Histopathological Subtypes Research Articles

Outcomes of Endoscopic Transsphenoidal Approach for More Aggressive Pediatric Pituitary Adenomas: Early- and Late-Term Results from a Single Center Experience

Pediatric pituitary adenomas are rare lesions and account for approximately 3% of all supratentorial tumors in children.There is a paucity of reports on endoscopic transsphenoidal surgery in children. The aim of this study was to assess the early/late outcomes of endoscopic pediatric pituitary adenoma surgery at a high-volume tertiary center, as well as to characterize the factors associated with aggressive growth, including the histopathological features. Between August 1997-June 2022, a total of 3256 patients underwent endoscopic transsphenoidal surgery for pituitary adenoma at the Department of Neurosurgery and Pituitary Research Center of the Kocaeli University School of Medicine. Of these, 70(2.1%) pediatric patients (25 male,45 female)(age ≤18 years) with a pathological diagnosis of pituitary adenoma were retrospectively reviewed. The mean age of patients was 15.5±2.3 years.Among the hormone-secreting adenomas, 19(34.5%) were adrenocorticotrophic hormone (ACTH)-secreting, 13(23.6%) were growth hormone (GH)-secreting, 19(34.5%) were prolactin (PRL)-secreting, and 4(7.2%) were both GH- and PRL-secreting.Gross total resection was achieved in 93.3% of nonfunctional tumors.The early/late surgical remission rates for hormone-secreting adenomas were 61.5%/46.1%(mean follow-up:63.7±49.3 months) for acromegaly, 78.9%/68.4%(47.8±51.0 months) for Cushing's disease, 57.8%/31.5%(72.2±59.5 months) for prolactinoma, and 25%/25%(35.2±31.4 months) for GH+PRL-secreting adenomas.Five sparsely-granulated corticotroph tumors, 5 sparsely-granulated somatotroph tumors, and 11 densely-granulated lactotroph tumors were classified as aggressive histopathological subtypes. The unique characteristics of the pediatric population and the aggressiveness of the disease in this population pose considerable therapeutic challenges. To increase treatment success, current adjuvant therapies that are appropriate for the morphological and biological characteristics of the tumor are required in addition to surgical treatment.

Comparing time to treatment for neoadjuvant chemotherapy for breast cancer across the urban-rural continuum.

e12619 Background: Time-to-treatment is a quality measure in breast cancer care that can impact breast cancer survival as delayed treatment can increase mortality. This study aims to determine whether differences exist in time-to-treatment for breast cancer patients receiving neoadjuvant chemotherapy (NAC) across the urban-rural continuum. Methods: The National Cancer Database (NCDB) was queried for women with a diagnosis of breast cancer between 1 January 2004 – 31 December 2019. Patients who fit criteria for NAC consideration according to NCCN guidelines were included (inflammatory breast cancer, HER2 positive with tumor stage >T1c, triple negative with tumor stage >T1c, HER2 positive or triple negative lymph node positive, and stage III estrogen receptor (ER) positive). Analysis was stratified according to histopathologic subtype and geographic location as defined by the NCDB. Differences were analyzed using χ2 tests. Results: For patients with NAC-eligible breast cancer, there was no statistically significant difference in terms of days until treatment for each histopathologic subtype across the urban-rural continuum. The distance to treatment facility increases the further away patients are from a large metropolitan area, with individuals located in an urban area that is not adjacent to a metro area traveling the furthest distance (12.7mi large metro, 18.1mi small metro, 36.7mi urban adjacent to metro, 62.6mi urban not adjacent to metro, 56.4mi rural). No significant difference in distance traveled was observed between tumor subtype group. Conclusions: While previous studies have determined that rural patients receive NAC at lower rates than those in large urban areas, this study shows that time to treatment and distance traveled is similar across rural urban continuum and different histopathologic subtypes. Future studies are needed to determine why patients receive NAC at lower rates in rural areas.

Overall survival after the introduction of adjuvant treatment in stage III melanoma: A nationwide registry based study.

9570 Background: Adjuvant treatments with PD-1 and BRAF+MEK inhibitors significantly prolong recurrence-free survival in stage III cutaneous melanoma. However, the effect on overall survival is still unclear. After the approval of adjuvant treatments with PD-1 inhibitors and BRAF+MEK inhibitors, based on recurrence-free survival data, these treatments have been widely implemented. However, there are significant side effects and costs of the treatment, and the overall survival effect remains a highly anticipated outcome. Methods: Clinical and histopathological parameters were obtained from the Swedish Melanoma Registry that covers nearly all (99%) primary cutaneous melanomas diagnosed. Information on deaths was received from the Cause of Death Registry, a virtually complete register of all deaths in Sweden. Patients diagnosed with stage III melanoma between 2016 and 2020 were included and divided depending on if they were diagnosed before or from July 2018, the timepoint when adjuvant treatment was introduced in Sweden (designated as pre- and post-cohorts). In Sweden, approved treatments are freely available for all residents and there is a high-adherence to national treatment guidelines. Data was retrieved for the age and sex of the patients, the site, histopathological subtype, Breslow thickness and ulceration of the primary melanoma, type of locoregional spread and numbers of affected lymph nodes. Patients were followed until the end of 2021. Melanoma-specific and overall survival were calculated using the Kaplan-Meier method and Cox regression analyses. Results: There were 1371 patients diagnosed with stage III melanoma in Sweden in 2016-2020. The median time of follow-up in the pre-cohort was 57 months (range 42-72 months) and in the post-cohort 27 months (range 12-42 months). The 2-year overall survival rates, comparing the 634 patients in the pre-cohort and the 737 in the post-cohort, were 84.3% (95% CI 81.4-87.3) and 86.1% (95% CI 83.4-89.0), respectively, with an adjusted HR 0.91 (95% CI 0.70-1.19, P= 0.51). Further, no significant overall or melanoma-specific survival differences were seen when comparing the pre- and the post-cohort in different subgroups depending on the age, sex or tumor characteristics. Conclusions: To our knowledge, this study is the first to assess the impact on overall survival from a national introduction of adjuvant treatment in stage III melanoma. In this nationwide, population and registry-based study, no survival benefit was detected in the cohort receiving adjuvant therapy. Considering also the significant side effects and costs, these findings encourage a careful assessment of the current recommendations on adjuvant treatment. To offer close follow-up, and only treat if relapse occurs, should be an option discussed with patients with fully resected stage III melanoma.

Perioperative toripalimab + platinum-doublet chemotherapy vs chemotherapy in resectable stage II/III non-small cell lung cancer (NSCLC): Interim event-free survival (EFS) analysis of the phase III NEOTORCH study.

8501 Background: Adjuvant and neoadjuvant immunotherapy have been approved by US FDA to treat early-stage NSCLC. However, the optimal neoadjuvant and adjuvant treatment, including duration of treatment, are unknown. We present the interim results of a randomized, double-blind, placebo-controlled, Phase III trial to evaluate the efficacy and safety of perioperative toripalimab plus chemotherapy followed by toripalimab maintenance vs chemotherapy in resectable stage III NSCLC. Methods: Patients with stage II/III resectable NSCLC, without EGFR/ALK alterations for non-squamous NSCLC, were randomized 1:1 to receive 240 mg toripalimab or placebo combined with chemotherapy Q3W for 3 cycles before surgery and one cycle after surgery, followed by toripalimab or placebo monotherapy Q3W for 13 cycles. Stratification variables for randomization included disease stage, histopathologic subtype, PD-L1 expression and surgical procedure. Primary endpoints were EFS by investigator and major pathological response (MPR) rate by a blinded independent pathologic review (BIPR) in the stage III and the ITT populations. Secondary endpoints included overall survival (OS), pathologic complete response (pCR) rate, EFS by independent review committee (IRC), and safety. A planned interim analysis was performed on the primary endpoint of EFS in the stage III subjects. Results: A total of 404 stage III NSCLC patients were randomized to toripalimab (n=202) or placebo (n=202). By the data cutoff date (November 30, 2022), the median follow-up was 18.3 months. Baseline characteristics were well balanced between the two arms. EFS was significantly improved in the toripalimab arm, HR=0.40, 95% CI (0.277-0.565), P<0.0001, and crossed the pre-specified efficacy boundary. The median EFS was not reached in the toripalimab arm and 15.1 months in the placebo arm. A consistent effect on EFS, favoring toripalimab, was observed in all subgroups. The MPR and pCR rates per BIPR were also higher in the toripalimab arm, 48.5% vs 8.4% and 24.8% vs 1.0%, respectively. The OS results showed a trend favoring toripalimab. The incidence of Grade ≥3 adverse events (AEs) (63.4% vs 54.0%), fatal AEs related to toripalimab/placebo (0.5% vs 0%) and AEs leading to discontinuation of toripalimab/placebo (9.4% vs 7.4%) were comparable between the two arms. However, the incidence of immune-related AEs (42.1% vs 22.8%) was more frequent in the toripalimab arm. Conclusions: The addition of toripalimab to perioperative chemotherapy showed statistically significant improvements in EFS for stage III NSCLC patients with a manageable safety profile. Patients will be followed for overall survival. Clinical trial information: NCT04158440 .

The five periampullary cancers: Not just different siblings but different families—An international multicenter cohort study.

4167 Background: Cancer arising in the periampullary region can be anatomically classified in pancreatic ductal adenocarcinoma (PDAC), distal cholangiocarcinoma (dCCA), duodenal adenocarcinoma (DAC) and ampullary adenocarcinoma (AAC). Based on histopathology, the AAC is currently subdivided in the intestinal (AmpIT) and pancreatobiliary (AmpPB) subtype. Despite close anatomical resemblance, it is unclear how the ampullary subtypes relate to the remaining periampullary cancers in tumor characteristics and behavior. Methods: This is an international multicenter cohort study, including patients after curative intent resection for periampullary cancer retrieved from 45 centers (from Europe, USA, Asia and Canada) between 2010 and 2021. Pre-operative CA19-9, differences in pathology and postoperative pancreatic fistula (POPF, grade B/C), 8-year overall survival (OS) and disease-free interval (DFI) were compared between DAC, AmpIT, AmpPB, dCCA and PDAC. Results: Overall, 3809 patients were included of which 348 DAC, 774 AmpIT, 848 AmpPB, 1036 dCCA and 803 PDAC. The best 8-years overall survival was found in patients with AmpIT and DAC (49.8% and 47.9%), followed by AmpPB (34.9%, p<0.001), dCCA (26.4%, p=0.020) and last, PDAC (12.9%, P<0.001). The best 8-years DFI was measured for AmpIT (62.7%) and the worst for both dCCA and PDAC (24.9% and 21.8%). This pattern correlated with the height of the pre-operative CA19-9 but not with the pathology, in which the largest and most progressed tumors were found in DAC. The incidence of POPF was lower in the pancreas-related tumor types (AmpPB 18.5%, PDAC 8.3%) compared to the non-pancreas related types (DAC 27.3%, AmpIT 25.5%, dCCA 27.6%). Conclusions: Despite the close anatomic relation of the five periampullary cancers, this study shows that there are prognostic and clinically relevant differences in terms of preoperative blood markers, pathology, complications, long-term survival, and recurrence. More characteristics are shared between DAC and AmpIT and between AmpPB and dCCA than between the two ampullary subtypes. Instead of using collective definitions for “periampullary cancers”, this study emphasizes the need for individual evaluation of each histopathological periampullary subtype with the ampullary subtypes as individual entities in future studies.

Demographic study of endocrine tumours in northwestern India: a five-year retrospective chart review analysis of 3081 thyroid and other endocrine lesions from Jaipur, Rajasthan

Endocrine tumours are commonly encountered in clinical practice. The demographic data in a specific part of the country can be harnessed only from a tertiary care referral center. We aimed to analyze the epidemiological pattern of various histopathological subtypes of four major endocrine glands in the body in Northwestern India. In this retrospective chart review analysis, we reviewed three lakh records of histopathologically proven tumours coming to four major pathology departments and laboratories in Jaipur, Rajasthan over five years; of which 3081 were from patients with endocrine tumours. We included these endocrine tumours in our study and the results were obtained. The collected data were analyzed and results were obtained using Microsoft Excel 2019 Version 2107. Thyroid tumours were the most common tumours (96.8%) with adrenal, parathyroid and pituitary in order. Percentage of malignant cases among the thyroid disorders was 20.55%. Multinodular goitre (50.3%) and papillary carcinoma thyroid (77.67%) topped the benign and malignant thyroid tumours respectively. Females in 21 to 40 years age group were most affected in thyroid tumours. Pheochromocytoma was the most common adrenal tumour (60%) most commonly affecting females in the age group pf 21 to 40 years of age. Parathyroid adenoma constituted the majorchunk of parathyroid tumours (86.9%) with no sex predilection and affecting patients mostly in the age group of 31 to 45 years. Pituitary adenoma was found in 34 of 35 cases with a female preponderance and a wide range of affected age groups (21 to 50 years). Different histopathological subtypes of endocrine gland tumours have a varied epidemiological profile in NorthwesternIndia and incorporation of this knowledge will help improve the clinical acumen of the treating personnel in this part of the country.

Uterine sarcoma patients who underwent morcellation: Who are they? Results of the prospective intergroup real-world registry for gynecological sarcoma in Germany (REGSA- NOGGO RU1).

e17632 Background: Uterine sarcomas represent a group of rare malignant mesenchymal neoplasms with most types of them being associated with poor prognosis. In clinical practice, it is challenging to distinguish them from the most common benign tumors in women, so-called leiomyomas. Due to erroneous diagnosis, there is a risk of morcellating an occult sarcoma. This often leads to the distribution of malignant tissue in the abdominal cavity and a worse prognosis in most of the patients. In order to better understand this high-risk group of patients we analyzed their characteristics and management based on data of the real-world German registry for gynecological sarcoma (REGSA). Methods: REGSA is a real-world multicenter prospective registry including patients with gynecologic sarcomas in the primary and the recurrent situation of disease. For this work, we performed a descriptive analysis with data from all available patients with documented morcellation of uterine sarcoma. Results: 8.7% (n=76) of a total of 874 patients (registration period 09/2015-05/2022) were morcellated. Those 76 patients had a median age of 50.5 years. Thirty-seven patients (48.7%) were ≥50 years of age at the time of surgery. Leiomyosarcoma was the most common histopathological subtype (n=42; 50.3%). Fifty-eight patients (76.3%) had laparoscopic operations. A subtotal hysterectomy was the most common procedure used in 40.8% (n=31). Diagnostic curettage was performed in 5.3% of all cases (n=4). The predominant preoperative symptom was "bleeding disorders" in 19 patients (25.0%). Follow-up treatment after morcellation was heterogeneous. 17 patients received chemotherapy, with docetaxel and gemcitabine being the most frequently used regimen (n=8; 47.1%), followed by combinations with anthracyclines in 5 patients (29.4%). Conclusions: Many patients were over 50 years of age at the time of morcellation, although it is undisputed that the risk of morcellating occult uterine sarcoma increases with age. Whether curettage has diagnostic value needs to be further investigated. There is a high clinical need to define a consensus on further management of this high-risk group, regarding adjuvant therapy and follow-up care for there seems to be a great deal of uncertainty regarding adjuvant management.

CT based radiomics signature for phenotyping histopathological subtype in patients with non-small cell lung cancer.

e20599 Background: The determination of the histopathology of non-small cell lung cancer (NSCLC) is crucial for guiding the appropriate therapeutic strategy, affecting prognosis and recurrence rates. In addition, targetable oncologic mutations are highly correlated to histological subtypes. Conventional methods such as biopsy or surgical excision are the primary methods for histology determination but are invasive, costly, and have limitations such as sampling error. Computed tomography (CT) scans, widely used for NSCLC diagnosis and follow-up, offer a non-invasive alternative through radiomics-based models that provide comprehensive analysis of the entire tumor and surrounding tissue, improving patient selection and stratification in clinical trials and enhancing the development of molecularly targeted drugs. The goal of this study was to evaluate the ability of a CT-based radiomics model to predict the subtype histopathology of NSCLC patients. Methods: A total of 678 patients with advanced-stage NSCLC with at least one measurable lung lesion (≥10mm) were selected from multicenter institutions; 531 were used for training and 147 for independent testing. The test set originates from centers unique from the training cohort. Semi-automatic segmentation of the lung lesions was performed and the segmentations were retrospectively reviewed by an experienced radiologist with > 20 years of experience. A total of 1246 radiomics features were extracted using the Pyradiomics package. Ten Robust features were selected first by removing all features with variances near zero, then by applying Maximum Relevance — Minimum Redundancy to the remaining features. All selected features were standardized before modeling. A support vector machines classifier was trained using a five-fold cross-validation and Random Over-Sampling Examples to classify the histology of NSCLC patients (Squamous vs. Non-Squamous). Results: The model trained with the radiomics features achieved a mean area under the curve (AUC) of 0.80 (95% CI, ±0.05) on the cross-validation and an AUC of 0.77 (95% CI, ±0.05) on the test set. Conclusions: Results showed that the model was able to accurately classify the histology of NSCLC patients as squamous vs. non-squamous in a multicenter setting. It highlights the promise of CT-based radiomics in determining the histopathology or other molecular biomarkers of NSCLC, offering a more efficient, cost-effective, and less invasive alternative to traditional tissue analysis methods. Our findings suggest that this non-invasive method has the potential to improve patient selection and stratification and enhance the development of molecularly targeted drugs. These results underscore the importance of incorporating advanced imaging techniques and machine learning algorithms into oncology practice for better patient outcomes.

Primary nephrotic syndrome in children in Cape Town, South Africa

Background. Histopathological patterns of childhood primary nephrotic syndrome (PNS) and clinical response to steroids have beenassociated with certain race groups in parts of South Africa. However, there are no recent studies of childhood PNS in Cape Town.Objectives. To describe the demographics, histological subtypes and steroid response of patients with PNS who underwent kidney biopsiesat Red Cross War Memorial Children’s Hospital (RCWMCH) over a 10-year period.Methods. Details of patients with PNS who underwent kidney biopsies in the Paediatric Nephrology Department at RCWMCH between2006 and 2015 were retrospectively recorded.Results. A total of 103 patients were included in the study. Most patients were either of mixed race (42%) or black (36%), with a mean age of6.8 years and a male-to-female ratio of 1.19:1. The most identified histopathological subtype was mesangioproliferative glomerulonephritis(MesPGN; 60% (n/N=62/103)). Of the patients with focal segmental glomerulosclerosis (FSGS), MesPGN and minimal change disease(MCD) 45% (n/N=43/95) were steroid-resistant, and 54% (n/N=51/95) were steroid-sensitive. There was no significant associationbetween any race group and steroid response. Patients with FSGS were more likely to be black, while MCD was more common in mixed-race patients (p=0.04). There was no difference in the likelihood of being mixed race or black between patients with FSGS and MesPGN(p=0.472).Conclusion. MesPGN was the most common histopathological subtype found in our study. There was no significant association betweenrace and steroid response. Patients with FSGS were more likely to be black than mixed race when compared with MCD patients. Race wasnot otherwise significantly associated with any histopathological subtype

The Profiling of Apoptosis-Associated MicroRNA Expressions of the Lung Adenocarcinoma.

The most common histopathological subtype of lung cancer is adenocarcinoma. MicroRNAs are a class of non-coding RNAs that play roles in the regulation of gene expression. MicroRNAs affecting apoptosis may have different roles in lung adenocarcinoma development, progression, and differentiation. The objective of this study is to profile all known microRNAs linked to apoptosis in normal and lung cancer tissue using real-time polymerase chain reaction. Tissues with adenocarcinoma and healthy tissues were taken from the same lung. The degree of differentiation of all tumors was determined. Expressions of 84 apoptosis-associated microRNAs in both tissues were analyzed by real-time polymerase chain reaction array. Eleven patients and 22 samples were included in the study. In the comparison of expression levels of apoptosis-associated microRNAs in normal and adenocarcinoma tissue, miR-134, miR-183-5p, miR-192-5p, miR-193b-3, miR-194-5p, miR-200c-3, miR212-3p, miR-25-3p, miR-449a, and miR-9-5p showed significant difference in downregulation. Receiver operating characteristic curve analysis of 10 identified microRNAs was performed, and cut-off values, sensitivity, and specificity were determined. No significant difference was found between microRNA expression levels in adenocarcinoma tissues classified as moderate-well to poorly differentiated. Differently, downregulated expressed apoptosis-associated microRNAs were detected in lung adenocarcinoma tissues. MicroRNAs can be used as biomarkers in the diagnosis in lung adenocarcinoma. The expression of microRNAs linked to apoptosis should be investigated in different lung cancer histological subtypes in order to identify potential biomarkers.

18 F-FDG PET/CT imaging in neuroendocrine prostate cancer: Relation to histopathology and prognosis.

This study aimed to evaluate the effectiveness of 18 F-fluoro-2-deoxy-D-glucose Positron emission tomography/computed tomography (18 F-FDGPET/CT) in predicting prognosis and characterizing the intratumoral glucose uptake of neuroendocrine prostate cancer (NEPC). We retrospectively reviewed 189 NEPC patients from two medical centers between January 2009 and April 2021. Of these, 44 patients met the inclusion criteria. The maximum standardized uptake value (SUVmax) was measured to assess the metabolic state of NEPC and comparison were made between different histopathological subtypes. Kaplan-Meier and Cox regression analyses were performed to evaluate the predictive value of SUVmax on overall survival (OS) and progression-free survival (PFS). This study analyzed 44 NEPCpatients and found that 13 patients had small cell neuroendocrine carcinoma (SCNC), while 31 were diagnosed with adenocarcinoma with neuroendocrine differentiation (Ad-NED) based on histopathology, and a positive correlation was found between SUVmax and SCNC via Spearman correlation test (rs = 0.60, p < 0.0001). Furthermore, SUVmax demonstrated good diagnostic accuracy in differentiating SCNC from Ad-NED (area under the curve 0.88, 95% confidence interval [CI] 0.76-0.99). Kaplan-Meier survival analyses and univariate analyses revealed that patients with SUVmax > 10.2 had a significantly shorter OS than patients with SUVmax ≤ 10.2 (hazard ratio = 4.83, 95%CI 1.45-16.1, p = 0.01). The histopathological subtypes in NEPC showed a close correlation with the glucose metabolic activity of primary tumors as assessed by 18 F-FDG PET/CT. High SUVmax values in primary prostate tumors were associated with a worse OS in NEPC patients.

Expression of Programmed Death Ligand 1 (PD-L1) in Breast Cancer patients in India and its Correlation with Prognostic Parameters

Background: The PD-1/PD-L1 pathway represents an adaptive immune resistance mechanism that is exerted by tumor cells. The study was conducted to evaluate the expression of PD-L1 in breast carcinoma in India and to find out its correlation with prognostic parameters. Despite numerous studies, there is a lack of literature for such studies in Indian patients. Moreover, the results obtained from these studies have not been uniform. Methods: A hospital-based cross-sectional study was conducted on 150 cases of breast carcinoma. The invasive cancer specimens were assessed for routine microscopy and classified into various histopathological subtypes. Bloom Richardson grading was done. Immunohistochemistry for surrogate molecular classification as well as PD-L1 was performed. PD-L1 expression was then compared with several prognostic parameters such as tumor subtype, tumor grade, surrogate molecular classification and pTNM stage. Data analysis was done using Statistical Package for Social Sciences (SPSS) version 21.0. A P value of &lt;0.05 was considered statistically significant. Results: PD-L1 was positive in 14.67% of patients with score 1 in 6% and score 2 in 8.67% of patients. The PD-L1 expression showed a positive correlation with the tumor of higher grades (grade3). It was significantly higher among IBC with medullary features as compared to IBC-NST, IBC with papillary features and the Lobular type. PD-L1 showed a significant association with surrogate molecular classification as well. Its expression was found to be the highest in Triple negative breast cancer subtype as compared to tumors showing ER/PR positivity (p&lt;0.05). However, there was no significant association between PD-L1 and TNM staging. Conclusion: This study revealed a significant association between PD-L1 several prognostic factors such as higher tumor grade (grade3), Triple Negative breast cancer, and IBC with the medullary pattern subtype. The association between PD-L1 and such prognostic parameters signifies its role in tumor mechanism and makes it a potential target for immunotherapy especially in Triple Negative breast cancer cases which lack specific targeted therapies. Moreover, paucity of literature on PD-L1 in breast cancer patients in India and the data showing conflicting results make this study valuable. Our study shall be helpful in further adding to the knowledge of PD-L1 expression in breast cancer especially in Indian women.

Hereditary Breast Cancer in Romania-Molecular Particularities and Genetic Counseling Challenges in an Eastern European Country.

In Romania, breast cancer (BC) is the most common malignancy in women. However, there is limited data on the prevalence of predisposing germline mutations in the population in the era of precision medicine, where molecular testing has become an indispensable tool in cancer diagnosis, prognosis, and therapeutics. Therefore, we conducted a retrospective study to determine the prevalence, mutational spectrum, and histopathological prediction factors for hereditary breast cancer (HBC) in Romania. A cohort of 411 women diagnosed with BC selected upon NCCN v.1.2020 guidelines underwent an 84-gene NGS-based panel testing for breast cancer risk assessment during 2018-2022 in the Department of Oncogenetics of the Oncological Institute of Cluj-Napoca, Romania. A total of 135 (33%) patients presented pathogenic mutations in 19 genes. The prevalence of genetic variants was determined, and demographic and clinicopathological characteristics were analyzed. We observed differences among BRCA and non-BRCA carriers regarding family history of cancer, age of onset, and histopathological subtypes. Triple-negative (TN) tumors were more often BRCA1 positive, unlike BRCA2 positive tumors, which were more often the Luminal B subtype. The most frequent non-BRCA mutations were found in CHEK2, ATM, and PALB2, and several recurrent variants were identified for each gene. Unlike other European countries, germline testing for HBC is still limited due to the high costs and is not covered by the National Health System (NSH), thus leading to significant discrepancies related to the screening and prophylaxis of cancer.

Magnetic Resonance Imaging Features of Zinc Finger Translocation Associated-RELA Fusion Ependymoma Compared to Its Wild-Type Counterpart

To explore the predictive value of quantitative features extracted from conventional magnetic resonance imaging (MRI) in distinguishing Zinc Finger Translocation Associated (ZFTA)-RELA fusion-positive and wild-type ependymomas. Twenty-seven patients with pathologically confirmed ependymomas (17 patients with ZFTA-RELA fusions and 10 ZFTA-RELA fusion-negative patients) who underwent conventional MRI were enrolled in this retrospective study. Two experienced neuroradiologists who were blinded to the histopathological subtypes independently extracted imaging features using Visually Accessible Rembrandt Images annotations. The consistency between the readers was evaluated with the Kappa test. The imaging features with significant differences between the 2 groups were obtained using the least absolute shrinkage and selection operator regression model. Logistic regression analysis and receiver operating characteristic analysis were performed to analyze the diagnostic performance of the imaging features in predicting the ZFTA-RELA fusion status in ependymoma. There was a good interevaluator agreement on the imaging features (kappa value range 0.601-1.000). Enhancement quality, thickness of the enhancing margin, and edema crossing the midline have high predictive performance in identifying ZFTA-RELA fusion-positive and ZFTA-RELA fusion-negative ependymomas (C-index=0.862 and area under the curve=0.8618). Quantitative features extracted from preoperative conventional MRI by Visually Accessible Rembrandt Images provide high discriminatory accuracy in predicting the ZFTA-RELA fusion status of ependymoma.

Ameloblastoma of the jaws in adult: A retrospective review of local recurrent lesions based on the resection margin in the adjacent apparent healthy tissues

BackgroundThe surgical treatment of ameloblastoma of the jaws remains contentious due to the variable recurrence rate amongst its variants, the tumor's local invasive behavior, and the lack of consensus among surgeons concerning the extent of resection in the contiguous healthy tissues. ObjectiveTo determine the recurrence rate of ameloblastoma and its association with the resection margins. Materials and methodsThis is a retrospective cohort study of the medical records of patients who underwent surgical resection of the jaws as the primary modality of treatment for ameloblastoma. Clinical data over the 26 years were analyzed for age, gender, site of the lesion, size, radiographic appearance, histopathological sub-type, and the incidence of recurrence post-treatment. Descriptive and bivariate statistics were computed. ResultsA retrospective audit of 234 cases was included in the study that was typical (solid/multicystic) ameloblastoma. The age of patients ranged from 20 to 66 years with a mean age of 33.4 ± 9.6 years, and a male-to-female ratio of 1.2: 1 (P = 0.52). The follicular and plexiform types accounted for the majority of histopathological variants (89.8%; P = 0.000). Overall, 6.8% of cases relapsed after the initial primary surgery. The rate of recurrence was high with a resection margin of 1.0 or 1.5 cm than 2.0 cm (P = 0.001). No case of recurrence was seen with a resection margin of 2.5 cm margin. ConclusionA low recurrence rate of 6.8% was noted in our series of cases. A wide 2.5 cm resection margin is recommended in the adjacent healthy tissues.

Cine MR feature tracking analysis for diagnosing thymic epithelial tumors: a feasibility study

BackgroundTo assess the feasibility of the cine MR feature tracking technique for the evaluation of cardiovascular-induced morphological deformation in the diagnosis of thymic epithelial tumors (TETs).MethodsOur study population consisted of 43 patients with pathologically proven TETs including 10 low-grade thymomas, 23 high-grade thymomas, and 10 thymic carcinomas. Cine MR images were acquired using a balanced steady-state free precession sequence with short periods of breath-hold in the axial and oblique planes in the slice with the largest lesion cross-sectional area. The tumor margin was manually delineated in the diastolic phase and was automatically tracked for all other cardiac phases. The change rates of the long-to-short diameter ratio (∆LSR) and tumor area (∆area) associated with pulsation were compared between the three pathological groups using the Kruskal–Wallis H test and the Mann–Whitney U test. A receiver-operating characteristic (ROC) curve analysis was performed to assess the ability of each parameter to differentiate thymic carcinomas from thymomas.Results∆LSR and ∆area were significantly different among the three groups in the axial plane (p = 0.028 and 0.006, respectively) and in the oblique plane (p = 0.034 and 0.043, respectively). ∆LSR and ∆area values were significantly lower in thymic carcinomas than in thymomas in the axial plane (for both, p = 0.012) and in the oblique plane (p = 0.015 and 0.011, respectively). The area under the ROC curves for ∆LSR and ∆area for the diagnosis of thymic carcinoma ranged from 0.755 to 0.764.ConclusionsEvaluation of morphological deformation using cine-MR feature tracking analysis can help diagnose histopathological subtypes of TETs and identify thymic carcinomas preoperatively.

RET rearrangements are relevant to histopathologic subtypes and clinicopathological features in Thai papillary thyroid carcinoma patients.

Background: Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. The RET gene rearrangements CCDC6::RET and NCOA4::RET are the most common RET gene rearrangements in PTC patients. Different RET::PTC rearrangements are associated with different PTC phenotypes. Methods: Eighty-three formalin-fixed paraffin-embedded (FFPE) PTC samples were examined. The prevalence and expression levels of CCDC6::RET and NCOA4::RET were determined using semi-quantitative polymerase chain reaction (qRT-PCR). The association of these rearrangements with clinicopathological data was investigated. Results: The presence of CCDC6::RET rearrangement was significantly associated with the classic subtype and absence of angio/lymphatic invasion (p < 0.05). While NCOA4::RET was associated with the tall-cell subtype, and presence of angio/lymphatic invasion and lymph node metastasis (p < 0.05). Multivariate analysis demonstrated that an absence of extrathyroidal extension and extranodal extension were independent predictive factors for CCDC6::RET, whereas the tall-cell subtype, large tumor size, angioinvasion, lymphatic invasion and perineural invasion were independent predictive factors for NCOA4::RET (p < 0.05). However, the mRNA expression level of CCDC6::RET and of NCOA4::RET were not significantly associated with clinicopathological data. Conclusion: CCDC6::RET was correlated with an innocent PTC subtype and characteristics, but NCOA4::RET correlated with an aggressive phenotype of PTC. Therefore, these RET rearrangements strongly associated with clinicopathological phenotypes and can be used as predictive markers in PTC patients.

Guardare oltre il tumore: le cancer-predisposing syndrome in età pediatrica

About 10% of children with cancer carry a pathogenic mutation in genes predisposing to tumourigenesis. These mutations are being identified more and more frequently thanks to the use of next-generation sequencing techniques in the diagnostic work-up of cancer, and their integration into clinical practice is a new challenge for oncogenetics. The diagnosis of a cancer predisposing syndrome (CPS) has important implications for the management of the patient, as well as for the patient’s family, who may also include potential carriers of the identified predisposing mutation. Clinical criteria have been developed to help clinicians suspect a predisposing condition: attention should be given to the family and patient’s medical history, to specific clinical signs and to specific histopathological tumour subtype. A multidisciplinary team with specific training is essential for the complex clinical management of these conditions.

Sinonasal Cancer: A National Population-based Study in Iran

Background: Cancer is a leading cause of death in the 21st century. Sinonasal malignancies comprise less than 0.5% of all cancers. There are limited epidemiologic studies on them. Objectives: The current study aimed to estimate the patient demographics, as well as the incidence rates of nasal cavity and paranasal sinuses (NC-PNS) cancers, using a population based registry. Methods: The current study was a descriptive cohort using the Iranian national population based cancer registry (INPCR) data in 2016. The incidence rate of NC-PNS cancer and its distribution considering age, gender, geographical location and histopathology were determined. Results: A total of 258 cases (62.4 % males) were included in the study. Age standardized incidence rate (ASIR) of NC-PNS cancer was 0.36 per 100,000 population. ASIR had the highest value in the 7th, 8th, and 6th decades of life, in descending order. Squamous cell carcinoma (SCC) was the most common histopathologic subtype (23.64%). The most frequent non-epithelial cancer were hematopoietic and lymphatic malignancies (12.40%). The most prevalent site of involvement was the nasal cavity (43.02%), followed by the maxillary sinus (24.81%). The geographical distribution of NC-PNS cancer did not follow any particular pattern. The highest crude incidences were detected in Chahar-Mahal-Bakhtiari, Kerman, and West Azarbaijan in decreasing order. Conclusion: As evidenced by the obtained results, NC-PNS cancers are rare malignancies. Men in their fifties and older are at a higher risk of involvement. Epithelial cancers are more prevalent, among which SCC is the most common histopathologic subtype.

Perioperative toripalimab + platinum-doublet chemotherapy vs chemotherapy in resectable stage II/III non-small cell lung cancer (NSCLC): Interim event-free survival (EFS) analysis of the phase III Neotorch study.

425126 Background: Adjuvant and neoadjuvant immunotherapy have been approved by US FDA to treat early-stage NSCLC. However, the optimal neoadjuvant and adjuvant treatment, including duration of treatment, are unknown. We present the interim results of a randomized, double-blind, placebo-controlled, phase III trial to evaluate the efficacy and safety of perioperative toripalimab plus chemotherapy followed by toripalimab maintenance vs chemotherapy in resectable stage III NSCLC. Methods: Patients with stage II/III resectable NSCLC, without EGFR/ALK alterations for non-squamous NSCLC, were randomly assigned 1:1 to receive 240 mg toripalimab or placebo combined with chemotherapy Q3W for 3 cycles before surgery and one cycle after surgery, followed by toripalimab or placebo monotherapy Q3W for 13 cycles. Stratification variables for randomization included disease stage, histopathologic subtype, PD-L1 expression and surgical procedure. Primary endpoints were EFS by investigator and major pathological response (MPR) rate by a blinded independent pathologic review (BIPR) in the stage III and the ITT populations. Secondary endpoints included overall survival (OS), pathologic complete response (pCR) rate, EFS by independent review committee (IRC), and safety. A planned interim analysis was performed on the primary endpoint of EFS in the stage III subjects. Results: A total of 404 patients with stage III NSCLC were randomly assigned to toripalimab (n=202) or placebo (n=202). By the data cutoff date (November 30, 2022), the median follow-up was 18.3 months. Baseline characteristics were well balanced between the two arms. EFS was significantly improved in the toripalimab arm, HR=0.40, 95% CI (0.277-0.565), P&lt;0.0001, and crossed the pre-specified efficacy boundary. The median EFS was not reached in the toripalimab arm and 15.1 months in the placebo arm. A consistent effect on EFS, favoring toripalimab, was observed in all subgroups. The MPR and pCR rates per BIPR were also higher in the toripalimab arm, 48.5% vs 8.4% and 24.8% vs 1.0%, respectively. The OS results showed a trend favoring toripalimab. The incidence of Grade ≥3 adverse events (AEs) (63.4% vs 54.0%), fatal AEs related to toripalimab/placebo (0.5% vs 0%) and AEs leading to discontinuation of toripalimab/placebo (9.4% vs 7.4%) were comparable between the two arms. However, the incidence of immune-related AEs (42.1% vs 22.8%) was more frequent in the toripalimab arm. Conclusions: The addition of toripalimab to perioperative chemotherapy showed statistically significant improvements in EFS for patients with stage III NSCLC with a manageable safety profile. Patients will be followed for overall survival. Clinical trial information: NCT04158440 .