FISH and FICTION in Lymphoma Research.

Fluorescence in situ hybridization (FISH) is a powerful and robust technique allowing the visualization of target sequences like genes in interphase nuclei. It is widely used in routine diagnostics to identify cancer-specific aberrations including lymphoma-associated translocations or gene copy number changes in single tumor cells. By combining FISH with immunophenotyping-a technique called fluorescence immunophenotyping and interphase cytogenetic as a tool for investigation of neoplasia (FICTION)-it is moreover possible to identify a cell population of interest. Here we describe standard protocols for FISH and FICTION as used in our laboratories in diagnosis and research.

Is annual screening by fecal immunochemical test necessary after a recent colonoscopy?

Objective: The population-based colorectal cancer screening guidelines in Japan recommend an annual fecal immunochemical test (FIT). However, there is no consensus on the need for annual FIT screening for patients who recently performed a total colonoscopy (TCS). Therefore, we evaluated the repeated TCS results for patients with positive FIT after a recent TCS to assess the necessity of an annual FIT. Methods: We reviewed patients with positive FIT in opportunistic screening from April 2017 to March 2022. The patients were divided into two groups: those who had undergone TCS within the previous 5 years (previous TCS group) and those who had not (non-previous TCS group). We compared the detection rates of advanced neoplasia and colorectal cancer between the two groups. Results: Of 671 patients, 151 had received TCS within 5 years and 520 had not. The detection rates of advanced neoplasia in the previous TCS and non-previous TCS groups were 4.6% and 12.1%, respectively (p < 0.01), and the colorectal cancer detection rates were 0.7% and 1.5%, respectively (no significant difference). The adenoma detection rates were 33.8% in the previous TCS group and 40.0% in the non-previous TCS group (no significant difference). Conclusions: Only a few patients were diagnosed with advanced neoplasia among the patients with FIT positive after a recent TCS. For patients with adenomatous lesions on previous TCS, repeated TCS should be performed according to the surveillance program without an annual FIT. The need for an annual FIT for patients without adenomatous lesions on previous TCS should be prospectively assessed in the future.

Steroid lifting method during endoscopic submucosal dissection: A novel strategy for stricture prevention.

A 73-year-old male patient was referred to us with a long Barrett's esophagus (BE). He had a history of pulmonary embolism under anticoagulant therapy. Esophagogastroduodenoscopy showed a C8M9 BE with no macroscopic lesions. Random biopsies from the BE revealed multifocal high-grade dysplasia. The case was discussed in a multidisciplinary team conference and the decision for full resection of BE with endoscopic submucosal dissection (ESD) was made. Considering the large ESD resection and the high risk of stricture, we developed a novel preventive technique: the "steroid lifting method" for submucosal injection during ESD. Complete circumferential ESD with en bloc resection was performed using the "steroid lifting method", without adverse events. Oral liquids were initiated on day 1 and the patient was discharged on day 4. Oral prednisolone (30 mg per day) was started and tapered for a total of 6 weeks. The pathological examination confirmed multifocal high-grade dysplasia, with radical and curative resection. The patient had neither stricture, dysphagia nor recurrence of Barrett's mucosa at the 2, 6, 12, and 24-month follow-up. International guidelines recommend oral prednisolone and triamcinolone injection to prevent stricture formation in large ESD of esophageal squamous cell carcinoma. However, there is no solid data on BE ESD. The risk factors for stricture formation and the optimal preventive management after large BE ESD is not known. The "steroid lifting method" might be an option in this context. Large prospective studies addressing stricture formation and preventive measures on BE ESD are necessary.

A Random Survival Forest Model for Predicting Residual and Recurrent High-Grade Cervical Intraepithelial Neoplasia in Premenopausal Women.

Purpose: Loop electrosurgical excision procedure (LEEP) for high-grade cervical intraepithelial neoplasia (CIN) carries significant risks of recurrence and persistence. This study compares the efficacy of a random survival forest (RSF) model with that of a conventional Cox regression model for predicting residual and recurrent high-grade CIN in premenopausal women after LEEP. Methods: Data from 458 premenopausal women treated for CIN2/3 at our hospital between 2016 and 2020 were analyzed. The RSF model incorporated demographic, pathological, and treatment-related variables. Feature selection utilizing LASSO and three other algorithms was performed to enhance the RSF model, which was further compared to a Cox regression model. Model performance was assessed using area under the curve (AUC), out-of-bag (OOB) error rates, and SHAP values to interpret predictor importance. Results: The RSF model showed superior performance compared to the Cox regression model, with AUC values of 0.767-0.901 and peak predictive performance at 36 months post-LEEP. In contrast, the highest AUC achieved by Cox regression was 0.880. The RSF model also exhibited relatively lower OOB error rates, indicating better generalizability. Moreover, SHAP value analysis identified margin status and CIN severity as the most prominent predictors that directly affected risk predictions. Lastly, an online tool providing real-time predictions in clinical settings was successfully implemented using the RSF model. Conclusion: The RSF model outperformed the traditional Cox regression model in predicting residual and recurrent high-grade CIN risks post-LEEP. This model may be a more accurate clinical tool that facilitates improved personalized care and early interventions in gynecological oncology.

Use of a PD-1 checkpoint inhibitor in a patient with ultra-high-risk gestational trophoblastic neoplasia and gastrointestinal metastases.

Gestational trophoblastic neoplasia (GTN) are rare diseases that are typically chemo-responsive. While the majority of patients are cured with chemotherapy alone, a small portion of cases are fatal due to chemotherapy resistance. Risk factors for treatment failure are liver and brain metastases, extensive disease, and chemo-refractory disease. Gastrointestinal (GI) metastases are extremely rare and indicate a poor prognosis. Treatment with immunotherapy has been studied and included in treatment guidelines for high-risk and chemotherapy-resistant GTN. This case reports on the early use of programmed cell death protein 1 (PD-1) inhibitor in combination with systemic chemotherapy in a patient with ultra-high risk GTN with GI metastases.

Comparing the performance of DeoxyriboNucleic Acid methylation analysis and cytology for detecting cervical (pre)cancer in women with high-risk human papillomavirus-positive status in a gynecologic outpatient population.

BACKGROUND: Primary screening for high-risk human papillomavirus (hrHPV) with cytological triage for women with non-16/18 hrHPV-positive status has become popular in China. However, cytology relies on the subjective judgment of pathologists, leading to inconsistent clinical performance. METHODS: A total of 657 hrHPV-positive women aged 25-64 years were enrolled in this cross-sectional study. All participants underwent colposcopic biopsy after cytology triage, with cytology residual specimens undergoing DNA methylation testing. CIN2+ and CIN3+ sensitivity and specificity were compared between the different triage strategies (n=487): PAX1 methylation (PAX1m) , Glycophorin C methylation (GYPCm), cytology, and combinations between them or with HPV16/18. RESULTS: The area under the receiver operating characteristic curves (AUCs) for PAX1m and GYPCm in detecting CIN2 or worse (CIN2+) were 0.867 (95% confidence interval [CI]: 0.796-0.937) and 0.873 (95% CI: 0.808-0.938), respectively. The sensitivities of PAX1m and GYPCm were consistent with those of cytology for both CIN2+ and CIN3+ detection. The relative specificities of PAX1m and GYPCm for CIN2+ detection compared to cytology were 2.83 (95% CI: 2.33-2.45) and 3.09 (95% CI: 2.40-3.98), respectively. The relative specificities of combining HPV 16/18 with PAX1m and GYPCm for CIN2+ detection compared to cytology were 3.38 (95% CI: 2.96-3.86) and 3.67 (95% CI: 3.15-4.27), respectively. Compared to low levels of DNA methylation, high levels of PAX1m and GYPCm resulted in odd ratios (ORs) of 57.66 (95% CI: 13.57-409.12, p < 0.001) and 23.87 (95% CI: 6.49-115.42, p < 0.001) for CIN3+, adjusted for HPV 16/18 and cytology results. CONCLUSIONS: PAX1m and GYPCm demonstrated superior ability to identify cervical precancerous lesions and cervical cancer, with AUC values exceeding 0.85. For detecting CIN2+/CIN3+ in women with hrHPV-positive status, DNA methylation (combined with HPV 16/18) showed higher specificity than cytology (combined with HPV 16/18) and is a potential molecular biomarker for detecting cervical (pre)cancer.

Microstructure and development of the dermal ossicles of Antarctopelta oliveroi (Dinosauria, Ankylosauria): A complex morphogenetic system deciphered through three-dimensional X-ray microtomography.

Ankylosaurs were a group of heavily armored non-avian dinosaurs (Dinosauria, Ankylosauria), represented by a relatively abundant fossil record from the Cretaceous of North and South America. Their dermal skeleton was characterized by large osteoderms whose development and functional role have been largely investigated. However, interstitial small ossicles, forming between these osteoderms, have been far more overlooked and it remains unknown whether they were formed through the ossification of a preexisting fibrous matrix of connective tissue (i.e., metaplasia) or by a cell-induced differentiation of new fiber bundles followed by mineralization (i.e., neoplasia sensu (Zeitschrift für Wissenschaftliche Zoologie, 1858, 9, 147)). Here, we propose a hypothesis on the developmental origin of these small ossicles in the ankylosaurian Antarctopelta oliveroi using light microcopy, scanning electron microscopy and three-dimensional virtual histology through propagation phase-contrast synchrotron radiation micro-computed tomography (PPC-SRµCT). Ossicles are located in the dermis. They are composed of two layers: (1) a thin external layer, and (2) a thick basal plate, composed of collagen fiber bundles, which forms the main part of the ossicle. The external layer is made of a smooth, vitreous mineralized tissue that does not look like bone. The basal plate, however, is of osseous origin. In this basal plate, the collagen fiber bundles are organized in two orthogonal systems: one horizontal-observable in cross-sections-and one vertical-observable in the primary plane of sections sensu (Journal of Vertebrate Paleontology, 2004, 24, 874). The horizontal system is itself composed of successive layers of collagen fiber bundles arranged into an orthogonal plywood-like structure. The bundles of the vertical system radiate from the center of the ossicle at the level of the transition between the external layer and the basal plate and run towards the periphery of the basal plate. Their thickness increases from the center of the ossicle towards its periphery. Numerous bundles of the vertical system form thin threads that interweave and penetrate within the thick bundles of the horizontal system. Our new data suggest that the ossicles were at least partially formed by metaplasia, that is, through the ossification of a preexisting fibrous matrix of connective tissue. This process was probably supplemented by a cell-induced differentiation of new fiber bundles laid down prior to their incorporation into the fibrous system and its mineralization. This process looks more akin to neoplasia sensu (Zeitschrift für Wissenschaftliche Zoologie, 1858, 9, 147) than to metaplasia. Consequently, metaplastic and neoplastic processes may coexist in these ossicles with a possible differential expression during ontogeny.

T2WI and ADC radiomics combined with a nomogram based on clinicopathologic features to quantitatively predict microsatellite instability in colorectal cancer.

RATIONALE AND OBJECTIVES: Microsatellite instability (MSI) stratification can guide the clinical management of patients with colorectal cancer (CRC). This study aimed to establish a radiomics model for predicting the MSI status of patients with CRC before treatment. MATERIALS AND METHODS: This retrospective study was performed on 366 patients diagnosed with CRC who underwent preoperative magnetic resonance imaging (MRI) and immunohistochemical staining between February 2016 and September 2023. The participants were divided randomly into training and testing cohorts in a 7:3 ratio. The tumor volume of interest (VOI) was manually delineated on T2-weighted imaging (T2WI) and apparent diffusion coefficient (ADC) sequences using 3D Slicer software, and radiomics features were extracted. Feature selection was performed using the least absolute shrinkage and selection operator method. A radiomics nomogram was developed using multiple logistic regression, and the predictive performance of the models was evaluated and compared using receiver operating characteristic curves. The calibration curve, clinical decision curve analysis (DCA) and clinical impact curve (CIC) were used to evaluate the clinical application value of the model. RESULTS: The radiomics normogram combined with history of chronic enteritis, tumor location, MR-reported inflammatory response, D2-40, carcinoembryonic antigen, tumor protein 53, and monocyte was an excellent predictive tool. The area under the curve for the training and testing cohorts were 0.927 and 0.984, respectively. The DCA and CIC demonstrated favorable clinical application and net benefit. CONCLUSIONS: A radiomics nomogram based on T2WI and ADC sequences and clinicopathologic features can effectively and noninvasively predict the MSI status in CRC. This approach helps clinicians in stratifying CRC patients and making clinical decisions for personalized treatment.

Blastic Plasmacytoid Dendritic Cell Neoplasm: A Single-Center Experience. Clinical Characterization, Mutational Landscape, and Clinical Outcome of Patients Undergoing Hematopoietic Stem Cell Transplantation Intensive Therapy.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematodermic neoplasm usually involving the skin. In this retrospective case series, 10 cases of BPDCN were identified, 90% of which had skin involvement and exhibited predominantly violaceous nodules and/or bruise-like plaques. Skin lesions showed diffuse or nodular dermal-based infiltrates of intermediate sized blasts with a grenz zone. Tumor immunophenotyping was CD4(+), CD56(+), CD123(+) and CD303(+). The most frequently mutated genes according to targeted next-generation sequencing were TET2 (3/7) and NRAS (2/7). Multiagent chemotherapy (CT) was administered as first-line therapy, and a total of 5 patients underwent allogenic hematopoietic stem cell transplantation (allo-HSCT). Better outcomes were observed in younger patients and those treated with acute lymphoblastic leukemia (ALL)-like CT followed by allo-HSCT. This study shows the clinical range of cutaneous lesions of BPDCN. Despite the absence of a gold standard therapy, patients treated with myeloablative intensive regimens and allo-HSCT seem to have a more favorable prognosis.

Early colorectal cancer diagnosis: A novel methylated stool DNA model enhanced the diagnostic efficiency.

BACKGROUND: Methylated stool DNA (sDNA) is a reliable noninvasive biomarker for early colorectal cancer (CRC) diagnosis. However, there are barely any diagnostic panels that can achieve both a sensitivity and specificity exceeding 90% simultaneously. OBJECTIVE: We aimed to identify a novel methylated sDNA panel and model for the early diagnosis of CRC. METHODS: We conducted methyl-CpG binding domain isolated genome sequencing (MiGS) on CpG island methylation phenotype (CIMP)-positive (n = 3) and CIMP-negative CRC tissues (n = 3) and their corresponding normal adjacent tissues. Subsequently, by utilizing both the aforementioned data and public datasets, we identified a set of promising methylated sDNA markers for CRC. Next, we validated 5 of these genes using pyrosequencing in CRC patients (n = 31). Then, we developed a combined diagnostic model (CDM) for CRC based on the methylation status of PRDM12, FOXE1, and SDC2 by a Training cohort (n = 231). Finally, the performance of CDM was evaluated in an independent multicenter Validation cohort (n = 800). RESULTS: A total of 1062 participants were included in this study. The area under the curve (AUC) of the CDM was 0.979 (95% CI: 0.960-0.997), and the optimal sensitivity and specificity were 97.35% and 99.05%, respectively, in the training cohort (n = 231). In the independent validation cohort (n = 800), the AUC was 0.950 (95% CI: 0.927-0.973), along with the optimal sensitivity of 92.75% and specificity of 97.21%. When CRC and advanced adenoma (AAD) were used as diagnostic targets, the model AUC was 0.945 (95% CI: 0.922-0.969), with an optimal sensitivity of 91.89% and a specificity of 95.21%. The model sensitivity for nonadvanced adenoma patients was 68.66%. CONCLUSION: The sDNA diagnostic model CDM, developed from both CIMP-P and CIMP-N, exhibited exceptional performance in CRC and could serve as a potential alternative strategy for CRC screening.

Ultrasound-guided percutaneous biopsy for challenging perihilar focal liver lesions: diagnostic accuracy and safety assessment.

PURPOSE: In cases of perihilar focal liver lesions, distinguishing between benign strictures and malignancies is critical to prevent unnecessary surgery. Although the use of contrast-enhanced CT or MRI in combination with clinical and laboratory findings can aid in diagnosis, histologic examination is often necessary. Histologic specimens can be obtained through various techniques, including ERCP-guided brush cytology or intraductal biopsy, cholangioscopy-directed biopsy or endoscopic ultrasound (EUS). However, these methods have been associated with suboptimal sensitivity and specificity, sometimes leading to inconclusive results. Therefore, ultrasound-guided percutaneous biopsy (US-guided PB) may play a crucial role, but data is lacking for perihilar lesions. The objective of our study was to assess the technical feasibility and safety of US-guided PB for perihilar lesions. METHODS: We included 20 consecutive patients who underwent US-guided PB of perihilar liver lesions that were not suitable for surgery between June 2018 and October 2023. RESULTS: All samples were obtained using a Menghini needle 20G and were adequate for histological examination, with a mean diameter of 12.3 mm (range 3-40 mm). Out of the 20 patients, 11 were diagnosed with malignancy while the remaining 9 had inflammatory or fibrotic tissue samples. No adverse events related to the procedure were reported. CONCLUSION: US-guided PB of perihilar liver lesions is a valuable and safe diagnostic approach to consider for patients who are not suitable for surgery.

Population-based risk factors and urogenital comorbidities associated with genital herpes: A nationwide study of 4 million women.

Objectives: To explore the population-based risk factors for genital herpes in women and examine whether genital herpes occurs at higher rates in women diagnosed with cervical neoplasia and common urogenital infections. Methods: An open cohort study consisting of 4,097,075 women ≥15 years of age in Sweden (2002-2018). The outcome was genital herpes diagnosis. The predictor variables were sociodemographic factors (age, educational level, family income, region of residence, and country of origin) and urogenital comorbidities (cervical carcinoma neoplasia, cystitis, vaginosis, and vulvovaginitis) and parity. National registers and primary health care data were used. Cox regression models were used to estimate hazard ratios with 95% confidence intervals. Interactions tests were conducted. Results: A total of 15,727 women received a genital herpes diagnosis in inpatient and outpatient specialist care settings during the study period. Sociodemographic factors and parity were associated with genital herpes. than women without these comorbidities. Conclusions: Genital herpes occurs with higher rates in women of high family income, young age, Swedish origin, co-occurrence of urogenital comorbidities, and nulliparity. The findings can be used by clinicians when encountering women with these risk factors.

When Do Tumours Develop? Neoplastic Processes Across Different Timescales: Age, Season and Round the Circadian Clock.

While it is recognised that most, if not all, multicellular organisms harbour neoplastic processes within their bodies, the timing of when these undesirable cell proliferations are most likely to occur and progress throughout the organism's lifetime remains only partially documented. Due to the different mechanisms implicated in tumourigenesis, it is highly unlikely that this probability remains constant at all times and stages of life. In this article, we summarise what is known about this variation, considering the roles of age, season and circadian rhythm. While most studies requiring that level of detail be done on humans, we also review available evidence in other animal species. For each of these timescales, we identify mechanisms or biological functions shaping the variation. When possible, we show that evolutionary processes likely played a role, either directly to regulate the cancer risk or indirectly through trade-offs. We find that neoplastic risk varies with age in a more complex way than predicted by early epidemiological models: rather than resulting from mutations alone, tumour development is dictated by tissue- and age-specific processes. Similarly, the seasonal cycle can be associated with risk variation in some species with life-history events such as sexual competition or mating being timed according to the season. Lastly, we show that the circadian cycle influences tumourigenesis in physiological, pathological and therapeutic contexts. We also highlight two biological functions at the core of these variations across our three timescales: immunity and metabolism. Finally, we show that our understanding of the entanglement between tumourigenic processes and biological cycles is constrained by the limited number of species for which we have extensive data. Improving our knowledge of the periods of vulnerability to the onset and/or progression of (malignant) tumours is a key issue that deserves further investigation, as it is key to successful cancer prevention strategies.

Open versus mini-invasive partial and radical nephrectomy complications: results from the French national health database.

BACKGROUND: Laparoscopic surgery is associated with a lower morbidity than open surgery. No recent data compared kidney cancer surgery in the French population using the National Health Insurance database (PMSI-MCO). AIMS: We explore and compare the surgical morbidity rates between laparoscopic and open laparotomy for kidney cancer. METHODS: The initial length of stay and complications parameters during the three postoperative months were described for renal cancer in every French center in 2018. We compared Relative Risks (RR [95% CI]) between laparoscopic and open surgery for both radical and partial nephrectomy. RESULTS: Among 8,162 patients, 3,525 had a radical nephrectomy, 978 open, 2,547 laparoscopic surgeries; 4,637 patients had partial nephrectomies, 1,778 open 2,859 laparoscopic surgeries. For radical surgery, the most common complications were urinary infections (7.8%), acute renal failure (8.9%), sepsis (8.4%), bleeding (9.3%), and postoperative anemia (5.9%); the RR for laparoscopic versus open surgery were respectively 0.68 [0.54;0.86], 0.71 [0.57;0.88], 0.69 [0.55;0.86], 0.83 [0.66;1.03], 0.56 [0.43;0.73]. For partial nephrectomies, the most common complications were urinary infections (7.7%), bleeding (11.6%), and postoperative anemia (5.8%), with RR of 0.71 [0.58;0.87], 0.61 [0.52;0.71], and 0.64 [0.51;0.81]. The mean length of stay was 7.7 for open radical nephrectomy, 6.3 for laparoscopic radical nephrectomy, 7.5 for open partial nephrectomy, and 5 for laparoscopic partial nephrectomy. CONCLUSIONS: The laparoscopic approach had fewer postoperative complications and a shorter length of stay than open surgery for partial and radical nephrectomy. The PMSI analysis provided an exhaustive description of surgical practice for kidney cancer and surgical complications in France. CLINICAL TRIAL NUMBER: Not applicable.

Long term outcomes of pituitary adenomas in Multiple Endocrine Neoplasia type 1: a nationwide study.

Introduction: Historically, Multiple Endocrine Neoplasia type 1 (MEN1)-related pituitary adenomas (PAs) were considered more aggressive and treatment-resistant than sporadic PAs. However, recent studies suggest similarities in their behavior. This study aimed to evaluate the long-term outcomes of MEN1 PAs and identify predictive factors. Methods: Nationwide multicenter retrospective cohort study of MEN1-related PAs with a minimum 1-year follow-up, collecting patient demographics, germline MEN1 pathogenic variants (PV), PA size, secretory profile, radiological characteristics, treatments, and outcomes. Results: We analyzed 84 PAs, 69%in females and 31% in males (P<0.001), diagnosed at a mean age of 35.2±14.9 years, mostly through screening (60.7%). Median follow-up was 9 years (IQR:4-16). Prolactin-secreting PAs (PRLomas) (53.5%) and microadenomas (65.5%) were most common. Dopamine agonist treatment was first line for 16 macroPRLomas and 25 microPRLomas, 60.9% of them achieved PRL normalization. There was no significant association observed with tumor size, sex, treatment duration or MEN1 PV. The risk of progression from micro-PA to invasive macro-PA was 7.2% (4/55), after 8 years (IQR:4-13), all of them were microPRLomas. Kaplan-Meier estimation curve showed significantly higher progression probability in microPRLomas than in other microadenomas subtypes (P=0.017) or microNFPAs (P=0.032). No differences were found between sex, age, or germline MEN1 PV. Conclusion: MEN1-related micro-PAs have a low risk of progressing to invasive macro-PAs, regardless of sex, age at diagnosis, or MEN1 germline PV. The risk is higher for microPRLomas over the long term. Therefore, long-term surveillance with reduced frequency, rather than intensive short-term monitoring, may be appropriate for patients with MEN1-related PAs.

A retrospective analysis of oral tumors in dogs in Switzerland identifies peripheral odontogenic fibroma and melanoma as the predominant tumor types.

OBJECTIVE: Determine the prevalence, types, and geographical distribution of oral tumors in dogs in Switzerland to provide insights into demographics, tumor characteristics, and trends. METHODS: The medical and pathology records of dogs diagnosed with oral tumors from 2012 to 2022 were sourced from diagnostic laboratories in Switzerland. The focus was on histopathologically confirmed oral neoplasms. Inflammatory, viral, and cystic lesions were excluded. Geographic trends were analyzed by use of postal addresses, revealing local distributions. RESULTS: Of the 948 reports, 773 cases fulfilled the study's criteria. Benign tumors constituted 63% (487 of 773), with peripheral odontogenic fibroma being the most common (77.8% [379 of 487]). Among the malignant tumors, malignant melanoma was the most frequent (38.1% [109 of 286]), followed by squamous cell carcinoma (21% [60 of 286]) and fibrosarcoma (8% [23 of 286]). The locations of tumors varied, with a higher prevalence of malignant melanoma on the lips. Histopathologic findings indicated ulceration and necrosis were more common in malignant tumors. Significant differences were noted in the mitotic index between benign and malignant groups. No tumor predisposition was noted for any breed. Oral tumors were prevalent in older dogs (median age, 9.4 years). CONCLUSIONS: The findings highlighted the predominance of benign tumors in dogs in Switzerland, with specific histopathologic features distinguishing benign from malignant cases. CLINICAL RELEVANCE: Understanding the prevalence, types, and geographic distribution of oral tumors based on the representation in dogs in Switzerland may aid in early detection, appropriate diagnostic workup, and informed treatment planning for oral tumors in dogs.

Novel diagnostic method for B cell vitreoretinal lymphoma by identification of regulatory T cells and PD-1+ cytotoxic T lymphocytes in the vitreous via flow cytometry.

AIMS: To investigate the significance of regulatory T cells (Tregs) and programmed cell death 1 (PD-1)+ cytotoxic T lymphocytes (CTLs) in the vitreous of patients with vitreoretinal lymphoma (VRL) and uveitis. METHODS: This study involved 51 patients with VRL and uveitis, 15 males and 36 females (mean age: 72 years, range: 51-86 years), who underwent vitrectomy at the Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan, from December 2019 to February 2024. All patients underwent lymphocyte surface antigen analysis via flow cytometry, and the proportion of Tregs in CD4+ T lymphocytes and PD-1+ CTLs in CD8+ T lymphocytes was measured. RESULTS: This study involved B cell VRL (B-VRL, n=16), sarcoidosis (n=8), human herpesvirus (HHV)-associated uveitis (n=7), human T cell lymphotropic virus type 1 associated uveitis (HAU, n=3) and unclassifiable uveitis (n=17) cases. The median proportions of Tregs were significantly lower in B-VRL (2.2%) compared with sarcoidosis (8.5%), HHV-associated uveitis (16.4%) and unclassifiable uveitis (10.1%) (p<0.05). Conversely, a significantly higher proportion of PD-1+ CTLs was found in B-VRL (95.6%) compared with sarcoidosis (61.1%), HHV-associated uveitis (67.1%) and unclassifiable (64.8%) (p<0.05). Receiver operating characteristic analysis of Tregs and PD-1+ CTLs proportions in B-VRL revealed high area under the curve values of 0.913 and 0.940, respectively. CONCLUSIONS: Our findings indicate that analysis of the ratio of Tregs and PD-1+ CTLs via flow cytometry is helpful in diagnosing B-VRL.

Diagnosis and management of pituitary adenomas in children and adolescents.

BACKGROUND: Pituitary adenomas (PAs)-also now called pituitary neuroendocrine tumours or Pit-NETS-are rare in children and adolescents and exceptional below the age of 10. Most evidence-based high-quality data are derived from larger studies in adult patients. AIMS: We will review recent knowledge on the epidemiology, clinical features, diagnosis, and treatment modalities of the different types of pituitary adenomas diagnosed in children and adolescents, emphasizing the many reasons why these cases should be discussed within pituitary-specific multidisciplinary teams with experts from both paediatric and adult practice. CONCLUSIONS: Paediatric PA presents multiple peculiarities that may challenge their adequate management. They are overall proportionally larger and more aggressive than in adults, with potential mass effects including hypopituitarism. Hormonal hypersecretion is frequent, resulting in clinical syndromes affecting normal growth and pubertal development. Prolactinomas represent the most frequent subtype of PA found during childhood, followed by adrenocorticotropin (ACTH) and growth hormone (GH)-secreting adenomas, while clinically non-functioning adenomas are exceptionally diagnosed before the age of 16. The occurrence of a pituitary tumour in a young individual should also prompt genetic testing in each case, searching for either germline mutations in one of the known genes that may drive inherited/familial PA (such as the multiple endocrine neoplasia type 1 or MEN1 gene, or the aryl hydrocarbon receptor interacting protein or AIP gene), or for a mosaic activating mutation of GNAS as found in the McCune-Albright syndrome.

Genetic Analysis of Biopsy Tissues from Colorectal Tumors in Patients with Ulcerative Colitis.

BACKGROUND/OBJECTIVES: Colorectal neoplasia developing from ulcerative colitis mucosa (CRNUC) can be divided into ulcerative colitis-associated neoplasia (UCAN) and non-UCAN; however, it is often difficult to distinguish UCAN from non-UCAN during a biopsy diagnosis. We investigated whether a genomic analysis could improve the diagnostic accuracy of UCAN using biopsy specimens. METHODS: In step 1, 14 CRNUCs were used to examine whether the genomic landscape of biopsy and resection specimens matched. In step 2, we investigated the relationship between the genomic landscapes and the pathological diagnosis of 26 CRNUCs. The cancer genome was analyzed by deep sequencing using a custom panel of 27 genes found to be mutated in our previous CRNUC analysis. RESULTS: In step 1, of the 27 candidate genes, 14 were mutated. The concordance rate of the pathogenic mutations in these 14 genes between the biopsy and resection specimens was 29% (4/14), while that of the pathogenic mutations in TP53 and KRAS was 79% (11/14). In step 2, the pathological diagnosis of biopsy specimens using only hematoxylin and eosin (HE) staining had a sensitivity of 33% and an accuracy of 38% for UCAN diagnosis. On the other hand, the combination of the HE pathology and p53 immunohistochemical staining had a sensitivity of 73% and an accuracy of 85% for UCAN diagnosis, while the combination of HE staining and a TP53 mutation had a sensitivity of 87% and an accuracy of 88% for UCAN diagnosis. CONCLUSIONS: An evaluation of TP53 mutations in biopsy specimens may be useful for diagnosing UCAN. However, further studies with larger sample sizes are required before this can be applied in clinical practice.