Histological Variants Research Articles

Histopathological findings and diagnosis of cutaneous leishmaniasis, confirmed by PCR, in an endemic region of Brazil.

Diagnosis of cutaneous leishmaniasis (CL) is difficult, and the correct use of histopathological criteria can be useful in clinical practice. The present study evaluates the association between histopathological findings and the results of polymerase chain reaction (PCR) in clinically suspected cases of CL. Skin samples were received in a laboratory from an endemic region of Brazil for over nine years. Associations were analyzed by means of the Chi square test with a 5% level of significance. Of the 222 examined samples, 190 (85.6%) tested positive by PCR. All 25 cases identified by microscopic examination also tested positive by PCR. Except for the more intense inflammatory infiltrate, all other evaluated histological variables (ulceration, epidermal hyperplasia, hyperkeratosis, presence of granuloma, neutrophils, histiocytes, lymphocytes, plasmocytes, and necrosis) were not significantly associated with PCR positivity. The intensity of the inflammatory infiltrate is a good indicator of the occurrence of CL. Histopathological aspects are useful to increase the predictive values of CL diagnoses, but PCR is still necessary to confirm or exclude the disease.

The effect of carotenoids of Rhodotorula glutinis and probiotic of Lactobacillus acidophilus on some physiological and histological variables of the pancreas and liver in male rats exposed to ultraviolet radiation.

ABSTRACT This study was conducted in the laboratory animal house at the College of Education/University of Samarra to establish and evaluate and treatment the effect of ultraviolet radiation (UV) on the health and functions of the pancreas and liver by use the carotenoids that extracted from Rhodotorula glutinis yeast and Lactobacillus acidophilus as probiotic. 28 male laboratory rats were used and divided into four groups with 7 animals in each group, the experiment period 28 days, including 24 hours representing the period of exposure to ultraviolet radiation before treatment. The results showed significant increase (P˂0.05) in concentrations of glucose, cholesterol, triglycerides, bilirubin and activity of ALT, AST and ALP in group that exposed to ultraviolet radiation in compared with the healthy control group, whereas, observed significantly decrease of all previous parameters in the groups that treated with probiotic and the carotenoids in comparison with ultraviolet radiation group, and repair of the damage that occur in tissues of pancreas and liver result from the effect of ultraviolet rays.

Assessing the Impact of Pomegranate Juice on Liver Tissue in Male Rats Exposed to a Commercial Energy Drink

The current study was designed to investigate the effect of pomegranate juice on some biochemical and histological variables resulting from dosing male rats with the energy drink Red Bull. In this study, 28 white male rats were used, divided into four groups, each involving seven animals, according to the following: G1 was given a physiological solution (5 ml/kg) and a standard diet for 120 days; G2 was given a dose of the energy drink Red Bull (volume 1 ml per 100 g); G3 was given pomegranate juice (5 ml/kg) first; then Red Bull; and G4 was given Red Bull first; and after six weeks, he was given pomegranate juice. The results showed that Red Bull consumption significantly elevated RBS, AST, ALT, TC, and TG levels. Pomegranate juice has the ability to reduce the concentration of RBS, AST, ALT, TC, and TG. Histological changes in the liver of animals that were given the Red Bull energy drink were represented by congestion of the central vein, degeneration, and necrosis of liver cells, with severe infiltration of inflammatory cells and a thick wall of the central vein (TW), as well as amyloid (AM) deposition, compared to the negative control group. The results of the histological examination showed that pomegranate juice could repair cellular tissue in the liver and make it similar to the tissue of a control normal group, denoting the possibility of using it in the diet and in treating atherosclerosis and heart disease. Keywords: Pomegranate juice, liver, rats, energy drink, rat model, atherosclerosis, heart disease.

A 2-center review of histopathology of variants of upper urinary tract urothelial carcinoma and their impact on clinical outcomes

IntroductionSimilar to bladder cancer, about one third of upper tract urothelial carcinoma (UTUC) present variant histology (VH). We aim to evaluate the incidence, clinical characteristics and the impact on outcomes of VH in UTUC. MethodsWe consecutively enrolled 77 patients treated between 2009 and 2022 by radical surgery for UTUC from a secondary and a tertiary referral center. A pathology review of all specimens was performed by 1 independent uropathologist for each center. We compared pure UTUC and UTUC with VH and the accuracy of endoscopic biopsy. Descriptive and comparative analysis was performed to assess the association with clinical characteristics and the Kaplan–Meier estimator to compare outcomes. ResultsMedian follow-up after surgery was 51 months. VH was present in 21/77 (28%) patients and 4/21 (19%) patients had multiple variants. The most frequent VH was squamous 12/21 (57%), followed by glandular 7/21 (33%) and micropapillary 3/21 variants (14%). Neuroendocrine carcinoma was present in 2 patients. Nested variant was found in 1 patient. Muscle invasive tumor (≥pT2) was present in 30/56 (54%) patients with pure UTUC and in 18/21 (86%) patients with VH (P < 0.05). Presence of carcinoma in situ was seen in 24/56 (43%) patients with pure UTUC and in 16/21 (76%) with VH (P < 0.05). Cumulative 8/56 (14%) with pure UTUC had a nonintravesical recurrence (6 patients with local and 2 distant recurrence) compared to 8/21 (38%) (3 local, 3 nodal, 2 distant) in the subgroup with VH (P < 0.05). Opposite effect was noted for bladder recurrence: 60% for pure UTUC vs. 29% for tumors with VH (P < 0.05). Review of preoperative endoscopic biopsy did not show the presence of VH in any patients. Differences in outcomes did not reach significance: 3yr-OS 63% vs. 42% (P 0.28) and 3yr-CSS 77% vs. 50% (P 0.7). ConclusionAlmost a third of UTUC present VH. Presence of VH is related to more aggressive tumor characteristics and associated with unfavorable outcomes. Due to a higher rate of extravesical recurrences in UTUC with VH, Follow-up controls should include cross sectional imaging and cystoscopy.

Critical appraisal of total gastrectomy plus total colectomy with hyperthermic intraperitoneal chemotherapy as a treatment for advanced pseudomyxoma peritonei

AbstractBackgroundThe absolute requirement for a long‐term favorable result with cytoreductive surgery for pseudomyxoma peritonei is a complete resection of all visible disease. A combination of parietal peritonectomy procedures and visceral resections is required for this to occur. The cytoreductive surgery is supplemented by hyperthermic intraperitoneal chemotherapy.MethodsWe searched our database and secured files for patients who required a total gastrectomy and a total colectomy to achieve a complete cytoreductive surgery. Survival of low‐grade mucinous neoplasm (LAMN) and mucinous appendiceal adenocarcinoma (MACA) histologies were determined. Clinical and histologic variables were assessed for their impact on survival.ResultsThirteen of 450 patients (2.9%) with LAMN histology and 14 of 186 patients (7.5%) with MACA histology had these visceral resections. Median survival of these 27 patients was 10 years. LAMN and MACA patients showed the same survival. For LAMN histology, this requirement for extensive visceral resection markedly reduced survival (p &lt; 0.0001). For MACA, there was no adverse impact on survival (p = 0.4359). Class 4 adverse events caused reduced survival (p = 0.0014).ConclusionsA 10‐year median survival accompanies total gastrectomy plus total colectomy for advanced pseudomyxoma peritonei. Systemic chemotherapy and class 4 adverse events reduced survival.

Predictive factors for recurrence and outcomes in T1a renal cell carcinoma: Analysis of the INMARC (International Marker Consortium for Renal Cancer) database

ObjectiveStage migration in renal cell carcinoma (RCC) has led to an increasing proportion of diagnosed small renal masses. Emerging knowledge regarding heterogeneity of RCC histologies and consequent impact on prognosis led us to further explore outcomes and predictive factors in surgically-treated T1a RCC. MethodsThe INMARC database was queried for T1aN0M0 RCC. Patients were stratified into groups based on recurrence. Primary outcome was overall survival (OS). Multivariable analyses (MVA) were performed for factors associated with recurrence, cancer-specific (CSM), and all-cause mortality (ACM). Kaplan-Meier analyses (KMA) assessed survival by histology and grade. Subset analysis for time to recurrence was conducted for grade and histologic groups and compared with recent AUA follow-up guidelines [low-risk (AUA-LR), intermediate-risk (AUA-IR), high-risk (AUA-HR), and very-high risk (AUA-VHR) groups]. ResultsWe analyzed 1,878 patients (median follow-up 35.2 months); 101 (5.4%) developed recurrence. MVA for recurrence demonstrated increasing age (P = 0.026), male sex (P = 0.043), diabetes (P = 0.007), high/unclassified grade (P < 0.001–0.007), and variant histology (P = 0.017) as independent risk factors for increased risk, while papillary (P = 0.016) and chromophobe (P = 0.049) were associated with decreased risk. MVA identified high/unclassified grade (P = 0.003–0.004) and pT3a upstaging (P = 0.043) as predictive factors for worsened risk of CSM while papillary (P = 0.034) was associated with improved risk. MVA for ACM demonstrated increasing age (P < 0.001), non-white (P < 0.001), high-grade (P = 0.022), variant histology (P = 0.049), recurrence (P = 0.004), and eGFR<45 at last follow-up (P < 0.001) to be independent risk factors. KMA comparing clear cell, chromophobe, papillary, and variant RCC revealed significant differences for 5-year CSS (P = 0.018) and RFS (P < 0.001), but not OS (P = 0.34). Median time to recurrence was 23.8 months for low-grade (AUA-LR), 17.3 months for high-grade (AUA-IR), 18 months for pT3a upstaging (AUA-HR), and 12 months for variant histology (AUA-VHR; P < 0.001). ConclusionWe noted differential outcomes in T1a RCC based on histology and grade for recurrence and CSM, while renal functional decline in addition to pathological factors and recurrence were predictive for ACM. Our findings support recently promulgated AUA follow-up guidelines for low-grade and variant histology pT1a RCC, but call for consolidation of follow-up protocols for high-grade pT1a and pT3a upstaged patients, with intensification of frequency of imaging follow-up in pT1a high-grade RCC.

Histological Variations in Cucumber Grafted Plants and Their Effect on Yield

Cucumber is a vegetable crop of economic importance in Mexico. In 2023, fresh or frozen cucumber and pickle international sales reached USD 783M, placing Mexico in second rank among countries with the highest currency inflow in the world. This crop is mostly grown under protected environments with new production technologies, including rootstocks that are tolerant to biotic and abiotic factors that limit the yield and quality of the harvest. Therefore, the goal of this work was to assess three cucurbits as rootstocks (Cucurbita maxima, Cucurbita moschata and Citrullus lanatus), as well as studying the response of cucumber crop to the tested rootstocks. The following treatments were assessed: T1:PSP = cucumber Cv. Paraizo F1 without rootstock; T2:P/MA = cucumber grafted over Cucurbita maxima; T3:P/MO = cucumber grafted over Cucurbita moschata; T4:P/CL = cucumber grafted over Citrullus lanatus Citroides Var. The assessed variables included the number of fruits per plant (NFPP), fruit weight per plant (PFPP), average fruit weight (PPF), plant dry weight (PSP), xylem vessel area (AVX), number of xylem vessels (NVX), vascular bundle area (AHV) and number of vascular bundles (NHV) in roots (R), basal stalk (TB) and apical stalk (AT). Significant differences among treatments were found in the results for variables: NFPP, highlighting that T2:P/MA was superior by 46.15% versus T1:PSP and by 67.69% versus T3:P/MO. Regarding PFPP, T2:P/MA achieved the highest weight (5445 g), as it proved superior by 99.45% than the cucumber without rootstock (T1:PSP). Regarding PSP, T2:P/MA achieved the highest weight (196.65 g), significantly exceeding T1 by 137.5%. Regarding AVXR, T4:P/CL had the highest value (30,063 µm2). Regarding NHVR, watermelon had (T4:P/CL) 39.33% more vascular bundles than the root system of cucumber (T1:PSP). Treatments T2:P/MA and T4:P/CL had the highest values at AVXTB, while for variable NVXTB, treatments T3:P/MO and T2:P/MA were almost equal, surpassing non-grafted cucumber by 175.47%. However, T2:P/MA showed the greatest AHVTB, and T1:PSP was significantly superior to T3:P/MO, by 34.93%, for NHVTB. Furthermore, positive and significant correlations were found among PFPP, AHVR, and AVXTB, as well as among PSP, AVXTB, and AHVTB. Therefore, we may say that having a larger area of vascular vessels in the roots and a larger area of xylem vessels in the basal stalk leads to higher fruit yields per plant. In the same vein, the use of rootstocks is a sustainable alternative to increase fruit yield.

Neoadjuvant Chemotherapy in Breast Cancer: Evaluation of the Impact on Surgical Outcomes and Prognosis.

The correlation between TNM staging and histology variations in a sample of patients who underwent neoadjuvant chemotherapy demonstrates a positive impact on both increasing conservative surgery and achieving pCR, resulting in better outcomes in terms of disease-free survival (DFS) and the risk of relapse. Benefits have also been highlighted in terms of cosmetic outcomes, postoperative complications, and psychological benefits. However, the overall outcomes must be evaluated according to the subtype and individual characteristics of the patients.

Assessing Morphological Diversity of Acinic Cell Carcinoma of Salivary Glands at a Tertiary Care Hospital in Pakistan.

Acinic cell carcinoma (AciCC) is a rare clinical entity and a salivary gland malignancy. It is associated with wide histological variations in the cytomorphological patterns. Sixty cases diagnosed as AciCC from 2002 to 2023 were assessed for diverse cytomorphological patterns. The mean age of patients at the time of diagnosis was 44.35±16.8 years ranging from 15 to 81 years. Females comprised 58.3% for a F: M ratio of 1.4:1. Fifty three cases (88.3%) occurred in the parotid gland, two cases in the nasal region (3.3%), and one case each in the soft plate and upper lip (1.7%). The location of the remaining three cases was not specified. The most common presenting complaint was a well-defined facial swelling associated with pain. The average tumor size was 3.8±1.9 cm. The most predominant architectural pattern was solid (83.3%) followed by microcystic (60%), then follicular (41.7%), papillary cystic (14.3%), and tubulocystic (28.6%), and AciCC with de-differentiation/high-grade transformation was reported in three cases (5%). In 83.3% of the cases (50 out of 60), we noticed a mixture of two or more growth patterns.Other degenerative changes included prominent lymphoid stroma, hemorrhage, and cystic change. Awareness and recognition of diverse cytomorphological patterns of AciCC, especially in institutions of a developing country where there is limited availability of highly specific and sensitive immunohistochemical stains or molecular diagnostics, are crucial and essential.

Pleomorphic Adenoma: Case Series and Literature Review

Pleomorphic adenoma, usually referred to as a ‘benign mixed tumor,’ is the ‘most prevalent’ salivary gland neoplasm. It typically arises in the parotid gland, one of the main salivary glands, and has a limited development potential. Pleomorphic adenoma can also occur in minor salivary glands located in the pharynx, oral cavity, and other areas. The purpose of this paper is to provide an overview of the histology, therapy, and clinical features of pleomorphic adenoma in a number of patients. This case series provides an overview of key characteristics, clinical presentation, diagnosis, and management of pleomorphic adenoma. A review of the update of histogenesis is also explored. Pleomorphic adenoma is typically characterized by its histological diversity. Early diagnosis, accurate imaging, and surgical intervention are crucial for effective management and avoiding potential complications. Regular surveillance following treatment helps ensure optimal patient outcomes. Pleomorphic adenoma can grow to large sizes, if untreated and hamper normal function. Hence early diagnosis and treatment are needed. The varied histopathological presentation of pleomorphic adenoma makes the diagnosis challenging in certain cases. Timely diagnosis and prompt treatment planning require a detailed history and clinical evaluation with radiographic and histopathological investigations. Thus, by documenting these instances, healthcare providers can enhance their ability to recognize and manage unusual presentations of the disease. This, in turn, helps in early diagnosis and appropriate treatment selection. Keywords - Benign mixed tumor, Histogenesis, Histopathology, Pleomorphic adenoma, Salivary glands

Morphometric, Histological Variations in the Placenta of Normotensive and Pregnancy Induced Hypertensive Mothers

Morphometric, Histological Variations in the Placenta of Normotensive and Pregnancy Induced Hypertensive Mothers

C4d expression in focal segmental glomerulosclerosis

BackgroundThere is a little information about of expression of C4d (complement fragment) in Focal segmental glomerulosclerosis (FSGS) subtypes. Our aim was to determine the expression of C4d in FSGS subtypes in percutaneous native renal biopsies in a second-level hospital and its correlation with clinical, biochemical and histological variables. Material and methodsA retrospective study in paraffin blocks of patients with biopsy with FSGS aged 16–65 years, indistinct sex, not diabetic or obese. Immunohistochemistry was performed for C4d and their expression was analyzing in non-sclerosed glomerular capillaries (GC) and sclerosis areas (SA). Clinical and biochemical variables were recorded. The cases were divided into C4d positive and C4d negative groups and compared. The correlation between C4d staining scores in CG and SA with clinical and biochemical variables were analyzed. ResultsTwenty samples were analyzed, 4 for each subtype. At the time of biopsy average age 38.8 ± 18.6 years, 65% male, 8.7% were hypertension. The percentage of positivity for C4d was 40% in GC, 30% SA and 35% in mesangium. The highest expression was for cellular and collapsing subtypes. C4d positivity cases had increased proteinuria (p = 0.035). A significant correlation was found between percentage of C4d expression in CG with SA (p = 0.012) and SA with tubular atrophy and interstitial fibrosis (p < 0.05). ConclusionsC4d expression in FSGS predominated in the cellular and collapsing subtypes, which translates complement activation. C4d is a possible surrogate marker in GSFS.

Exploring the Clinicopathological Diversity in Sarcomatous Transformations in the Uterus.

Introduction Uterine sarcomas are a rare group of mesenchymal tumors.They originate either from the uterine smooth muscle or from the endometrial stroma. The spectrum of malignant uterine sarcomatous transformations includes leiomyosarcoma, low-grade endometrial stromal sarcoma (LG-ESS), high-grade endometrial stromal sarcoma (HG-ESS), undifferentiated uterine sarcoma, and carcinosarcoma. The purpose of this study is to determine the distribution of malignant uterine sarcomatous transformations, in relation to the patient's age, epidemiological aspects, and clinical features, and to analyze the different histological types of uterine sarcomas diagnosed at our institutionand thereby to quantify their frequency and determine the most common histopathological subtype occurring in the population. Materials and methods This was a retrospective descriptive study of 21 cases of malignant uterine sarcomatous transformations, diagnosed in Saveetha Medical College, Chennai, between January 2019 and December 2022. Data was collected from the archives of the department of pathologyand from the department of medical records in the hospital. The spectrum of uterine sarcomas was analyzed in relation to the patient's age, menopausal status, presenting symptoms, preoperative diagnosis, biopsy and frozen section reports wherever available, and histopathological reports with pathological staging. Results The most common age group in which uterine sarcoma was diagnosed was found to be 61-70 years. All 10 patients who were diagnosed with carcinosarcoma were aged 60 years, andall seven patients diagnosed with low-grade endometrial stromal sarcoma were less than 50 years of age. Most of the patients were postmenopausal females, except for one patient who was premenopausal. The most common histological variety found was carcinosarcoma, malignant mixed mullerian tumor (47.6%), followed by LG-ESS (33.3%), leiomyosarcoma (14.28%), and HG-ESS (4.7%). Conclusion Uterine sarcomas are anaggressive group of tumors having a very poor prognosis. Due to its rarity and histopathological diversity, there is a lack of consensus on the risk factors.

Differences between Patients with Sporadic and Familial Pheochromocytoma-Is It Possible to Avoid Genetic Testing in Certain Patients?

Pheochromocytoma (PHEO) is a rare neuroendocrine tumour with a strong genetic link, which therefore may modify its clinical behaviour and prognosis. The aim of the study is to evaluate the epidemiological and clinical differences between patients with sporadic and familial PHEO, as well as the specific differences in the index cases. A retrospective analysis of 136 patients in a tertiary hospital (1984-2021). Epidemiological, clinical, and histological variables were analysed. SPSS 28.0 software was used. Univariate and multivariate logistic regression analyses were performed. p < 0.05 was considered statistically significant. 64.71% of the cases (n = 88) presented a genetic mutation (familial cases). Additionally, 32.39% (n = 23) corresponded to index cases and the rest to screening cases. The main differences between patients with familial and sporadic PHEO were age (OR = 0.93 (0.89-0.97)), blood pressure-related symptoms (OR = 0.22 (0.06-0.89)), bilaterality (OR = 15.49 (3.76-63.84)), and size (OR = 0.70 (0.54-0.92)). Among patients with sporadic PHEO and index cases, only bilaterality was significant (OR = 13.53 (1.24-144.34)). Patients with familial PHEO diagnosed by screening differ from sporadic cases in terms of age, clinical features, and size. However, patients with sporadic PHEO only differ from index cases by a lower presence of bilaterality, which reaffirms the importance of genetic screening of patients with PHEO and their relatives.

PATH-03. FOXR2-OVEREXPRESSING CENTRAL NERVOUS SYSTEM (CNS) TUMORS EXHIBIT SUBSTANTIAL DIVERSITY ACROSS HISTOLOGICAL, MOLECULAR, AND CLINICAL DIMENSIONS

Abstract BACKGROUND FOXR2 activation is regarded as the pathognomonic molecular signature of CNS neuroblastoma. However, a comprehensive understanding of the landscape for CNS tumors exhibiting FOXR2 activation is lacking. METHODS Integrated histopathologic, molecular, and clinical data analysis of 36 FOXR2-overexpressing CNS tumors identified through screening of an institutional dataset. RESULTS FOXR2-overexpressing CNS tumors showed a broad anatomic distribution throughout the neuraxis. Of the 36 tumors, 17 (47.2%) were gliomas and 17 (47.2%) were embryonal tumors. The gliomas included 16 high-grade gliomas (eight histone H3 K27M-mutant diffuse midline gliomas, seven radiation-associated tumors, and one with MN1::PATZ1 fusion) and one pilocytic astrocytoma. The embryonal tumors included ten CNS neuroblastomas, six pineoblastomas, and one medulloblastoma. Two were difficult-to-classify high-grade neuroepithelial tumors. The gliomas and embryonal tumors demonstrated comparable FOXR2 expression based on normalized RNA-sequencing data. FOXR2-overexpressing gliomas, but not embryonal tumors, displayed diverse concomitant genetic alterations. The most common mechanisms of FOXR2 activation involved structural alterations leading to proximity effects, frequently incorporating non-canonical non-coding exons, followed by activation of the exon -3 promoter. Tumor location, histology, and concomitant alterations correlated with patient outcomes. While FOXR2-overexpressing gliomas were aggressive with a 5-year overall survival of 13.3%, FOXR2-overexpressing embryonal tumors showed a diverse prognosis. FOXR2-activated CNS neuroblastoma showed a 5-year overall survival of 100%. Pineoblastomas with FOXR2 activation in the PB-FOXR2 DNA methylation group showed a 3-year survival of 0% despite multimodal therapy. The one medulloblastoma patient in the cohort is alive at three years post-diagnosis. CONCLUSION FOXR2-overexpressing CNS tumors manifest significant histological, molecular, and clinical diversity and can occur as post-radiation tumors. Glioma histology and concomitant genetic alterations correlate with treatment resistance and inferior prognosis, while FOXR2-overexpressing embryonal tumors show more heterogeneous outcomes. Integrating histologic and molecular diagnostic approaches along with therapeutic interventions and clinical outcomes is imperative for accurate prognostication and optimal therapeutic decision-making.

STEM-04. BIOBANKING PATIENT-DERIVED MODELS OFFERS A PRECISE SPATIAL AND EPIGENETIC APPROACH TO UNRAVEL THE INITIATION, PROGRESSION, AND THERAPEUTIC RESISTANCE OF PEDIATRIC BRAIN TUMORS

Abstract BACKGROUND Aggressive brain cancers represent the most lethal forms of tumors in pediatric population. Their molecular drivers and co-alterations are currently guiding therapeutic strategies. Due to heterogeneous nature of these tumors, they are quickly developing resistance to treatment. Recognizing intrinsic and extrinsic mechanisms underlying therapeutic resistance, international scientific community has recognized an urgent need to create precise models of brain tumors capable of predicting therapeutic responses. So far, patient-derived cell lines (PDCL) remain the most reliable model to estimate and mimic evolving scenarios. The primary challenges lie in derivation methods and in cellular and spatial validation. METHODS In the context of the PEDIAMODECAN program, we collected 105 fresh brain tumor samples, including 34 LGG, 24 HGG, 19 ependymomas, 19 medulloblastomas, and 9 other rare entities, to concurrently generate PDCLs and patient-derived xenografts (PDX). RESULTS Regarding the derivation process itself, we successfully maintained 80% of samples in 2D and 54% in PDX models. As anticipated, the LGG group showed the higher percentage of PDX failure (90%). Nevertheless, for high-grade subtypes, PDX generation rate increased to 85,7%. No correlation was found between derivation success and a shorter interval between surgical removal and dissociation processes. Histological analysis of PDXs models confirmed the similar microscopic features to those of primary tumors. Next-Generation Sequencing (NGS), methylome assays and spatial transcriptomic analyses of derived models matched those of the original patient tumors. Epigenetic approaches were proved to be the most effective methods for validating models, in addition to spatial transcriptomic analyses that highlighted similar inter-tumor heterogeneity between PDX models and primary tumor counterparts. CONCLUSIONS Establishing a systematic PDCL/PDX biobank for all pediatric brain tumors represents one of the most effective approaches to develop models capable of accurately reproducing tumoral heterogeneity, histological and molecular diversity, and facilitating the design predictive screenings for targeted therapies combined with irradiation.

Cloacal microanatomy of tropical male butterfly lizards (genus Leiolepis) during the annual reproductive cycle

Cloacal microanatomy of male Leiolepis ocellata during the reproductive cycle was examined using histochemistry and light microscopy. The cloaca is divided into three contiguous regions: the coprodeum, urodeum, and proctodeum. The coprodeum has anterior and posterior connections to the intestine and the urodeum, respectively. A bladder stalk and paired ampulla ureters open to the ventral and the dorsal urodeal walls, respectively. Paired, bilateral anterior dorsal recesses of the urodeum lie ventrally to ureters and ampulla ductus deferentes. A cloacal triad junction is indicated by confluence of the coprodeum, urodeum, and bladder stalk. The proctodeum is subdivided into the anterior and the posterior regions; the latter bears dorsal and ventral proctodeal glands. In general, similar histological profiles of each cloacal region are noticeable among animals from different reproductive periods. However, mucosal glycoconjugate production in the cloacae of reproductively inactive males is slightly less than that in the active males. Seasonal histological changes of proctodeal glands are appreciable, with the reproductively active males having structurally and functionally active glands. As expected, spermatozoa are found in the urodeal and the proctodeal lumina of the active males, while residual round germ cells are occasionally found in the cloacae of the inactive males. Overall, male L. ocellata exhibits seasonal cyclicity of microanatomy and histochemistry of the proctodeal glands, with marginal histological variability in other parts of the cloacae. Hence, the present study provides improved knowledge on dynamic microanatomical variation of the male reproductive system of reptiles in relation to the annual reproductive cycle.

PATH-13. LEARNED RESIZING WITH EFFICIENT TRAINING (LRET) FACILITATES IMPROVED PERFORMANCE OF LARGE-SCALE BRAIN TUMOR HISTOLOGY IMAGE CLASSIFICATION MODELS

Abstract BACKGROUND Histologic examination is vital in oncology research and diagnostics. The adoption of digital scanning of whole slide images (WSI) has created an opportunity to leverage deep learning-based image classification methods to enhance diagnosis and risk stratification. However, technical limitations prevent training and deployment of accurate comprehensive multiclass deep convolutional neural networks (DCNN) models for histopathology image classification. The input dimensions of DCNN architectures are small compared to the typical pathologist field of view, degrading performance by excluding important architectural features. Furthermore, data requirements for comprehensive models are sufficiently large to overwhelm the system memory during training. METHODS A method termed Learned Resizing with Efficient Training (LRET) was developed to address the main limitations of traditional histopathology classification model training. The LRET method couples efficient training techniques with image resizing to facilitate seamless integration of larger histology image patches into state-of-the-art classification models while preserving important structural information. The LRET method was coupled with two distinct resizing techniques to train three diverse histology image datasets using five different DCNN architectures. Performance metrics were compared on cross validation and hold out test sets. RESULTS LRET-trained models were flexible to multiple input patch dimensions and DCNN models. We demonstrated performance improvement across all datasets while significantly reducing the training time and resources over traditional methods. Using a large-scale, multiclass brain tumor classification dataset consisting of 74 distinct histopathologic classes, LRET-trained models outperformed existing methods by 15-28% in accuracy, yielding 94% accuracy for the best model. CONCLUSION The LRET method for DCNN training significantly enhances the performance of large-scale multiclass histopathology image classification. The implications of this work extend to broader applications within medical imaging and beyond, where efficient integration of high-resolution images into deep learning pipelines is paramount for driving advancements research and clinical practice.

Incidence, Timing, and Pattern of Atypical Recurrence after Minimally Invasive Surgery for Urothelial Carcinoma.

The management of urothelial carcinoma has evolved with the introduction of minimally invasive techniques such as laparoscopic or robotic procedures, challenging the traditional approach of open surgery, and giving rise to atypical recurrences (ARs). ARs include port-site metastasis and peritoneal carcinomatosis, yet discrepancies persist among authors regarding their precise classification. Incidence rates of ARs vary widely across studies, ranging from less than 1% to over 10% in both muscle-invasive bladder cancer (MIBC) and upper tract urothelial tumor (UTUC). Peritoneal metastases predominate as the most common ARs in patients with MIBC, while retroperitoneal metastases are prevalent in those with UTUC due to differing surgical approaches. The timing of AR presentation and survival outcomes closely mirror those of conventional recurrences, with which they are frequently associated. Pneumoperitoneum has progressively been regarded less as the cause of ARs, while surgical-related risk factors have gained prominence. Current major surgical-related causes include tumor spillage and urinary tract violation during surgery, avoidance of endo bag use for specimen extraction, and low surgical experience. Factors such as tumor stage, histological variants, and lympho-vascular invasion correlate with the risk of ARs, suggesting a close association with tumor biology. Further studies are required to better understand the incidence, risk factors, characteristics, and outcomes of ARs.

Perioperative sacituzumab govitecan (SG) alone or in combination with pembrolizumab (Pembro) for patients with muscle-invasive urothelial bladder cancer (MIBC): SURE-01/02 interim results.

LBA4517 Background: SG is an antibody-drug conjugate composed of an anti-trophoblast cell surface antigen 2 (Trop-2) antibody coupled to SN-38 (a topoisomerase-I inhibitor) with US FDA-accelerated approval for locally advanced or metastatic urothelial carcinoma (mUC). A multi-cohort, open-label, phase 2 SURE study is evaluating neoadjuvant SG (SURE-01, NCT05226117) or neoadjuvant SG+pembrolizumab followed by adjuvant pembrolizumab (SURE-02, NCT05535218) in MIBC in a flexible design allowing a bladder-sparing approach. We report interim results from SURE-01. Methods: Pts with cT2-4N0M0 MIBC who were ineligible for or refused cisplatin-based neoadjuvant chemotherapy were planned to receive 4 cycles of neoadjuvant SG 10 mg/kg intravenously (IV) on days 1 and 8, Q3W, followed by radical cystectomy (RC). The trial included pre-post MRI imaging of the pelvis and ctDNA analysis. Pts with clinical complete response (cCR, defined with negative MRI, cystoscopy and ctDNA assays) refusing RC were offered redo transurethral resection of the bladder tumor (reTURBT) followed by observation in case no viable high-grade tumor in the bladder was found. The primary endpoint of the study is to assess the proportion of ypT0N0. The assumptions include a ypT0N0≤20% as H0 and ≥45% as H1 in a single-stage A’Hern’s design. Secondary end points include event-free survival (EFS), cCR rate and OS. Treatment-related adverse events (TRAEs) and safety are assessed using standard criteria (CTCAE v5). Tumor samples underwent comprehensive genomic profiling assay. Results: From 03/22 to 11/23, 21 pts were enrolled. After the initial 8 pts the study was amended with SG at 7.5 mg/Kg dose due to a Grade 5 TRAE. Median age was 71y, 7 pts (33.3%) had a cT3-4N0. Ten pts (47.6%) had a mixed variant histology. All pts received at least 1 cycle of SG: Grade ≥3 TRAE occurred in 9 pts (42.5%), including one Grade 5 event (at 10mg/Kg dose). Toxicity was unrelated to UGT1A1 polymorphism. Ten pts (47.6%) achieved a cCR. Sixteen pts are evaluable for final response at treatment completion: one pt had a disease progression and started palliative therapy, two did not undergo RC due to TRAE. Thirteen pts have undergone surgery (RC: N=10; reTURBT: N=3). ypT0N0-x response was achieved in 6/16 pts (37.5%), 7 (43.7%) an ypT≤1N0-x response. All pts with a residual disease revealed a ctDNA-negative test post-RC. Tumor samples from pts with cCR were enriched in ARID1A and BRCA1/2 mutations vs nonCR: 40 vs 9%, 30 vs 18%; nonCR were enriched in ERBB2 mutations vs cCR: 44 vs 10%. Conclusions: Observed ypT0N0-x responses after neoadjuvant SG showed promising activity in MIBC who have a high unmet need, with a potential to avoid RC. Reduced dose of SG was feasible and the data support the ongoing SURE studies in MIBC. Clinical trial information: NCT05226117 ; NCT05535218 .