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Background Breast implant-related health problems are a subject of fierce debate. Reliable population-based estimates of implant prevalence rates are not available, however, due to a lack of historical registries and incomplete sales data, precluding absolute risk assessments. Objectives This study aimed to describe the methodology of a novel procedure to determine Dutch breast implant prevalence based on the evaluation of routine chest radiographs. Methods The validity of the new method was first examined in a separate study. Eight reviewers examined a series of 180 chest radiographs with (n = 60) or without (n = 120) a breast implant confirmed by a computed tomography or magnetic resonance imaging scan. After a consensus meeting with best-performing expert reviewers, we reviewed 3000 chest radiographs of women aged 20 to 70 years in 2 large regional hospitals in the Netherlands in 2015. To calculate the national breast implant prevalence, regional prevalence variations were corrected utilizing the National Breast Cancer Screening Program. Results Eight reviewers scored with a median sensitivity of 71.7% (range, 41.7%-85.0%) and a median specificity of 94.6% (range, 73.4%-97.5%). After a consensus meeting and a reevaluation by best-performing expert reviewers, sensitivity was 79.9% and specificity was 99.2%. The estimated national prevalence of breast implants among women between 20 and 70 years was 3.0%, ranging from 1.7% at 21 to 30 years to 3.9% between 51 and 60 years. Conclusions The novel method in this study was validated with a high sensitivity and specificity, resulting in accurate prevalence estimates and providing the opportunity to conduct absolute risk assessment studies on the health consequences of breast implants. Level of Evidence: 2

Objective Autopsy rates have been declining worldwide. The present study reports the outcome of a retrospective analysis of all non-forensic autopsies in the Netherlands over a course of 25 years, and compares these with the most recent Dutch study.Method Retrospectively, 25 years of data on clinical autopsies from the Nationwide Network and Registry of Histo- and Cytopathology in the Netherlands (PALGA) was paired with the mortality registry ( Statistics Netherlands).Results The crude prevalence of autopsies declined from 7.07% in 1991 to 2.73% in 2015. After adjusting for age at death, there was no difference in autopsy rate between males and females. An increasing age significantly decreased the autopsy rate.Conclusion In the Netherlands, clinical autopsies have been declining over the last quarter century. Age at death, but not sex, was associated with the autopsy rate. These different results stress the importance of correct collection and analysis methods of data.

PURPOSE The use of standardized structured reporting (SSR) can improve communication between cancer specialists, which might improve clinical care; however, there are no reliable data on whether the introduction of SSR is associated with improvements in clinical outcome. PATIENTS AND METHODS We performed a retrospective cohort study in the Netherlands, including all patients with colorectal cancer (CRC) from 2009 to 2014. As a reference, cohorts of 2007 and 2008 were included. Data from the Netherlands Cancer Registry were used and combined with data from the Dutch Pathology Registry (PALGA) and the Dutch ColoRectal Audit. We tested the preformulated hypothesis that use of SSR improves the care of patients with CRC by improving the completeness of the pathology reports, the quality of the pathology evaluation, and patient outcomes with respect to treatment and survival. RESULTS We included 72,859 patients with CRC (23.8% reference, 32.9% SSR, and 43.3% narrative reports). Use of SSR increased over time, which resulted in more complete pathology reports (95.8% v 89.8%; P < .001). Risk assessment in stage II colon cancer was more adequate and resulted in an increased delivery of adjuvant therapy in patients with SSR (19.6% v 15.1%; P = .001). Risk of death for patients in the SSR group was significantly lowered (corrected hazard ratio, 0.94; 95% CI 0.90 to 0.97). CONCLUSION We demonstrate that use of SSR improved patient care in those with CRC by providing more complete reports of higher quality, which had significant effects on the delivery of adjuvant therapy and patient outcomes.

Background: The association between celiac disease (CD) and the development of lymphoid and gastrointestinal (GI) malignancies have been reported. However, data are scarce yet needed to develop evidence-based follow-up programs.Objective: The objective of this article is to assess relative (RR) and absolute risks of lymphoma and GI carcinoma for newly diagnosed patients.Methods: A case-control design to determine RR was performed with cases (lymphoma or GI carcinoma) and controls (melanoma or basal cell carcinoma) diagnosed 1994-2014, retrieved from the Dutch nationwide population-based pathology database (PALGA). Within this population, individuals with histologically proven CD before or simultaneously diagnosed with the malignancy were identified.Results: A total of 349/301,425 cases (0.1%) and 282/576,971 (0.05%) controls were diagnosed with CD. Risk of T-cell lymphoma, predominantly enteropathy-associated T-cell lymphoma (EATL), was strongly associated with CD diagnosis (RR = 35.8 (95% CI 27.1-47.4)). Although most often synchronously diagnosed, T-cell lymphoma RR ≥ 1 year after CD diagnosis was still elevated (RR = 12.7 (95% CI 7.6-21.3)). Other CD-associated malignancies were small bowel adenocarcinoma (RR = 11.9 (95% CI 8.2-17.2)) and esophageal squamous cell carcinoma (RR = 3.5 (95% CI 2.1-5.8)). Absolute risks were relatively low. Other types of lymphomas and GI carcinomas were not associated with CD.Conclusion: Increased risk for specific malignancies in CD should alert physicians for EATL (both intestinal and extraintestinal) and small bowel adenocarcinoma in patients with CD diagnosed at age ≥ 50 years.

Rubinstein–Taybi syndrome (RSTS) is a multiple congenital anomalies syndrome associated with mutations in CREBBP (70%) and EP300 (5–10%). Previous reports have suggested an increased incidence of specific benign and possibly also malignant tumors. We identified all known individuals diagnosed with RSTS in the Netherlands until 2015 (n = 87) and studied the incidence and character of neoplastic tumors in relation to their CREBBP/EP300 alterations. The population–based Dutch RSTS data are compared to similar data of the Dutch general population and to an overview of case reports and series of all RSTS individuals with tumors reported in the literature to date. Using the Nationwide Network and Registry of Histopathology and Cytopathology in the Netherlands (PALGA Foundation), 35 benign and malignant tumors were observed in 26/87 individuals. Meningiomas and pilomatricomas were the most frequent benign tumors and their incidence was significantly elevated in comparison to the general Dutch population. Five malignant tumors were observed in four persons with RSTS (medulloblastoma; diffuse large‐cell B‐cell lymphoma; breast cancer; non‐small cell lung carcinoma; colon carcinoma). No clear genotype–phenotype correlation became evident. The Dutch population‐based data and reported case studies underscore the increased incidence of meningiomas and pilomatricomas in individuals with RSTS. There is no supporting evidence for an increased risk for malignant tumors in individuals with RSTS, however, due to the small numbers this risk may not be fully dismissed.

Standardized structured reporting (SSR) enables high-quality pathology reporting, but implementing SSR is slow. The objective of this study is to identify both barriers and facilitators that pathologists encounter in SSR, in order to develop tailored implementation tools to increase SSR usage. We used a mixed method design: a focus group interview helped to identify barriers and facilitators in SSR. The findings were classified into the following domains: innovation, individual professional, social setting, organization, and economic and political context. We used a web-based survey among Dutch pathologists to quantify the findings. Ten pathologists participated in the focus group interview, and 97 pathologists completed the survey. The results of both showed that pathologists perceive barriers related to SSR itself. Particularly its incompatibility caused lack of nuance (73%, n = 97) in the standardized structured pathology report. Regarding the individual professional, knowledge about available SSR-templates was lacking (28%, n = 97), and only 44% (n = 94) of the respondents agreed that using SSR facilitates the most accurate diagnosis. Related to social setting, support from the multidisciplinary team members was lacking (45%, n = 94). At organization level, SSR leads to extra work (52%, n = 94) because of its incompatibility with other information systems (38%, n = 93). Main facilitators of SSR were incorporation of speech recognition (54%, n = 94) and improvement in communication during multidisciplinary team meetings (69%, n = 94). Both barriers and facilitators existed in various domains. These factors can be used to develop implementation tools to encourage SSR usage. Electronic supplementary material The online version of this article (10.1007/s00428-019-02609-6) contains supplementary material, which is available to authorized users.

Item does not contain fulltext BACKGROUND: Recurrence rates after Mohs micrographic surgery (MMS) for rare cutaneous tumours are poorly defined. OBJECTIVE: To investigate the recurrence rate after MMS for rare cutaneous tumours at a university centre. METHODS & MATERIALS: Retrospective review of all rare cutaneous tumours treated with MMS at a large university centre between January 2008 and December 2012. To detect all recurrences, patients were linked to The Nationwide Network and registry of histo- and cytopathology (PALGA). RESULTS: In total, 80 patients with 80 tumours were included. Tumour types included dermatofibrosarcoma protuberans (27), atypical fibroxanthoma (22), Merkel cell carcinoma (8), microcystic adnexal carcinoma (9), sebaceous carcinoma (6), extramammary Paget's disease (2) and other (6). Mean follow-up time was 3.7 years (standard deviation 1.4) during which two atypical fibroxanthomas recurred (2.5%). CONCLUSION: This large case series shows that MMS is an appropriate treatment for rare cutaneous tumours with a recurrence rate less than 3%. Preferably, MMS for rare cutaneous tumours is performed in experienced multidisciplinary centres to further improve the quality of treatment.

Background & Aims: Both chronic inflammation and reduced immunosurveillance contribute to malignancy development in inflammatory bowel disease (IBD). Previous literature suggests that especially Crohn’s disease patients are at an increased risk for developing gastric cancer (GC). This study aimed to identify risk factors for GC development in IBD and to compare the clinical characteristics of GC in IBD to those in the general population. Methods: We retrospectively searched the Dutch Pathology Database to identify all Dutch IBD patients with GC between January 2004 and December 2008. Two case-control studies were performed. I: to identify risk factors for GC in IBD, with controls from the IBD South Limburg (IBDSL) population-based cohort; and II: to compare GC disease course in IBD patients with the general population. General population data were obtained from the Eindhoven Cancer Registry (ECR). Results: We included 59 patients with IBD and GC (cases). Cases were significantly older at IBD diagnosis than IBDSL controls (median age 61 years versus 40; p

Differentiation grade of colorectal adenocarcinoma (CRC) is a prognostic factor and important for therapy selection. In patients with stage II colon cancer, poor differentiation is an indication for adjuvant chemotherapy. The variability in daily practice in the grading of CRC was assessed in a nationwide cohort. Using the Dutch Pathology Registry (PALGA), all synoptically reported CRC resections from 2010 to 2013 were identified. Proportions of poorly differentiated (PD) adenocarcinomas were determined and compared between 35 laboratories by univariable and multivariable logistic regression analyses. In total, 11,719 resections of 11,681 patients were included, of which 1427 (12.2%) were PD (range between 35 laboratories: 5.0% to 33.2%). After adjustment for case mix, 4 (11%) laboratories still reported a significantly lower (n=2) or higher (n=2) proportion of PD adenocarcinoma compared with the reference laboratory. Seven of 8 investigated laboratories showed considerable intralaboratory variation between pathologists as well. In a subgroup of 2812 patients (2813 tumors) who could have been eligible for adjuvant chemotherapy solely on the basis of the differentiation grade (stage II colon cancer patients without other high-risk factors [ie, T4

Aims: Variation in health-care is undesirable, as this is potentially harmful for patients. In the Netherlands, an e-learning module was developed to standardise pathological evaluation of colorectal adenomas. We studied the effect of e-learning on interlaboratory variability in grading of dysplasia in screened conventional colorectal adenomas. Methods and results: A cross-sectional retrospective study was performed, including all colorectal adenomas from the Dutch population-based colorectal cancer screening programme, retrieved from the Dutch Pathology Registry (PALGA) from January 2014 to July 2015. The e-learning tool, commissioned by the National Institute for Public Health, was implemented among screening pathologists from October 2014. Proportions of high-grade dysplasia (HGD) were compared before (January–July 2014) and after implementation (October 2014–July 2015) of the e-learning module. Interlaboratory variation was assessed by multilevel mixed-effects analysis. In total, 20 713 colonoscopies (20 546 patients) were performed after a positive faecal immunochemical screening test, resulting in the inclusion of 56 355 conventional adenomas from 37 pathology laboratories. Before implementation, 12 614 adenomas were diagnosed, including 4.3% with HGD. After implementation, 43 741 adenomas were diagnosed, and the HGD proportion decreased to 3.9%. Univariable analysis showed less deviant proportions of HGD after implementation in 62% of the laboratories (P = 0.019). Multilevel analysis confirmed decreased variation in the risk of diagnosing HGD (P = 0.021). Conclusions: Interlaboratory variability in grading HGD in colorectal adenomas after a positive screening test decreased after implementation of an e-learning module for pathologists. We therefore conclude that e-learning has a favourable influence on decreasing diagnostic variability, making this a relevant strategy for health-care standardisation.

The objective of this study is to determine at a national level whether patients with metastatic non-small cell lung cancer (NSCLC) are adequately tested for EGFR mutations and ALK rearrangement, because targeted therapy is tailored to the results of molecular diagnostics.Retrospective cohort study.Data from all patients with metastatic non-squamous NSCLC diagnosed in 2013 or 2015 were identified from the Netherlands Cancer Registry, and coupled with data from the Netherlands national pathology registry (PALGA). Using information extracted from PALGA we determined what percentage of the tumours were tested for EGFR or KRAS mutations and ALK rearrangement, identified the variables that were associated with the performance of molecular diagnostics and investigated the differences between 48 laboratories.A total of 6,619 patients were included (2013: n = 3,195; 2015: n = 3,424). In 2013, EGFR or KRAS testing was performed on 73.1% of the tumours (variation between laboratories 30.6-91.7%); in 2015 this was 78.9% (variation 40.0-91.0%). In 2013 49.5% of the tumours without EGFR or KRAS mutations underwent ALK testing (variation between laboratories 6.3-100%) and in 2015 ALK testing was performed on 77.4% (32.5-100%). In 2015, 6 and 7 laboratories tested significantly fewer EGFR and ALK tests, respectively, than the national average.In 2013, molecular testing for EGFR and KRAS mutations and, in particular, for ALK rearrangement was suboptimal. EGFR and ALK testing was performed significantly more often in 2015. Despite this increase, there is room for improvement in a number of laboratories and hospitals, considering that some patients were possibly wrongly not eligible for targeted therapy.

Objective: The study aims to evaluate all patients who underwent liver resection for metastatic disease for demographics, characteristics of the primary tumor and metastasis, volume of liver resection specimens per pathology laboratory and to describe trends in surgical treatment. Methods: Data were prospectively collected using the Dutch nationwide pathology network. All pathology reports containing details on liver resections for metastatic disease between January 2001 and December 2010 were evaluated. Results: A total of 3,916 liver resections were performed in 3,699 patients with a median age of 63 years (range 1-91). The primary tumor was mainly colorectal (n = 3,256; 88.0%). The number of ‘high volume liver centers' increased from 2 to 12 in the study period, whereas the number of ‘low volume centers' decreased. The number of liver resections increased from 224 to 596 per year (p ≤ 0.0001). A significant increase was demonstrated in elderly patients, patients with multiple metastases, liver resections for smaller metastases and minor liver resections. Conclusion: Although the majority of patients were young and had solitary metastasis, indications for liver resection are expanding as indicated by increasing numbers of elderly and patients with multiple liver metastases. Patients with non-colorectal liver metastases were seldom candidates for resection.

// Jannemarie de Ridder 1 , Johannes H.W. de Wilt 1 , Femke Simmer 2 , Lucy Overbeek 3 , Valery Lemmens 4, 5 , Iris Nagtegaal 2 1 Department of Surgical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands 2 Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands 3 Foundation PALGA, Nationwide Network and Registry of Histo- and Cytopathology in the Netherlands, Utrecht, The Netherlands 4 Netherlands Cancer Registry, Comprehensive Cancer Organisation the Netherlands (IKNL), Eindhoven, The Netherlands 5 Department of Public Health, Erasmus Medical Center, Rotterdam, The Netherlands Correspondence to: Jannemarie de Ridder, email: Jannemarie@hotmail.com Keywords: liver metastases, histology, incidences, colorectal liver metastases, non-colorectal liver metastases Received: December 05, 2015 Accepted: May 12, 2016 Published: July 13, 2016 ABSTRACT Background: The liver is a common metastatic site for a large variety of primary tumors. For both patients with known and unknown primary tumors it is important to understand metastatic patterns to provide tailored therapies. Objective: To perform a nationwide exploration of the origins of histological confirmed liver metastases. Results: A total of 23,154 patients were identified. The majority of liver metastases were carcinomas (n=21,400; 92%) of which adenocarcinoma was the most frequent subtype (n=17,349; 75%). Most common primary tumors in patients with adenocarcinoma were from colorectal (n=8,004), pancreatic (n=1,755) or breast origin (n=1,415). In women of 50 years and younger, metastatic adenocarcinoma originated more frequently from breast cancer, while in women older than 70 years liver metastases originated more frequently from gastrointestinal tumors. Liver metastases in men older than 70 years originated often from squamous cell lung carcinoma. An unknown primary tumor was detected in 4,209 (18%) patients, although tumor type could be determined in 3,855 (92%) of them. Methods: Data were collected using the nationwide network and registry of histo- and cytopathology in the Netherlands (PALGA). All histological confirmed liver metastases between January 2001 and December 2010 were evaluated for tumor type, origin of the primary tumor and were correlated with patient characteristics (age, gender). Conclusion: The current study provides an overview of the origins of liver metastases in a series of 23,154 patients.

There are three types of monozygotic (MZ) twins. MZ twins can either share one chorion and one amnion, each twin can have its own amnion, or MZ twins can—like dizygotic twins—each have their own chorion and amnion. Sharing the same chorion may create a more similar/dissimilar prenatal environment and bias heritability estimates, but most twin studies do not distinguish between these three types of MZ twin pairs. The aim of this paper is to investigate the effect of chorion sharing on the similarity within MZ twin pairs for a large number of traits. Information on chorion status was obtained for the Netherlands twin register (NTR) by linkage to the records from the database of the dutch pathological anatomy national automated archive (PALGA). Record linkage was successful for over 9000 pairs. Effect of chorion type was tested by comparing the within-pair similarity between monochorionic (MC) and dichorionic (DC) MZ twins on 66 traits including weight, height, motor milestones, child problem behaviors, cognitive function, wellbeing and personality. For only 10 traits, within-pair similarity differed between MCMZ and DCMZ pairs. For traits influenced by birth weight (e.g. weight and height in young children) we expected that MC twins would be more discordant. This was found for 5 out of 13 measures. When looking at traits where blood supply is important, we saw MCMZ twins to be more concordant than DCMZ’s for 3 traits. We conclude that the influence on the MZ twin correlation of the intra-uterine prenatal environment, as measured by sharing a chorion type, is small and limited to a few phenotypes. This implies that the assumption of equal prenatal environment of mono- and DC MZ twins, which characterizes the classical twin design, is largely tenable. Electronic supplementary material The online version of this article (doi:10.1007/s10519-015-9745-3) contains supplementary material, which is available to authorized users.

BACKGROUND: The purpose of this study was to determine time trends for primary treatment modalities in advanced laryngeal cancer, overall survival (OS), and laryngectomy-free interval (LFI) over the last 2 decades in The Netherlands. METHODS: We conducted an analysis of T3 to T4 laryngeal cancer data from 2 combined national (population-based and pathology-based) cancer registries. RESULTS: A total of 2072 T3 cases (14.7%) and 1722 T4 cases (12.2%) were identified. Total laryngectomy as primary treatment modality decreased, whereas radiotherapy (RT) increased. For T3 disease, 5-year OS after primary total laryngectomy (+/- adjuvant RT), RT, and chemoradiotherapy (CRT) was 49%, 47%, and 45%, respectively. For T4 disease, this was 48%, 34%, and 42% (overall p

Contains fulltext : 155323.pdf (Publisher’s version ) (Closed access) We describe a patient diagnosed with a noninvasive intestinal-type mucinous ovarian borderline tumor presenting with pleural metastases 4 yr later. This was confirmed by an identical mutation in TP53 in both tumors. Metastases of ovarian borderline tumors outside the pelvis or abdominal cavity are extremely rare. A large epidemiologic search in the Dutch Pathology Registry that was conducted in support of this case, identifying 1812 intestinal-type mucinous ovarian borderline tumors, suggests that microinvasion is associated with a higher risk of disease spread. Our case illustrates that intestinal-type mucinous ovarian borderline tumor with intraepithelial carcinoma might also have a higher risk of metastasis, assuming that microinvasion occurs in the presence of intraepithelial carcinoma. Both intraepithelial carcinoma and microinvasion could be a trigger for more extensive tumor sampling to prevent sampling error of (micro)invasive adenocarcinoma. In addition, this case draws attention to the developmental spectrum of Types I and II ovarian carcinomas. Borderline tumors harboring a TP53 mutation require further studying to examine whether they might develop into high-grade Type II carcinomas.

IMPORTANCE Breast implants are among the most commonly used medical devices. Since 2008, the number of women with breast implants diagnosed with anaplastic large-cell lymphoma in the breast (breast-ALCL) has increased, and several reports have suggested an association between breast implants and risk of breast-ALCL. However, relative and absolute risks of breast-ALCL in women with implants are still unknown, precluding evidence-based counseling about implants. OBJECTIVE To determine relative and absolute risks of breast-ALCL in women with breast implants. DESIGN, SETTING, AND PARTICIPANTS Through the population-based nationwide Dutch pathology registry we identified all patients diagnosed with primary non-Hodgkin lymphoma in the breast between 1990 and 2016 and retrieved clinical data, including breast implant status, from the treating physicians. We estimated the odds ratio (OR) of ALCL associated with breast implants in a case-control design, comparing implant prevalence between women with breast-ALCL and women with other types of breast lymphoma. Cumulative risk of breast-ALCL was derived from the age-specific prevalence of breast implants in Dutch women, estimated from an examination of 3000 chest x-rays and time trends from implant sales. MAIN OUTCOMES AND MEASURES Relative and absolute risks of breast-ALCL in women with breast implants. RESULTS Among 43 patients with breast-ALCL (median age, 59 years), 32 had ipsilateral breast implants, compared with 1 among 146 women with other primary breast lymphomas (OR, 421.8; 95% CI, 52.6-3385.2). Implants among breast-ALCL cases were more often macrotextured (23 macrotextured of 28 total implants of known type, 82%) than expected (49 193 sold macrotextured implants of total sold 109 449 between 2010 and 2015, 45%) based on sales data (P < .001). The estimated prevalence of breast implants in women aged 20 to 70 years was 3.3%. Cumulative risks of breast-ALCL in women with implants were 29 per million at 50 years and 82 per million at 70 years. The number of women with implants needed to cause 1 breast-ALCL case before age 75 years was 6920. CONCLUSIONS AND RELEVANCE Breast implants are associated with increased risk of breast-ALCL, but the absolute risk remains small. Our results emphasize the need for increased awareness among the public, medical professionals, and regulatory bodies, promotion of alternative cosmetic procedures, and alertness to signs and symptoms of breast-ALCL in women with implants.

Hypopharynx cancer has the worst prognosis of all head and neck squamous cell cancers. Since the 1990s, a treatment shift has appeared from a total laryngectomy towards organ preservation therapies. Large randomized trials evaluating treatment strategies for hypopharynx cancer, however, remain scarce, and frequently this malignancy is evaluated together with larynx cancer. Therefore, our aim was to determine trends in incidence, treatment and survival of hypopharynx cancer. We performed a population-based cohort study including all patients diagnosed with T1–T4 hypopharynx cancer between 1991 and 2010 in the Netherlands. Patients were recorded by the national cancer registry database and verified by a national pathology database. 2999 patients were identified. The incidence increased significantly with 4.1% per year until 1997 and decreased non-significantly afterwards. For women, the incidence increased with 1.7% per year during the entire study period. Total laryngectomy as primary treatment significantly decreased, whereas radiotherapy and chemoradiation increased. The 5-year overall survival significantly increased from 28% in 1991–2000 to 34% in 2001–2010. Overall survival for T3 was equal for total laryngectomy and (chemo)radiotherapy, but for T4-patients the survival was significantly better after primary total laryngectomy (± adjuvant radiotherapy). This large population-based study demonstrates a shift in treatment preference towards organ preservation therapies. The 5-year overall survival increased significantly in the second decade. The assumed equivalence of organ preservation and laryngectomy may require reconsideration for T4 disease. Electronic supplementary material The online version of this article (doi:10.1007/s00405-017-4766-6) contains supplementary material, which is available to authorized users.

Contains fulltext : 155223.pdf (Publisher’s version ) (Open Access) A significant proportion of ovarian malignancies consists of metastatic tumors, with a wide variety in site of origin. Differentiating between a primary and metastatic malignancy of the ovaries can be difficult and misdiagnosis might have considerable impact on both treatment and prognosis. To further examine the origin of malignancies metastatic to the ovary, we performed a large-scale, nationwide search for ovarian metastases in the Dutch Pathology Registry (PALGA). All pathology reports concerning malignancies metastatic to the ovary and associated primary tumors in the Netherlands between 2000 and 2010 were collected. Age, year of diagnosis, tumor type, location of the primary tumor, and side of the ovarian tumor were extracted from the database. We identified 2312 patients fulfilling our selection criteria. The most common primary malignancy sites were colon (33.2%), endometrium (17.1%), breast (14.3%), appendix (7.3%), and stomach (4.5%). The metastases were most frequently bilateral (46.3%) followed by unilateral metastases in the right (26.7%) and left ovary (19.8%), while side was unknown in 7.2% of cases. Of colorectal carcinomas, only 40.2% metastasized bilaterally, compared to 63.9% of breast, 62.9% of gastric, and 58.9% of appendix carcinomas. Left-sided colorectal carcinomas most often metastasized to the left ovary (p < 0.0001). We found colon carcinomas to be most frequently responsible for metastases to the ovaries, followed by endometrial and breast carcinomas. Metastases from breast, stomach, and appendix carcinomas were mostly bilateral, whereas metastases from colorectal carcinomas were mostly unilateral. The mechanisms underlying preferred sites for metastasis or side remain unclear.

Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a rare but serious complication in patients with breast implants, Patients are at risk of BIA-ALCL whether they receive breast implants for cosmetic reasons or for reconstructive purposes after surgery for breast cancer or prophylactic mastectomy. During the past decade, an increased number of reports have addressed BIA-ALCL. Herein, we describe BIA-ALCL in a transgender woman. The patient received breast implants as part of her gender transition and was diagnosed with BIA-ALCL 20 years later. The patient underwent several revisional operations in the 20 years after her primary breast surgery to treat unexplained pain with low-grade fever, severe capsular contracture (Baker grade III-IV), and several instances of implant rupture. In July 2016, the patient presented to our office with "late-onset" periprosthetic seroma 5 years after her last revisional breast surgery. She was diagnosed with BIA-ALCL without capsular invasion based on results of cytologic analysis of the periprosthetic seroma and histologic evaluation of the periprosthetic capsule. This diagnosis was verified further by results of immunohistochemical testing, which indicated expression of CD30 and T-cell markers in the periprosthetic seroma only. Our intentions with this case report are to demonstrate that all patients who undergo breast implantation, including transgender women, are at risk of BIA-ALCL and to highlight the importance of cytomorphologic and immunohistochemical screening of seroma fluid in patients with late-onset periprosthetic seroma. Level of evidence 5.

Contains fulltext : 178204.pdf (Publisher’s version ) (Open Access) Objective To compare the cumulative incidence of cervical cancer diagnosed within 72 months after a normal screening sample between conventional cytology and liquid based cytology tests SurePath and ThinPrep.Design Retrospective population based cohort study.Setting Nationwide network and registry of histo- and cytopathology in the Netherlands (PALGA), January 2000 to March 2013.Population Women with 5 924 474 normal screening samples (23 833 123 person years).Exposure Use of SurePath or ThinPrep versus conventional cytology as screening test.Main outcome measure 72 month cumulative incidence of invasive cervical cancer after a normal screening sample for each screening test. Cox regression analyses assessed the hazard ratios, adjusted for calendar time, age, screening history, and socioeconomic status and including laboratories as random effects.Results The 72 month cumulative cancer incidence was 58.5 (95% confidence interval 54.6 to 62.7) per 100 000 normal conventional cytology samples, compared with 66.8 (56.7 to 78.7) for ThinPrep and 44.6 (37.8 to 52.6) for SurePath. Compared with conventional cytology, the hazard of invasive cancer was 19% lower (hazard ratio 0.81, 95% confidence interval 0.66 to 0.99) for SurePath, mainly caused by a 27% lower hazard (0.73, 0.57 to 0.93) of a clinically detected cancer. For ThinPrep, the hazard was on average 15% higher (hazard ratio 1.15, 0.95 to 1.38), mainly caused by a 56% higher hazard of a screen detected cancer (1.56, 1.17 to 2.08).Conclusions These findings should provoke reconsideration of the assumed similarity in sensitivity to detect progressive cervical intraepithelial neoplasia between different types of liquid based cytology and conventional cytology.

Contains fulltext : 172841pub.pdf (Publisher’s version ) (Closed access) AIMS: Although high-grade dysplasia (HGD) is a risk factor for malignant transformation and the future development of adenomas/carcinomas, grade is not incorporated in the Dutch guidelines for colonoscopy surveillance, partly because of presumed interobserver variability. The aim of this study was to analyse, in a nationwide cohort of colorectal adenomas, the interlaboratory variability in the grading of dysplasia in daily practice. METHODS AND RESULTS: From the Dutch Pathology Registry, all synoptically reported classic adenomas in The Netherlands in 2013 were identified. The proportion of adenomas with HGD was determined for biopsies and polypectomies, and compared between 37 laboratories by the use of multivariable logistic regression analyses. In total, 21 030 colonoscopies of 20 270 patients were included. HGD was reported in 530 (3.6%) of 14 866 adenomas diagnosed on biopsies (range between laboratories: 0-13.6%) and in 983 (11.8%) of 8346 adenomas diagnosed on polypectomies (range: 3.1-42.9%). After adjustment for case mix, 13 (35%) laboratories reported a significantly lower or higher frequency of HGD than average. CONCLUSIONS: We observed considerable interlaboratory variation in the grading of dysplasia in colorectal adenomas, which could be only partly explained by differences in case mix. Therefore, better standardization of grading criteria is needed before grade of dysplasia can usefully be incorporated in colonoscopy surveillance guidelines.

Contains fulltext : 165695pub.pdf (Publisher’s version ) (Open Access) Regional lymph node metastases in colorectal cancer (CRC) decrease outcome. Whether nodal metastases function as a biomarker, i.e. as a sign of advanced disease, or are in fact involved in the metastatic process is unclear. We evaluated metastatic patterns of CRC according to the lymph node status of the primary tumor.A retrospective review of 1393 patients with metastatic CRC who underwent autopsy in the Netherlands was performed. Metastatic patterns of regional lymph node positive and negative CRC were compared and validated by population-based data from the Eindhoven Cancer Registry (ECR).Patients with regional lymph node positive CRC more often developed peritoneal metastases (28% vs. 21%, p=0.003) and distant lymph node metastases (25% vs. 15%, p

Pathology reporting is evolving from a traditional narrative report to a more structured synoptic report. Narrative reporting can cause misinterpretation due to lack of information and structure. In this systematic review, we evaluate the impact of synoptic reporting on completeness of pathology reports and quality of pathology evaluation for solid tumours. Pubmed, Embase and Cochrane databases were systematically searched to identify studies describing the effect of synoptic reporting implementation on completeness of reporting and quality of pathology evaluation of solid malignant tumours. Thirty-three studies met the inclusion criteria. All studies, except one, reported an increased overall completeness of pathology reports after introduction of synoptic reporting (SR). Most frequently studied cancers were breast (n = 9) and colorectal cancer (n = 16). For breast cancer, narrative reports adequately described ‘tumour type’ and ‘nodal status’. Synoptic reporting resulted in improved description of ‘resection margins’, ‘DCIS size’, ‘location’ and ‘presence of calcifications’. For colorectal cancer, narrative reports adequately reported ‘tumour type’, ‘invasion depth’, ‘lymph node counts’ and ‘nodal status’. Synoptic reporting resulted in increased reporting of ‘circumferential margin’, ‘resection margin’, ‘perineural invasion’ and ‘lymphovascular invasion’. In addition, increased numbers of reported lymph nodes were found in synoptic reports. Narrative reports of other cancer types described the traditional parameters adequately, whereas for ‘resection margins’ and ‘(lympho)vascular/perineural invasion’, implementation of synoptic reporting was necessary. Synoptic reporting results in improved reporting of clinical relevant data. Demonstration of clinical impact of this improved method of pathology reporting is required for successful introduction and implementation in daily pathology practice. Electronic supplementary material The online version of this article (doi:10.1007/s00428-016-1935-8) contains supplementary material, which is available to authorized users.

Contains fulltext : 49608.pdf (Publisher’s version ) (Closed access) AIM: To renew the echocardiographic reference values of heart dimensions in healthy children. METHODS AND RESULTS: Group 1 consisted of 587 children, of which 361 boys and 226 girls, age from birth to 18 years, body weight over 2500 g, who visited the Pediatric Cardiology outclinic during the period January 2000 till March 2004. All included children were diagnosed as normal, or as having innocent heart murmur. The second group was taken from an earlier study and comprised 160 children (77 boys and 83 girls). The echocardiographic measures were taken from conventional M-mode recording of the left ventricle (LV) parasternal long axis view. End diastolic septal (IVS) and LV posterior wall thickness (LVPW) and end diastolic as well as end systolic LV intracavity dimensions were retrospectively analyzed. The regression lines from all measured sizes are significantly different from those collected in the early eighties. Especially the thickness of the IVS is smaller. The regression lines are independent of gender. CONCLUSIONS: New reference values have been found which should replace the presently used ones. There is no difference between boys and girls. Why the muscular wall thicknesses are thinner than found 20 years ago needs to be further explored.

The purpose of this study was to determine time trends for primary treatment modalities in advanced laryngeal cancer, overall survival (OS), and laryngectomy-free interval (LFI) over the last 2 decades in The Netherlands.We conducted an analysis of T3 to T4 laryngeal cancer data from 2 combined national (population-based and pathology-based) cancer registries.A total of 2072 T3 cases (14.7%) and 1722 T4 cases (12.2%) were identified. Total laryngectomy as primary treatment modality decreased, whereas radiotherapy (RT) increased. For T3 disease, 5-year OS after primary total laryngectomy (+/- adjuvant RT), RT, and chemoradiotherapy (CRT) was 49%, 47%, and 45%, respectively. For T4 disease, this was 48%, 34%, and 42% (overall p .0001), respectively. Five-year LFI for T3 disease was 81% (RT) and 77% (CRT), and for T4 disease it was 81% and 87%, respectively.From 1991 to 2010 total laryngectomy as primary treatment modality for advanced laryngeal cancer decreased and RT increased. T3 disease showed similar survival rates for all primary treatment modalities. For T4 disease, total laryngectomy (+ adjuvant RT) showed the best survival. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1247-E1255, 2016.

Contains fulltext : 137129.pdf (Publisher’s version ) (Closed access) BACKGROUND: Cytology is a widely used method of triaging women who test positive for human papillomavirus (HPV). However, self-sampled specimens, which can substantially increase participation in screening programmes, are not suitable for accurate cytological assessment. We investigated whether direct DNA methylation-based molecular triage on self-sampled cervicovaginal specimens was non-inferior to cytology triage on additional physician-collected cervical samples in the detection of cervical intraepithelial neoplasia grade 2 (CIN2) or worse in women who did not attend cervical screening programmes. METHODS: In this randomised controlled non-inferiority trial, we invited women (aged 33-63 years) registered as non-attendees of cervical screening in the Netherlands in 2007 to submit a self-collected cervicovaginal sample for HPV testing. Using a computer-generated sequence, we randomly allocated women who tested positive for high-risk hrHPV on a self-sample to either triage by cytology on an additional physician-taken smear or direct triage on the self-sample by methylation analysis of MAL and miR-124-2 genes (1:1; stratified by age and region, with block sizes by age group). Triage-positive women in either group were referred for colposcopy. The primary endpoint was detection of CIN2 or worse, analysed by intention to treat. The non-inferiority margin was 0.80. This study is registered in the Primary Trial Register of the Netherlands, number NTR6026. FINDINGS: We invited 46 001 women to participate, 12 819 of whom returned self-sampled material; 1038 samples tested positive for high-risk HPV. Between Nov 1, 2010, and Dec 31, 2011, after exclusion of women who were ineligible, we enrolled and randomly allocated 515 women to methylation triage and 509 to cytology triage. The detection of CIN2 or worse with methylation triage was non-inferior to that with cytology triage (90 [17%] of 515 women vs 75 [15%] of 509 women; relative risk 1.19, 95% CI 0.90-1.57). Referral for colposcopy was more common in the molecular group (284 [55%] women) than in the cytology group (149 [29%] women; p

PURPOSE: In this cohort study, the rates of pulmonary embolism (PE), myocardial infarction (MI), and ischemic stroke (IS) before and after lung cancer (LC) diagnosis were compared to cancer-free controls.METHODS: Patients with LC during 2000-2007 were selected from PALGA, the Dutch Pathology Registry, and linked to the PHARMO medical record linkage system, including drug use and hospitalizations of 3 million inhabitants in the Netherlands. Included LC patients were matched 1:10 by age and gender to cancer-free controls. Hospitalizations for PE, MI, and IS were assessed in the 12 months before and after LC diagnosis.RESULTS: LC patients (N = 3,717) were six times more likely than cancer-free controls to have had a PE in the 12 months before diagnosis. After LC diagnosis, patients experienced an extremely increased risk of PE in the first 6 months (hazard ratio [HR] 16.8; 95 % confidence interval [CI] 7.6-36.8) compared with controls), which decreased to a five times increased risk (HR 5.1; 95 % CI 2.7-9.4) thereafter. However, there were less than two events per 100 person years during both time periods. LC patients receiving chemotherapy were eight times more likely to develop PE, whereas surgery increased the risk on PE three times. For MI and IS, no significant difference was observed compared with cancer-free controls before or after LC diagnosis.CONCLUSIONS: LC patients have a higher risk of developing PE compared with cancer-free controls, although the frequency of PE hospitalizations was low. Surgery and chemotherapy were associated with an increased risk of PE.

Lynch syndrome is the most common cause of hereditary intestinal cancer, with a 30-70% risk of colorectal cancer (CRC). Prevention of CRC by colonoscopy in family members with Lynch syndrome is highly effective; therefore, it is important to trace as many people with this syndrome as possible. Criteria have been developed in the Netherlands to increase detection of hereditary colorectal cancer in a practically feasible and cost-effective way. Based on these criteria, the pathologist can perform microsatellite instability testing in patients recently diagnosed with CRC. The criteria are: CRC under the age of 50, second CRC under the age of 70, or CRC under the age of 70 with a concurrent or previous malignancy associated with Lynch syndrome. For family members and patients diagnosed with CRC more than a year ago, a digital test can be used to determine whether genetic counselling by a geneticist is indicated (www.umcn.nl/verwijzers).

Birth weight in triplets is, on average, lower than in singletons and twins, and more children are classified as having very low or extremely low birth weight. Still, there is limited research on factors that affect triplet birth weight, and samples under study are often small. Chorionicity and zygosity influence triplet birth weight, but it is unknown whether the effect of zygosity can be entirely ascribed to the effect of chorionicity or whether zygosity has an additional effect on triplet birth weight. This question was investigated in 346 triplets (from 116 trios) registered with the Netherlands Twin Register for whom data on chorionicity were available. 'Triplet' refers to one child and the set of three triplets is referred to as 'trio'. Trios and triplets were classified based on zygosity and chorionicity. With regression analysis, the effects of zygosity and chorionicity on triplet birth weight were examined, while controlling for gestational age, sex, and maternal smoking during pregnancy. In addition, within the dizygotic trios a within-family comparison was made between the birth weight of the triplets that were part of a monozygotic pair (with some pairs sharing a chorion), and the birth weight of the dizygotic triplet. Based on the classification on individual level, monozygotic, monochorionic triplets had a lower mean birth weight than dizygotic, dichorionic triplets. Most remarkably, in dizygotic trios, monozygotic pairs only had a lower mean birth weight than their dizygotic sibling triplet when the pair shared a chorion. We conclude that having shared a chorion, rather than being monozygotic, increases the risk of a low birth weight. © 2012 Cambridge University Press.

Background. Data is limited on the burden of common comorbidities, such as cardiovascular disease (CVD), respiratory disease and diabetes, or comorbidities related to cancer and its treatment, such as anemia and depression, in patients with soft tissue sarcoma (STS).Patients and Methods. From the Dutch Pathology Registry linked to the PHARMO database (including data on drug use and hospitalizations), 533 patients with STS were selected during 2000–2007 and matched 1 : 10 to cancer-free controls. The occurrences of comorbidities were assessed in the 12 months before and after STS diagnosis.Results. STS patients were 2–4 times more likely to have comorbidities at diagnosis compared with cancer-free controls. The incidence of CVD, anemia, and depression after STS diagnosis differed significantly from cancer-free controls and decreased during followup from 40–124 per 1,000 person-years (py) during the first six months to 11–38 per 1,000 py more than 12 months after diagnosis. The incidence of respiratory disease and diabetes among STS patients remained stable during followup (5–21 per 1,000 py) and did not differ significantly from cancer-free controls.Conclusions. STS patients were more likely to have comorbidities before cancer diagnosis and to develop CVD, anemia, and depression after diagnosis compared to cancer-free controls.

Contains fulltext : 51431.pdf (Publisher’s version ) (Open Access) The cancer risk is unknown for those families in which a microsatellite instable tumour is neither explained by MLH1 promoter methylation nor by a germline mutation in a mismatch repair (MMR) gene. Such information is essential for genetic counselling. Families suspected of Lynch syndrome (n = 614) were analysed for microsatellite instability, MLH1 promoter methylation and/or germline mutations in MLH1, MSH2, MSH6, and PMS2. Characteristics of the 76 families with a germline mutation (24 MLH1, 2 PMS2, 32 MSH2, and 18 MSH6) were compared with those of 18 families with an unexplained microsatellite instable tumour. The mean age at diagnosis of the index patients in both groups was comparable at 44 years. Immunohistochemistry confirmed the loss of an MMR protein. Together this suggests germline inactivation of a known gene. The Amsterdam II criteria were fulfilled in 50/75 families (66%) that carried a germline mutation in an MMR gene and in only 2/18 families (11%) with an unexplained microsatellite instable tumour (P

Objective: A significant part of ovarian malignancies are metastatic tumors with a wide variety in site of origin. Differentiating between a primary and metastatic malignancy of the ovaries can be difficult, especially in case of mucinous carcinomas, and misdiagnosis might have considerable impact on both treatment and prognosis. To further examine the origin of metastatic tumors in the ovary, we performed a large scale, nationwide search for metastatic ovarian malignancies in the Dutch Pathology Registry (PALGA). Materials and methods: All pathology reports concerning metastatic ovarian carcinomas and associated primary tumors in the Netherlands from 2000-2010 were collected. Age, year of diagnosis, tumor type, location of the primary tumor and laterality of the ovarian tumor were extracted from the database. Tumors without a proven primary tumor were excluded. The Chi-square test was used to compare multiple nominal variables. Results: 2,312 patients were identified. The most common primary sites were colon (33.2%), endometrium (17.1%), breast (14.3%), appendix (7.3%) and stomach (4.5%). Bilateral tumors were the most frequent mode of presentation (46.3%) followed by right (26.7%) and left side metastases (19.8%). In 7.2% of cases, laterality was unknown. Mucinous carcinomas were the most common histological type (46.7%), followed by signet-ring cell carcinomas (7.9%) and endometrioid carcinomas (7.7%). Of colorectal tumors, only 40.2% metastasized bilaterally, compared to 64% of breast, 63% of gastric and 59% of appendix tumors. Left sided ovarian tumors originated more often from the left colon than the right colon (69.4%, p Conclusion: The most common histological tumor type in metastatic ovarian carcinomas is mucinous carcinoma. The colon is the most frequent primary site of metastatic malignancies to the ovaries, followed by endometrium, breast, appendix and stomach. Breast, stomach and appendix tumors metastasized mostly bilateral, whereas colorectal tumors metastasized mostly unilateral and ipsilateral. The mechanisms underlying these preferred sites for metastasis or laterality are still unclear. Citation Format: Michiel Simons, Jolien Bruls, Lucy Overbeek, Johan Bulten, Leon Massuger, Iris Nagtegaal. The origin of metastatic ovarian tumors: A national population-based analysis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3716. doi:10.1158/1538-7445.AM2015-3716