Pathology Registry Research Articles

Lymphomas of the submandibular gland: a nationwide cohort study.

This study explores the epidemiology, incidence, and survival outcomes associated with lymphomas of the submandibular gland (SMG) and examines the influence of autoimmune diseases on these parameters. This retrospective nationwide cohort study analysed data from patients diagnosed with SMG lymphomas in Denmark between 2000 and 2020. Information was extracted from medical records, the National Pathology Register, and the Danish Lymphoma Database. Survival analyses were conducted using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models, focusing on lymphoma subtypes and autoimmune diseases. The cohort consisted of 101 patients with a lymphoma diagnosis and involvement of the SMG. Large B-cell lymphoma (LBCL) was diagnosed in 33 cases (32.7%), follicular lymphoma (FL) in 29 cases (28.7%), extranodal marginal zone lymphoma (EMZL) in 27 cases (26.7%), and 12 cases (11.9%) with other subtypes. EMZL had a significantly longer overall survival (OS) compared to other subtypes, with a median OS of 12.4 years (95% CI 11.2-12.4) vs. 8.4 years (95% CI 6.0-12.2). EMZL and FL showed favourable 5-year OS rates of 95% and 89%, respectively. LBCL had a 5-year OS rate of 65%. Age over 60 significantly negatively impacted OS. Traditional poor prognostic indicators did not significantly affect OS. A notable association between EMZL and autoimmune diseases was observed, particularly with Sjögren's syndrome, indicated by an increased relative risk of 2.67 (CI 95% 0.45-16.01). Lymphomas of the SMG are rare and have ambiguous clinical presentations. This study provides novel epidemiological, clinical, and prognostic information.

A-179 The Cutaneous Lymphoma International DIgital PAthology (CLIDIPA) Registry - a multi-center, collaborative initiative to facilitate Artificial Intelligence-driven research within Cutaneous Lymphomas

A-179 The Cutaneous Lymphoma International DIgital PAthology (CLIDIPA) Registry - a multi-center, collaborative initiative to facilitate Artificial Intelligence-driven research within Cutaneous Lymphomas

The incidence of atypical fibroxanthoma and pleomorphic dermal sarcoma in Denmark from 2002 to 2022

BackgroundThe purpose of this study was to assess trends in the incidence rates and overall survival of atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) in the Danish population from 2002 to 2022. MethodsWe included all patients diagnosed with AFX or PDS in the Danish National Pathology Register (DNPR) during the study period. We computed the age-adjusted incidence rate (AAIR) per 100,000 and the average annual percent change (AAPC) and developed an age-period-cohort (APC) model of incidence. ResultsWe included a total of 1118 patients, 78.3 % of whom were men. The median age upon diagnosis for AFX and PDS was 77.6 and 78.4 years, respectively. 84.5 % of the 1118 patients received an AFX diagnosis, while 15.5 % received a PDS diagnosis. The AAIR rose from 0.2 per 100,000 individuals in 2002 to 0.5 per 100,000 by 2022, with a peak increase of 0.75 per 100,000 in 2014. The AAPC for both tumors was 5.3 (95 % CI 2.9 %–7.7 %). We found a significant difference in overall survival between AFX and PDS, with PDS having worse overall survival than AFX. ConclusionThis study, which included the largest non-selected national population to date, found a significant increase in the incidence of AFX and PDS between 2002 and 2015, followed by a decrease.

Retrospective Analysis of Etiology, Pattern, and Determinants of Pediatric Maxillofacial Injuries

Abstract Context: Children sustain facial skeletal and soft-tissue injuries, which are often seen in the preschool age; however, severe facial injuries involving facial bones occur in ages above 11 years. There have been several postulated reasons for the reduction in the incidence of skeletal fractures in children. These include sutural pliability of pediatric facial bones, increased subcutaneous fat, and a greater ratio of cranial to facial bones. Aims: The study aimed to report our institutional experience of the pattern of presentation in pediatric maxillofacial trauma and report its main etiologies. Methods and Materials: Clinical and demographic information was retrieved from the maxillofacial registers, day clinics, and pathology registers. The etiology of the trauma and associated injuries were also noted. Statistical Analysis: Descriptive statistics were performed on demographic variables such as age, gender, and location of trauma. Categorical variables were analyzed in frequencies and proportions. Association analyses across variables were done using student t-test, ANOVA, and Pearson’s Chi-square after normality test had been conducted. Dunn’s test and Tukey’s post-hoc analysis were conducted after significant observations. Results: The mean age observed in the study was 7.3 years ± 5.3 SD (range: 2.6 months–16 years). There was a slight male predilection with 58.6%. Falls were the most common etiology in the ≤5-years group. RTC accounted for most injuries in children above 11 years. Soft-tissue-only injuries were observed in 51.4% of all cases. In facial bone fractures, mandibular fractures accounted for 40% of all cases. Conclusion: Male children experienced the greatest impact from maxillofacial trauma. The primary factor contributing to this was falls among preschool children. Soft-tissue injuries were found to be more prevalent among preschool children, whereas the incidence of facial fractures increased as age advanced.

Exploring the incidence of dysplasia or adenocarcinoma in early onset Barrett's esophagus.

Currently data on the risk of progression to and lifetime risk of cancer are not available for patients with young onset Barrett's esophagus (BE). Our aim was to obtain epidemiologic data on the incidence of dysplasia or adenocarcinoma in young onset BE in the Netherlands by collecting data on all histologically confirmed cases over a prolonged period of 25 years between January 1, 1991 and December 31, 2015. Data were obtained from the Dutch National Pathology Registry. Patients were included if there was a suspicion of BE visualized in the esophagus during the endoscopic examination in combination with a concordant histologic diagnosis of intestinal metaplasia. 231 patients with early onset BE were identified (median age 26 years [range 0-29 years]), with 17 progressing to dysplasia (6 prevalent and 11 incident). For the patients with incident dysplasia, the median surveillance time between the diagnosis of early onset BE and diagnosis of dysplasia was 5 years (range 0-16 years). The incidence rate of dysplasia was 7.3 per 1000 person-years. There were three patients who developed adenocarcinoma (1 prevalent and 2 incident), who were diagnosed at ages 28, 35, and 36 years. The incidence rate of adenocarcinoma was 1.3 per 1000 person-years. In this 25-year period, 231 patients were diagnosed with early onset BE in the Netherlands, with 17 patients progressing to dysplasia and three developing adenocarcinoma. This corresponded to incidence rates of 7.3 per 1000 person-years for dysplasia and 1.3 per 1000 person-years for adenocarcinoma.

Histopathological response to chemotherapy and survival of mucinous type gastric cancer.

Data on the clinicopathological characteristics of mucinous gastric cancer (muc-GC) are limited. This study compares the clinical outcome and response to chemotherapy between patients with resectable muc-GC, intestinal (int-GC) and diffuse (dif-GC) gastric cancer. Patients from the D1/D2 study or the CRITICS trial were included in exploratory surgery-alone (SAtest) or chemotherapy test (CTtest) cohorts. Real-world data from the Netherlands Cancer Registry on patients treated between with surgery-alone (SAvalidation), and receiving preoperative chemotherapy with or without postoperative treatment (CTvalidation) were used for validation. Histopathological subtypes were extracted from pathology reports filed in the Dutch Pathology Registry and correlated with tumor regression grade (TRG) and relative survival (RS). In SAtest (n = 549) and SAvalidation (n = 8062) cohorts, muc-GC patients had a five-year RS of 39% and 31%, similar to or slightly better than dif-GC (43% and 29%, p = .52 and p = .011), but worse than int-GC (55% and 42%, p = .11 and p < .001). In CTtest (n = 651) and CTvalidation (n = 2889) cohorts, muc-GC showed favorable TRG (38% and 44% (near-)complete response) compared to int-GC (26% and 35%) and dif-GC (10% and 28%, p < .001 and p = .005). The 5-year RS in CTtest and CTvalidation cohorts for muc-GC (53% and 48%) and int-GC (58% and 59%) was significantly better compared to dif-GC (35% and 38%, p = .004 and p < .001). Recognizing and incorporating muc-GC into treatment decision-making of resectable GC can lead to more personalized and effective approaches, given its favorable response to preoperative chemotherapy in relation to int-GC and dif-GC and its favorable prognostic outcomes in relation to dif-GC.

791. ONLY HALF OF THE PATIENTS TREATED ENDOSCOPICALLY FOR EARLY BARRETT RELATED NEOPLASIA IS DETECTED DURING BARRETT SURVEILLANCE

Abstract Background Barrett’s esophagus (BE) with early neoplasia is an indication for endoscopic treatment. Patients with non-dysplastic BE are typically enrolled in an endoscopic surveillance program to enable early detection, and treatment, of BE related neoplasia. In contrast, a subset of patients with early BE neoplasia is concurrently diagnosed with BE and early neoplasia. Our goal was to distinguish cases detected through endoscopic surveillance programs (i.e. initial detection of non-dysplastic BE with progression to neoplasia later in time (metachronous neoplasia)) from cases where BE and neoplasia were diagnosed simultaneously (synchronous neoplasia). Methods We obtained data from the Dutch Barrett Expert Center Registry, a comprehensive nationwide registry encompassing data from all BE patients who underwent endoscopic treatment in Barrett expert Centers in the Netherlands. To enhance data completeness, we supplemented the registry with pathology reports sourced from the national pathology registry (PALGA). Primary endpoint was the proportion of patients diagnosed with BE and neoplasia simultaneously (synchronous neoplasia). Enrollment in an endoscopic surveillance program was defined as the presence of at least one endoscopy with non-dysplastic BE ≥12 months prior to endoscopic treatment initiation. Results A total of 2,091 patients were identified from the registry with a mean age of 66 years (SD±10) and 81% of the cohort being male. Median BE length was C2M5 (IQR 0-6; 3-8) and treatment indication encompassed low-grade dysplasia (LGD; 23%), high-grade dysplasia (HGD; 25%), or cancer (52%). Overall, 1149/2,091 patients (55%) underwent an endoscopy that revealed a new diagnosis of BE with synchronous neoplasia. Conversely, the remaining 942/2,091 patients (45%) were enrolled in endoscopic surveillance programs at the moment neoplasia was diagnosed, with a median duration of endoscopic surveillance prior to neoplasia detection of 8 years (IQR 4-13). The proportion of patients with new BE and synchronous neoplasia increased along with more severe histology at the moment of neoplasia detection. Specifically, the proportion of patients with synchronous neoplasia was 42% (198/475) for a treatment indication of LGD, 50% (260/520) for HGD and 63% (690/1096) for cancer (P &amp;lt;0.01). There was no significant difference observed concerning varying lengths of BE. Conclusions Remarkably, less than half of the patients with early Barrett’s neoplasia and neoplasia, receive a neoplasia diagnosis following enrollment in endoscopic surveillance programs, while the remaining patients present with de novo diagnosis of BE containing synchronous neoplasia. Notably, for patients with more severe histologic changes at the moment of neoplasia detection, the proportion of de novo BE with synchronous neoplasia is even higher. These findings support further critical view regarding the benefits of BE surveillance.

Recurrent Laryngeal Papillomatosis in Denmark from 1994 to 2021: A Nationwide Register Study.

The aim of this study is to describe the incidence and demographics of laryngeal papillomatosis (LP) in Denmark, including sex and age distribution, recurrence rates, and HPV subtypes, using a new method of register identification. The data were extracted from the Danish Pathology Data Bank using SNOMED codes instead of the usual method using ICD codes from the Danish National Health Register. The derived pathology records were manually verified by three medical doctors. The study period was 1994-2021. Patients were categorized according to age as either juvenile-onset RRP (JoRRP) if <18 years or adult-onset RRP (AoRRP) if 18 years or older. We identified 1819 RRP patients (JoRRP: 56; AoRRP:1763). The overall incidence per 100,000 inhabitants were 0.17 for JoRRP and 1.45 for AoRRP. The vast majority (72%) of the patients were male, but there was no significant difference in age at onset of RRP or recurrence rates between the sexes. Children below 3 years of age had the highest recurrence probability. Extracting data using SNOMED codes resulted in a positive predictive value of 99% regarding total number of biopsies and 98% regarding individuals. The incidence decreased throughout the study period. Comparable incidence and recurrence rates of RRP were found between Denmark and Norway. In this study, the Danish Pathology Register was found to be a highly valuable method for identifying LP patients. The effect of the nationwide HPV vaccination program can be evaluated using this method as the vaccinated cohort is starting to grow older and reproduce. Retrospective registry-based national cohort study, level of evidence 3 Laryngoscope, 2024.

Emerging cancer disease burden in a rural sub-Saharan African population: northeast Nigeria in focus.

Sub-Saharan Africa (SSA) is plagued by myriads of diseases, mostly infectious; but cancer disease burden is rising among non-communicable diseases. Nigeria has a high burden of cancer, however its remote underserved culturally-conserved populations have been understudied, a gap this study sought to fill. This was a cross-sectional multi-institutional descriptive study of histologically diagnosed cancers over a four-year period (January 2019-December 2022) archived in the Departments of Pathology and Cancer Registries of six tertiary hospitals in the northeast of Nigeria. Data obtained included age at diagnosis, gender, tumor site and available cancer care infrastructure. Population data of the study region and its demographics was obtained from the National Population Commission and used to calculate incident rates for the population studied. A total of 4,681 incident cancer cases from 2,770 females and 1,911 males were identified. The median age at diagnosis for females was 45 years (range 1-95yrs), and 56 years (range 1-99yrs) for males. Observed age-specific incidence rates (ASR) increased steadily for both genders reaching peaks in the age group 80 years and above with the highest ASR seen among males (321/100,000 persons) compared to females (215.5/100,000 persons). Breast, cervical, prostatic, colorectal and skin cancers were the five most common incident cancers. In females, breast, cervical, skin, ovarian and colorectal cancers were the top five malignancies; while prostate, haematolymphoid, skin, colorectal and urinary bladder cancers predominated in men. Remote SSA communities are witnessing rising cancer disease burden. Proactive control programs inclusive of advocacy, vaccination, screening, and improved diagnostics are needed.

Biopsy-verified vulvar lichen sclerosus and the risk of non-vulvar cancer: A nationwide cohort study.

Vulvar lichen sclerosus (VLS) is a chronic inflammatory mucocutaneous disease known to be associated with human papillomavirus-independent vulvar squamous cell carcinoma. Evidence on the association with other types of cancer, however, is sparce. We conducted a large nationwide cohort study examining the incidence of non-vulvar cancers among women with biopsy-verified VLS compared with the general female population. By using the nationwide Pathology Registry, we identified all women in Denmark with a biopsy-verified VLS diagnosis during 1978-2019 (n = 16,921). The cohort was followed up in the Danish Cancer Registry until 2022 for a subsequent non-vulvar cancer diagnosis. Standardized incidence ratios (SIRs) were computed with 95% confidence intervals (CIs) as relative risk estimates of all specific non-vulvar cancer sites. Compared with general female population rates, women with biopsy-verified VLS had decreased rates of several non-vulvar cancers, including HPV-related cancers (combined estimate: SIR = 0.5; 95% CI: 0.3-0.7), and lung (SIR = 0.6; 95% CI: 0.5-0.7), liver (SIR = 0.5; 95% CI: 0.2-0.9), and thyroid cancer (SIR = 0.5; 95% CI: 0.3-0.9). The decreased SIRs tended to sustain throughout the follow-up period following the VLS diagnosis. This large nationwide cohort study shows that women with biopsy-verified VLS may have a long-term reduced risk of developing HPV-related (cervical, vaginal, oropharyngeal, and anal) and smoking-associated cancers (lung, liver, and cervical) as well as thyroid cancer. Future studies focusing on the mechanisms behind the decreased cancer risk are needed.

Tumor-Infiltrating Lymphocytes in Patients With Stage I Triple-Negative Breast Cancer Untreated With Chemotherapy

The absolute benefit of chemotherapy for all patients with stage I triple-negative breast cancer (TNBC) is unclear, and biomarkers are not currently available for selecting patients with an excellent outcome for whom neoadjuvant or adjuvant chemotherapy may have negligible benefit. High levels of stromal tumor-infiltrating lymphocytes (sTILs) are associated with favorable survival in TNBC, but data solely in stage I TNBC are lacking. To examine the outcomes of patients of all ages with stage I TNBC solely and who received neither neoadjuvant nor adjuvant chemotherapy, according to centrally reviewed sTIL levels at prespecified cutoffs. This cohort study used the Netherlands Cancer Registry to identify patients diagnosed with stage I TNBC between January 1, 2005, and December 31, 2015, who were not treated with chemotherapy. Only patients who did not receive neoadjuvant and/or adjuvant chemotherapy were selected. The clinical data were matched with their corresponding pathology data provided by the Dutch Pathology Registry. Data analysis was performed between February and October 2023. The primary end point was breast cancer-specific survival (BCSS) at 5, 10, and 15 years for the prespecified sTIL level cutoffs of 30%, 50%, and 75%. Hematoxylin and eosin-stained slides were used for central review of histologic subtype, grade, and lymphovascular invasion. The International Immuno-Oncology Biomarker Working Group guidelines were used to score the sTIL levels; these levels were determined for 1041 patients. Of a total of 4511 females with stage I TNBC, patients who were not treated with chemotherapy were selected and tissue blocks requested; sTILs were scored in 1041 patients (mean [SD] age at diagnosis, 64.4 [11.1] years, median follow-up 11.4 [95% CI, 10.9-11.9] years) who were included in the analyses.. Most tumors (952 [91.5%]) were invasive carcinomas of nonspecial histologic subtype. Most patients (548 [52.6%]) had pT1cN0 tumors. Median (range) sTIL level was 5% (1%-99%). A total of 775 patients (74.4%) had sTIL levels below 30%, 266 (25.6%) had 30% or greater, 203 (19.5%) had 50% or greater, and 141 (13.5%) had 75% or greater. Patients with pT1abN0 tumors had a more favorable outcome vs patients with pT1cN0 tumors, with a 10-year BCSS of 92% (95% CI, 89%-94%) vs 86% (95% CI, 82%-89%). In the overall cohort, sTIL levels of at least 30% were associated with better BCSS compared with sTIL levels less than 30% (96% and 87%, respectively; hazard ratio [HR], 0.45; 95% CI, 0.26-0.77). High sTIL levels of 50% or greater were associated with a better outcome than low sTIL levels of less than 50% (HR, 0.27; 95% CI, 0.10-0.74) in patients with pT1C tumors, with a 10-year BCSS of 95% increasing to 98% with sTIL levels of 75% or greater. Results of this study showed that patients with stage I TNBC and high level of sTILs who did not receive neoadjuvant or adjuvant chemotherapy had excellent 10-year BCSS. The findings further support the role of sTILs as integral biomarkers in prospective clinical trials of therapy optimization for this patient population.

Screening outcome of HPV-vaccinated women: Data from the Danish Trial23 cohort study.

Danish women-who were HPV-vaccinated as girls-are now reaching an age where they are invited to cervical cancer screening. Because of their expected lower cervical cancer risk, we must reassess our screening strategies. We analyzed Danish HPV-vaccinated women's outcomes after the first screening test at age 23. Our study was embedded in Danish routine cytology-based screening. We conducted an observational study and included women born in 1994, offered the 4-valent HPV vaccine at age 14, and subsequently invited to screening at age 23. Cervical cytology was used for diagnostics and clinical management. Residual material was HPV tested with Cobas® 4800/6800. The most severe histology diagnosis within 795 days of screening was found through linkage with the Danish National Pathology Register. We calculated the number of women undergoing follow-up (repeated testing and/or colposcopy) per detected cervical intraepithelial neoplasia (CIN2+). A total of 6021 women were screened; 92% were HPV-vaccinated; 12% had abnormal cytology; 35% were high-risk HPV-positive, including 0.9% HPV16/18 positive, and 20% had follow-up. In women that were cytology-abnormal and HPV-positive (Cyt+/HPV+), 610 (98.5%) had been followed up, and 138 CIN2+ cases were diagnosed, resulting in 4.4 (95% CI 3.9-5.2) women undergoing follow-up per detected CIN2+. In contrast to recommendations, 182 (12.2%) cytology-normal and HPV-positive (Cyt-/HPV+) women were followed up within 795 days, and 8 CIN2+ cases were found, resulting in 22.8 (95% CI 13.3-59.3) women undergoing follow-up per detected CIN2+. Overall, HPV prevalence was high in HPV-vaccinated women, but HPV16/18 had largely disappeared. In the large group of cytology-normal and HPV-positive women, 23 had been followed up per detected CIN2+ case. Our data indicated that primary HPV screening of young HPV-vaccinated women would require very effective triage methods to avoid an excessive follow-up burden. Trial registration number: NCT0304955.

Cervical intraepithelial neoplasia and fecundability: a prospective cohort study.

Is cervical intraepithelial neoplasia (CIN) associated with reduced fecundability, defined as the probability of conceiving per menstrual cycle? Overall, we observed no meaningful association between CIN and fecundability, regardless of surgical status, although a recent diagnosis of moderate or severe CIN might be associated with slightly reduced fecundability for 2 years after diagnosis. About 15% of couples experience infertility. Few studies have examined the influence of CIN on fertility, and the results have been inconsistent. No study has investigated the association between fecundability and pathologist-reported CIN diagnoses, particularly with respect to the recency of the specific CIN diagnoses. This prospective cohort study included 9586 women trying to conceive. The women were enrolled from 1 June 2007 to 3 February 2020. Women were invited to complete a baseline questionnaire and bimonthly follow-up questionnaires for up to 12 months or until pregnancy occurred. Data on cervical cytologies and biopsies were retrieved from The National Pathology Registry (DNPR), which holds records of all cervical specimens examined in Denmark. Women were categorized based on their most severe diagnosis of CIN: no lesion, other cervical changes, mild CIN (CIN1), or moderate/severe CIN (CIN2+) with or without surgery. To investigate the association between CIN and fecundability, we computed fecundability ratios (FR) and 95% confidence intervals (CI) using a proportional probabilities regression model. We adjusted for age at study entry, partner age, body mass index, smoking status, timing of intercourse, parity, education, number of sexual partners, and household income. Compared with no lesion, the adjusted FRs (95% CI) for the association between CIN and fecundability were: other cervical lesions, 0.97 (0.91-1.04); CIN1, 1.04 (0.96-1.13); CIN2+ no surgery, 1.00 (0.82-1.22); and CIN2+ with surgery 0.99 (0.89-1.10). The FRs (95% CI) for a recent diagnosis (<2 years) of CIN were 0.98 (0.86-1.11) for other cervical lesions; 1.13 (0.99-1.29) for CIN1; 0.89 (0.62-1.26) for CIN2+ no surgery and 0.91 (0.75-1.10) for CIN2+ with surgery compared with the no lesion group. In the analyses, we adjusted for several covariates related to the women. However, we had little information on the male partners which could lead to unmeasured confounding as fecundability is a couple-based measure of fertility. Furthermore, a CIN diagnosis may not be constant as it may regress or progress spontaneously; therefore, it is possible that we have misclassified some women, especially women categorized as having normal cells or CIN1. Our results contribute important knowledge to women who are concerned about their future fertility after receiving a CIN diagnosis. This study was funded by The Danish Cancer Society (R167-A11036-17-S2). The overall cohorts were funded by the National Institute of Child Health and Human Development (R01-HD086742 and R03-HD094117). The authors report no competing interests. N/A.

Predictors for dMMR colorectal cancer in patients with serrated lesions and polyps – A register-based cohort study

BackgroundSerrated lesions and polyps (SP) are precursors of up to 30 % of colorectal cancers (CRC) through the serrated pathway. This often entails early BRAF mutations and MLH1 hypermethylation leading to mismatch repair deficient (dMMR) CRC. We investigated predictors of dMMR CRC among patients with co-occurrence of CRC and SP to increase our knowledge on the serrated pathway. MethodsWe used data from The Danish Pathology Registry and Danish Colorectal Cancer Groups Database from the period 2010–2021 to investigate risk factors for development of dMMR CRC. We used logistic regression models to identify difference in risk factors of developing dMMR CRC in comparison to CRC with proficient MMR (pMMR). ResultsWe included 3273 patients with a median age of 70.7 years [64.3,76.4] of which 1850 (56.5 %) were male. dMMR CRC was present in 592 patients (18.1 %), with loss of MLH1/PMS2 being most common. The risk of dMMR CRC was significantly higher in females OR 3.47 [2.87;4.20]. When adjusting for age, SP subtype, conventional adenomas (CA), anatomical location and lifestyle factors, female sex remained the strongest predictor OR 2.84 [2.27;3.56]. The presence of sessile serrated lesions with or without dysplasia was related to higher risk OR 1.60 [1.11;2.31] and OR 1.42 [1.11;1.82] respectively, while conventional adenomas constituted a lower risk OR 0.68 [0.55;0.84]. ConclusionIn conclusion we found several predictors of whom female sex had the strongest correlation with dMMR CRC in patients with SP.

Disease relapse in relation to lymph node sampling in lung carcinoid patients.

The predictive value of the extent of peri-operative lymph node (LN) sampling in relation to disease relapse in patients with pulmonary carcinoid (PC) is unknown. Furthermore, post-surgery follow-up recommendations rely on institutional retrospective studies with short follow-ups. We aimed to address these shortcomings by examining the relation between LN sampling and relapse in a population-based cohort with long-term follow-up. By combining the Dutch nationwide pathology and cancer registries, all patients with surgically resected PC (2003-2012) were included in this analysis (last update 2020). The extent of surgical LN dissection was scored for the number of LN samples, location (hilar/mediastinal), and completeness of resection according to European Society of Thoracic Surgeons (ESTS) guidelines. Relapse-free interval (RFI) was evaluated using Kaplan Meier and multivariate regression analysis. 662 patients were included. The median follow-up was 87.5 months. Relapse occurred in 10% of patients, mostly liver (51.8%) and locoregional sites (45%). The median RFI was 48.1 months (95% CI 36.8-59.4). Poor prognostic factors were atypical carcinoid, pN1/2, and R1/R2 resection. In 546 patients LN dissection data could be retrieved; at least one N2 LN was examined in 44% and completeness according to ESTS in merely 7%. In 477 cN0 patients, 5.9% had pN1 and 2.5% had pN2 disease. In conclusion, relapse occurred in 10% of PC patients with a median RFI of 48.1 months thereby underscoring the necessity of long-term follow-up. Extended mediastinal LN sampling was rarely performed but systematic nodal evaluation is recommended as it provides prognostic information on distant relapse.

AI-enabled digital test to predict disease recurrence for patients with early-stage invasive breast cancer and performance in a MammaPrint low-risk cohort from the Netherlands with a median 6-year follow-up.

1569 Background: Traditional invasive breast cancer (IBC) grading, although useful, remains limited due to diagnostic subjectivity and absence of phenotypic diversity including the recently observed importance of tumor epithelial – stromal interactions and lymphocyte content-distribution. We developed and validated a clinical grade digital test (PreciseDx Breast, PDxBr) which combines image-derived Artificial Intelligent (AI)-grading features and clinical data (i.e. age, stage, tumor size, LN status) to predict recurrence in early-stage IBC and sought to understand performance in a MammaPrint cohort with outcome data. Methods: A MammaPrint cohort with median 6-year follow-up was identified at the Laboratory of Pathology, Dordrecht, the Netherlands (NTH). H&amp;E stained images (digitized at Philips, Eindhoven, NTH) with clinical data (from the pathology and Dutch cancer registries) including demographics, pathology results, MammaPrint risk classification, treatment type and recurrence events were obtained. Performance of the PDxBr validated model (AI-grade + clinical) on the MammaPrint cohort was evaluated using the AUC/concordance index, along with NPV, PPV, Hazards ratio (HR), sensitivity, and specificity. Results: 250 patients, median age 57 years, majority stage 1-IIIa, 100% HR+ve, Her2-ve, 84% LN-ve, 67% grade 2 and 66% MammaPrint low risk. There were 15 events (6%: 7 deaths, 3 second primaries,4 metastases and 1 local regional). PDxBR model classified 134 patients as high risk and 116 as low with 10 of 15 (67%) events identified as high risk. The NPV for PDxBr was 96% with a HR 1.63, Se 70%, Sp 46% vs. MammaPrint with an NPV of 94%, HR of 0.96, Se 40%, Sp 66%; identifying only 5 of the 15 events (33%) as high risk while missing 10. Of note, the AI- grade/imaging model (without clinical features) yielded an NPV of 95% with a HR of 1.46, Se 70%, Sp 42% and correctly identified 10 of 15 events. Conclusions: The results from this observational study suggest that triaging patients with the PDxBr test could potentially be adjunctive to the management decision process of patients with early-stage IBC including the use and subsequent interpretation of genomic tests such as MammaPrint. Additional studies are underway to confirm these initial findings.

Validation of the Bethesda System for Reporting Thyroid Cytopathology in a Danish tertiary centre

INTRODUCTION. The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) is used to categorise thyroid fine-needle aspiration (FNA). The aim of this study was to validate the BSRTC in a consecutive cohort and to evaluate the derived management in terms of performing repeat FNA or thyroid surgery. METHODS. Results of thyroid FNAs assessed at the Department of Pathology, Aarhus University Hospital, in the period 2016-2019 were retrieved from The Danish Pathology Registry. FNA category according to the BSRTC along with the histological diagnosis (if available) were linked to the individual patient. RESULTS. In total, 3,669 biopsies were included from 2,873 thyroid nodules in 2,547 patients. Repeat FNA was performed in 23.6% of nodules. The majority of primary FNAs were Benign (BSRTC II; 52.4%). Non-diagnostic (ND) (BSRTC I) was found in 26.3% and BSRTC III-VI were found in 3.6-7.5%. Compared with the first with the last FNA, the frequency of Benign (BSRTC II) increased (61.3%), whereas the frequency of ND (BSRTC I) decreased (14.8%). Surgery was performed in 38.2% (n = 1,097) of nodules. The malignancy rate of 11.5% correlated positively with the BSRTC category, being 2.8% in Benign (BSRTC II) and 95.7% in Malignant (BSRTC VI). CONCLUSIONS. The malignancy rates in the BSRTC categories were in accordance with reports from other countries. Since the BSRTC ensures a standardised and concise communication of cytopathology assessments, application of the BSRTC for thyroid nodule management in a Danish setting is recommended. FUNDING. None. TRIAL REGISTRATION. Not relevant.

#340 Time dependent changes in the treatment of relapsing Minimal Change Disease – a multicenter cohort study

Abstract Background and Aims Prednisolone monotherapy is the most used initial immunosuppressive treatment for nephrotic syndrome in adults with Minimal Change Disease (MCD) but choice of treatment in relapsing MCD is not as well described. With the introduction of new drugs and increased concern relating to the adverse events of prednisolone, treatment might have changed over time. The aim of this study is to describe changes in daily clinical practice of relapsing MCD within the last 35 years. Method A multicenter, retrospective analysis of adult patients with biopsy proven MCD from 13 hospitals from 1987-2022 in Denmark and the Netherlands. Patients were identified from the pathology registers. Information on treatment and clinical outcomes was retrieved from health records. Relapse is defined when the nephrologist found indication to restart an immunosuppressive treatment or increase the ongoing immunosuppression in patients in partial or complete remission. Results We included 167 Dutch and 72 Danish patients (n = 239) with MCD. Most patients (n = 205, 86%) were initially treated with prednisolone monotherapy. Overall, 93% (n = 220) gained remission and 56% (n = 123) of those who went into remission had one or more relapse with 68% of these occurring in the first year after remission. At the time of relapse, 89% were in complete remission and 11% were in partial remission. At first relapse, prednisolone monotherapy was the most prescribed treatment both before and after 2010 (69% and 45%, respectively), while the use of CNI tripled after 2010 (p = 0.002) (10% to 32%). At second relapse, prescription of CNI after 2010 showed a five-fold increase compared with before 2010 (49% vs 10%, respectively) while the use of prednisolone monotherapy was halved (50% to 24%). The use of cyclophosphamide decreased by two-thirds (32% to 10%) after 2010. Before 2010, 54% of patients received prednisolone monotherapy for their third to 14th relapse, but after 2010 this decreased to 26%. The use of rituximab and CNI both increased and after 2010 these were both prescribed to about one third of patients at third to 14th relapse. The use of cyclophosphamide decreased from 30% to 2% comparing before and after 2010. Rituximab was only used after 2010, and more frequently with the number of relapses (6% at first relapse and 36% at third to 14th relapse). Regardless of the choice of treatment the rates of remission were high. Conclusion The treatment of relapses has changed over time with a reduced use of prednisolone monotherapy and cyclophosphamide and increased use of CNI and rituximab.

THE PREVALENCE OF SARCOMA IN LATVIA DEPENDING ON GENDER AND AGE OVER A 10-YEAR PERIOD

Sarcomas are a heterogeneous group of malignant neoplasms that arise from the mesenchymal tissues, including bone, cartilage, fat, muscle, blood vessels, nerves, and deep skin tissues. The World Health Organization (WHO) Classification of Tumors of Soft Tissue and Bone encompasses over 80 distinct histologic subtypes of sarcomas, each with unique morphologic and molecular features. The high degree of histologic diversity among sarcomas underlies their capacity to arise in virtually any anatomic site. Sarcomas represent a relatively uncommon form of cancer, accounting for less than 1% of all new cancer diagnoses in adults and approximately 15% in children. The global incidence of sarcomas is estimated to be approximately 8 cases per million per year for bone sarcomas and 30 cases per million per year for soft tissue sarcomas. The objectives of the study to provide a comprehensive overview of the gender and age differences in the epidemiology of sarcomas in Latvia across 10 years. This retrospective population-based study draws on epidemiological data regarding cases of bone sarcomas and soft tissue sarcomas collected by the pathological registry of the hospital of Traumatology and Orthopaedics. From 2012 to 2022, 146 new cases of sarcoma were diagnosed in Latvia. Of these, 74 (50.7%) were men and 72 (49.3%) were women. The average annual number of new cases was 6.73 for men and 6.55 for women. The age-standardized incidence rate per 100,000 people per year was 0.8 for men and 0.5 for women. The youngest patient was 14 years old and the oldest was 87 years old. The most common age group for the sarcomas was between 61-70 years old (19.2%). The study found that the incidence of sarcomas in Latvia was higher in males than in females, and that the incidence was highest in 2020 and lowest in 2016.

Characterization of discordance between mismatch repair deficiency and microsatellite instability testing may prevent inappropriate treatment with immunotherapy.

In the Drug Rediscovery Protocol (DRUP), patients with cancer are treated based on their tumor molecular profile with approved targeted and immunotherapies outside the labeled indication. Importantly, patients undergo a tumor biopsy for whole-genome sequencing (WGS) which allows for a WGS-based evaluation of routine diagnostics. Notably, we observed that not all biopsies of patients with dMMR/MSI-positive tumors as determined by routine diagnostics were classified as microsatellite-unstable by subsequent WGS. Therefore, we aimed to evaluate the discordance rate between routine dMMR/MSI diagnostics and WGS and to further characterize discordant cases. We assessed patients enrolled in DRUP with dMMR/MSI-positive tumors identified by routine diagnostics, who were treated with immune checkpoint blockade (ICB) and for whom WGS data were available. Patient and tumor characteristics, study treatment outcomes, and material from routine care were retrieved from the patient medical records and via Palga (the Dutch Pathology Registry), and were compared with WGS results. Initially, discordance between routine dMMR/MSI diagnostics and WGS was observed in 13 patients (13/121; 11%). The majority of these patients did not benefit from ICB (11/13; 85%). After further characterization, we found that in six patients (5%) discordance was caused by dMMR tumorsthat did not harbor an MSI molecular phenotype by WGS. In six patients (5%), discordance was false due to the presence of multiple primary tumors (n = 3, 2%) and misdiagnosis of dMMR status by immunohistochemistry (n = 3, 2%). In one patient (1%), the exact underlying cause of discordance could not be identified. Thus, in this group of patients limited to those initially diagnosed with dMMR/MSI tumors by current routine diagnostics, the true assay-based discordance rate between routine dMMR/MSI-positive diagnostics and WGS was 5%. To prevent inappropriate ICB treatment, clinicians and pathologists should be aware of the risk of multiple primary tumors and the limitations of different tests. © 2024 The Pathological Society of Great Britain and Ireland.