Tumor Histopathology Research Articles

Survival in Patients with Uveal Melanoma Is Linked to Genetic Variation at HERC2 Single Nucleotide Polymorphism rs12913832

Uveal melanoma (UM) is a rare disease, with the highest incidence in people with fair skin and light eyes. Eye color is largely genetically determined and is defined by a set of single nucleotide polymorphisms (SNPs). We set out to determine whether we could identify a SNP related to prognosis. We sequenced DNA from peripheral blood mononuclear cells of 392 patients with UM and obtained the genotype of 6 common eye color-related SNPs. Clinical and histopathologic tumor characteristics, tumor chromosome status, and patient survival were compared among patients with different genotypes. Three hundred ninety-two patients who underwent enucleation for UM at the Leiden University Medical Center, Leiden, The Netherlands. We isolated DNA from peripheral blood leukocytes of 392 patients with UM and performed sequencing, using 6 eye color SNPs from the HIrisPlex-S assay (Erasmus MC, Walsh lab). The genotypes extracted from the sequencing data were uploaded onto the HIrisPlexwebtool (https://hirisplex.erasmusmc.nl/) for eye color prediction. We tested the association of eye color SNPs with tumor characteristics and chromosome aberrations using Pearson's chi-square test and the Mann-Whitney U test and evaluated survival with Kaplan-Meier curves with the log-rank test and Cox regression. Uveal melanoma-related survival. Of 392 patients with analyzable genotype data, 307 patients (78%) were assigned blue eyes, 74 patients (19%) were assigned brown eyes, and 11 patients (3%) could not be assigned to either blue or brown. Patients with a genetically blue eye color showed worse survival (P= 0.04). This was related to 1 genotype: patients with the G/G genotype of rs12913832 (HERC2), which codes for blue eye color showed a worse prognosis (P= 0.017) and more often had high-risk tumors (monosomy of chromosome 3; P= 0.04) than in patients with an A/G or A/A genotype. The G/G genotype of rs12913832 (HERC2), which is related to blue eye color, not only is a genetic factor related to the risk of UM develop, but also is linked to a worse prognosis because of an association with a higher risk of a high-risk UM developing (carrying monosomy of chromosome 3). The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Clinical Outcomes and Histologic Findings of Patients With Hepatocellular Carcinoma With Durable Partial Response or Durable Stable Disease After Receiving Atezolizumab Plus Bevacizumab.

Durable partial response (PR) and durable stable disease (SD) are often seen in patients with hepatocellular carcinoma (HCC) receiving atezolizumab plus bevacizumab (atezo-bev). This study investigates the outcome of these patients and the histopathology of the residual tumors. The IMbrave150 study's atezo-bev group was analyzed. PR or SD per RECIST v1.1 lasting more than 6 months was defined as durable. For histologic analysis, a comparable real-world group of patients from Japan and Taiwan who had undergone resection of residual tumors after atezo-bev was investigated. In the IMbrave150 study, 56 (77.8%) of the 72 PRs and 41 (28.5%) of the 144 SDs were considered durable. The median overall survival was not estimable for patients with durable PR and 23.7 months for those with durable SD. The median progression-free survival was 23.2 months for patients with durable PR and 13.2 months for those with durable SD. In the real-world setting, a total of 38 tumors were resected from 32 patients (23 PRs and nine SDs) receiving atezo-bev. Pathologic complete responses (PCRs) were more frequent in PR tumors than SD tumors (57.7% v 16.7%, P = .034). PCR rate correlated with time from atezo-bev initiation to resection and was 55.6% (5 of 9) for PR tumors resected beyond 8 months after starting atezo-bev, a time practically corresponding to the durable PR definition used for IMbrave150. We found no reliable radiologic features to predict PCR of the residual tumors. Durable PR patients from the atezo-bev group showed a favorable outcome, which may be partly explained by the high rate of PCR lesions. Early recognition of PCR lesions may help subsequent treatment decision.

Serous Tubal Intraepithelial Carcinoma After Neoadjuvant Chemotherapy: A Report of 2 Cases.

Serous tubal intraepithelial carcinoma (STIC) is regarded as the origin of most high-grade serous carcinomas (HGSC). After a diagnosis of isolated STIC, risk of developing HGSC is substantial. Since surveillance cannot detect HGSC in time to cure the disease, there is no consensus on the optimal treatment after a diagnosis of isolated STIC, but chemotherapy is considered one of the possible strategies. In this case report, we describe 2 women with advanced-stage HGSC treated with 3 cycles of neoadjuvant chemotherapy followed by interval debulking surgery. In both women, histopathological examination showed a complete histopathological tumor response, but a vital STIC was found in both cases. The 2 cases presented here indicate that STICs may not respond to chemotherapy. Further research focused on the underlying biology and chemosensitivity of STIC, as well as the effectiveness of treatment to prevent HGSC in case of isolated STIC, is needed.

Effectiveness of Apparent Diffusion Coefficient Values in Predicting Pathologic Subtypes and Grade in Non-Small-Cell Lung Cancer.

The aim of this study is to evaluate the effectiveness of apparent diffusion coefficient (ADC) values in predicting pathologic subtypes and grade in non-small-cell lung cancer (NSCLC). From January 2018 to March 2020, 48 surgically diagnosed NSCLC cases were included in this study. To obtain ADC values, ADC maps were constructed, and a region of interest was put on the tumor. The values were measured three times from different places of the lesion, and the mean value of these measurements was recorded. All MRI scans were evaluated by two radiologists in consensus. A total of 14 cases were squamous cell cancer, 32 cases were adenocarcinoma, and 2 cases were large cell carcinoma. The mean ADC values of adenocarcinoma, squamous cell carcinoma, and large cell cancer were 1.51 ± 0.19 × 10-3 mm2/s, 1.32 ± 0.15 × 10-3 mm2/s, and 1.39 ± 0.25 × 10-3 mm2/s, respectively. There were 11 grade 1, 27 grade 2, and 10 grade 3 NSCLC cases. The mean ADC value was 1.44 ± 0.14 × 10-3 mm2/s in grade 1 tumors, 1.25 ± 0.10 × 10-3 mm2/s in grade 2 tumors, and 1.07 ± 0.15 × 10-3 mm2/s in grade 3 tumors. The cut-off value to discriminate grade 2 from grade 1 tumors was 1.31 ± 0.11 × 10-3 mm2/s (85% sensitivity, 75% specificity). The cut-off value to discriminate grade 3 from grade 2 tumors was 1.11 ± 0.15 × 10-3 mm2/s (87% sensitivity, 69% specificity). ADC values can accurately predict NSCLC histopathologic subtypes and tumor grade.

Accuracy of Intra-Axial Brain Tumor Characterization in the Emergency MRI Reports: A Retrospective Human Performance Benchmarking Pilot Study.

Demand for emergency neuroimaging is increasing. Even magnetic resonance imaging (MRI) is often performed outside office hours, sometimes revealing more uncommon entities like brain tumors. The scientific literature studying artificial intelligence (AI) methods for classifying brain tumors on imaging is growing, but knowledge about the radiologist's performance on this task is surprisingly scarce. Our study aimed to tentatively fill this knowledge gap. We hypothesized that the radiologist could classify intra-axial brain tumors at the emergency department with clinically acceptable accuracy. We retrospectively examined emergency brain MRI reports from 2013 to 2021, the inclusion criteria being (1) emergency brain MRI, (2) no previously known intra-axial brain tumor, and (3) suspicion of an intra-axial brain tumor on emergency MRI report. The tumor type suggestion and the final clinical diagnosis were pooled into groups: (1) glial tumors, (2) metastasis, (3) lymphoma, and (4) other tumors. The final study sample included 150 patients, of which 108 had histopathological tumor type confirmation. Among the patients with histopathological tumor type confirmation, the accuracy of the MRI reports in classifying the tumor type was 0.86 for gliomas against other tumor types, 0.89 for metastases, and 0.99 for lymphomas. We found the result encouraging, given the prolific need for emergency imaging.

Targeted gene sequencing reveals disparate genomic mutations between young and older adults in renal cell carcinoma

BackgroundRenal cell carcinoma (RCC) is a type of cancer that can develop at any point in adulthood, spanning the range of age-related changes that occur in the body. However, the specific molecular mechanisms underlying the connections between age and genetic mutations in RCC have not been extensively investigated.MethodsClinical and genetic data from patients diagnosed with RCC were collected from two prominent medical centers in China as well as the TCGA dataset. The patients were categorized into two groups based on their prognosticated age: young adults (YAs) and older adults (OAs). Univariate and multivariate analysis were employed to evaluate the relationships between age and genetic mutations. Furthermore, a mediation analysis was conducted to assess the association between age and overall survival, with genetic disparities serving as a mediator.ResultsOur analysis revealed significant differences in clinical presentation between YAs and OAs with RCC, including histopathological types, histopathological tumor stage, and sarcomatoid differentiation. YAs were found to have lower mutation burden and significantly mutated genes (SMGs) of RCC. However, we did not observe any significant differences between the two groups in terms of 10 canonical oncogenic signaling pathways-related genes mutation, telomerase-related genes (TRGs) mutation, copy number changes, and genetic mutations associated with clinically actionable targeted drugs. Importantly, we demonstrate superior survival outcomes in YAs, and we confirmed the mediating effect of genetic disparities on these survival outcome differences between YAs and OAs.ConclusionOur findings reveal previously unrecognized associations between age and the molecular underpinnings of RCC. These associations may serve as valuable insights to guide precision diagnostics and treatments for RCC.

Initial interpretation scores of screening mammograms and cancer detection in BreastScreen Norway

PurposeTo explore the association between radiologists’ interpretation scores, early performance measures and cumulative reading volume in mammographic screening. MethodWe analyzed 1,689,731 screening examinations (3,379,462 breasts) from BreastScreen Norway 2012–2020, all breasts scored 1–5 by two independent radiologists. Score 1 was considered negative/benign and score ≥2 positive in this scoring system. We performed descriptive analyses of recall, screen-detected cancer, positive predictive value (PPV) 1, mammographic features and histopathological characteristics by breast-based interpretation scores, and cumulative reading volume by examination-based interpretation scores. ResultsCounting breasts and not women, 3.9 % (132,570/3,379,462) had a score of ≥2 by one or both radiologists. Of these, 84.8 % (112,440/132,570) were given a maximum score 2. Total recall rate was 1.6 % (53,735/3,379,462), 69.3 % (37,220/53,735) given maximum score 2. Among the 0.3 % (9733/3,379,462) diagnosed with screen-detected cancer, 34.6 % (3369/9733) had maximum score 3. The percentages of recall, screen-detected cancer and PPV-1 increased by increasing the sum of scores assigned by two radiologists (p < 0.001 for trend). Higher proportions of masses were observed among recalls and screen-detected cancers with low scores, and higher proportions of spiculated masses were observed for high scores (p < 0.001). Proportions of invasive carcinoma, histological grade 3 and lymph node positive tumors were higher for high versus low scores (p < 0.001). The proportion of examinations scored 1 increased by cumulative reading volume. ConclusionsWe observed higher rates of recall and screen-detected cancer and less favorable histopathological tumor characteristics for high versus low interpretation scores. However, a considerable number of recalls and screen-detected cancers had low interpretation scores.

Direct correlation of MR-DWI and histopathology of Wilms' tumours through a patient-specific 3D-printed cutting guide.

The International Society of Paediatric Oncology-Renal Tumour Study Group (SIOP-RTSG) discourages invasive procedures to determine the histology of paediatric renal neoplasms at diagnosis. Therefore, the histological subtype of Wilms' tumours (WT) is unknown at the start of neoadjuvant chemotherapy. MR-DWI shows potential value as a non-invasive biomarker through apparent diffusion coefficients (ADCs). This study aimed to describe MR characteristics and ADC values of paediatric renal tumours to differentiate subtypes. Children with a renal tumour undergoing surgery within the SIOP-RTSG 2016-UMBRELLA protocol were prospectively included between May 2021 and 2023. In the case of a total nephrectomy, a patient-specific cutting guide based on the neoadjuvant MR was 3D-printed, allowing a correlation between imaging and histopathology. Whole-tumour volumes and ADC values were statistically compared with the Mann-Whitney U-test. Direct correlation on the microscopic slide level was analysed through mixed model analysis. Fifty-nine lesions of 54 patients (58% male, median age 3.0 years (range 0-17.7 years)) were included. Forty-four lesions involved a WT. Stromal type WT showed the lowest median decrease in volume after neoadjuvant chemotherapy (48.1 cm3, range 561.5-(+)332.7 cm3, p = 0.035). On a microscopic slide level (n = 240 slides) after direct correlation through the cutting guide, stromal areas showed a significantly higher median ADC value compared to epithelial and blastemal foci (p < 0.001). With a cut-off value of 1.195 * 10-3 mm2/s, sensitivity, and specificity were 95.2% (95% confidence interval 87.6-98.4%) and 90.5% (95% confidence interval 68.2-98.3%), respectively. Correlation between histopathology and MR-DWI through a patient-specific 3D-printed cutting guide resulted in significant discrimination of stromal type WT from epithelial and blastemal subtypes. Stromal Wilms' tumours could be discriminated from epithelial- and blastemal lesions based on high apparent diffusion coefficient values and limited decrease in volume after neoadjuvant chemotherapy. This may aid in future decision-making, especially concerning discrimination between low- and high-risk neoplasms. MR-DWI shows potential value as a non-invasive biomarker in paediatric renal tumours. The patient-specific cutting guide leads to a correlation between apparent diffusion coefficient values and Wilms' tumour subtype. Stromal areas could be discriminated from epithelial and blastemal foci in Wilms' tumours based on apparent diffusion coefficient values.

Prediction of nodal disease in oral squamous cell carcinoma of the tongue: histopathological risk assessment with the focus on depth of invasion.

Cervical lymph node metastasis (CLNM) is one of the most relevant influencing factors for the oncological outcome of patients with oral squamous cell carcinoma (OSCC). Several studies showed that the tumors depth of invasion (DOI) influences the risk for CLNM, however varying across the oral subsites. The aim of this study is to investigate the role of DOI and other risk factors in OSCC of the tongue in relation to the occurrence of occult CLNM. In this retrospective study, n = 139 patients with primary OSCC of the tongue, treated by complete surgical resection (R0) with curative intention between 2013 and 2021, were included. For data analysis, epidemiologic data as well as preoperative tumor staging, surgical therapy including neck management, histopathological tumor data and follow-up were considered. Uni- and multivariate logistic regression were used to determine association between histopathological risk factors and the occurrence of occult CLNM. The rate of occult cervical metastasis was 19.4%. T-staging, cervical nodal disease (pN+) and lymphatic invasion were significantly associated with reduced OS and RFS. While DOI had no relevant influence on the OS and RFS (p = 0.88 and p = 0.91 respectively), there was significant correlation between DOI and the occurrence of occult CLNM (OR: 1.17, 95%CI: 1.05-1.30; p < 0.01). The optimal cutoff in predicting occult CLNM was 6mm (Sensitivity: 84.2%, Specificity: 73.5%, AUC: 0.75). The DOI is a helpful risk parameter to predict the occurrence of occult nodal disease in OSCC of the tongue. Given the critical decision cutoff between 2 and 4mm DOI for performing elective neck dissection in the current guidelines, our data suggests that in these cases, surgical de-escalation could be feasible with close follow-up. This study highlights the relevance of DOI as a risk parameter in the prediction of CLNM with the aim to specify the individual patient risk and to deescalate surgical therapy in order to decrease comorbidities while improving the oncological prognosis.

Clinical characteristics and surgical outcomes of vertebral lesions associated with tumor-induced osteomalacia: report of 16 patients and review of the literature

SummaryVertebral tumors in patients with tumor-induced osteomalacia (TIO) have a low diagnostic rate and poor postoperative outcomes. The application of 68 Ga-DOTATATE-PET/CT significantly increased the detection rate. Compared with tumor curettage, segmental resection was recommended as the preferred surgical type due to its high recovery rate.PurposeTumor-induced osteomalacia (TIO) is an acquired hypophosphatemic osteomalacia, and surgery is the first-line therapy. Most TIO tumors are found in the bones of the appendicular skeleton, cranium, and paranasal sinuses but rarely in the vertebrae. Tumor curettage and segmental resection are the two main surgical options for vertebral TIO patients. However, research on the clinical characteristics and surgical prognosis of vertebral TIO patients is rare. In the present study, for the first time, we investigated the clinical characteristics of 16 vertebral TIO patients and compared the surgical outcomes of patients who underwent surgery via two different surgical methods.MethodsThis was a retrospective cohort study. In this study, we included 16 adult TIO patients with lesions in vertebrae from Peking Union Medical College Hospital (PUMCH), all of whom underwent surgery. Baseline laboratory data were collected through medical records review. Technetium-99 m octreotide scintigraphy (99Tcm-OCT) and 68gallium-DOTA-TATE-positron emission tomography/computed tomography (68 Ga-DOTATATE-PET/CT) were conducted at the Department of Nuclear Medicine of PUMCH. The tumor histopathology was confirmed by a senior pathologist at our center.ResultsVertebral TIO patients had lower serum phosphorus and TmP/GFR and higher serum alkaline phosphatase (ALP), serum parathyroid hormone (PTH), and serum C-terminal cross-linked telopeptide of type I collagen (β-CTX) levels than the normal range. The sensitivity of 68 Ga‒DOTATATE PET/CT was 100%, significantly greater than that of 99Tcm-OCT (40%). After comparing the outcomes between the two surgical methods, we found that the recovery rate after segmental resection (62.5%) was greater than that after tumor curettage (12.5%). In the thoracic and sacral vertebrae, segmental resection surgery had a good prognosis.Conclusion68 Ga-DOTATATE PET/CT could serve as the first diagnostic tool in patients with vertebral TIO, and segmental resection could be used as the preferred surgery. This study would raise awareness of the clinical features and management of these rare vertebral TIO patients.

Effects of Simvastatin on Inflammatory Response and Biological Behaviour of Adamantinomatous Craniopharyngioma

Introduction: The aim of this study was to investigate the autoinflammatory effect and biological behaviour of simvastatin (SIM) on adamantinomatous craniopharyngioma (ACP) cells. Methods: Craniopharyngiomas imaging, intraoperative observations, and tumour histopathology were employed to investigate the correlation between esters and craniopharyngiomas. Filipin III fluorescent probe verified the validity of SIM on the alternations of synthesized cholesterol in craniopharyngioma cells. The cell counting kit-8 (CCK8) assay detected the impacts of SIM on cell proliferation and determined the IC50 value of tumour cells. Reverse transcription polymerase chain reaction (RT-PCR) measured the expression of inflammatory factors. Flow cytometry technique detected the cell cycle and apoptosis, and cell scratch assay judged the cell migration. Meanwhile, Western blot was adopted to determine the expression of proteins related to inflammation, proliferation, and apoptosis signalling pathways. Results: In the ACP tumour parenchyma, many cholesterol crystalline clefts were observed, and the deposition of esters was closely associated with craniopharyngioma inflammation. After SIM intervention, a reduction in cholesterol synthesis within ACP was noted. RT-PCR analysis revealed SIM inhibited the transcription of inflammatory factors in ACP cells. Western blot analysis demonstrated SIM inhibited nuclear factor-kappa B p65 activation expression while promoted the expressions of Cl-caspase-3 and P38 MAPK. CCK8 assay indicated a decrease in ACP cell activity upon SIM treatment. Scratch assay signified that SIM hindered ACP cell migration. Flow cytometry results suggested that the drug promoted ACP cell apoptosis. Conclusion: SIM suppressed the inflammatory response to craniopharyngiomas by inhibiting craniopharyngioma cholesterol synthesis, inhibited proliferation of ACP cells, and promoted their apoptosis.

Clinical characteristics and factors associated with survival rate of patients with non-muscle invasive bladder cancer attending at a Tertiary Hospital in Somalia

BackgroundA few studies regarding the epidemiology and risk factors of Non-muscle Invasive Bladder Cancer (NMIBC) are reported from Sub-Saharan African countries (SSA), including Somalia, and the African literature is scant on the management of NMIBC. The present study aims to evaluate the clinical-histopathological characteristics and factors associated with the survival rate of patients with NMIBC.MethodThis six-year cohort study included 196 patients with NMIBC. It reviewed the clinical and histopathological characteristics and factors predicting cancer-specific survival for these patients.ResultsThe mean patient age was 59.01 ± 11.50 years, with a male-to-female ratio of 2.8:1. Urothelial carcinoma (UC) constituted the most common pathological type, accounting for 90.8%; Ta LG and T1HG were the most common histopathological tumour stage and grade (n = 90, 45.9%, vs. n = 56, 28.6%), respectively. The mean tumour size was 4.72 ± 2.81 cm. The cancer-specific mortality(CSM) was 13.3%. Age [2.252(2.310–2.943], p < 0.001], Gender [1.031(0.981-1.1.242),p < 0.001], tumour stage and grade [4.902(3.607–5.614),p < 0.001], tumour location [1.135(0.806–1.172),p < 0.001], number [0.510(0.410–0.920),p = 0.03], tumour size [1.523(0.936–1.541),p < 0.001], use of intravesical chemotherapy or BCG [2.810(1.972–4.381),p < 0.001], preoperative hydronephrosis grade [1.517(1.172–2.154),p < 0.001], and follow-up compliance [3.376(2.633–5.018),p < 0.001] were all associated with CSM. The 5-year overall survival was 57.1%, and cardiovascular diseases were the leading cause of mortality (n = 34), followed by diabetes (n = 28).ConclusionOur study findings revealed that UC constituted the most common pathological subtype, though less than forty per cent of our patients receive intravesical adjuvant therapies, which are crucial to minimizing disease morbidity and mortality. Initiatives improving uro-oncological care, including subspecialty training in oncology and essential cancer therapies, better access to urology services, and cancer screening programs, are much needed for optimal management plans and care in the country.

Tumor regression following autologous tumor lysate-loaded dendritic cell vaccination immunotherapy: illustrative case.

Despite years of research, the standard of care (SOC) treatment for grade 4 glioma has remained virtually unchanged for the last 2 decades. Autologous tumor lysate-loaded dendritic cell vaccination (DCVax-L), a novel immunotherapy, has demonstrated a significant survival benefit in a phase 3 trial. A 34-year-old male presented with episodes of lightheadedness and was subsequently diagnosed with a large fronto-insulo-temporal tumor, likely to be high grade. He underwent an asleep craniotomy for debulking, with a residual tumor noted in the frontal lobe and amygdala. Tumor histopathology was reported as isocitrate dehydrogenase (IDH) mutant methylated grade 4 astrocytoma. He received SOC treatment, alongside a course of DCVax-L. Surveillance imaging showed cystic transformation followed by a reduction in size of the residual tumor in the frontal lobe; the residual in the amygdala had regressed entirely. The patient remained clinically well and had returned to his preoperative functionality. The authors report a patient with grade 4 astrocytoma who received DCVax-L treatment in addition to SOC adjuvant therapy. The pattern and extent of tumor regression are highly unusual and atypical for what is seen or expected with adjuvant SOC treatment alone. The addition of DCVax-L to SOC opens new avenues in the management of this difficult disease. https://thejns.org/doi/10.3171/CASE24112.

Predicting the Lymphovascular Invasion in Carcinoma Bladder at Transurethral Resection.

Bladder cancer is among the most common malignant neoplasms in the world. Transurethral resection of bladder tumor (TURBT) is consideredthe standard procedure for diagnosis, staging, and risk classification of bladder tumors. Lymphovascular invasion (LVI) is considered a poor prognostic factor. Its assessment of TURBT is very important for risk stratification and decision-making for further treatment. The purpose of our clinical study is to attempt to predict/assess the correlation between LVI and various preoperative (age, gender, history of smoking, hematuria, urine cytology, and hydronephrosis/hydroureteronephrosis), intraoperative (tumor number, size, and appearance - sessile/ pedunculated) and histopathological (tumor histology, grading, and muscle invasion) factors. In this prospective study, 75 patients with bladder tumors underwent TURBT (standard monopolar TURBT with 1.5% glycine as irrigation solution) in the Department of Urology at Sri Venkateswara Institute of Medical Sciences (SVIMS), Tirupati between October 2021 and March 2023. Histopathological examination (HPE) reports were looked for the presence or absence of LVI. Accordingly, patients were divided into two groups, i.e., those with LVI and those without LVI. Various preoperative and intraoperative variables were analyzed for each subject in both groups. Statistically significant variables occurring in those patients with LVI compared to those without LVI were considered predictors of LVI in bladder tumors. Results: Sixteen patients out of 75 (21.33%) had LVI on their histopathology examination. The mean age was 68.19 years in the group with LVI and 64.14 years in the group without LVI. A total of 60 men (80%) and 15 women (20%) were included in our study. Thirteen men (21.7%) and three women (20%) were found to have LVI. We observed a significant association between the appearance of the tumor and LVI. Fifty-four subjects in our study had sessile tumors. Fifteen out of them (27.8%) hadLVI, while only one out of 21 patients (4.8%) with pedunculated tumors had LVI (p-value=0.028). 30% of subjects who had high-grade tumors on HPE also had LVI. On the contrary, only one of 25 patients (4%) with low-grade tumors had LVI (p-value=0.010). Our study also showed a significant association between muscle invasion and LVI. Thirty-four (45.3%) and 41 (54.7%) patients had muscle-invasive and non-muscle-invasive tumors, respectively. While 12 (35.3%) patients with muscle-invasive tumors had LVI, only four (9.8%) patients with non-muscle-invasive tumors showed LVI (p-value=0.007). We observed that LVI of bladder tumors at first TURBT is significantly associated with tumor grade, tumor appearance, and depth of invasion of the tumor. Though statistically not significant, we further observed that LVI was more commonly found in smokers, patients with hematuria, and larger tumor sizes. We conclude that these factors can be used as reliable predictors of LVI of bladder tumors at their first TURBT.

Can Pretreatment MRI and Planning CT Radiomics Improve Prediction of Complete Pathological Response in Locally Advanced Rectal Cancer Following Neoadjuvant Treatment?

The treatment response to neoadjuvant chemoradiation (nCRT) differs largely in individuals treated for rectal cancer. In this study, we investigated the role of radiomics to predict the pathological response in locally advanced rectal cancers at different treatment time points: (1) before thestart of any treatment using baseline T2-weighted MRI (T2W-MR) and (2) at the start of radiation treatment using planning CT. Patients on nCRT followed by surgery between June 2017 to December 2019 were included in the study. Histopathological tumour response grading (TRG) was used for classification, and gross tumour volume was defined by the radiation oncologists. Following resampling, 100 and 103 pyradiomic features were extracted from T2W-MR and planning CT images, respectively. Synthetic minority oversampling technique (SMOTE) was used to address class imbalance. Four machine learning classifiers built clinical, radiomic, and merged models. Model performances were evaluated on a held-out test dataset following 3-fold cross-validation using area under the receiver operator characteristic curves (AUC) with bootstrap 95% confidence intervals. One hundred and fiftypatients were included; 58/150 with TRG 1 were classified as complete responders, and rest were incomplete responders (IR). Clinical models performed better (AUC = 0.68) compared to radiomics models (AUC = 0.62). Overall, the clinical + T2W-MR model showed best performance (AUC = 0.72) in predicting the pathological response prior to therapy. Clinical + Planning CT-merged models could only achieve the highest AUC of 0.66. Merging clinical and baseline T2W-MR radiomics enhances predicting pathological response in rectal cancer. Validation in larger cohorts is warranted, especially for watch and wait strategies.

Updated endometrial cancer FIGO staging: the role of MRI in determining newly included histopathological criteria.

Endometrial cancer (EC) is among the prevalent malignancies in gynecology, showing an increasing occurrence and mortality rate. The updated 2023 FIGO staging integrates both histopathological and molecular analyses, which significantly impact the prognosis and treatment approaches. This research aims to examine the effectiveness of MRI in identifying essential histopathological tumor features, including histological subtype, grade, and lymphovascular space invasion. A total of 106 patients diagnosed with EC from February 2018 to December 2023 underwent preoperative pelvic MRI. Surgical procedures followed ESMO guidelines, with histopathological assessments using FIGO 2009 criteria. Two radiologists independently evaluated MRI images, measuring maximum tumor size, minimum tumor ADC value (using a free-hand ROI technique), and ADC tumor/myometrium ratio. MRI findings were compared with histopathological data. Peritoneal implant presence and tumor size exhibited significant differences between endometrioid adenocarcinoma (EAC) and non-endometrioid endometrial carcinoma (NEEC), with p values of < 0.001 and 0.003, respectively. Significant differences in age, tumor size, ADC tumor, and ADC tumor/myometrium between low-grade and high-grade tumors were observed, with p values of < 0.001, 0.004, 0.006, and 0.011, respectively. Increased tumor size, reduced ADC tumor, ADC tumor/myometrium, and pelvic peritoneal implant presence were significantly associated with LVSI, with p values of < 0.001, 0.001, 0.002, and 0.001, respectively. The AUC values for tumor size, ADC tumor, and ADC tumor/myometrium were 0.842, 0.781 and 0.747, respectively, in distinguishing between low and high-grade endometrial tumors. Similarly, obtained AUC values for predicting LVSI were 0.836, 0.719, and 0.696, respectively. Our study emphasizes MRI's role in predicting tumor characteristics such as histological subtype, grade, and LVSI based on updated FIGO criteria. By highlighting the potential of MRI, this research contributes to our comprehension of improving diagnostic and clinical management for EC. Further multicenter studies are warranted to validate these findings and establish MRI's role in EC management.

Associations of body composition parameters with postoperative outcome and perineural tumour invasion after oncological pancreatic resection

BackgroundPancreatic cancer is often accompanied by wasting conditions. While surgery is the primary curative approach, it poses a substantial risk of postoperative complications, hindering subsequent treatments. Therefore, identifying patients at high risk for complications and optimizing their perioperative general condition is crucial. Sarcopenia and other body composition abnormalities have shown to adversely affect surgical and oncological outcomes in various cancer patients. As most pancreatic tumours are located close to the neuronal control centre for the digestive tract, it is possible that neural infiltration in this area deranges bowel functions and contributes to malabsorption and malnutrition and ultimately worsen sarcopenia and weight loss.MethodsA retrospective analysis of CT scans was performed for pancreatic cancer patients who underwent surgical tumour resection at a single high-volume centre from 2007 to 2023. Sarcopenia prevalence was assessed by skeletal muscle index (SMI), and visceral obesity was determined by the visceral adipose tissue area (VAT). Obesity and malnutrition were determined by the GLIM criteria. Sarcopenic obesity was defined as simultaneous sarcopenia and obesity. Postoperative complications, mortality and perineural tumour invasion, were compared among patients with body composition abnormalities.ResultsOf 437 patients studied, 46% were female, the median age was 69 (61;74) years. CT analysis revealed 54.9% of patients with sarcopenia, 23.7% with sarcopenic obesity and 45.9% with visceral obesity. Sarcopenia and sarcopenic obesity were more prevalent in elderly and male patients. Postoperative surgical complications occurred in 67.7% of patients, most of which were mild (41.6%). Severe complications occurred in 22.7% of cases and the mortality rate was 3.4%. Severe postoperative complications were significantly more common in patients with sarcopenia or sarcopenic obesity. Visceral obesity or malnutrition based on BMI alone, did not significantly impact complications. Perineural invasion was found in 80.1% of patients and was unrelated to malnutrition or body composition parameters.ConclusionsThis is the first and largest study evaluating the associations of CT-based body mass analysis with surgical outcome and histopathological perineural tumour invasion in pancreatic cancer patients. The results suggest that elderly and male patients are at high risk for sarcopenia and should be routinely evaluated by CT before undergoing pancreatic surgery, irrespective of their BMI. Confirmation of the results in prospective studies is needed to assess if pancreatic cancer patients with radiographic sarcopenia benefit from preoperative amelioration of muscle mass and function by exercise and nutritional interventions.

Perimarginal lymph node metastasis in gingivo-buccal complex carcinoma: Is it time to push the limits of neck dissection?.

6069 Background: Perimarginal nodes (PMN) are a group of perifacial lymph nodes that lie in close relationship with marginal mandibular nerve (MMN). They lie in the lymphatic drainage pathway of gingivo-buccal cancers (GBC), above the lower border of mandible which forms the superior limit of conventional neck dissection and thus remain unaddressed. With reported incidence of metastasis as high as 20.5%, we aimed to explore incidence of PMN metastasis in GBC, its correlation with histopathological tumor and nodal characteristics. Methods: A prospective study was conducted on 112 consecutive treatment naïve patients of GB squamous cell carcinoma. Patients with unresectable nodal disease, distant metastasis and prior radiotherapy or surgery to neck were excluded. PMN dissection was performed in the quadrangle bounded superiorly by the mandibular alveolar ridge, inferiorly by lower border of mandible, anteriorly by mental foramen and posteriorly by anterior border of masseter. On histopathological analysis, serial step sectioning and cytokeratin immunohistochemistry were performed. Prospective clinical characteristics analyzed were subsite, clinical tumor, nodal stage, location of primary and clinical skin involvement. PMN positivity was correlated with demographic, clinical, nodal status. Histopathological characteristics analyzed included tumor grade, pathological tumor, nodal stage, tumor size, skin and/or bone involvement, depth of invasion, Brandwein Gensler histological risk score and lympho-vascular emboli. MMN functional outcome was graded according to House-Brackman (HB) grading recorded at 3 and 6 months post-operatively. Results: Baseline characteristics are summarized in the table. The PMN were identified histologically in 75.89% (85/112) patients. Metastasis in these nodes were identified in 15.2% (17/112) patients. Our study revealed an occult PMN metastasis of 16.67% (13/78). None of the pre-operative clinical factors was found to be significant in predicting incidence of metastasis. Higher nodal burden (p=0.01) and pathological skin involvement (p=0.03) had statistically significant odds of having PMN metastasis on multivariable analysis. At 6 months follow-up, none of the patients had any MMN functional deformity at rest. Conclusions: There is a high incidence of occult PMN metastasis from gingivo-buccal complex cancer. High nodal stage and pathological skin involvement are independent adverse prognostic factors for PMN metastasis. The limits of conventional neck dissection should be expanded to include clearance of PMN in all cases of gingivo-buccal cancers. [Table: see text]

Epidemiology, symptomatology, diagnosis and clinical implications of cystic tumors of atrioventricular node (CTAVN): A systematic review.

e23561 Background: Primary cardiac tumors have an incidence of 0.0017% to 0.03% of all autopsies. CTAVN is a rare tumor associated with sudden cardiac death, and its incidence cannot be accurately determined as the diagnosis has been historically made on incidental or intentional autopsy with careful microscopic examination of the conduction system. To date, no systematic evaluation has been made of its clinical outcomes and diagnosis methods; hence, we sought to perform a systematic analysis based on available literature. Methods: A systematic literature search was performed on PubMed, Embase, Cochrane, and Scopus. Studies with a confirmed pathological diagnosis of CTAVN were included. All statistical analyses were conducted on R version 4.1.2. Results: 34 studies with 42 patients with a diagnosis of CTAVN were included. A significant majority of patients were female (n = 29,69%), mean age (±SD) of patients was 47.7 ± 9.33 years. Dyspnea was the most commonly reported symptom among 12 patients (28.5%), followed by palpitations (10,23.8%), syncope (6,14.2%), chest pain (6, 14.2%), dizziness (4,9.5%) and, fatigue (3,7.1%). Third-degree AV block was the most common EKG finding (11,26.1%), followed by first-degree (8, 19.0%) and ventricular fibrillation (n = 2, 4.6%). Transthoracic, transesophageal echo, and cardiac MRIs were done in the majority of the patients. The tumors were most commonly located in the lower part of the interatrial septum in 33% (14), AV node (13, 30.9%), followed by tumors involving both AVN and proximal His bundle/interventricular septum (7, 16.67%). Histopathologically, multiple different lining epithelia were reported: cuboidal cell lining (18, 42.8%), squamous lining (6, 14.2%) and transitional lining (7, 16.6%), most of the tumors (n = 15, 30.9%) were endodermal in origin. Immunohistochemically, 38% of patients had positive epithelial membrane antigen. 45.2% of patients were positive for carcinoembryonic antigen. Cytokeratin was positive in 47.6% of the tumors. Due to varying degrees of AV block, a significant number of patients required pacemaker implantation (13, 30.9%), and 1 patient required intracardiac defibrillator placement. In 9 patients (21.4%), the AV nodal cystic tumor was surgically removed. 21/42 patients were alive; mortality due to CTAVN was reported in 10(23.8) percent of patients. Causes of mortality included cardiac complications (8,19%), respiratory complications (5,11.9%), central nervous system complications (2, 4.7%), sepsis (2,4.7%), and surgical complication (1, 2.3%) Conclusions: To our knowledge, this is the first and largest review on CTAVN. This review contributes valuable insights into the diagnosis, histopathology, and management of cystic tumors of the AV node, offering a foundation for further research on workup, clinical considerations, and treatment of this rare cardiac pathology.

Whole transcriptome analysis to reveal epithelial-mesenchymal transition after neoadjuvant therapy with or without additional anti-EGFR treatment: Subgroup analysis of esophageal squamous cell carcinomas of the SAKK 75/08 and the EORTC AIO POWER study.

4071 Background: In localized disease of esophageal squamous cell cancer (ESCC), a trend in higher pathological response rates and longer time to treatment failure was seen by addition of anti-EGFR treatment to radio-chemotherapy (RCTX) compared to RCTX alone (SAKK 75/08 trial and others). On the contrary, the effect of anti-EGFR treatment to chemotherapy (CTX) remains unclear as no survival benefit was detected within advanced patients (EORTC-AIO-POWER study). Since perfect discrimination and selection of subgroups with highest benefit for anti-EGFR treatment (AB) is missing, we investigated the predictive values of whole transcriptomic gene expression analysis (WTGE) applied on biopsy tissue. Methods: 50 pretherapeutic formalin fixed paraffin embedded specimens of ESCC patients from SAKK 75/08 study were analyzed for the effect of RCTX with and without anti-EGFR AB. As well as 26 historic controls of primary resected tumor stage equally distributed ESCC were analyzed. For the advanced setting, we analyzed 28 additional pretherapeutic biopsies and compared groups from CTX to CTX plus AB. The HTG EdgeSeq method was used for NGS-based WTGE. Response to treatment was assessed by histopathological tumor regression in localized disease and clinical courses. Response to treatment in the advanced tumor setting was assessed to the clinical course of stable disease and partial response versus non-responders. Results: Firstly, NGS-based WTGE failed to show significant differences in expression patterns between responding and non-responding ESCC patients, irrespective of treatment protocols and EGFR AB in the localized as well in advanced disease setting. Secondly however, comparison between pre-treatment biopsies and posttreatment residual tumor tissues detected 781 genes that were upregulated and 623 that were downregulated with gene sets associated with muscle processes and epithelial-mesenchymal transition (EMT) in the localized disease. EMT genes were also enriched in residual tumors after neoadjuvant RCTX compared to primary resection in an independent control cohort. Additionally performed immunohistochemical studies showed lower numbers of ZEB-1 positive ESCC in an independent collection of tumors treated by neoadjuvant RCTX compared to primary resection. Conclusions: Our Whole transcriptomic gene expression analyses suggest that EMT is involved in responses to neoadjuvant protocols including EGFR targeting therapies. Targeting EMT may be a molecular pathway to increase complete responses after neoadjuvant RCTX in ESCC.