Search Results (1,900)

Background/Objectives: Myeloproliferative neoplasms are a group of clonal myeloid malignancies that affect bone marrow and include polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). PV is caused in most patients by the JAK2-V617F mutation and is characterized at the phenotypic level by overproduction and accumulation of red blood cells. PV is associated with significant morbidity, including risk of thrombotic events and of hematologic evolution (myelofibrotic or leukemic transformation) and reduced survival. In addition to the JAK2-V617F mutation, PV patients display additional molecular abnormalities. The aim of this study is to review recent studies investigating molecular abnormalities observed in PV. Methods: An extensive search of the most recent literature was performed, selecting and critically analyzing the most relevant studies. Results: The studies carried out in recent years have provided an extensive molecular analysis of PV, showing its heterogeneity, characterized in many patients by the presence of additional cytogenetic and gene mutations that contribute to the disease development and evolution. Conclusions: PV is a complex disease that needs to be carefully characterized at the molecular level at diagnosis, to be monitored in time to predict the risk for thrombotic complications and hematologic evolution and to receive an adequate treatment. Full article

Pancreatic adenocarcinoma (PDAC) remains one of the most lethal malignancies worldwide, with limited improvements in long-term survival despite significant progress in systemic therapy. This review focuses predominantly on pancreatic ductal adenocarcinoma (PDAC), the most common and best-studied pancreatic malignancy, while referencing other pancreatic neoplasms only where directly relevant to intrapancreatic fat biology. Obesity has emerged as a major modifiable risk factor for PDAC. In addition, increasing attention has focused on ectopic fat depots, particularly intrapancreatic fat, as potential mediators linking metabolic disease to pancreatic carcinogenesis. This narrative review summarizes the classification and epidemiology of PDAC, the relationship between obesity and pancreatic cancer risk, the biology of intrapancreatic fat, as well as putative mechanisms by which intrapancreatic fat may promote pancreatic carcinogenesis. In addition, we will review current diagnostic approaches, therapeutic and preventive considerations, and key unanswered questions for future research on the relevance of intrapancreatic fat deposits. Collectively, available evidence supports intrapancreatic fat as a biologically plausible and potential mediator of pancreatic cancer risk, warranting further prospective investigation. Full article

Carcinoma of unknown primary origin (CUP) involving the skeletal system is rare in dogs and may closely mimic primary bone neoplasia or multicentric lymphoma, creating substantial diagnostic challenges. A 15-year-old spayed female Jindo-mix dog was referred for rapidly progressive tetralimb lameness and inability to stand following a 2-week history of worsening forelimb lameness. Computed tomography revealed aggressive multifocal osteolytic and osteoproliferative lesions involving the pelvis, distal femur, and lumbar vertebra, accompanied by generalized lymphadenopathy, raising differential diagnoses including osteosarcoma, lymphoma, and metastatic neoplasia. Serial CT examinations demonstrated rapid progression of the dominant left ischial lesion, which was considered most consistent with a primary bone neoplasm and was surgically excised for definitive diagnosis. MRI failed to identify clinically significant neurologic disease. Histopathologic examination of a surgically excised ischial lesion favored poorly differentiated epithelial malignancy, although lymphoma could not initially be excluded. During hospitalization, serial thromboelastography (TEG) and coagulation testing demonstrated a predominantly hypercoagulable profile despite antithrombotic therapy. Following acute clinical deterioration, contrast-enhanced CT identified thrombosis involving the splenic vein and caudal vena cava, pulmonary thromboembolism (PTE), and concurrent multi-organ infarction. Cytology of an enlarged peripheral lymph node suggested metastatic carcinoma, and postmortem immunohistochemistry supported epithelial differentiation, and in the absence of an identifiable primary tumor despite comprehensive diagnostic evaluation, the case was clinically classified as carcinoma of unknown primary origin. This case highlights an unusual diagnostic presentation of skeletal CUP mimicking osteosarcoma or lymphoma and complicated by fatal cancer-associated thrombosis. Rapidly progressive multifocal bone lesions accompanied by hypercoagulability should prompt consideration of metastatic carcinoma, including carcinoma of unknown origin, even in the absence of an identifiable primary tumor. Full article

Neuroinflammation within the tumor microenvironment (TME) of central nervous system (CNS) neoplasms, particularly glioblastoma (GBM), is no longer viewed merely as a reactive phenomenon but rather as a major driver of gliomagenesis and malignant transformation. This process involves a shift from acute immune activation to a chronic, sterile state that reshapes the CNS borders and immune niches to favor tumor evasion. This narrative review provides a comprehensive mechanistically focused analysis of the mechanisms governing the inflammatory stroma in primary and metastatic brain neoplasms. It critically examines the ontogeny and transcriptomic profile of myeloid and glial populations, dismantling the binary M1/M2 polarization model in favor of a continuum of functional states determined by metabolic and oxygenation gradients. It also analyzes intracellular signaling cascades, the subversion of innate immunity sensors such as the cGAS-STING pathway, the epigenetic reprogramming of stromal cells, and the role of extracellular vesicles. The electrochemical integration of tumor cells into neuronal circuits via glutamatergic synapses and connexin 43 gap junction coupling is addressed in detail, defining the mitogenic impact of neuronal activity on the tumor. The inflammatory profiles of IDH-wildtype and IDH-mutant gliomas and of secondary brain metastases are contrasted. Finally, the correlates of functional neuroimaging, liquid biopsies, and resistance mechanisms to conventional therapies are analyzed, including the GIANT and SENIPERA clinical trials, CARv3-TEAM-E bivalent cellular immunotherapy preconditioned with the LDC + R regimen, and the accelerated approval of dordaviprone (Modeyso) in H3 K27M-mutant diffuse midline gliomas. Full article

Background: Oral cavity cancer is a clinically relevant subgroup of head and neck malignancies and is associated with substantial treatment burden and healthcare utilization. Hospital length of stay (LOS) is an important indicator of inpatient resource use and complexity of care, yet large multicenter data from Germany are limited. Methods: This retrospective multicenter analysis used anonymized inpatient administrative data from 49 German hospitals; eligible oral cavity cancer hospitalizations were contributed by 34 of these hospitals. Adult inpatient hospitalizations (≥18 years) with malignant neoplasms of the oral cavity, defined using ICD-10-GM codes C00–C06, recorded between January 1 2019 and 31 December 2024 were included. The primary outcome was hospital LOS in days. Multimorbidity was quantified using the van Walraven-weighted Elixhauser Comorbidity Score. Prolonged hospitalization was defined as LOS ≥ 7 days and LOS ≥ 14 days. Associations between demographic, clinical, and treatment-related variables and LOS were examined using multivariable Poisson regression models. Because overdispersion was present, a negative binomial mixed model was additionally fitted as a sensitivity analysis. To account for inter-hospital variability, hospital was included as a random intercept in all multivariable models. Associations with prolonged LOS were analyzed using multivariable logistic regression models. All analyses were performed at the hospitalization level. Results: A total of 3957 inpatient hospitalizations for oral cavity cancer were included. Mean age was 65.6 years, and 66.2% of hospitalizations involved male patients. The median LOS was 6 days (interquartile range [IQR] 3–13; mean 10.2 days, standard deviation 11.8). Overall, 49.4% of hospitalizations had an LOS ≥ 7 days and 23.5% had an LOS ≥ 14 days. Older age, particularly >80 years, and higher comorbidity burden were associated with longer LOS (adjusted Poisson rate ratio [RR] for age > 80 years 1.17, 95% CI 1.13–1.21; high comorbidity burden RR 1.58, 95% CI 1.54–1.63). Several treatment-related variables, including surgical procedures in the oral and facial region, lymphatic system operations, blood transfusions, and complex intensive care treatment, were associated with prolonged hospitalization (e.g., blood transfusion RR 1.80, 95% CI 1.76–1.85; complex intensive care RR 1.70, 95% CI 1.65–1.75). Chemotherapy-related hospitalizations were associated with shorter LOS. Conclusions: LOS varied substantially across inpatient hospitalizations for oral cavity cancer in Germany. Older age, higher comorbidity burden, and markers of more complex inpatient treatment were associated with extended hospital stay. These findings may help identify hospitalizations at increased risk of prolonged LOS and inform inpatient planning and resource allocation. Full article

Background: Prostatic adenoid cystic carcinoma/basal cell carcinoma (ACC/BCC) has been reclassified under the fifth edition of the World Health Organization’s classification of tumors, distinguishing it from basal cell cancer of the skin. This malignant neoplasm exhibits distinct biological characteristics that differ from those of typical prostatic adenocarcinoma. However, optimal clinical management of prostatic ACC/BCC remains uncertain because of its rarity and the limited evidence available. Methods: This study retrospectively reviews the treatment course of a 62-year-old male patient presenting with more than six months of dysuria. Initial management included transurethral plasmakinetic resection of the prostate (TUPKP), followed by robot-assisted radical prostatectomy and bilateral pelvic lymph node dissection. Postoperative fluorescence in situ hybridization (FISH) demonstrated MYB rearrangement, providing molecular support for the pathological classification of prostatic ACC/BCC and facilitating diagnostic reclassification. Results: Pathological examination of the TUPKP specimen indicated poorly differentiated carcinoma, with findings consistent with prostatic ACC/BCC. Preoperative imaging showed an irregular soft-tissue lesion in the prostate/bladder neck region, without definite pelvic lymph node or distant organ metastasis. Histological analysis demonstrated cribriform structures and perineural invasion, while immunohistochemistry supported a basal cell phenotype; together with these findings, detection of MYB rearrangement via FISH supported reclassification of the tumor as prostatic ACC/BCC. Following radical surgery, adjuvant paclitaxel plus carboplatin was administered as an individualized empirical treatment in the absence of an established disease-specific standard. The patient completed six cycles of adjuvant chemotherapy and remained clinically stable during follow-up, with no radiological evidence of recurrence at the latest evaluation. Conclusions: This case highlights the diagnostic challenges of prostatic ACC/BCC and underscores the value of integrating molecular findings with histopathological and immunohistochemical features to support accurate tumor classification and individualized clinical management. MYB rearrangement may provide useful molecular support for diagnosis and classification; however, its biological and potential therapeutic significance in prostatic ACC/BCC requires further investigation in larger cohorts. Full article

Background: Vulvar syringoma is a rare benign adnexal neoplasm originating from eccrine sweat ducts. Although syringomas most commonly occur in the periorbital region, vulvar involvement is uncommon and frequently underrecognized. Due to its nonspecific clinical appearance, vulvar syringoma may mimic more common vulvar conditions, resulting in delayed diagnosis and repeated ineffective treatments. Case Presentation: A 41-year-old multiparous woman presented with a several-year history of recurrent pruritic papular lesions involving the right vulva. The lesions were repeatedly diagnosed as condyloma acuminata and treated with topical imiquimod, cryotherapy, carbon dioxide laser ablation, and local excision, without sustained improvement. Persistent symptoms and recurrence prompted repeat surgical excision. Histopathological examination revealed a well-circumscribed dermal lesion composed of multiple small eccrine ducts, cysts, and epithelial cords embedded within a dense sclerotic fibrotic stroma. The ducts were lined by two layers of bland cuboidal epithelial cells and demonstrated characteristic comma-shaped and tadpole-like configurations, confirming the diagnosis of vulvar syringoma. No cytologic atypia, increased mitotic activity, dysplasia, or malignancy was identified. The postoperative course was uncomplicated, with satisfactory wound healing and symptomatic improvement during follow-up. Conclusions: Vulvar syringoma should be considered in the differential diagnosis of persistent or treatment-resistant vulvar papules, particularly when lesions recur despite conventional therapy for presumed condyloma acuminata or other benign vulvar disorders. Early biopsy and histopathological evaluation remain essential for establishing an accurate diagnosis, preventing unnecessary interventions, and guiding appropriate management. Full article

Purpose: Cutaneous melanoma (CM) and uveal melanoma (UM) derive from melanocytes. Nevertheless, they differ in genetic drivers and progression pathways. Previous research examining the relationship between CM and UM has been constrained by small cohorts and the rarity of UM. The aim of this study was to determine whether UM occurs more frequently in patients with a CM compared to matched patients with keratinocyte carcinoma (KC, squamous or basal cell carcinoma of the skin). Patients with KC were selected as the control to account for the excess risk due to sun exposure and access to healthcare. Methods: We performed a large, multicenter retrospective cohort study using TriNetX, a global health research network and real-world data platform. Cohort 1 had CM or melanoma in situ (MIS) and no history of KC. Cohort 2 had KC and no history of CM or MIS. The main outcome was the incidence of malignant neoplasms of the choroid or ciliary body over a 5-year follow-up, including diagnoses recorded before the index skin cancer. Patients who had metastatic disease were excluded to remove potential misidentifications of choroidal metastasis as UM. A 1:1 propensity score matching (PSM) was used to match demographic and clinical characteristics. Odds ratios (ORs) with 95% confidence intervals (CIs) and corresponding two-sided p-values were used to compare categorical outcomes. Ophthalmologic follow-up was evaluated to rule out surveillance bias. Results: The CM cohort included 57,352 patients. The KC cohort included 137,083 patients. After PSM each cohort included 52,860 patients. UM occurred in 53 CM patients (0.1%) compared with 13 KC patients (0.02%). This corresponds to an OR of 4.08 (95% CI [2.22, 7.49]; p < 0.001). UM diagnosis preceded CM in 70% of patients with both diagnoses. The association persisted in a sensitivity analysis after excluding patients with UM documented before CM (HR 14.32; 95% CI 7.96–25.76). Conclusions: Cutaneous melanoma is associated with a significantly higher risk of UM compared to KC. These findings suggest a link between cutaneous and uveal melanoma and may offer a possible role for ophthalmic surveillance in CM patients and dermatology surveillance in UM patients. Full article

Introduction: Cutaneous adnexal tumours are a heterogeneous group of tumours arising from the adnexal structures of the skin. These include follicular, eccrine, apocrine, and sebaceous lineages. These entities display a wide morphological spectrum with overlapping histopathological features, posing significant diagnostic challenges. This study aims to provide a detailed analysis of these neoplasms. Materials and Methods: We conducted a retrospective observational study including patients with primary cutaneous adnexal tumours diagnosed in excisional specimens at our centre between 2018 and 2025. Results: A total of 82 primary cutaneous adnexal tumours were analysed in patients aged 24–90 years. A female predominance was observed (62.19%), with a mean age of 56 years among female patients and 60 years among male patients. The head and neck region was the most frequently affected site (70.73%), followed by the upper limb, thorax, and lower limb. Sweat gland tumours markedly outnumbered follicular tumours (79.27% vs. 20.73%), with hidrocystomas and spiradenomas representing the most common benign lesions. Most tumours were benign (91.46%), while atypical spiradenoma (3.66%) and malignant tumours such as eccrine porocarcinoma, trichilemmal carcinoma, and basal cell carcinoma arising in association with trichoblastoma (4.88%) were rare but clinically significant findings. Surgical specimen volumes varied significantly by anatomical site, with scalp and limb lesions reaching the largest dimensions. Margin status differed according to biological behaviour, with malignant tumours showing greater proportion of close or infiltrated margins, while margins were non-assessable in all three atypical cases. Immunohistochemical evaluation supported diagnostic confirmation in atypical and malignant cases. Conclusions: Our findings highlight the broad clinical and morphological spectrum of cutaneous adnexal tumours and contribute data from an Eastern European cohort. This study adds regional data to the limited literature on the clinicopathological distribution of cutaneous adnexal tumours and emphasises rare, atypical, and malignant diagnostic scenarios. Full article

Primary hepatic perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms that involve both melanocytic and smooth muscle differentiation. Primary hepatic PEComas remain a challenging condition for radiologists, pathologists, and surgeons. Our review provides an updated, clinically oriented synthesis of the available evidence on primary hepatic PEComas, integrating recent developments in diagnosis, imaging, histopathology, molecular biology, prognostic stratification, surgical and systemic treatment, and long-term surveillance. Although the majority of hepatic PEComas generally exhibit a slowly progressive clinical course, a small subgroup of them is characterized by aggressive biological behavior with an increased risk of recurrence, distant metastases, and disease-related mortality. As PEComas can resemble other hypervascular liver lesions such as hepatocellular carcinoma and hemangioma, preoperative diagnosis based on imaging techniques can be very difficult. Furthermore, the final diagnosis is usually made by histopathological examination of the surgical specimen, which reports characteristic expression of both smooth muscle markers and melanocytic markers such as HMB-45 and Melan-A. Although mTOR inhibitors have demonstrated antitumor activity in advanced PEComas, evidence specifically supporting their use in primary hepatic PEComas remains limited. Prognostic stratification, treatment selection, and long-term follow-up of primary hepatic PEComa remain major challenges. Further multicenter studies are needed to improve risk assessment and develop evidence-based guidelines for the management of these rare primary liver neoplasms. Full article

Background/Objectives: In the operating room, surgical staff are exposed to inhalation of smoke from the combustion of tissues when using electrocautery. By introducing HIPEC/peritonectomy in the treatment of malignant neoplasms of the peritoneum, exposure to smoke is significantly increased. To adequately perform this procedure, high-power monopolar cautery is used. The aim of this study was to assess carbon monoxide exposure associated with surgical smoke generated during peritonectomy procedures and to compare it with exposure during standard colorectal resections. Methods: In this prospective observational study, a total of 360 blood samples were collected and analyzed from surgeons participating in surgical procedures. The study cohort was divided into two groups: the HIPEC/peritonectomy group and the standard resection group. Blood samples were obtained from three surgeons who participated in a total of 30 procedures, comprising 15 HIPEC/peritonectomy procedures and 15 standard resection procedures. Samples were collected at the start of the intervention, at the 20th and 40th minutes, and at the end of procedures. Results: COHb values increased over time, and levels were higher in the peritonectomy group. An increase in MetHb levels was seen in HIPEC/peritonectomy, but not in the standard colorectal resection group. The observed values did not lead to symptoms of acute CO poisoning. Conclusions: The results suggest that the use of electrocautery increases carboxyhemoglobin (COHb) and methemoglobin (MetHb) levels in surgical staff; however, these increases did not reach clinical significance. The long-term health consequences of repeated exposure to surgical smoke, as well as the effectiveness of personal protective equipment and smoke evacuation systems in reducing this exposure, should be investigated in future studies. Full article

Background/Objectives: Borderline ovarian tumours (BOTs) are distinct epithelial neoplasms with excellent survival but variable recurrence, including late relapse and occasional malignant transformation. Follow-up strategies remain inconsistent internationally, with no standardised, risk-adapted framework. We aimed to synthesise the evidence on BOT recurrence patterns, risk factors and surveillance strategies, and to propose a structured, risk-adapted surveillance framework. Methods: This is a narrative expert synthesis rather than a systematic review. Three evidence sources were combined: our previously published comprehensive review of BOTs, our recent meta-analysis of recurrence and malignant transformation, and an appraisal of contemporary international guidelines. Clinicopathological and surgical determinants of recurrence were then mapped onto the available follow-up tools through a three-step approach, and the resulting risk strata, surveillance intervals and total follow-up duration were agreed on by consensus within a single tertiary gynaecological oncology centre (the “Barts Framework”). Results: Recurrence occurs in 3–10% of patients, with up to one-third arising beyond five years. Key predictors include fertility-sparing surgery (particularly cystectomy), incomplete staging, advanced stage, residual disease, and adverse histological features such as micropapillary/cribriform architecture and invasive implants. Three targets for surveillance were identified: early detection of recurrence, detection of malignant transformation, and optimisation of fertility. Transvaginal ultrasound emerged as the cornerstone modality, with cross-sectional imaging and tumour markers applied selectively. Four risk strata were derived, each specifying follow-up intensity, modality, total duration and care setting. Low-risk patients can be managed in decentralised settings (gynaecological units), whereas high-risk groups warrant specialist oversight (gynaecological oncology centres). Patient-initiated follow-up is incorporated to minimise unnecessary interventions. Conclusions: This risk-adapted approach provides a scalable framework to standardise BOT surveillance whilst reducing overuse and maintaining oncological safety. The framework is consensus-based and single-institution in origin, and prospective external validation with long-term outcome data is required before wider adoption. Integration of molecular stratification and artificial-intelligence-assisted imaging represents a key future direction. Full article

While pathogenic germline CHEK2 variants are known to increase cancer risk, there is currently insufficient evidence regarding the precise risk of developing malignant neoplasms associated with specific missense variants or variants of uncertain significance. As a result, no clear clinical guidelines exist regarding consultation, monitoring and specific treatment options for those patients. For the first time in Russia, clinical data and whole-genome sequencing (WGS) results were analyzed for 3150 patients with cancer and suspected hereditary cancer syndromes (HCS) and 5163 healthy individuals. This dataset formed the basis for assessing the role of germline CHEK2 variants in the development of different cancer types. The chromosomal coordinates and coding sequence coordinates are given in accordance with the GRCh38 (hg38) genome assembly and the NM_007194.4 transcript. Pathogenic (P) and likely pathogenic (LP) variants of CHEK2 significantly increased the risk of breast cancer (OR = 2.015 [95% CI: 1.27–3.21]; p = 0.0031), but the association with colorectal cancer was not statistically significant (OR = 1.354 [95% CI: 0.42–4.42]; p = 0.616). A moderate increase in cancer risk was identified for the c.1100del variant (OR = 2.263 [95% CI: 1.19–4.32]; p = 0.0132) and for the common P/LP variants c.1100del, c.444+1G>A and c.433C>T (OR = 2.219 [95% CI: 1.40–3.51]; p = 0.0007). Notably, our study confirmed that CHEK2 c.470T>C (p.Ile157Thr) is the most common variant in the patient group, identified in 3.8% of cases (120/3150), compared with 3.0% in the control group (155/5163). Although the association between the most common CHEK2 variant c.470T>C and cancer risk reached nominal statistical significance (OR = 1.279 [95% CI: 1.00–1.63]; p = 0.0463), the effect size was minimal, suggesting that the contribution of this variant to hereditary cancer risk in the Russian population is modest. Additional studies are required before this variant can be definitively excluded from clinical interpretation. Full article

Background: Cancer is one of the leading causes of morbidity and mortality worldwide, and epidemiological projections indicate that its incidence will continue to increase. Gastrointestinal cancers are among the most frequently diagnosed malignant neoplasms. Quality of life is a key component of oncology care and is significantly influenced by nutritional status and dietary habits. Methods: The study included 52 adult patients diagnosed with gastrointestinal cancer. Data were collected using an anonymous questionnaire based on the QEB (Questionnaire of Eating Behaviour) and WHOQOL-BREF (World Health Organization Quality of Life—BREF) instruments, supplemented with questions regarding changes in dietary habits and the use of dietary counseling following diagnosis. Nutritional knowledge, dietary habits, and quality of life across four domains (physical, psychological, social, and environmental) were assessed. Statistical analysis was performed using descriptive statistics and appropriate tests of statistical significance. Results: Cancers of the colon and rectum—reported either as unspecified colorectal cancer or as separately specified colon or rectal cancer—together accounted for the largest share of diagnoses (26 diagnoses, representing 44.8% of the 58 total reported diagnoses). Quality-of-life assessment revealed the lowest scores in the physical domain and the highest scores in the social domain. The youngest participants achieved the highest scores in the psychological domain, whereas the lowest scores across all domains were observed among individuals aged over 60 years. Following diagnosis, 63.5% of participants reported reviewing and modifying their dietary habits; however, the majority had not received dietary counseling. Women reported higher fruit and vegetable consumption than men, while higher educational attainment was associated with greater self-assessed nutritional knowledge. Conclusions: Among patients with gastrointestinal cancers surveyed in this study, the physical domain of quality of life had the lowest WHOQOL-BREF score. Most participants reported modifying their dietary habits after diagnosis, although most had not received formal dietary counseling. Higher educational attainment was associated with higher self-assessed nutritional knowledge. Given the small convenience sample and cross-sectional design, these findings should be considered exploratory. Full article