Introduction:Fibroblast growth factor receptor (FGFR) signalling is implicated in breast cancer (BC) progression, but little is known about FGFR status as the disease develops. We evaluated FGFR1-4 expression changes in primary tumours (PT) and matched lymph node metastases (LNM) in the context of BC phenotype and circulating tumour cell (CTC) burden. Material and methods:Fibroblast growth factor receptor 1-4, oestrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2) and Ki-67 were assessed immunohistochemically in paired PT and LNM. Circulating tumour cells were quantified by imaging flow cytometry in 67 BC patients and correlated with BC phenotype and FGFR status. Results:Switch of the BC subtype between PT and LNM was observed in 3/23 cases (13.0%). In contrast, discordance in FGFR expression occurred in 11/22 (50.0%), 5/22 (22.7%), 12/22 (54.5%), and 5/21 (23.8%) cases for FGFR1, FGFR2, FGFR3, and FGFR4, respectively; in most discordant cases, the difference reflected increased expression in LNM. Circulating tumour cells were detected in 22/67 patients (32.8%), with a median burden of 5.7 CTCs per 1 million peripheral blood mononuclear cells (interquartile ranges: 3.0-17.8). Circulating tumour cell presence was not associated with lymph node (LN) status (p = 0.806). Circulating tumour cell presence was more frequent in cases with FGFR1 discordance than in FGFR1-concordant tumours (63.6% vs. 9.1%; p = 0.024). Circulating tumour cell burden correlated inversely with FGFR1 level in LNM (Spearman's ρ = -0.49, p = 0.021). A shift in the FGFR1 status was noted exclusively in HER2-negative tumours. Conclusions:The observed association between CTCs and FGFR1 status conversion, but not LN involvement in the context of disease progression, may reflect a previously unrecognised biological feature of FGFR1- positive cells, most likely restricted to HER2-negative breast cancer.

Extracranial metastasis of glioblastoma (GBM) is an extremely rare phenomenon and is associated with a poor prognosis. Here, we present the case of a 55-year-old woman who developed pleural metastasis of GBM, manifesting non-specific breathing difficulties during treatment. This case highlights the importance of integrating multiple diagnostic approaches, as only the comparison of histopathological examination results with the patient's clinical history - right temporal lobe GBM - enabled the final diagnosis of GBM metastasis. Next-generation sequencing was performed as part of the diagnostic workup and revealed a p.G266R TP53 mutation. Additionally, imaging revealed an extensive heterogeneous lesion at the site of the previously resected GBM, which proved to be an inoperable gliosarcoma (World Health Organization grade 4). This rare presentation of GBM with distant pleural metastasis, combined with the identification of an uncommon TP53 mutation, represents a unique diagnostic and clinical challenge and underscores the novelty of this case.

BACKGROUND:Surgical treatment of entrapment neuropathies based on nerve decompression. A different approach applies in the case of meralgia paraesthetica affecting the purely sensory lateral femoral cutaneous nerve (LFCN). Established treatment options include both decompression and LFCN neurectomy. The latter not only provides symptomatic relief but also enables proper histopathological analysis, offering deeper insight into the etiopathogenesis of meralgia paraesthetica. MATERIAL AND METHOD:14 LFCNs neurectomies were performed 13 patients at our department between 2015 and 2022. Histopathological specimens were available for 12 LFCNs. We analyzed selected pathological features, for example interfascicular multifocal fiber loss, perivascular epineurial inflammation, perineurium thickness (μm), collagen content (%). RESULTS:Based on histopathological findings, patients were divided into three groups according to symptom duration: <1 year, 1-3 years, and >3 years. In the <1 year group, interfascicular multifocal fiber loss and loss of large myelinated fibers with signs of regeneration were observed, while perineurial thickening and subperineurial edema were absent. In the 1-3 year group, all three features were present in the majority of cases, except one (20 %) lacking perineurial changes. In the >3 year group, neither fiber loss nor regeneration was observed, while perineurial thickening and subperineurial edema were present in 50 % of cases. No correlation was found between the histopathological patterns and clinical parameters. CONCLUSION:LFCN neurectomy provided a unique opportunity to examine the histopathological features of entrapment neuropathy. Our findings indicate that histopathological changes correlate primarily with the duration of symptoms rather than with the severity of clinical presentation or the degree of postoperative improvement.

Splenic rupture is a critical surgical condition that poses an immediate threat to the patient's life. In most cases, mechanical trauma to the organ results in the rupture of the capsule, leading to hemorrhage into the peritoneal cavity. Spontaneous (pathological) spleen rupture (SPSR) is considered when the etiology of the rupture is non-traumatic. Spontaneous (pathological) spleen rupture is most commonly associated with hematological malignancies, though it remains a rare condition. Only 8 cases have been caused by mantle cell lymphoma (MCL). This review presents the case of a 59-year-old male patient who was treated with emergency splenectomy due to SPSR. Histopathological examination revealed MCL.

Background:Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases. Accurate differentiation between adenocarcinoma (ADC) and squamous cell carcinoma (SCC) is critical for informing personalized therapies. Thyroid transcription factor-1 (TTF-1) and p40 are traditionally regarded as mutually exclusive markers of ADC and SCC, respectively. However, a subset of tumors exhibits co-expression of TTF-1 and p40, presenting diagnostic challenges and suggesting underlying biological distinctiveness. This study aimed to characterize the clinicopathological, molecular, and immunohistochemical features of NSCLCs co-expressing TTF-1 and p40, in order to clarify their biological and clinical significance. Methods:A retrospective analysis was performed on NSCLC cases diagnosed at the Central Clinical Hospital of the Medical University of Łódź between May 2021 and November 2022. Clinicopathological and survival data were collected. Tumors co-expressing TTF-1 and p40 underwent immunohistochemical evaluation and RNA/DNA-based next-generation sequencing (NGS). Results:Of 94 NSCLC cases analyzed, 18 (19.1%) demonstrated co-expression of TTF-1 and p40. These tumors were significantly more likely to exhibit solid growth patterns compared to control cases (P=0.03), but no significant difference in overall survival (OS) was observed (P=0.46). Among 17 samples subjected to NGS, genetic alterations were identified in 15 (88.2%) cases, with TP53 mutations in 11 (64.7%), KRAS in 4 (23.5%), FGFR1-3 in 4 (23.5%) and EGFR in 2 (11.8%) cases. Immunohistochemical analysis of 18 tumors revealed strong p63 and p53 expression in 11 (61.1%) and 13 (72.2%) cases, respectively. FGFR4 protein was abundantly expressed in 15 cases (83.3%, H-score >150), while elevated H-scores for FGFR1, FGFR2, and FGFR3 were observed in 10 (55.6%), 7 (38.9%), and 2 (11.1%) cases, respectively. Conclusions:NSCLCs co-expressing TTF-1 and p40 appear to represent a biologically distinct and poorly differentiated subgroup, frequently associated with TP53 mutations and FGFR pathway alterations. These tumors may arise from basal reserve cells and undergo TP53-driven reprogramming, diverging from the classical pathways of ADC and SCC. Accordingly, they may be more appropriately classified as NSCLC, not otherwise specified (NOS), rather than strictly as ADC or SCC. Given their molecular complexity, broader genomic profiling may be warranted in these cases, even though current guidelines do not recommend routine molecular testing for SCC.

Background:Fibroblast growth factor receptor 2 (FGFR2) is an oncogenic driver in luminal breast cancer (BCa), with emerging evidence linking it to tumour immune microenvironment (TIME) modulation. While FGFR2's role in endocrine resistance is established, its potential involvement in shaping immune infiltration-particularly in the transition from ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC)-remains underexplored. Methods:This retrospective study analysed 99 BCa specimens collected between 2004-2019. Immunohistochemistry was used to assess FGFR2 expression and immune markers (CD8, CD68, CD163, FOXP3). Clinical and pathological variables were evaluated, and immune cell densities were compared across disease stages and BCa subtypes (luminal vs. non-luminal). Correlations between FGFR2 expression and immune markers were assessed using non-parametric statistical tests. Results:Progression from DCIS to IDC was associated with increased infiltration by CD8+ T cells and CD68+ macrophages. FGFR2 expression showed differences between DCIS and IDC with an extensive DCIS component and was positively correlated with CD8+, CD163+, and FOXP3+ cell densities. The latter associations were exclusive to luminal A tumours, with no such correlations observed in non-luminal subtypes. Conclusions:FGFR2 expression in luminal A BCa correlates with markers of immunosuppressive TIME, particularly CD163+ macrophages and FOXP3+ T cells. These subtype-specific interactions suggest a synergistic role of FGFR2 and estrogen receptor signalling in immune evasion and tumour progression, warranting further mechanistic and therapeutic investigation. However, the small number of cases in certain subgroups, particularly DCIS and non-luminal tumours, limits the generalizability of these findings and warrants cautious interpretation.

BACKGROUND:The number of prognostic and predictive factors for pancreatic ductal adenocarcinoma (PDAC) is limited. Fibroblast growth factor receptors (FGFRs) are emerging as potential therapeutic targets, especially in cases with FGFR2 gene fusions. However, the prognostic relevance of FGFR1, FGFR2, and FGFR4 protein expression in PDAC remains unclear. METHODS:Immunohistochemical analysis of FGFR1, FGFR2, and FGFR4 was performed on 99 PDAC and 60 adjacent normal pancreatic tissue samples. Protein expression was quantified using the H-score method and correlated with clinicopathological variables and survival. Publicly available datasets from the GEO repository and the cancer genome atlas (TCGA) were used for pathway enrichment analysis and validation of findings at the mRNA level. RESULTS:FGFR2 and FGFR4 showed differential expression between tumor and normal tissues, while FGFR1 did not. High FGFR4 protein expression was significantly associated with shorter disease-free survival (DFS) in both univariable and multivariable analyses. FGFR2 high expression cases showed a trend towards poor DFS, while FGFR1 had no prognostic impact. In silico analysis confirmed that high FGFR4 mRNA levels are associated with worse DFS. Co-expression and enrichment analysis linked FGFR4 overexpression with developmental, metabolic, and stemness-related processes. CONCLUSION:FGFR4 showed the strongest prognostic association among the FGFR family members studied, with high protein expression correlating with shorter disease-free survival in PDAC patients. These findings underscore the potential of FGFR4 as a biomarker for recurrence risk, while also highlighting the complexity of FGFR-related signaling and its context-dependent clinical relevance.

Introduction:Fibroblast growth factor receptor 2 (FGFR2) activation is associated with endocrine therapy resistance in luminal breast cancer (BC) in vitro, but clinical evidence remains inconsistent. Given the role of FGFRs in mediating tumour microenvironment (TME) interactions, the prognostic value of FGFR2 may depend on the stromal component. This study aimed to validate the association between FGFR-related profile of the stroma and FGFR2 prognostic value in oestrogen receptor-positive invasive ductal carcinoma (IDC). Material and methods:An in silico gene expression analysis identified 12 stromal factors (FAP, CXCL12, PDGFRA, COL1A1, HSPG2, CCL2, MMP14, S100A4, MMP9, PDGFA, MCAM, IL6) forming an "FGFR-related profile of the stroma". A cohort of 257 ER+ IDC patients from The Cancer Genome Atlas (TCGA) was analysed. Tumours were clustered using k-means based on stromal gene expression, and Cox proportional hazards regression models were used to assess the association between FGFR2 and overall survival (OS). Results:Two clusters of ER+ IDC tumours were identified based on the stromal gene expression profile. While both clusters had similar tumour stages and hormone receptor statuses, multivariable analysis adjusted for clinical factors revealed a significant association between FGFR2 expression and cluster assignment. In Cluster I (high expression of stromal genes), high FGFR2 was linked to poor prognosis, whereas in Cluster II (low expression), high FGFR2 indicated favourable prognosis. FGFR1, FGFR3, and FGFR4 showed no significant prognostic value. Conclusions:Stromal profiles modulate the prognostic significance of FGFR2 in luminal breast carcinoma, highlighting the importance of TME profiling for biomarker assessment and explaining inconsistencies in FGFR2 studies.

While preclinical studies consistently implicate FGFR‑signalling in breast cancer (BC) progression, clinical evidence fails to support these findings. It may be that the clinical significance of FGFR ought to be analysed in the context of the stroma, activating or repressing its function. The present review aimed to provide such a context by summarizing the existing data on the prognostic and/or predictive value of selected cancer‑associated fibroblasts (CAFs)‑related factors, that either directly or indirectly may affect FGFR‑signalling. PubMed (https://pubmed.ncbi.nlm.nih.gov/) and Medline (https://www.nlm.nih.gov/medline/medline_home.html) databases were searched for the relevant literature related to the prognostic and/or predictive significance of: CAFs phenotypic markers (αSMA, S100A4/FSP‑1, PDGFR, PDPN and FAP), CAFs‑derived cognate FGFR ligands (FGF2, FGF5 and FGF17) or inducers of CAFs' paracrine activity (TGF‑β1, HDGF, PDGF, CXCL8, CCL5, CCL2, IL‑6, HH and EGF) both expressed in the tumour and circulating in the blood. A total of 68 articles were selected and thoroughly analysed. The findings consistently identified upregulation of αSMA, S100A4/FSP‑1, PDGFR, PDPN, HDGF, PDGF, CXCL8, CCL5, CCL2, IL‑6, HH and EGF as poor prognostic markers in BC, while evaluation of the prognostic value of the remaining markers varied between the studies. The data confirm an association of CAFs‑specific features with BC prognosis, suggesting that both quantitative and qualitative profiling of the stroma might be required for an assessment of the true FGFR's clinical value.

Chondromyxoid fibromas (CMF) are uncommon benign bone tumours, known for their moderate risk of local recurrence, that may manifest through various symptoms such as pain, swelling, tenderness, or be asymptomatic. Diagnosing CMF is challenging and requires a comprehensive, multidisciplinary diagnostic approach because the tumour frequently resembles numerous other bone lesions. This report describes a case of a 66-year-old female patient with a tumour in her right fibula. The initial diagnosis of a neuroma of the right tibial nerve was based on a magnetic resonance imaging scan. The lesion was surgically removed. Preliminarily subsequent histopathological evaluation identified the mass as a parosteal osteosarcoma. However, due to the uncharacteristic presentation of the tumour, further investigation was carried out. Using immunohistochemical and genetic analyses focused on the expression of MDM-2 and RB-1, along with an examination for alterations in the GNAS gene, the mass has been finally and conclusively identified as a chondromyxoid fibroma. This case demonstrates the ambiguity of the CMF presentation, the accurate diagnosis of which may frequently rely on additional diagnostic measures, including histopathology and targeted genetic tests. Furthermore, this report illustrates an atypical diagnostic journey, from an initial neuroma through a low-grade osteosarcoma, to a final benign chondromyxoid fibroma.

Skin autofluorescence (sAF) measurement is a non-invasive method used to assess tissue advanced glycation end product (AGE) accumulation. This study aims to characterize sAF’s association with (1) glycated hemoglobin (HbA1c) values, (2) cardiovascular risk markers, and (3) common comorbidities (autoimmune thyroiditis, celiac disease) in children with type 1 diabetes (T1D). Materials and methods: A total of 348 children with T1D aged 3–18 years and 85 age- and gender-matched control subjects were enrolled. sAF was quantified using an AGE Reader (Diagnoptics BV, The Netherlands). The analysis covered HbA1c, blood lipid, and C-reactive protein (CRP) levels, ambulatory blood pressure monitoring records, and body composition parameters. The associations between variables and sAF were assessed using the Mann–Whitney U test and Spearman correlation. Results: We observed significantly higher sAF values in the T1D group compared to the control (1.40 [1.27–1.53] vs. 1.20 [1.07–1.30, AU]; p = 0.004), consistent across all tested age groups. In the T1D group, sAF was positively correlated with current HbA1c, mean of historical HbA1c values, and T1D duration (r values, respectively: 0.27, 0.22, 0.14, all p < 0.01). Percentage of body fat was positively correlated with sAF (r = 0.120; p = 0.044). No significant correlations were found between sAF and lipid fractions, Z-score of BMI, parameters from 24 h ambulatory blood pressure monitoring, or the amount of albumin excreted in urine. sAF was positively correlated with CRP (r = 0.17, p < 0.05). sAF was significantly higher in patients with concomitant celiac disease (1.53 [1.43–1.63] vs. 1.40 [1.27–1.53, AU], p = 0.001). Conclusion: Among young T1D patients with relatively brief diabetes duration, sAF effectively mirrors prior glycemic control, as presented by historical average HbA1c. However, associations with conventional CV risk markers are not evident. The higher sAF values in patients with celiac disease warrant further exploration.

INTRODUCTION:In this paper, we have analysed all hand glomangioma cases referred to our clinic in the context of symptoms, time to diagnosis, and the role of surgical resection of the lesion.MATERIAL AND METHODS:We have collected the following data: the presence of risk factors, manifestation, time to diagnosis, the treatment applied, and follow-up of patients.RESULTS:We have collected medical records from six patients, three males and three females. The median age was 45 (IQR: 29.5-65.75). The main symptom in all patients was severe pain and tenderness. The first-choice physician(s) were: general practitioners, general surgeons, and neurologists. The median time to diagnosis was 7 (IQR: 5-10) years. The main complaint of our patients was severe pain - 9 (IQR: 9-10) on the VAS scale, which was significantly alleviated after surgical treatment - 0 (IQR: 0-0; p = 0.043).CONCLUSIONS:Extremely long times to final diagnosis, and excellent outcomes of surgical treatment, highlight the necessity of raising awareness of glomangiomas among clinicians.

Primary pulmonary Hodgkin's lympho-ma (PPHL) is a rare subtype of lympho-ma that comprises a small percentage of primary pulmonary lymphomas. Due to its rarity and nonspecific symptoms, PPHL often presents diagnostic challenges. This case report presents a unique case of PPHL mimicking granulomatosis with polyangiitis, emphasizing the difficulties encountered during the diagnostic process. A 53-year-old female presented with vague symptoms including weakness, oedema, dry cough, and nasal cavity ulceration. Laboratory investigations revealed elevated C-reactive protein levels, a white blood cell count with neutrophilia, and lymphopaenia. Initial treatment with oral corticosteroids for suspected polyangiitis yielded no response. The patient subsequently developed a low-grade fever and pruritic erythematous rash. Diagnostic procedures, including bronchial brush biopsy, bronchial washing, mediastinal lymph node biopsy, nasal cavity ulceration biopsy, and initial lung biopsy, were inconclusive and resulted in exclusion of granulomatosis with polyangiitis. A subsequent computed tomography scan indicated disease progression in the left lung. A lung biopsy revealed fibrotic tissue with nodules containing Hodgkin -Reed-Sternberg cells, leading to the final diagnosis of classic Hodgkin lymphoma, nodular sclerosis subtype. Positron emission tomography scan findings confirmed PPHL. The patient received multiple chemotherapeutic regimens, with brentuximab vedotin demonstrating efficacy as the sole effective treatment. This exceptional case of PPHL underscores the extensive diagnostic and therapeutic work-up involving a multidisciplinary team of clinicians, radiologists, and pathol-ogists. Increased awareness of PPHL and its distinctive features will aid in the diagnosis of similar cases in the future, benefitting both clinicians and pathologists.

Background Previous studies explored multifactorial interactions and sirtuin expression in the aortic cells of laboratory rodents and humans. Human studies were limited due to the availability of biological material exclusively in the advanced stage of the disease. The role of sirtuins in aortic pathology has not been explained extensively therefore the aim of the study was to assess the plasma concentrations of human sirtuin 1 (SIRT1) and human sirtuin 2 (SIRT2) in patients with ascending aortic dissection and ascending aortic aneurysm. Material and methods The study group included 43 adults (34 males and 9 females) aged 44–92 years with ascending aortic dissection ( n = 10) or with ascending aortic aneurysm ( n = 33). The SIRT1 and SIRT2 plasma concentrations in patients’ blood samples were determined, and the differences between groups were observed ( p = 0.02 for SIRT1, p = 0.04 for SIRT2). Results Levels of both SIRT1 and SIRT2 were lower in patients with ascending aortic dissection (SIRT1: median = 6.5 ng/mL; SIRT2: median = 5.7 ng/mL) than in patients with ascending aortic aneurysm (SIRT1: median = 9.2 ng/mL; SIRT2: median = 7.8 ng/mL). The SIRT1 and SIRT2 cut-off levels differentiating both groups of patients were 6.7 ng/mL and 3.2 ng/mL, respectively. Conclusions The patients with ascending aortic dissection had lower plasma concentrations of SIRT1 and SIRT2 than the patients with ascending aortic aneurysm. Calculated cut-off values for both enzymes may be helpful in laboratory differentiation of ascending aortic dissection from ascending aortic aneurysm.

Background: Primary glioblastoma is characterized by an extremely poor prognosis. The promoter methylation of GATA4 leads to the loss of its expression in many cancer types. The formation of high-grade astrocytomas can be promoted by the concurrent loss of TP53 and GATA4 in normal human astrocytes. Nevertheless, the impact of GATA4 alterations with linkage to TP53 changes in gliomagenesis is poorly understood. This study aimed to evaluate GATA4 protein expression, GATA4 promoter methylation, p53 expression, TP53 promoter methylation, and mutation status in patients with primary glioblastoma and to assess the possible prognostic impact of these alterations on overall survival. Materials and Methods: Thirty-one patients with primary glioblastoma were included. GATA4 and p53 expressions were determined immunohistochemically, and GATA4 and TP53 promoter methylations were analyzed via methylation-specific PCR. TP53 mutations were investigated via Sanger sequencing. Results: The prognostic value of GATA4 depends on p53 expression. Patients without GATA4 protein expression were more frequently negative for TP53 mutations and had better prognoses than the GATA4 positive patients. In patients positive for GATA4 protein expression, p53 expression was associated with the worst outcome. However, in patients positive for p53 expression, the loss of GATA4 protein expression seemed to be associated with improved prognosis. GATA4 promoter methylation was not associated with a lack of GATA4 protein expression. Conclusions: Our data indicate that there is a possibility that GATA4 could function as a prognostic factor in glioblastoma patients, but in connection with p53 expression. A lack of GATA4 expression is not dependent on GATA4 promoter methylation. GATA4 alone has no influence on survival time in glioblastoma patients.

BACKGROUND:Polymorphous low-grade adenocarcinoma (PLGA) is an extremely rare finding in the nasopharynx. There are no guidelines for the treatment of PLGA in this localization. Radiotherapy may be administered to treat this malignancy; however, in radiosensitive individuals, it is associated with a risk of severe radiotherapy-induced toxicity. METHODS:We present a case of a 73-year-old woman with locally advanced polymorphous low-grade adenocarcinoma of the nasopharynx who developed a severe adverse acute reaction to radiotherapy leading to treatment discontinuation. Despite intensive treatment, the patient died 40 days after RT initiation. Whole genome sequencing was performed using DNA from peripheral blood mononuclear cells in the search for variants that could explain such extreme toxicity. RESULTS:We identified a combination of pathogenic variants that may have contributed to the patient's reaction to radiation therapy, including predisposing variants in XRCC1, XRCC3, and LIG4. We also identified candidate variants, not previously described in this context, which could be associated with radiation toxicity based on plausible mechanisms. We discuss previous reports of this rare tumor from the literature and known contributors to radiation-induced toxicity. CONCLUSIONS:Genetic causes should be considered in cases of extreme radiosensitivity, especially when is not explained by clinical factors.

Increasing evidence suggests that the significance of the tumour immune microenvironment (TIME) for disease prognostication in invasive breast carcinoma is subtype-specific but equivalent studies in ductal carcinoma in situ (DCIS) are limited. The purpose of this paper is to review the existing data on immune cell composition in DCIS in relation to the clinicopathological features and molecular subtype of the lesion. We discuss the value of infiltration by various types of immune cells and the PD-1/PD-L1 axis as potential markers of the risk of recurrence. Analysis of the literature available in PubMed and Medline databases overwhelmingly supports an association between densities of infiltrating immune cells, traits of immune exhaustion, the foci of microinvasion, and overexpression of HER2. Moreover, in several studies, the density of immune infiltration was found to be predictive of local recurrence as either in situ or invasive cancer in HER2-positive or ER-negative DCIS. In light of the recently reported first randomized DCIS trial, relating recurrence risk with overexpression of HER2, we also include a closing paragraph compiling the latest mechanistic data on a functional link between HER2 and the density/composition of TIME in relation to its potential value in the prognostication of the risk of recurrence.

Neurovascular compression syndromes (NVC) are challenging disorders resulting from the compression of cranial nerves at the root entry/exit zone. Clinically, we can distinguish the following NVC conditions: trigeminal neuralgia, hemifacial spasm, and glossopharyngeal neuralgia. Also, rare cases of geniculate neuralgia and superior laryngeal neuralgia are reported. Other syndromes, e.g., disabling positional vertigo, arterial hypertension in the course of NVC at the CN IX-X REZ and torticollis, have insufficient clinical evidence for microvascular decompression. The exact pathomechanism leading to characteristic NVC-related symptoms remains unclear. Proposed etiologies have limited explanatory scope. Therefore, we have examined the underlying pathomechanisms stated in the medical literature. To achieve our goal, we systematically reviewed original English language papers available in Pubmed and Web of Science databases before 2 October 2021. We obtained 1694 papers after eliminating duplicates. Only 357 original papers potentially pertaining to the pathogenesis of NVC were enrolled in full-text assessment for eligibility. Of these, 63 were included in the final analysis. The systematic review suggests that the anatomical and/or hemodynamical changes described are insufficient to account for NVC-related symptoms by themselves. They must coexist with additional changes such as factors associated with the affected nerve (e.g., demyelination, REZ modeling, vasculature pathology), nucleus hyperexcitability, white and/or gray matter changes in the brain, or disturbances in ion channels. Moreover, the effects of inflammatory background, altered proteome, and biochemical parameters on symptomatic NVC cannot be ignored. Further studies are needed to gain better insight into NVC pathophysiology.