1%-20%). Compared with OGA, GA-FG and GA-FGM were more prominent in the macroscopic view ( < 0.05) and had larger sizes ( < 0.0001). Additionally, GA-FG and GA-FGM exhibited higher Ki67 indices than OGA ( < 0.0001). Specimens with Ki-67 proliferation indices >2.5% and size >4.5 mm are more likely to be diagnosed with GA-FG and GA-FGM than OGA.
CONCLUSION
GEN-FGMLs are group of well-differentiated gastric tumors with favourable biological behaviours, low cellular atypia, and low proliferation. Immunohistochemistry is critical for confirming diagnosis. Compared with OGA, GA-FG and GA-FGM have larger sizes and higher Ki67 proliferation indices, indicating that they play a critical role in the identification of GEN-FGML. Pathologists and endoscopists should be cautious to prevent misdiagnosis and overtreatment, especially in biopsy specimens.
Topics: Humans; Stomach Neoplasms; Male; Female; Middle Aged; Aged; Adult; Ki-67 Antigen; Gastric Mucosa; Biomarkers, Tumor; Adenocarcinoma; Gastric Fundus; Adenoma; Prognosis
PubMed: 38873175
DOI: 10.3389/pore.2024.1611734 -
Cell Death Discovery Jun 2024Heat exposure is an environmental stressor that has been associated with cognitive impairment. However, the neural mechanisms that underlie this phenomenon have yet to...
Heat exposure is an environmental stressor that has been associated with cognitive impairment. However, the neural mechanisms that underlie this phenomenon have yet to be extensively investigated. The Morris water maze test was utilized to assess cognitive performance. RNA sequencing was employed to discover the primary regulators and pathological pathways involved in cognitive impairment caused by heat. Before heat exposure in vivo and in vitro, activation of the sarco/endoplasmic reticulum (SR/ER) calcium (Ca)-ATPase (SERCA) was achieved by CDN1163. Hematoxylin-Eosin, Nissl staining, calcium imaging, transmission electron microscopy, western blot, and immunofluorescence were utilized to visualize histological changes, intracellular calcium levels, endoplasmic reticulum stress (ERS) markers, apoptosis, and synaptic proteins alterations. Heat stress (HS) significantly induced cognitive decline and neuronal damage in mice. By the transcriptome sequencing between control (n = 5) and heat stress (n = 5) mice in hippocampal tissues, we identified a reduction in the expression of the atp2a gene encoding SERCA, accompanied by a corresponding decrease in its protein level. Consequently, this dysregulation resulted in an excessive accumulation of intracellular calcium ions. Furthermore, HS exposure also activated ERS and apoptosis, as evidenced by the upregulation of p-PERK, p-eIF2α, CHOP, and caspase-3. Consistently, a reduction in postsynaptic density protein 95 (PSD95) and synaptophysin (SYN) expressions indicated modifications in synaptic function. Notably, the impacts on neurons caused by HS were found to be mitigated by CDN1163 treatment both in vivo and in vitro. Additionally, SERCA-mediated ERS-induced apoptosis was attenuated by GSK2606414 treatment via inhibiting PERK-eIF2α-CHOP axis that not only curtailed the level of caspase-3 but also elevated the levels of PSD95 and SYN. These findings highlight the significant impact of heat stress on cognitive impairment, and further elucidate the underlying mechanism involving SERCA/PERK/eIF2α pathway.
PubMed: 38862478
DOI: 10.1038/s41420-024-02047-7 -
Cureus May 2024Pleuropulmonary blastoma (PPB) is a rare malignant tumor arising from the lung and pleura. It has three types based on the solid and cystic components. The prognosis of...
Pleuropulmonary blastoma (PPB) is a rare malignant tumor arising from the lung and pleura. It has three types based on the solid and cystic components. The prognosis of PPB varies depending on the type. Here, we present two female patients who come with complaints of breathlessness. Contrast-enhanced computed tomography (CECT) chest showed a pleural-based mass. Biopsy from the pleural-based mass showed a tumor with features of the malignant mesenchymal tumor. Tumor cells in both cases were positive for vimentin and negative for PanCK. In addition, tumor cells of one case showed positive for BCL2 and α-1 antitrypsin and negative for desmin, CD99, NSE, and p53. Tumor cells of another case are negative for CD99, WT-1, S100, synaptophysin, and chromogranin. In addition, some of the cells have abundant eosinophilic cytoplasm. Desmin shows positive in many cells and highlights rhabdomyoblasts. Morphological and immunohistochemical findings were correlated with the CECT diagnosis of PPB. Both cases were started on neoadjuvant chemotherapy and kept under follow-up. Both the patient's condition improved.
PubMed: 38854270
DOI: 10.7759/cureus.60021 -
Cureus May 2024Well-differentiated neuroendocrine tumors of the testis are exceedingly rare. Here, we report the case of a 47-year-old male patient complaining of cardiac symptoms with...
Well-differentiated neuroendocrine tumors of the testis are exceedingly rare. Here, we report the case of a 47-year-old male patient complaining of cardiac symptoms with a right testicular mass. A right radical orchiectomy was performed. The histopathological findings showed a well-differentiated neuroendocrine tumor with positive synaptophysin and chromogranin A immunostains.
PubMed: 38854200
DOI: 10.7759/cureus.59955 -
Surgical Neurology International 2024Neuroblastomas are rare tumors activated by the gene commonly found in pediatric patients. Due to the novelty of these tumors, there is no standard diagnostic profile....
BACKGROUND
Neuroblastomas are rare tumors activated by the gene commonly found in pediatric patients. Due to the novelty of these tumors, there is no standard diagnostic profile. However, they have been found to express , and synaptophysin, and they can be identified with magnetic resonance imaging (MRI). Treatment with chemotherapy combined with stem cell rescue and craniospinal irradiation can improve non-infant patient outcomes.
CASE DESCRIPTION
We report a case of a 2-year-old patient who was diagnosed with a neuroblastoma through MRI imaging and pathology that confirmed gene activation. The tumor was successfully removed. However, the tumor was not high-grade like most neuroblastomas.
CONCLUSION
The unusual presentation of a low-grade neuroblastoma demonstrates the necessity to conduct further research into the characteristics of these tumors.
PubMed: 38840609
DOI: 10.25259/SNI_794_2023 -
Neurologia Jun 2024Ataxias are characterized by aberrant movement patterns closely related to cerebellar dysfunction. Purkinje cell axons are the sole outputs from the cerebellar cortex,...
Ataxias are characterized by aberrant movement patterns closely related to cerebellar dysfunction. Purkinje cell axons are the sole outputs from the cerebellar cortex, and dysfunctional activity of Purkinje cells has been associated with ataxic movements. However, the synaptic characteristics of Purkinje cells in cases of ataxia are not yet well understood. The nicotinamide antagonist 3-acethylpyridine (3-AP) selectively destroys inferior olivary nucleus neurons so it is widely used to induce cerebellar ataxia. Five days after 3-AP treatment (65mg/kg) in adult male Sprague-Dawley rats, motor incoordination was revealed through BBB and Rotarod testing. In addition, in Purkinje cells from lobules V-VII of the cerebellar vermis studied by the Golgi method, the density of dendritic spines decreased, especially the thin and mushroom types. Western blot analysis showed a decrease in AMPA and PSD-95 content with an increase of the α-catenin protein, while GAD-67 and synaptophysin were unchanged. Findings suggest a limited capacity of Purkinje cells to acquire and consolidate afferent excitatory inputs and an aberrant, rigid profile in the movement-related output patterns of Purkinje neurons that likely contributes to the motor-related impairments characteristic of cerebellar ataxias.
Topics: Animals; Purkinje Cells; Male; Rats, Sprague-Dawley; Rats; Cerebellum; Cerebellar Ataxia; Pyridines; Neuronal Plasticity
PubMed: 38830720
DOI: 10.1016/j.nrleng.2021.09.015 -
Research (Washington, D.C.) 2024Consuming a high-fat diet (HFD) is widely recognized to cause obesity and result in chronic brain inflammation that impairs cognitive function. Repetitive transcranial...
Consuming a high-fat diet (HFD) is widely recognized to cause obesity and result in chronic brain inflammation that impairs cognitive function. Repetitive transcranial magnetic stimulation (rTMS) has shown effectiveness in both weight loss and cognitive improvement, although the exact mechanism is still unknown. Our study examined the effects of rTMS on the brain and intestinal microecological dysfunction. rTMS successfully reduced cognitive decline caused by an HFD in behavioral assessments involving the Y maze and novel object recognition. This was accompanied by an increase in the number of new neurons and the transcription level of genes related to synaptic plasticity (spindlin 1, synaptophysin, and postsynaptic protein-95) in the hippocampus. It was reached that rTMS decreased the release of high mobility group box 1, activation of microglia, and inflammation in the brains of HFD rats. rTMS also reduced hypothalamic hypocretin levels and improved peripheral blood lipid metabolism. In addition, rTMS recovered the HFD-induced gut microbiome imbalances, metabolic disorders, and, in particular, reduced levels of the microvirus. Our research emphasized that rTMS enhanced cognitive abilities, resulting in positive impacts on brain inflammation, neurodegeneration, and the microbiota in the gut, indicating the potential connection between the brain and gut, proposing that rTMS could be a new approach to addressing cognitive deficits linked to obesity.
PubMed: 38826566
DOI: 10.34133/research.0384 -
World Journal of Gastrointestinal... May 2024Neuroendocrine carcinoma (NEC) of the extrahepatic bile duct is very rare, and the treatment and prognosis are unclear. Herein, we report the case of a middle-aged...
BACKGROUND
Neuroendocrine carcinoma (NEC) of the extrahepatic bile duct is very rare, and the treatment and prognosis are unclear. Herein, we report the case of a middle-aged female with primary large cell NEC (LCNEC) of the common hepatic duct combined with distal cholangiocarcinoma (dCCA). Additionally, after a review of the relevant literature, we summarize and compare mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) and pure NEC to provide a reference for selecting the appropriate treatment and predicting the prognosis of this rare disease.
CASE SUMMARY
A 62-year-old female presented to the hospital due to recurrent abdominal pain for 2 months. Physical examination showed mild tenderness in the upper abdomen and a positive Courvoisier sign. Blood tests showed elevated liver transaminase and carbohydrate antigen 199 levels. Imaging examination revealed a 1-cm tumour in the middle and lower segments of the common bile duct. Pancreaticoduodenectomy + lymph node dissection was performed, and hepatic duct tumours were unexpectedly found during surgery. Pathology suggested poorly differentiated LCNEC (approximately 0.5 cm × 0.5 cm × 0.4 cm), Ki-67 (50%), synaptophysin+, and chromogranin A+. dCCA pathology suggested moderately differentiated adenocarcinoma. The patient eventually developed lymph node metastasis in the liver, bone, peritoneum, and abdominal cavity and died 24 months after surgery. Gene sequencing methods were used to compare gene mutations in the two primary bile duct tumours.
CONCLUSION
The prognosis of MiNEN and pure NEC alone is different, and the selection of treatment options needs to be differentiated.
PubMed: 38817298
DOI: 10.4240/wjgs.v16.i5.1449 -
Brazilian Journal of Medical and... 2024Clinical studies have found that neonatal sevoflurane exposure can increase the risk of cognitive dysfunction. However, recent studies have found that it can exhibit...
Clinical studies have found that neonatal sevoflurane exposure can increase the risk of cognitive dysfunction. However, recent studies have found that it can exhibit neuroprotective effects in some situations. In this study, we aimed to explore the effects of sevoflurane neonatal exposure in rats. A total of 144 rat pups (72 males and 72 females) were assigned to six groups and separately according to sevoflurane exposure of different times on the seventh day after birth. Blood gas analysis and western blot detection in the hippocampus were conducted after exposure. The Morris water maze test was conducted on the 32nd to 38th days after birth. The expression of PSD95 and synaptophysin in the hippocampus was detected after the Morris water maze test. We found that neonatal exposure to sevoflurane promoted apoptosis in the hippocampus, and Bax and caspase-3 were increased in a dose-dependent manner. The 2-h exposure had the greatest effects on cognitive dysfunction. However, with the extension of exposure time to 6 h, the effects on cognitive function were partly compensated. In addition, sevoflurane exposure decreased synaptogenesis in the hippocampus. However, as the exposure time was extended, the suppression of synaptogenesis was attenuated. In conclusion, neonatal sevoflurane exposure exhibited duration-dependent effects on cognitive function via Bax-caspase-3-dependent apoptosis and bidirectional effects on synaptogenesis in rats.
Topics: Sevoflurane; Animals; Female; Animals, Newborn; Male; Hippocampus; Rats; Cognition; Time Factors; Maze Learning; Anesthetics, Inhalation; Apoptosis; Sex Factors; Rats, Sprague-Dawley; Methyl Ethers; Blotting, Western; Blood Gas Analysis; Cognitive Dysfunction
PubMed: 38808889
DOI: 10.1590/1414-431X2024e13437 -
World Journal of Clinical Cases May 2024Neuroendocrine prostate cancer (NEPC) shows an aggressive behavior compared to prostate cancer (PCa), also known as prostate adenocarcinoma. Scanty foci in PCa can...
Neuroendocrine prostate cancer (NEPC) shows an aggressive behavior compared to prostate cancer (PCa), also known as prostate adenocarcinoma. Scanty foci in PCa can harbor genetic alternation that can arise in a heterogeneity of prostate cancer. NEPC may arise or develop following androgen deprivation therapy (ADT). NEPC that arise following ADT has the nomenclature "treatment-emerging/induced NEPC (t-NEPC)". t-NEPC would be anticipated in castration resistant prostate cancer (CRPC) and metastatic PCa. t-NEPC is characterized by low or absent androgen receptor (AR) expression, independence of AR signaling, and gain of neuroendocrine phenotype. t-NEPC is an aggressive metastatic tumor, develops from PCa in response to drug induced ADT, and shows very short response to conventional therapy. t-NEPC occurs in 10%-17% of patients with CRPC. NEPC is rare and is accounting for less than 2% of all PCa. The molecular mechanisms underlying the trans-differentiation from CRPC to t-NEPC are not fully elucidated. Sphingosine kinase 1 plays a significant role in t-NEPC development. Although neuroendocrine markers: Synaptophysin, chromogranin A, and insulinoma associated protein 1 () are expressed in t-NEPC, they are non-specific for diagnosis, prognosis, and follow-up of therapy. t-NEPC shows enriched genomic alteration in tumor protein P53 () and retinoblastoma 1 (). There are evidences suggest that t-NEPC might develop through epigenetic evolution. There are genomic, epigenetic, and transcriptional alterations that are reported to be involved in development of t-NEPC. Knock-outs of and were found to contribute in development of t-NEPC. PCa is resistant to immunotherapy, and at present there are running trials to approach immunotherapy for PCa, CRPC, and t-NEPC.
PubMed: 38808339
DOI: 10.12998/wjcc.v12.i13.2143