Histopathological Confirmation Research Articles

Metabolomic profiling of pheochromocytomas in dogs: Catecholamine phenotype and tricarboxylic acid cycle metabolites.

In humans with pheochromocytomas (PCCs), targeted metabolomics is used to determine the catecholamine phenotype or to uncover underlying pathogenic variants in tricarboxylic acid (TCA) cycle genes such as succinate dehydrogenase subunits (SDHx). To analyze catecholamine contents and TCA cycle metabolites of PCCs and normal adrenals (NAs). Ten healthy dogs, 21 dogs with PCC. Prospective observational study. Dogs diagnosed with PCC based on histopathological and immunohistochemical confirmation were included. Tissue catecholamine contents and TCA metabolites in PCCs and NAs were measured by liquid chromatography with mass spectrometry or electrochemical detection. Compared to NAs, PCCs had significantly higher tissue proportion of norepinephrine (88% [median: range, 38%-98%] vs 14% [11%-26%]; P < .001), and significantly lower tissue proportion of epinephrine (12% [1%-62%] vs 86% [74%-89%]; P < .001). Pheochromocytomas exhibited significantly lower fumarate (0.4-fold; P < .001), and malate (0.5-fold; P = .008) contents than NAs. Citrate was significantly higher in PCCs than in NAs (1.6-fold; P = .015). One dog in the PCC group had an aberrant succinate : fumarate ratio that was 25-fold higher than in the other PCCs, suggesting an SDHx mutation. This study reveals a distinct catecholamine content and TCA cycle metabolite profile in PCCs. Metabolite profiling might be used to uncover underlying pathogenic variants in TCA cycle genes in dogs.

Population-Based Incidence and Clinical Characteristics of Ocular Adnexal Tumors in Olmsted County, Minnesota

ABSTRACT Purpose To determine the incidence and clinical characteristics of ocular adnexaltumors in Olmsted County, Minnesota. Methods Retrospective population-based cohort study of all patients residing in Olmsted County, Minnesota diagnosed with any ocular tumor from January 1, 2006, to December 31, 2015. The medical records of all patients with an incident diagnosis of any ocular adnexal tumor were reviewed using the Rochester Epidemiology Project medical record linkage system for patient demographics, tumor type, and histopathologic confirmation. Incidence rates were calculated per 100,000 person-years. Poisson regression analysis was used to analyze changes in incidence over time. Results There were 717 patients diagnosed with ocular adnexal tumors during the 10-year study period, yielding an age- and sex-adjusted incidence rate of 59.7 per 100,000 (95% CI 55.4 to 64.0, p < 0.05) per year. In total, 764 tumors were diagnosed. Most tumors were eyelid lesions (N = 756, 99.0%), which were mostly benign (N = 512, 67.8%) with epidermal inclusion cysts (N = 275, 36.0%), hidrocystoma (N = 70, 9.2%), and eyelid sebaceous cysts (N = 46, 6.1%) accounting for the majority. Malignant eyelid lesions (N = 244, 31.9%) were relatively common with basal cell carcinoma (N = 184, 24.1%) and squamous cell carcinoma (N = 49, 6.4%) having the highest frequencies. Orbital tumors (N = 8, 1.0%) were infrequent. Of the orbital tumors, the most common was lacrimal gland adenoidcystic carcinoma (N = 2, 25.0%). Conclusions In a population-based setting, most ocular adnexal tumors were benign eyelid lesions. Understanding the epidemiology of ocular adnexal tumors is important to aid providers in diagnosing and facilitating appropriate referrals of potentially vision- and life-threatening malignancies.

Cutaneous Complications after Autologous Stem Cell Transplantation

Autologous stem cell transplantation (ASCT) has become more prevalent for high-grade non-Hodgkin's lymphoma (NHL) over the past decade. ASCT serves as a salvage treatment for high-risk or relapsed patients, offering potential long-term remission. Cutaneous modifications post-ASCT can be classified as early (within 100 days) and late (after 100 days). Understanding these changes is crucial for timely diagnosis and management. Early modifications typically include transient erythema, hyperpigmentation, and acute dermatitis, often linked to the conditioning regimen. Late modifications, occurring months to years posttransplantation, can encompass chronic skin changes such as scleroderma-like features and persistent pigmentary alterations. Emerging evidence challenges the notion that ASCT is free of graft-versus-host disease (GVHD), with incidences of auto-GVHD reported. However, cutaneous GVHD post-ASCT, though uncommon, poses significant diagnostic challenges. Cutaneous GVHD manifestations range from mild eruptions to severe, systemic involvement. The role of skin biopsy in these cases is invaluable, providing histopathological confirmation and distinguishing GVHD from other dermatoses. Recognizing the early and late cutaneous modifications following ASCT is essential for clinicians. Despite the rarity of skin GVHD in ASCT, awareness and prompt biopsy can facilitate accurate diagnosis and appropriate management, improving patient outcomes.

Sublobar resection for lung adenocarcinoma less than 2 cm containing solid or micropapillary components radiologically presented as consolidation-to-tumor ratio (CTR) ≤0.25 [ground-glass opacity (GGO)

The suitability of sublobar resection as a surgical approach for early-stage non-small cell lung cancer (NSCLC) remains unclear. This study investigated the feasibility of sublobar resection in patients with pathological-stage IA adenocarcinoma less than 2 cm characterized by a high-risk pathological subtype but exhibiting radiologically noninvasive features. We conducted a retrospective review of patients diagnosed with pathological stage IA lung adenocarcinoma who underwent surgical intervention between 2013 and 2017. The inclusion criteria included a maximum tumor diameter of 2.0 cm or less, a consolidation-to-tumor ratio (CTR) of 0.25 or less, and a histopathological confirmation of a solid or micropapillary component. Patients were categorized into sublobar resection and lobectomy groups, and propensity score matching was employed to mitigate potential confounders. The primary endpoints were lung cancer-specific survival (LCSS) and overall survival (OS). The study comprised 149 patients, with 84 in the lobectomy group and 65 in the limited resection group. In the overall cohort, the 5-year LCSS was 100% for both groups, while the 5-year OS was 97.6% (95% CI: 94.41-100.00%) in the lobectomy group and 100% in the sublobar resection group (P=0.21). After propensity score matching, the LCSS remained at 100% for both groups, and the 5-year OS was 97.14% in the lobectomy group and 100% in the sublobar resection group (P=0.32). Based on our experience, for lung adenocarcinoma containing solid/micropapillary subtype, a size less than 2 cm, and a CTR ≤0.25, the oncological outcomes appeared to be comparable between sublobar resection and lobectomy, suggesting that sublobar resection might serve as an equivalent alternative to lobectomy for such lesions.

Necrotizing fasciitis of the head and neck in era of COVID-19: a single-institution experience

ObjectivesNecrotizing fasciitis (NF) of the head and neck is a critical condition, known for its severe impact and high mortality rates, often linked with diabetes, odontogenic infections, and immunosuppression. Observations from the University of Ottawa's Department of Otolaryngology – Head and Neck Surgery indicate an increase in NF cases since the COVID-19 pandemic began, suggesting a possible association between COVID-19 and NF. This study aims to assess the incidence of NF since the pandemic's onset and explore its association with COVID-19. DesignConducted as a single-center retrospective review from January 1, 2015 to April 7, 2023, this study included patients aged over 18 years with histopathologic confirmation of NF, analyzing clinical risk factors, treatment, and outcomes. Patients were divided into pre- and post–COVID-19 groups for comparison. ResultsOf 16 patients, 68.7% were in the post–COVID-19 group, with a notable increase in 2022. The most common risk factors were diabetes mellitus (43.8%) and history of odontogenic infection or extraction (31.3%). Only one patient (6.3%) presented with concomitant COVID-19 infection and NF. All patients underwent treatment with serial surgical debridement and intravenous antibiotics with mortality rates rising to 12.5% after the pandemic. ConclusionsOur study demonstrates an increased incidence of NF cases in our institution after the COVID-19 pandemic.

Factors associated with pathological up-staging in MRI cT3a prostate cancer - a retrospective study from a high-volume centre.

Multiparametric MRI (mpMRI) parameters of pT3a prostate cancer have not been examined in large cohort studies. Therefore, we aimed to identify factors associated with up-staging of mpMRI cT3a in post-operative histopathological confirmation. Retrospective analysis of a prospectively maintained database of a single UK cancer centre. Only cT3a cases who underwent robotic-assisted radical prostatectomy (RARP) were included (N = 383). MRI and specimen histopathology was reviewed independently by expert uro-radiologists and uro-histopathologists, respectively. Factors included age, BMI, prostate-specific antigen (PSA) level, biopsy international society of urological pathology (ISUP) grade, Prostate Imaging Reporting & Data System (PI-RADS®) score, tumour size, tumour coverage of gland (%), gland weight and surgical margins were analysed as predictors of pT3a prostate cancer. N = 383. Mean age 66 years (58-71), mean BMI 27.1kg/m2 (25.0-30.0). 314 (82.0%) cases down- unchanged or down-staged, and 69 (18.0%) cases upstaged. PSA level (P = 0.002), PI-RADS score (P < 0.001) and ISUP grade (P < 0.001) are positively associated with upstage categories. ISUP grade ≥3 (OR 5.45, CI 1.88, 9.29, P < 0.002), PI-RADS score ≥4 (OR 3.92, CI 1.88-9.29, P < 0.001) and tumour coverage (OR 1.06, CI 1.05-1.08, P < 0.001) significantly positively associated with upstaging disease, with concurrent decreased probability of downstaging (OR 0.55, 0.14, 0.44, respectively, P < 0.05). Tumour coverage was positively correlated with increasing positive surgical margins (P < 0.05). Capsular contact > 15mm was very unlikely to be upstaged (OR 0.36, CI 0.21-0.62, P < 0.001), aligning with published results past the widely accepted significant level for extracapsular disease on MRI. The study has identified PSA level, ISUP, PI-RADS score, tumour volume and percentage coverage are key predictive factors in cT3a upstaging. This study uniquely shows tumour coverage percentage as a predictor of cT3a upstaging on mpMRI. ISUP is the strongest predictor, followed by PI-RADS score and tumour coverage of gland. Multi-institutional studies are needed to confirm our findings.

Deep learning algorithms for melanoma detection using dermoscopic images: A systematic review and meta-analysis

BackgroundMelanoma is a serious risk to human health and early identification is vital for treatment success. Deep learning (DL) has the potential to detect cancer using imaging technologies and many studies provide evidence that DL algorithms can achieve high accuracy in melanoma diagnostics. ObjectivesTo critically assess different DL performances in diagnosing melanoma using dermatoscopic images and discuss the relationship between dermatologists and DL. MethodsOvid-Medline, Embase, IEEE Xplore, and the Cochrane Library were systematically searched from inception until 7th December 2021. Studies that reported diagnostic DL model performances in detecting melanoma using dermatoscopic images were included if they had specific outcomes and histopathologic confirmation. Binary diagnostic accuracy data and contingency tables were extracted to analyze outcomes of interest, which included sensitivity (SEN), specificity (SPE), and area under the curve (AUC). Subgroup analyses were performed according to human-machine comparison and cooperation. The study was registered in PROSPERO, CRD42022367824. Results2309 records were initially retrieved, of which 37 studies met our inclusion criteria, and 27 provided sufficient data for meta-analytical synthesis. The pooled SEN was 82 % (range 77–86), SPE was 87 % (range 84–90), with an AUC of 0.92 (range 0.89–0.94). Human-machine comparison had pooled AUCs of 0.87 (0.84–0.90) and 0.83 (0.79–0.86) for DL and dermatologists, respectively. Pooled AUCs were 0.90 (0.87–0.93), 0.80 (0.76–0.83), and 0.88 (0.85–0.91) for DL, and junior and senior dermatologists, respectively. Analyses of human-machine cooperation were 0.88 (0.85–0.91) for DL, 0.76 (0.72–0.79) for unassisted, and 0.87 (0.84–0.90) for DL-assisted dermatologists. ConclusionsEvidence suggests that DL algorithms are as accurate as senior dermatologists in melanoma diagnostics. Therefore, DL could be used to support dermatologists in diagnostic decision-making. Although, further high-quality, large-scale multicenter studies are required to address the specific challenges associated with medical AI-based diagnostics.

Cerebral Amyloid Angiopathy-Related Inflammation and Biopsy-Positive Primary Angiitis of the CNS: A Comparative Study.

Cerebral amyloid angiopathy-related inflammation (CAA-RI) and biopsy-positive primary angiitis of the CNS (BP-PACNS) have overlapping clinicoradiologic presentations. It is unknown whether clinical and radiologic features can differentiate CAA-RI from BP-PACNS and whether both diseases have different relapse rates. The objectives of this study were to compare clinicoradiologic presentations and relapse rates in patients with CAA-RI vs BP-PACNS. Patients with CAA-RI and BP-PACNS were enrolled from 2 retrospective multicenter cohorts. Patients with CAA-RI were biopsy-positive or met probable clinicoradiologic criteria. Patients with BP-PACNS had histopathologic confirmation of CNS angiitis, with no secondary etiology. A neuroradiologist read brain MRIs, blinded to the diagnosis of CAA-RI or BP-PACNS. Clinicoradiologic features were compared using univariable logistic regression models. Relapse rates were compared using a univariable Fine-Gray subdistribution hazard model, with death as a competing risk. This study enrolled 104 patients with CAA-RI (mean age 73 years, 48% female sex) and 52 patients with BP-PACNS (mean age 45 years, 48% female sex). Patients with CAA-RI more often had white matter hyperintense lesions meeting the probable CAA-RI criteria (93% vs 51%, p < 0.001), acute subarachnoid hemorrhage (15% vs 2%, p = 0.02), cortical superficial siderosis (27% vs 4%, p < 0.001), ≥1 lobar microbleed (94% vs 26%, p < 0.001), past intracerebral hemorrhage (17% vs 4%, p = 0.04), ≥21 visible centrum semiovale perivascular spaces (34% vs 4%, p < 0.01), and leptomeningeal enhancement (70% vs 27%, p < 0.001). Patients with BP-PACNS more often had headaches (56% vs 31%, p < 0.01), motor deficits (56% vs 36%, p = 0.02), and nonischemic parenchymal gadolinium enhancement (82% vs 16%, p < 0.001). The prevalence of acute ischemic lesions was 18% in CAA-RI and 22% in BP-PACNS (p = 0.57). The features with the highest specificity for CAA-RI were acute subarachnoid hemorrhage (98%), cortical superficial siderosis (96%), past intracerebral hemorrhage (96%), and ≥21 visible centrum semiovale perivascular spaces (96%). The probable CAA-RI criteria had a 71% sensitivity (95% CI 44%-90%) and 91% specificity (95% CI 79%-98%) in differentiating biopsy-positive CAA-RI from BP-PACNS. The rate of relapse in the first 2 years after remission was lower in CAA-RI than in BP-PACNS (hazard ratio 0.46, 95% CI 0.22-0.96, p = 0.04). Clinicoradiologic features differed between patients with CAA-RI and those with BP-PACNS. Specific markers for CAA-RI were hemorrhagic signs of subarachnoid involvement, past intracerebral hemorrhage, ≥21 visible centrum semiovale perivascular spaces, and the probable CAA-RI criteria. A biopsy remains necessary for diagnosis in some cases of CAA-RI. The rate of relapse in the first 2 years after disease remission was lower in CAA-RI than in BP-PACNS.

Solitary cutaneous neoplasms: analysing the uncertain behaviour with the aid of histopathology

BACKGROUND: Skin tumours can be classified as either benign or malignant, resulting due to the proliferation of one or more components of the skin. Reportedly, there has been a rise in the prevalence of skin cancer in recent decades, which has led to rely on histological evidence to distinguish between various types of skin cancer. AIM: This study aims to provide a comprehensive description of the occurrence, symptoms, unpredictable nature, and range of histopathological spectrum in different types of skin tumours. METHODS: This prospective research was conducted in the outpatient department of the Department of Dermatology at the Government General Hospital in Anantapur from July 2019 to July 2023. Patients who did not provide informed consent, those with infectious or cystic swellings, or those with multiple lesions were excluded from this study. Histopathological confirmation is obtained from all excisional biopsies of single cutaneous swellings, and tumours are classified based on the criteria established by the World Health Organization (WHO). RESULTS: The study included a total of 123 individual cutaneous tumours, with 98 cases (79.67%) being classified as benign and 25 cases (20.32%) classified as malignant. The age group most affected is adults between the ages of 26 and 44, with a prevalence rate of 31.7%. Following closely behind are middle-aged individuals, with a prevalence rate of 30.08%. The males constitute 46.34% (57 cases) and the females constitutes 53.65% (66 cases). The extremities were the most frequently affected site, accounting for 53 cases (43.08%), followed by the head and neck region (29.26%). Based on the WHO classification of skin tumours, there were 42 cases (34.14%) of subcutaneous tissue tumours and 31 cases (25.20%) of soft tissue tumours. The prevalence of keratinocyte tumours is 26 (21.13%), whereas appendageal tumours account for 16 (13%) of cases. Melanocytic and neural tumours are the least prevalent, each representing 4 (3.25%) of cases. The majority of benign tumours arise from the subcutaneous tissues, whereas malignant tumours grow from keratinocytic differentiation. CONCLUSION: Our study revealed that the majority of tumours displayed ambiguous clinical behaviour, which resulted in erroneous diagnoses. Hence confirmation by histopathology is crucial for accurate diagnosis and prompt management.

Diagnostic and Prognostic Values of miRNAs in High-Grade Gliomas: A Systematic Review

Abstract* Background Gliomas, particularly glioblastomas, have grim prognoses, necessitating early diagnostic and prognostic indicators. MicroRNAs (miRNAs), influential in cancer research, show potential as glioma biomarkers. This systematic review aimed to examine the efficacy of miRNAs in the diagnosis and prognosis of high-grade glioma. Methods A comprehensive search was conducted of PubMed, EMBASE, Cochrane Library, and Web of Science for studies published from 2013 to 2023. The eligibility criteria included high-grade glioma, histopathological confirmation, miRNA samples from cerebrospinal fluid or plasma, and relevant outcome data. Studies were excluded if they were experimental or reviews and not in English. Results Of the 1120 initial results, 8 studies involving 660 subjects met the inclusion criteria. Several studies have assessed miRNA expression and its association with diagnosis and prognosis of high-grade gliomas. Overexpression of miR-221, miR-222, miR-210, miR-21, miR-125b, and miR-223 and under-expression of miR-15b and miR-124-3p showed significant potential in differentiating high-grade glioma patients from controls. Additionally, miRNAs are associated with distinct tumorigenic pathways. Conclusion Elevated or depressed expression levels of specific circulating miRNAs hold significant promise as noninvasive biomarkers for the diagnosis and prognosis of high-grade glioma. These miRNAs offer valuable insights into disease progression and patient outcome. Further validation through extensive clinical trials and in-depth mechanistic studies is essential to realize their full clinical utility.

Assessing DNA methylation of ATG 5 and MAP1LC3Av1 gene in oral squamous cell carcinoma and oral leukoplakia- a cross sectional study

BackgroundThe progression and pathogenesis of oral cancer is greatly impacted by epigenetic modifications, such as DNA methylation. Autophagy, is an adaptive mechanism used to maintain the survival and integrity of cells. Oral squamous cell carcinoma is linked to a number of autophagy indicators, although it is yet unknown if DNA methylation of autophagy-related genes promotes the development of oral leukoplakia (OL), oral squamous cell carcinoma (OSCC). AimOur study was aimed to assess, compare and evaluate the DNA methylation of ATG5 and MAP1LC3Av1 genes in oral leukoplakia, oral squamous cell carcinoma. Materials and methodsThis cross-sectional study was designed with sample size of 48 tissues which was clinically and histopathologically diagnosed as OL, OSCC and normal tissue. The samples were divided into three groups (Group A, Group B, and Group C; (n = 16 each). Following histopathological confirmation, the tissue was stored in the RNA reagent, then subjected to DNA extraction, methylation-sensitive polymerase chain reaction (MS-PCR). DNA methylation of the ATG5 and MAP1LC3Av1 genes were assessed. ResultsShapiro-Wilk and Kolmogorov-Smirnov tests showed that the values were normally distributed. Both the ATG5 and MAP1LC3Av1 genes were methylated in OSCC, OL tissues compared to normal tissues. A statistically significant results was seen among the three study groups. ConclusionA significant difference was noted in the hypermethylation status of the promoter regions of the ATG5 and MAP1LC3Av1 genes. This provides some insight into their crucial role in the development of tumors. Future research with larger sample is needed to assess its potential clinical implications in oral carcinoma.

Intraoperative and Postoperative Outcomes of Pfannenstiel and Midline Skin Incisions in Placenta Accreta Spectrum Disorders: Single-Center Experience.

Background: We compared Pfannenstiel and midline skin incisions for cesarean hysterectomy in women with confirmed Placenta Accreta Spectrum Disorders. Aims: A retrospective cohort study was conducted to evaluate the outcomes of Pfannenstiel and midline skin incisions in women undergoing cesarean section hysterectomy for suspected placenta accreta at Akdeniz University Hospital between January 2010 and February 2022. Histopathological confirmation was obtained for all cases. Demographic, perioperative, and postoperative data, along with neonatal outcomes, were extracted from the hospital's electronic database. Possible complaints related to the incision site or other issues (e.g., vaginal dryness or sexual life) were identified through telephone interviews. Subjects were stratified into Pfannenstiel and midline incision cohorts, with subsequent data comparison. Results: Data from 67 women with a histopathologically confirmed PAS diagnosis were analyzed. Of these, 49 (73.1%) underwent Pfannenstiel incision, and 18 (26.9%) had a midline skin incision. Incisions were based on the surgeon's experience. Pfannenstiel incision was more common in antepartum hemorrhage, preoperative hemorrhage, and emergency surgery (p = 0.02, p = 0.014, p = 0.002, respectively). Hypogastric artery ligation occurred in 30 cases (61.2%) in the Pfannenstiel group but none in the midline group. Cosmetic dissatisfaction and sexual problems were more prevalent in the midline group (p < 0.05, all). Preoperative and postoperative blood parameters, transfused blood products, and neonatal outcomes were similar between the two groups. Conclusions: Relaparotomy, bladder injury, blood loss, and need for blood transfusion were more prevalent in the Pfannenstiel group, while greater dissatisfaction with the incision was observed in the midline incision group. Midline incision seems to be more favorable in patients with Placenta Accreta Spectrum (PAS). Patients may be informed regarding the worse cosmetic outcomes and possible sexual problems related to vaginal dryness when midline laparotomy is planned. But before opting for a Pfannenstiel incision, patients should receive comprehensive information regarding the potential risks of relaparotomy and bladder injury.

Cardiac sarcoidosis and neurosarcoidosis - multidisciplinary approach for diagnosis.

The current review aims to highlight the role of multidisciplinary approach in the diagnosis of patients with cardiac and neurosarcoidosis. Multidisciplinary approach integrates the available clinical information, imaging and histopathological results aiming to reach a definite or at least provisional diagnosis and allow appropriate management. Multidisciplinary approach is the reference standard for diagnosis of interstitial lung disease and should be strongly considered in complex clinical conditions such as cardiac sarcoidosis (CS) and neurosarcoidosis. Histopathological confirmation of noncaseating granulomatous inflammation provides a definite diagnosis of sarcoidosis involving any organ. However, a provisional high confidence or even definite clinical diagnosis can be reached using multidisciplinary evaluation of all available evidence. The diagnosis of cardiac sarcoidosis and neurosarcoidosis requires the integration of different expertise based on the current diagnostic criteria sets. Identifying typical or at least compatible patterns on advanced imaging modalities (CMR and Fluro-Deoxy-Glucose Positron Emission Tomography (FDG-PET)) seems key for the diagnosis of CS, while a confident diagnosis of extra-cardiac disease supports an at least provisional diagnosis. Similarly, in neurosarcoidosis integrating compatible MRI appearances and cerebrospinal fluid results in patients with systemic sarcoidosis allows an at least provisional diagnosis. Exclusion of alternative differential diagnoses is crucial and requires high clinical suspicion, imaging review expertise and appropriate tests performance. There have been considerable advances in the diagnostic approach of patients with cardiac and neurosarcoidosis. Multidisciplinary approach for both diagnosis and management is required to reach a confident clinical diagnosis and should be applied when possible.

Intravenous Immunoglobulins for Recurrent Chronic Histiocytic Intervillositis: A Series of Case Studies.

Chronic histiocytic intervillositis (CHI) is a rare inflammatory placental disease characterized by diffuse infiltration of monocytes into the intervillous space and is associated with adverse pregnancy outcomes. No treatment is currently validated and although in some small reports, steroids with hydroxychloroquine have been described. There are no data for other therapies in refractory cases. We here report four cases of patients with a history of CHI treated with immunoglobulins during a subsequent pregnancy. The four patients with recurrent CHI had failed to previous immunomodulatory therapies with steroids and hydroxychloroquine. All patients had at least four pregnancy losses with histopathological confirmation of CHI for at least one pregnancy loss. The usual pregnancy-loss etiology screening and immunological screening were negative for all the patients. For three patients, intravenous immunoglobulins were initiated at the βHCG positivity at 1g/kg every 15 days until delivery. In one case with combined therapy since the beginning of the pregnancy, intravenous immunoglobulins were introduced at 20 WG because of severe growth restriction. Two patients had live births at 36 WG and one patient at 39 WG. One patient, who presented early first-trimester hypertension and severe placental lesions, failed to intravenous immunoglobulins and had a pregnancy loss at 15 WG. This is the first report demonstrating the potential benefit of intravenous immunoglobulins in recurrent chronic intervillositis. Larger studies are needed to confirm this potential benefit for patients presenting severe cases of recurrent CHI.

Fibrolipoma of the lower lip: A case report and review of the literature.

Fibrolipoma of the lower lip is an uncommon condition with limited documentation in the literature. This paper provides updated insights into oral and maxillofacial lipomas through a detailed case report and comprehensive literature review, discussing clinical features, pathogenesis, diagnostic approaches, histopathology, and therapeutic strategies. A 54-year-old female presented with a painless, enlarging mass on the inner aspect of her right lower lip, first noticed 2 years prior. The mass, now the size of a peanut, interfered with her eating and speech. Physical examination revealed a 2.0 × 2.5 × 1.0 cm mass beneath the mucous membrane of the right lower lip. It was firm, well-demarcated, and mobile. Surgical excision was performed, and histopathological analysis confirmed the diagnosis of a lower lip fibrolipoma. The lesion was successfully removed without recurrence. Lipomas in the oral and maxillofacial regions are rare, slow-growing benign tumors, particularly within the lips. Although their diagnosis is straightforward based on clinical presentation, histopathological confirmation is essential. Surgical resection remains the treatment of choice, with excellent prognostic outcomes.

LMIC-27. MEK INHIBITORS IN PEDIATRIC LOW-GRADE GLIOMAS (PLGG)- EARLY EXPERIENCE IN A RESOURCE LIMITED SETTING

Abstract BACKGROUND Pediatric Low-Grade Gliomas (PLGG), encompass a heterogenous set of tumours, with upregulation of RAS/MAPK pathway, making them amenable to therapeutic targeting. MEK inhibitors are emerging as a promising alternative to conventional chemotherapy strategies which have modest efficacy with significant toxicity/hospitalisation and hence long periods of stay away from home (&amp; school). Recently, we transitioned to use of MEK inhibitors, where feasible, in children with PLGG. METHODOLOGY Retrospective analysis of children(&amp;lt;15 years) with newly diagnosed, recurrent/progressive PLGG who received Trametinib at Tata Memorial Hospital, India between September’2021-October’2023. Diagnosis of PLGG was by histopathology/radiology. Molecular testing was performed by qualitative real-time PCR for BRAFV600E and KIAA1549:BRAF fusion. Decision to start MEK inhibitors was taken at the Neuro-oncology MDT meeting. Financial support for therapy was provided through the childhood cancer foundation (ImPaCCT) and other agencies. RESULTS Twenty four children were treated with Trametinib, of which 22 were evaluable for response (&amp;gt;3 months therapy). Median age at start of Trametinib was 6.4 years(2.3–14.5years). Histopathological confirmation of PLGG was done in 19 patients and 5 had a clinico-radiological diagnosis. 13/18(72%) had KIAA1549:BRAF fusion, and 5 were BRAF-Wild type. While 12/22 children received Trametinib as salvage therapy, 10 children received it upfront. 2 received Trametinib due to chemotherapy intolerance. At a median therapy duration of 18 months(3-28 months), 17/22(77%) showed stable disease and 3/22 showed response(2 Partial and 1 minor) as per RANO criteria. Two patients had disease progression [BRAF status included unavailable (n=1), wild-type (n=1)]. Toxicities noted were skin rash(n=8), paronychia(n=3), oral ulcers(n=2) &amp; thrombocytopenia(n=1). Dose reduction due to toxicity was done in one child. School attendance increased and frequency of hospital visits significantly decreased in this cohort. CONCLUSIONS Early experience with Trametinib as an effective/well tolerated alternative to chemotherapy in PLGG is encouraging. Long-term treatment related toxicities and disease control after Trametinib withdrawal are yet unanswered questions.

MDB-81. THE ROLE OF SURVEILLANCE IMAGING IN DETECTING RECURRENCE OF MEDULLOBLASTOMA

Abstract BACKGROUND In patients with medulloblastoma, imaging with magnetic resonance imaging (MRI) of the brain and spine plays an integral role in surveillance following treatment completion. The primary objective of imaging surveillance is to detect early recurrences, possibly leading to better salvage treatment. However, there is a lack of data to demonstrate the utility of imaging with possible demerits associated with increased resource utilization, scan-related anxiety, and lead or length time bias. METHODS Patients with histopathological confirmation of medulloblastoma treated in our institute between 2005 and 2022 were screened to identify patients with image-detected recurrences and corresponding documentation of symptoms and imaging intent (surveillance or directed by symptoms). RESULTS From a cohort of 545 patients treated during the period, 212 had disease recurrence, of which 153 had known symptomatology during the first recurrence. A total of 114 patients (75%) were having recurrence detected prompted by symptoms. Group 4 medulloblastomas were commonly seen to have recurrence detected on surveillance imaging (35%) compared to the SHH subgroup (25%) and group 3 (12%). During the final analysis, 141 of 153 patients had died. The median survival of patients detected to have asymptomatic relapse was 14 months compared to 5 months for symptomatic recurrences (p=0.03). The overall survival (calculated from index diagnosis) was not statistically significant between the two groups, with a 3-year survival of 53% (asymptomatic) vs 46% (symptomatic) (p=0.51). CONCLUSION In most patients, recurrences were detected by unplanned imaging ahead of scheduled surveillance imaging prompted by symptoms. Although the survival after recurrence is better in patients diagnosed on surveillance imaging, the overall survival was not different between the two groups, suggesting the possibility of lead time bias. Prospective studies are warranted to determine the role and appropriate frequency of surveillance imaging in patients with medulloblastoma.

Assessment of quality of life among breast cancer patients undergoing different Treatment Modalities at tertiary hospitals in north Karnataka, India

IntroductionBreast cancer treatment is an aggressive therapy that affects the patient's quality of life (QoL). This study aims to assess the impact of breast cancer treatment on the QoL of breast cancer patients undergoing treatment. MethodsThis cross-sectional study was conducted among breast cancer patients attending two tertiary care hospitals between August 2021 to December 2022. QoL of female patients above 18 years of age with a histopathological confirmation of Stage I-III breast cancer and an ECOG Performance Status between 0 and 1 was assessed using European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ C30) and Breast Cancer Specific Quality of Life Questionnaire (QLQ BR 23). Kruskal -Wallis and Mann Whitney U tests were used to assess the impact of treatment on QoL of breast cancer patients. Linear regression was used to identify predictors of QoL. ResultsA total of 428 respondents with a mean age of 48.67 years participated in the study. Mean score for Global Health Status was 59.87. High mean scores for functional scales were observed in cognitive functioning (79.17), followed by role functioning (72.04) and physical functioning (71.45). Among the symptom scales, high scores were noted for financial difficulty (67.60) followed by hair loss (54.52). QoL score of patients who underwent surgery was high (54.93) as compared to patients undergoing radiation (49.37) and chemotherapy (44.96). ConclusionThe overall QoL of women with breast cancer undergoing treatment was good. QoL of patients undergoing chemotherapy was the lowest, while patients who underwent surgery exhibited a better QoL.

LIBRETTO-432: A phase 3 study of adjuvant selpercatinib or placebo in stage IB-IIIA RET fusion-positive (RET+) NSCLC.

TPS8115 Background: Around 30% of NSCLC patients (pts) present with stage IB-IIIA disease. Standard treatment options are definitive locoregional therapies w/wo chemotherapy (CT) and/or immunotherapy, followed by surveillance until disease recurrence. Targeted therapies are standard for metastatic NSCLC with driver alterations and recent Phase III trial data has emerged in support of their use in the adjuvant setting for stage IB-IIIA (ADAURA and ALINA). RET is a key oncogenic driver in NSCLC and a promising target for adjuvant targeted therapy. Selpercatinib, a highly selective, potent and CNS active RET inhibitor, recently demonstrated longer PFS than platinum-based CT as 1L treatment in pts with RET+ advanced NSCLC (Zhou et al. NEJM 2023). LIBRETTO-432 is a Phase 3, global, multicenter, randomized, double-blind, controlled trial evaluating efficacy and safety of adjuvant selpercatinib v Placebo in pts with RET+ Stage IB-IIIA NSCLC following completion of definitive therapies with curative intent, and other adjuvant therapy if indicated (NCT04819100). Methods: Pts (n≈170) will be randomized (1:1) to selpercatinib BID [160mg ≥50kg; 120mg &lt; 50kg], or Placebo, in continuous 28-day cycles for a maximum treatment duration of 3y. Stratification factors include disease stage (IB/II/IIIA) and prior definitive therapy. Treatment will continue until disease recurrence/progression, unacceptable toxicity, or another protocol-defined reason. Crossover is allowed for Placebo pts who experience disease recurrence/progression. Key eligibility criteria include age ≥18 y; histologically confirmed Stage IB/II/IIIA NSCLC; RET+ tumor by PCR/NGS; prior definitive locoregional therapy with curative intent (surgery, radiotherapy) for Stage IB/II/IIIA NSCLC; and ECOG performance status 0-1. Maximum time allowed from definitive therapy completion to randomization is 26 w. Key exclusion criteria are evidence of other known oncogenic drivers; SCLC; and disease recurrence/progression following definitive therapy. Primary endpoint is investigator-assessed event-free survival (IAEFS) in the primary analysis population (pts with Stage II-IIIA). EFS is defined as time from randomization until locoregional disease recurrence with histopathological confirmation, distant disease recurrence per RECIST v1.1 or histopathological confirmation, or death. Gated secondary endpoints include IAEFS in the overall population (pts with Stage IB-IIIA) and OS in both primary analysis and overall populations. Non-gated secondary efficacy endpoints include BICR-assessed EFS, BICR and investigator-assessed time to distant disease recurrence in the CNS, and PFS on next line of treatment. Recruitment is ongoing, with enrollment across ~170 sites and 30 countries. Results from this trial will further inform the value of RET inhibition and genomic testing for adjuvant NSCLC pts. Clinical trial information: NCT04819100 .

Cytomegalovirus-Associated Colitis as a Cause of Lower Gastrointestinal Bleeding in Kidney Transplant Recipients: A Single-Centered Study.

Introduction Cytomegalovirus (CMV) is the most common viral pathogen affecting patients undergoing solid organ transplantation. It is often the most important infection for patients who have undergone kidney transplantation. Clinical presentations of cytomegalovirus infection range from asymptomatic infection to organ-specific involvement. This study aimed to determine the frequency of cytomegalovirus-associated colitis in kidney transplant recipients (KTRs) presenting with lower gastrointestinal bleeding. Methods After the approval of the ethical review committee of the Sindh Institute of Urology and Transplantation (ERC-SIUT), this cross-sectional study was conducted at the Department of Hepatogastroenterology at the Sindh Institute of Urology and Transplantation from January 2021 to December 2021. All the KTRs (six months after the transplantation) of either gender and aged between 18 and 65 years, presenting with lower gastrointestinal (GI) bleeding as per the operational definition, were enrolled in the study. Those patients who were either unfit for the endoscopy or refused to give consent were excluded from the study. Colonic biopsies were reviewed by a consultant histopathologist for the features of CMV infection. Results A total of 95 renal transplant recipients of either gender or age above 18 to 65 years with lower GI bleeding were included in the study. Among them, 84 (88.4%) were males, while 11 (11.6%) were females. The mean age of the patients included in the study was 37±11 years. The most common presenting complaint was fresh bleeding per rectum, which was observed in 73 (76.8%). The most common findings observed on colonoscopy in KTRs with bleeding per rectum were colonic ulcers and erosions noted in 41 (43.1%) and 36 (37.3%) patients, respectively. On histopathology, CMV colitis was noted in 21 (22.1%) patients. On comparison of different baseline variables, the presence of fresh bleeding per rectum and the presence of both ulcers and erosions on colonoscopy were the factors significantly associated with CMV colitis in KTRs. Conclusion CMV colitis is a prevalent condition in KTRs, presenting with lower GI bleeding. Despite the significant occurrence, the levels of CMV viremia were not associated with CMV colitis, suggesting that diagnosis should rely on histopathological confirmation. Prophylaxis during periods of high immunosuppression is crucial to reducing the incidence of CMV infections and improving both graft function and patient survival.