Unveiling The Neuropathology Tumour Landscape: 10-Year Statistical Analysis With Global Comparison - Single Centre Experience.

Introduction: Central nervous system (CNS) tumours represent a significant public health issue worldwide, and their incidence and distribution vary across different populations. Although studies on CNS tumours have been conducted in various countries, there is a lack of information regarding their patterns in Macedonia. Therefore, this study is aimed at investigating the distribution, histopathological types and subtypes and demographic features of CNS tumours in our country. Materials and Methods: A cross sectional study was conducted using the electronic database of the Institute of Pathology - Medical Faculty, University "Ss. Cyril and Methodius" in Skopje which contains data from 3286 received and analysed surgical specimens, mainly from the University Clinic of Neurosurgery in Skopje, and a smaller number of surgical specimens from the University Surgical Centre "St. Naum Ohridski" in Skopje between 2012 and 2022. The collected and analysed data includes patient age, sex and histopathological types and subtypes of the tumours. Results: The majority of CNS tumours were diagnosed in adults aged between 50-70, with a male to female ratio of 1.5:1. The most common location of the tumours was the cerebrum, followed by the pituitary gland and cerebellum. The most frequent histological groups were gliomas, with glioblastoma as the most common diagnosis, followed by meningiomas. Conclusion: Following a detailed and thorough review of the CNS tumours in our study, we can conclude that the R. of Macedonia follows global statistics and trends regarding brain tumours.

Large Neck Teratoma in a Newborn with Respiratory Distress Syndrome.

Neonatal tumours in the neck region are a rare finding. Teratomas typically comprise all three germ cell layers with tissues usually foreign to the anatomic site of origin. Head and neck teratomas account a smaller part of congenital teratomas. They can cause major airway obstruction due to the external compression that oropharyngeal or neck masses produce. In addition, there can be an intrinsic lesion in the larynx or trachea. We describe a premature, 30-gestational week-old newborn with large subcutaneous neck mass. Pre-delivery ultrasound showed heterogeneous tumor structure and displaced larynx. The intubation was successful. The newborn developed respiratory distress syndrome immediately after birth which rendered the surgical removal of the neck tumor impossible. An autopsy was done, and the histopathology revealed mature teratoma comprising muscle, brain, salivary and pulmonary tissues, as well as well-developed hyaline membranes in the alveoli. The combination of the respiratory distress syndrome and the neck tumor compression proved fatal. Prenatal diagnosis, therapeutic options and ex utero intrapartum treatment (EXIT) procedures are discussed for the diagnosis and management of this very rare tumor.

Signet ring cell carcinoma of rectum metastasizing to synchronous renal cell carcinoma: a case report.

BACKGROUND: Rectal signet ring cell carcinoma is a rare type of colorectal adenocarcinoma characterized by an aggressive biological behavior and poor prognosis. The co-occurrence of colorectal carcinoma and renal cell carcinoma (RCC) has found in many hundreds of patients, many of whom also have additional malignancies. Cancer to cancer metastasis is rare and an uncommon phenomenon in malignancy, especially at the time of initial diagnosis, suggesting a genetic susceptibility. CASE PRESENTATION: We present the case of a 66-year-old Macedonian man with synchronous rectal signet ring cell carcinoma and RCC with tumor to tumor metastasis feature. He underwent a left nephrectomy and anterior rectal resection after complaining of constipation for 3-4 months and the appearance of synchronous tumors on the imaging studies. Morphology and immunohistochemical analysis of specimens from the RCC revealed signet ring cells identical to the rectal signet ring cell carcinoma. The next-generation sequencing study revealed mutations in TP53 and ERBB2, and microsatellite stable signet ring cell carcinoma was determined by deoxyribonucleic acid (DNA) sequencing. CONCLUSIONS: Cancer to cancer metastasis, although rare, needs to be considered in synchronous tumors. RCC, when diagnosed in multiple synchronous tumors, should be examined carefully. The paucity of reported cases indicates the need for advanced research in imaging methods for metastasis and new therapeutic approaches.

"Transforming the Beast to A Beauty"- Fifteen Years into the Making - Case Report of Congenital Neurofibromatosis.

BACKGROUND: In 1882, the German pathologist Friedrich Daniel von Recklinghausen described a series of patients with a combination of cutaneous lesions and tumours of the peripheral and central nervous system. Succeeding this paper, all of the patients with similar symptoms were given the diagnosis "von Recklinghausen disease". In the 20th century, a distinction was made between Neurofibromatosis type 1 (NF1) and Neurofibromatosis type 2 (NF2) with the help of molecular testing. CASE REPORT: We are presenting the results from multiple surgical esthetic and reconstructive surgical procedures performed on a female patient with severe congenital neurofibromatosis during 15 years (2000-2015). The external appearance of our patient was not reflected in the general public's beauty standards. Convinced that she was unusual and unaccepted by the society, she gathered all of the strength and became our patient at 15 years of age. CONCLUSION: Transforming the patient's life in the next fifteen years improved her overall health and her life quality.

Surgical Treatment of Meningiomas - Outcome Associated With Type of Resection, Recurrence, Karnofsky Performance Score, Mitotic Count.

BACKGROUND: Meningiomas are the type of central nervous system tumours, derived from the cells of the arachnoid membrane that are well constrained from surrounding tissues, mainly no infiltrating neoplasm with benign features. Meningiomas consist about 15-20% of all primary intracranial neoplasms. AIM: The evaluation of the outcome of the operatively treated meningiomas in relation with the Karnofsky performance score, survival, recurrence, type of the surgical excision, histological type, mitotic count (MC), localisation and volume of the lesion. METHODS: In this article 40 operatively treated patients are reviewed for the outcome of the operation about the Karnofsky performance score, survival, recurrence, type of the surgical excision, histological type, mitotic count (MC), localisation and volume of the lesion. RESULTS: Association/interconnection between the mitotic count grade I and the regrowth of meningioma have been verified. Association/interconnection between the mitotic count grade I and the regrowth of meningioma have been verified. Association/interconnection between the mitotic count grade I and the regrowth of meningioma have been established. CONCLUSION: Gender, age and Karnofsky performance score have predictive value in the treatment of different types of meningiomas. The magnitude of surgical resection is associated with the regrowth of a tumour. The mitotic count in different types of meningiomas presents significant feature in the appearance of meningioma recurrence. The surgical resection and the quality and quantity of patient's survival have a significant relation to the mitotic count of the meningiomas. There is no connection between the size and the localisation of a tumour related to different values of the mitotic count.

Low-Grade Malignancy Glomus Tumor in a Setting of Multiple Glomus Tumors - Case Report.

BACKGROUND: Glomus tumors are rare neoplasms accounting for less than 2% of all soft tissue tumors but multiple lesions may be seen in up to 10% of the patients. Solitary glomus tumor (GT) most frequently appears as small nodule in specific locations such as subungual region or deep dermis. However, rarely these entities have been observed in extracutaneous locations such as the gastrointestinal, cardiovascular, respiratory tracts, and other visceral organs. A small fraction of the GTs may present as tumors of uncertain malignant potential or as malignant glomus tumors. CASE PRESENTATION: We report a patient with multiple glomus tumors on the time of diagnosis, which was histologically diagnosed as an atypical glomus tumor following resection of a tumor thrombus in the left renal vein, inferior vena cava trombus with intracardial extension, and mitral valve specimen. The intramuscular lesion from the thigh was diagnosed as a glomus tumor of uncertain malignant potential. Further examinations revealed multiple lesions trough her body: kidneys, breast, heart and subcutaneous tissue. The diagnosis of glomus tumor of uncertain malignant potential versus glomus tumor with low malignant potential could be quite challenging, and the clinical course may be as a determining factor for final diagnosis. CONCLUSION: To our knowledge, this is the only known case of glomus tumor with multiple organ involvement and aggressive biological behavior at presentation.

Quantitative mass spectrometry reveals changes in SNAP-25 isoforms in schizophrenia.

SNAP-25 and syntaxin are presynaptic terminal SNARE proteins altered in amount and function in schizophrenia. In the ventral caudate, we observed 32% lower SNAP-25 and 26% lower syntaxin, but greater interaction between the two proteins using an in vitro assay. SNAP-25 has two isoforms, SNAP-25A and B, differing by only 9 amino acids, but with different effects on neurotransmission. A quantitative mass spectrometry assay was developed to measure total SNAP-25, and proportions of SNAP-25A and B. The assay had a good linear range (50- to 150-fold) and coefficient of variation (4.5%). We studied ventral caudate samples from patients with schizophrenia (n=15) previously reported to have lower total SNAP-25 than controls (n=13). We confirmed 27% lower total SNAP-25 in schizophrenia, and observed 31% lower SNAP-25A (P=0.002) with 20% lower SNAP-25B amounts (P=0.10). Lower SNAP-25A amount correlated with greater SNAP-25-syntaxin protein-protein interactions (r=-0.41, P=0.03); the level of SNAP-25B did not. Administration of haloperidol or clozapine to rats did not mimic the changes found in schizophrenia. The findings suggest that lower levels of SNAP-25 in schizophrenia may represent a greater effect of the illness on the SNAP-25A isoform. This in turn could contribute to the greater interaction between SNAP25 and syntaxin, and possibly disturb neurotransmission in the illness.

Genome-wide divergence of DNA methylation marks in cerebral and cerebellar cortices.

BACKGROUND: Emerging evidence suggests that DNA methylation plays an expansive role in the central nervous system (CNS). Large-scale whole genome DNA methylation profiling of the normal human brain offers tremendous potential in understanding the role of DNA methylation in brain development and function. METHODOLOGY/SIGNIFICANT FINDINGS: Using methylation-sensitive SNP chip analysis (MSNP), we performed whole genome DNA methylation profiling of the prefrontal, occipital, and temporal regions of cerebral cortex, as well as cerebellum. These data provide an unbiased representation of CpG sites comprising 377,509 CpG dinucleotides within both the genic and intergenic euchromatic region of the genome. Our large-scale genome DNA methylation profiling reveals that the prefrontal, occipital, and temporal regions of the cerebral cortex compared to cerebellum have markedly different DNA methylation signatures, with the cerebral cortex being hypermethylated and cerebellum being hypomethylated. Such differences were observed in distinct genomic regions, including genes involved in CNS function. The MSNP data were validated for a subset of these genes, by performing bisulfite cloning and sequencing and confirming that prefrontal, occipital, and temporal cortices are significantly more methylated as compared to the cerebellum. CONCLUSIONS: These findings are consistent with known developmental differences in nucleosome repeat lengths in cerebral and cerebellar cortices, with cerebrum exhibiting shorter repeat lengths than cerebellum. Our observed differences in DNA methylation profiles in these regions underscores the potential role of DNA methylation in chromatin structure and organization in CNS, reflecting functional specialization within cortical regions.

A novel mechanism and treatment target for presynaptic abnormalities in specific striatal regions in schizophrenia.

Abnormalities of amount and function of presynaptic terminals may have an important role in the mechanism of illness in schizophrenia. The SNARE proteins (SNAP-25, syntaxin, and VAMP) are enriched in presynaptic terminals, where they interact to form a functional complex to facilitate vesicle fusion. SNARE protein amounts are altered in the cortical regions in schizophrenia, but studies of protein-protein interactions are limited. We extended these investigations to the striatal regions (such as the nucleus accumbens, ventromedial caudate (VMC), and dorsal caudate) relevant to disease symptoms. In addition to measuring SNARE protein levels, we studied SNARE protein-protein interactions using a novel ELISA method. The possible effect of antipsychotic treatment was investigated in parallel in the striatum of rodents that were administered haloperidol and clozapine. In schizophrenia samples, compared with controls, SNAP-25 was 32% lower (P=0.015) and syntaxin was 26% lower (P=0.006) in the VMC. In contrast, in the same region, SNARE protein-protein interactions were higher in schizophrenia (P=0.008). Confocal microscopy of schizophrenia and control VMC showed qualitatively similar SNARE protein immunostaining. Haloperidol treatment of rats increased levels of SNAP-25 (mean 24%, P=0.003), syntaxin (mean 18%, P=0.010), and VAMP (mean 16%, P=0.001), whereas clozapine increased only the VAMP level (mean 13%, P=0.004). Neither drug altered SNARE protein-protein interactions. These results indicate abnormalities of amount and interactions of proteins directly related to presynaptic function in the VMC in schizophrenia. SNARE proteins and their interactions may be a novel target for the development of therapeutics.

Absence of histological lesions in primate models of ECT and magnetic seizure therapy.

OBJECTIVE: The authors present preliminary findings from the first nonhuman primate neuropathological study of ECT to use perfusion fixation and adequate controls and the first to compare ECT with magnetic seizure therapy, to their knowledge. METHOD: Twelve Macaca mullata received 6 weeks of daily ECT, magnetic seizure therapy, or anesthesia alone. After perfusion fixation, their brains were examined while masked to intervention. RESULTS: No identified lesions were attributable to the interventions. Cortical and hippocampal immunoreactivity for glial fibrillary acidic protein (an astrocytic marker) was most intense in the group that received ECT. CONCLUSIONS: This small but rigorous primate study supports the view that ECT does not produce histological lesions in the brain and provides the first comparable safety data on magnetic seizure therapy.

Optimization of Golgi methods for impregnation of brain tissue from humans and monkeys.

Golgi impregnation is unique in its ability to display the dendritic trees of large numbers of individual neurons. However, its reputation for inconsistency leaves many investigators reluctant to embrace this methodology, particularly for the study of formalin-fixed human brain tissue. After reviewing the literature, testing a variety of technical variations, and discussing the procedure with experienced practitioners, we have concluded that much of the unpredictability can be removed by matching the Golgi technique to the conditions that were used for fixation of the tissue. Briefly fixed tissues worked best with the rapid Golgi technique, which includes osmium during the initial chromation step, and with the Golgi-Cox method, which includes mercuric chloride during chromation. For tissues that have been fixed for several years or even for several decades, superior results are obtained with the Golgi-Kopsch technique, using multiple changes of a chromation solution that contains paraformaldehyde. In the Golgi-Kopsch technique, pH should be used to monitor the reduction of Cr6+ to Cr3+, which is a crucial determinant of successful chromation. With any Golgi technique, agitation throughout the impregnation helps to avoid precipitates and to improve the quality of impregnation. When the appropriate method is chosen, Golgi impregnation is a useful technique for the neuropathologist.