Gastrointestinal cancer precursor risk and mortality in pancreatic intraductal papillary mucinous neoplasms: a nationwide cohort study.

BACKGROUND AND AIMS: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a precursor of pancreatic cancer. While earlier research has shown a high prevalence of synchronous/metachronous extrapancreatic tumors in IPMN patients, these studies have often been small with retrospective data collection. The aim of the study was to examine absolute and relative risks of non-pancreatic gastrointestinal (GI) cancer precursors and mortality in histologically confirmed IPMN. METHODS: Through the nationwide ESPRESSO histopathology cohort, we retrieved data on IPMN between 1965 and 2016. Each index case was matched to ≤5 general population controls. Through Cox regression, we estimated hazard ratios (HRs) for future GI cancer precursors and death. RESULTS: A total of 117 patients with IPMN and 539 age- and sex-matched controls were included. Over a median of 2.1 years of follow up, we confirmed two (1.7%) incident GI cancer precursors in IPMN vs. four (0.7%) in controls, corresponding to an HR of 1.89 (95%CI = 0.34-10.55). By contrast, IPMN patients were at increased risk of death (HR 3.61 (95%CI = 1.79-7.27)). The most common cause of death in IPMN was pancreatic cancer (n = 14; 45.2% of all deaths). CONCLUSIONS: We found no association between IPMN and other GI cancer precursors. This argues against comprehensive routine surveillance for other GI cancer precursors in IPMN patients. Mortality was increased in IPMN with pancreatic cancer being the most common cause of death, indicating the need for lifelong follow up in all resected and non-resected patients with IPMN. However, results should be confirmed in larger cohorts.

Tumour origin, diagnostic accuracy and histopathological evaluation in patients with periampullary cancer: nationwide cohort study.

BACKGROUND: The prevalence of different periampullary cancers (pancreatic ductal adenocarcinoma, distal cholangiocarcinoma, ampullary cancer and duodenal cancer) is heterogeneous in the literature. During the 2010s, a standardized histopathological protocol for pancreatoduodenectomy specimens based on axial slicing was adopted in Sweden. The present study sought to provide information about periampullary cancers with regard to tumour types in curative and noncurative settings, preoperative diagnostic accuracy and the impact of a standardized evaluation of the surgical specimen on diagnosis, R status and lymph node assessment. METHODS: Data from patients diagnosed with periampullary cancer from 2010 to 2019 were retrieved from the Swedish National Registry for Pancreatic and Periampullary Cancer. RESULTS: Among non-curative patients, 3704 (83.6 per cent) were diagnosed with pancreatic ductal adenocarcinoma. Among patients treated with pancreatoduodenectomy, diagnosis was pancreatic ductal adenocarcinoma in 1380 (50.0 per cent), distal cholangiocarcinoma in 284 (10.3 per cent), ampullary cancer in 376 (13.6 per cent), duodenal cancer in 160 (5.8 per cent) and other diagnoses in 560 (20.3 per cent) patients. The preoperative diagnosis corresponded to the postoperative in 1177 (67.5 per cent) patients for pancreatic ductal adenocarcinoma, 162 (37.4 per cent) patients for distal cholangiocarcinoma, 220 (61.3 per cent) patients for ampullary cancer and 120 (53.6 per cent) patients for duodenal cancer. A higher rate of pancreatic ductal adenocarcinoma was seen in surgical specimens who underwent standardized evaluation, from 56.8 per cent to 64.3 per cent (P = 0.003). After standardization, higher rates of R1 resection (31.7 per cent versus 44.6 per cent, P < 0.001) and N1 stage (62.1 per cent versus 77.0 per cent, P < 0.001) were found. CONCLUSION: The proportion of pancreatic ductal adenocarcinoma was higher in patients in a non-curative setting compared with patients who underwent surgery. The rate of misdiagnosis for periampullary cancers was confirmed to be high. Thus, it should be taken into account when preoperative oncological treatment is considered. Standardized evaluation of the surgical specimen has increased pancreatic ductal adenocarcinoma, R1 and N1 rates.

Autoimmune Pancreatitis Type 1 with Biliary, Nasal, Testicular, and Pulmonary Involvement: A Case Report and a Systematic Review.

INTRODUCTION: Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated condition associated with fibroinflammatory lesions that can occur at almost any anatomical site. It often presents as a multiorgan disease that may mimic malignancy, infection, or other immune-mediated conditions. Autoimmune pancreatitis (AIP) type 1 is the most prominent manifestation of IgG4-RD in the digestive tract, with common extra-pancreatic inflammation. We present the first patient with AIP and involvement of the testicles and nasal cavity. PATIENT AND METHODS: A case of a patient with AIP type 1 and other organ involvement (bile ducts, testicles, nasal polyps, and lungs) is described. Additionally, a systematic review of AIP type 1 with testicular and nasal involvement was conducted. RESULTS: The systematic review found two cases of AIP type 1 with testicular involvement and 143 cases with AIP type 1 with nasal cavity involvement. None of them had both testicular and nasal involvement. CONCLUSIONS: This is the first case of AIP type 1 with other organ involvement, including testicular and nasal involvement, to be described. The number of patients with nasal and testicular involvement described in the literature is low. Creating awareness of this rare clinical condition is necessary, especially due to the very effective available treatment with corticosteroids and rituximab.

The prognostic significance of microsatellite instability in colorectal cancer: a Swedish multi-center study.

PURPOSE: About 10 to 15% of patients with sporadic colorectal cancer display mutations in DNA mismatch repair (MMR) genes shown as microsatellite instability (MSI). Previous reports of colorectal cancer (CRC) indicate a better prognosis for patients with MSI tumors compared to patients with microsatellite stable (MSS) tumors. In this study, our aim was to investigate whether MSI is an independent prognostic factor in CRC. PATIENTS AND METHODS: Patients with stage I-III colorectal cancer and subject to curative surgery during 2002-2006 in the Swedish low-risk colorectal cancer study group cohort were eligible for inclusion. Deficient MMR (dMMR) status was analyzed by immunohistochemistry (IHC) and/or by MSI testing with polymerase chain reaction (PCR). Prognostic follow-up and treatment data were retrieved from patient records. Statistical analyses to assess MSI-status and prognosis were done using logistic regression and survival analyses using the Kaplan-Meier method and Cox regression hazards models adjusted for age, sex, stage, comorbidity, and tumor location. RESULTS: In total, 463 patients were included, MSI high tumors were present in 66 patients (14%), and the remaining 397 were MSS/MSI low. Within 6 years, distant recurrences were present in 9.1% and 20.2% (P = 0.049), and death occurred in 25.8% and 31.5% in MSI and MSS patients, respectively. There was no statistically significant difference in overall mortality (HR 0.80, 95% CI 0.46-1.38), relapse-free survival (HR 0.82, 95% CI 0.50-1.36), or cancer-specific mortality (HR 1.60, 95% CI 0.73-3.51). CONCLUSION: Despite distant metastases being less common in patients with MSI, there was no association between MSI and overall, relapse-free, or cancer-specific survival.

Surgery in Autoimmune Pancreatitis.

INTRODUCTION: Autoimmune pancreatitis (AIP) is a disease that may mimic malignant pancreatic lesions both in terms of symptomatology and imaging appearance. The aim of the present study is to analyze experiences of surgery in patients with AIP in one of the largest European cohorts. PATIENTS AND METHODS: We performed a single-center retrospective study of patients diagnosed with AIP at the Department of Abdominal Diseases at Karolinska University Hospital in Stockholm, Sweden, between January 2001 and October 2020. RESULTS: There were 159 patients diagnosed with AIP, and among them, 35 (22.0%) patients had surgery: 20 (57.1%) males and 15 (42.9%) females; median age at surgery was 59 years (range 37-81). Median follow-up period after surgery was 50 months (range 1-235). AIP type 1 was diagnosed in 28 (80%) patients and AIP type 2 in 7 (20%) patients. Malignant and premalignant lesions were diagnosed in 8 (22.9%) patients for whom AIP was not the primary differential diagnosis, but in all cases, it was described as a simultaneous finding and recorded in retrospective analysis in histological reports of surgical specimens. CONCLUSIONS: Diagnosis of AIP is not always straightforward, and in some cases, it is not easy to differentiate it from the malignancy. Surgery is generally not indicated for AIP but might be considered in patients when suspicion of malignant/premalignant lesions cannot be excluded after complete diagnostic workup.

Integrated targeted metabolomic and lipidomic analysis: A novel approach to classifying early cystic precursors to invasive pancreatic cancer.

Pancreatic cystic neoplasms (PCNs) are a highly prevalent disease of the pancreas. Among PCNs, Intraductal Papillary Mucinous Neoplasms (IPMNs) are common lesions that may progress from low-grade dysplasia (LGD) through high-grade dysplasia (HGD) to invasive cancer. Accurate discrimination of IPMN-associated neoplastic grade is an unmet clinical need. Targeted (semi)quantitative analysis of 100 metabolites and >1000 lipid species were performed on peri-operative pancreatic cyst fluid and pre-operative plasma from IPMN and serous cystic neoplasm (SCN) patients in a pancreas resection cohort (n = 35). Profiles were correlated against histological diagnosis and clinical parameters after correction for confounding factors. Integrated data modeling was used for group classification and selection of the best explanatory molecules. Over 1000 different compounds were identified in plasma and cyst fluid. IPMN profiles showed significant lipid pathway alterations compared to SCN. Integrated data modeling discriminated between IPMN and SCN with 100% accuracy and distinguished IPMN LGD or IPMN HGD and invasive cancer with up to 90.06% accuracy. Free fatty acids, ceramides, and triacylglycerol classes in plasma correlated with circulating levels of CA19-9, albumin and bilirubin. Integrated metabolomic and lipidomic analysis of plasma or cyst fluid can improve discrimination of IPMN from SCN and within PMNs predict the grade of dysplasia.

Testing strategies to reduce morbidity and mortality from Lynch syndrome.

OBJECTIVE: Lynch syndrome (LS) has an autosomal dominant inheritance pattern and is associated with increased risk for colorectal cancer (CRC) and other cancers. Various strategies are used to identify patients at risk and offer surveillance and preventive programs, the cost effectiveness of which is much dependent on the prevalence of LS in a population. Universal testing (UT) is proposed as an effective measure, targeting all newly diagnosed CRC patients under a certain age. MATERIALS AND METHODS: LS cases were identified in a cohort of 572 consecutive CRC patients. Immunohistochemistry was performed in 539 cases, using antibodies against mismatch repair proteins MLH1, PMS2, MSH2, and MSH6. Microsatellite instability and gene mutation screening were performed in 57 cases. RESULTS: In total 11 pathogenic variants were detected, identifying LS in 1.9% of new CRC cases. Comparing the results with current clinical methods, 2 pathogenic variants were found with Amsterdam criteria and 9 when using either Bethesda guidelines or our institution's prior clinical criteria. Pathogenic variants in MSH6 were the most common in our series. We also found different outcomes using different age cut offs. CONCLUSION: Our study demonstrates that UT of tumors before age on onset at 75 years would most likely be cost-efficient and essentially equivalent to applying the Bethesda guidelines or our institution's prior clinical criteria on all new CRC.

Defining New Colorectal Cancer Syndromes in a Population-based Cohort of the Disease.

BACKGROUND/AIM: Most known cancer syndromes confer an increased risk of more than one tumour types, and families with more than one colorectal cancer often segregate other cancers as well. The aim of this study was to examine if there is a general increased risk of other cancers in colorectal cancer families, which are defined as having two or more cases of colorectal cancer in close relatives. MATERIALS AND METHODS: The study used a detailed family history of cancer diagnoses in a cohort of more than 3,000 consecutive colorectal cancer cases. A comparison was made between families with sporadic and those with familial colorectal cancer cases. Detailed morphology data were used to find further support for putative syndromes. RESULTS: There were significantly more non-colorectal cancers in the family history of the familial CRC cases (p<0.001), with significantly more gastric cancers (p<0.001), prostate cancers (p<0.001), urinary bladder cancers (p<0.001) and melanomas (p=0.002), leukaemia/lymphomas (p=0.004), gynaecological cancers (p=0.007) and breast cancers (p=0.023). There was also some support for different morphological profiles for four of the five tested syndromes. CONCLUSION: This study found support for a general increased risk of one or more different cancer syndromes involving families with colorectal cancer and other cancers. Further studies will define the different possible syndromes and determine the genetic background.

A Preliminary Report: Radical Surgery and Stem Cell Transplantation for the Treatment of Patients With Pancreatic Cancer.

We examined the immunologic effects of allogeneic hematopoietic stem cell transplantation (HSCT) in the treatment of pancreatic ductal adenocarcinoma, a deadly disease with a median survival of 24 months for resected tumors and a 5-year survival rate of 6%. After adjuvant chemotherapy, 2 patients with resected pancreatic ductal adenocarcinoma underwent HSCT with HLA-identical sibling donors. Comparable patients who underwent radical surgery, but did not have a donor, served as controls (n=6). Both patients developed humoral and cellular (ie, HLA-A*01:01-restricted) immune responses directed against 2 novel tumor-associated antigens (TAAs), INO80E and UCLH3 after HSCT. Both TAAs were highly expressed in the original tumor tissue suggesting that HSCT promoted a clinically relevant, long-lasting cellular immune response. In contrast to untreated controls, who succumbed to progressive disease, both patients are tumor-free 9 years after diagnosis. Radical surgery combined with HSCT may cure pancreatic adenocarcinoma and change the cellular immune repertoire capable of responding to clinically and biologically relevant TAAs.

Clinicopathological analysis of colorectal cancer: a comparison between emergency and elective surgical cases.

BACKGROUND: Approximately 15 to 30% of colorectal cancers present as an emergency, most often as obstruction or perforation. Studies report poorer outcome for patients who undergo emergency compared with elective surgery, both for their initial hospital stay and their long-term survival. Advanced tumor pathology and tumors with unfavorable histologic features may provide the basis for the difference in outcome. The aim of this study was to compare the clinical and pathologic profiles of emergency and elective surgical cases for colorectal cancer, and relate these to gender, age group, tumor location, and family history of the disease. The main outcome measure was the difference in morphology between elective and emergency surgical cases. METHODS: In total, 976 tumors from patients treated surgically for colorectal cancer between 2004 and 2006 in Stockholm County, Sweden (8 hospitals) were analyzed in the study. Seventeen morphological features were examined and compared with type of operation (elective or emergency), gender, age, tumor location, and family history of colorectal cancer by re-evaluating the histopathologic features of the tumors. RESULTS: In a univariate analysis, the following characteristics were found more frequently in emergency compared with elective cases: multiple tumors, higher American Joint Committee on Cancer (AJCC), tumor (T) and node (N) stage, peri-tumor lymphocytic reaction, high number of tumor-infiltrating lymphocytes, signet-ring cell mucinous carcinoma, desmoplastic stromal reaction, vascular and perineural invasion, and infiltrative tumor margin (P<0.0001 for AJCC stage III to IV, N stage 1 to 2/3, and vascular invasion). In a multivariate analysis, all these differences, with the exception of peri-tumor lymphocytic reaction, remained significant (P<0.0001 for multiple tumors, perineural invasion, infiltrative tumor margin, AJCC stage III, and N stage 1 to 2/3). CONCLUSIONS: Colorectal cancers that need surgery as an emergency case generally show a more aggressive histopathologic profile and a more advanced stage than do elective cases. Essentially, no difference was seen in location, and therefore it is likely there would be no differences in macro-environment either. Our results could indicate that colorectal cancers needing emergency surgery belong to an inherently specific group with a different etiologic or genetic background.

Analysis of colorectal cancer morphology in relation to sex, age, location, and family history.

BACKGROUND: Studies of colorectal cancer (CRC) have suggested different mechanisms of carcinogenesis in men and women, young and old patients, right- and left sided tumors, and sporadic and familial tumors. These differences might be reflected in morphology. METHODS: CRCs from 1613 patients operated on in 2004-2006 in Sweden were histologically reviewed. Morphology was examined in relation to sex, age groups, location, and family history. RESULTS: Tumors in the right colon were larger, of higher stage, more often poorly differentiated, more mucin-producing, more often had a peritumoral lymphocytic infiltrate and a high level of tumor-infiltrating lymphocytes (TILs), and more seldom had an infiltrating margin than tumors in the left colon and rectum (p < 0.0001 for most features). Young patients (<60 years) more seldom had multiple tumors but more often had perineural invasion, an infiltrative tumor margin, and high-stage tumors. Three features, TILs, medullary tumors, and invasive tumor margin, were related to sex. Only vascular invasion was related to familiality. CONCLUSION: Location is the factor that has the most influence on tumor morphology. The results support the idea that different carcinogenic mechanisms may be involved in the right and left colon. Age is the most important determinant for the presence of multiple tumors and is a crucial factor for the aggressiveness of the disease.

Development of fetal intestinal length during 2nd-trimester in normal and pathologic pregnancies.

Linear growth of the human fetal gastrointestinal tract is not often discussed in the literature, and little is known about the effects of chromosomal abnormalities and intrauterine growth restriction (IUGR) on intestinal length, especially during the 2nd trimester. Accurate evaluation of intestinal length and knowledge of normal and reference values are of clinical importance. For example, intestinal resection may be necessary in preterm infants with necrotizing enterocolitis or mid-gut volvulus, and the surgeon should use data to be judicious in the amount removed. Linear measurements are essential in evaluating fetal development ultrasonographically and are an integral part of the postmortem examination. The intestinal lengths of 203 2nd-trimester fetuses and premature infants were measured. Small intestine length (SIL), colon length (CL), total bowel length (TBL; TBL  =  SIL + CL), and the length of the appendix (AL) increased with gestational age. No differences between the genders were observed. Colon length increased secondary to maceration, but no such effects were shown on SIL, TBL, or AL. No differences were shown in relation to IUGR. Small intestine length, CL, and TBL, but not AL, were shorter in fetuses with trisomy 21. Appendix length was not affected by any of the studied factors. We propose that the measurement of the length of the appendix may be used as an additional parameter for the postmortem evaluation of gestational age. Furthermore, its assessment may have potential as an ultrasonographic indicator of gestational age, particularly for the 2nd trimester.

The severity of clinical manifestations in preeclampsia correlates with the amount of placental infarction.

OBJECTIVE: To correlate placental histopathology, in particular ischemic changes, with the clinical severity of preeclampsia. DESIGN: A blinded retrospective study. SETTING: One Swedish hospital. SAMPLE: One hundred and fifty-seven women with severe (n= 116) or mild (n= 41) preeclampsia and 157 normotensive women matched according to gestational-age. METHODS: One senior pathologist, blinded to clinical data and group, examined all histological slides. In the statistical analyses, adjustment for gestational week was done when appropriate. MAIN OUTCOME MEASURES: Placental histopathological findings. RESULTS: Amount of infarction increased with the severity of preeclampsia (p < 0.001). Infarction involving ≥5% of the placental tissue was seen in 39.7% of severe preeclampsia, 17.1% of mild preeclampsia and 5.1% of non-preeclampsia. When comparing placentas in severe preeclampsia, mild preeclampsia and non-preeclampsia, there was an increase in the presence of any infarction (80.2%, 61.0%, vs. 20.4%). Also, there was a difference in the presence of decidual arteriopathy (35.3%, 22.0%, vs. 3.8%) and accelerated villous maturation (71.6%, 53.3%, vs. 12.6%). We found no difference in intervillous thrombosis, abruption placenta or placental weight in relation to gestational week. CONCLUSIONS: In pregnancies with mild or severe preeclampsia, a large proportion of the placentas had histological signs of pathology, in particular signs of ischemia. The pathology was similar, but more pronounced in severe compared to mild preeclampsia, suggesting mild and severe preeclampsia to have similar underlying etiology.

Colorectal cancer susceptibility loci in a population-based study: Associations with morphological parameters.

Recent genome-wide association studies have identified multiple genetic loci and single nucleotide polymorphisms (SNPs) associated with either increased or decreased risk of colorectal cancer (CRC). In the present study, our objective was to determine whether 11 of the new susceptibility CRC loci are associated with tumor morphology and to confirm these loci as distinct and etiologically different risk factors in the development of CRC. The following clinical and morphological parameters were analyzed in 1572 samples: tumor size, T-stage, lymph node metastases, degree of differentiation, mucin production, Crohn-like peritumoral lymphocytic infiltration, tumor-infiltrating lymphocytes, desmoplastic reaction, necrosis, invasion of blood or lymph vessels, perineural growth, medullary type, budding, and tumor margin. One SNP from each of the 11 loci (rs6983267 on 8q24.21, rs16892766 on 8q23.3, rs719725 on 9p24.1, rs10795668 on 10p14, rs3802842 on 11q23.1, rs4444235 on 14q22.2, rs4779584 on 15q13.3, rs9929218 on 16q22.1, rs4939827 on 18q21.1, rs10411210 on 19q13.11, and rs961253 on 20p12.3) was genotyped for all cases. Odds ratios, 95% confidence intervals, and the corresponding P values were calculated for the 11 SNPs identified above. A cross tabulation between SNPs and morphology was performed. Several loci showed statistically significant associations with specific phenotypes. The findings are consistent with pathogenic variants in several loci that act in distinct CRC and morphogenetic pathways. Further large-scale studies are required to validate these findings.

The number of CD68(+) (Hofbauer) cells is decreased in placentas with chorioamnionitis and with advancing gestational age.

Hofbauer cells are placental macrophages found in chorionic villous stroma; they express classic monocyte/macrophage markers, such as CD68. Little is known about their participation in placental disease and immunologic interactions at the placental interface. The aim of this study was to quantify the amount of Hofbauer cells in placentas complicated, or not, by chorioamnionitis and in placentas from different gestational ages. Fifty-eight 2nd- and 3rd-trimester placentas with the histologic diagnosis of acute chorioamnionitis were compared with 42 control placentas matched according to gestational age. Immunohistochemistry evaluation was performed with a monoclonal anti-CD68 antibody. Five areas of each placenta were photographed and 5 investigators, with the help of a computerized image analysis program, independently evaluated the number of CD68(+) cells. Our results showed that there are significantly fewer CD68(+) cells per villous area in placentas diagnosed with chorioamnionitis than in those of controls (P < 0.001). Moreover, there was a significant overall decrease in the number of these cells in 3rd as compared with 2nd trimester placentas (P  =  0.02), as well as in placentas from term as compared to preterm pregnancies (P  =  0.004). Our data indicate that CD68(+) Hofbauer cells may be involved in placental infection and possibly associated with the developmental maturation of the fetoplacental unit.

Severe liver damage associated with celiac disease: findings in six toddler-aged girls.

OBJECTIVE: Light-to-moderate liver damage is often seen in children diagnosed with celiac disease, but severe liver damage is rarely observed. METHODS: During a 12-year-long period our center took care of six 13-36-month-old girls who developed severe liver damage 1-24 months after the diagnosis of celiac disease. RESULTS: Four girls had acute liver failure; two of them had to be liver transplanted. The other four girls recovered without transplantation and none of the six patients developed autoimmune disease during the 2-14-year-long follow-up period. Although adenovirus type 2 was found in the urine and stools of one girl, her liver histopathology did not resemble viral hepatitis. Certain autoimmune features could be observed initially in some of the children but finally none of them fulfilled the criteria for autoimmune liver disease and this pattern did not change during the several years of follow-up. Thorough investigation could not find any alternative pathogenetic cause and thus, the association with celiac disease is obvious. Histopathology showed various degrees of intralobular inflammation, necrosis, involvement of the small bile ducts, and in one case interface hepatitis; but in general, histopathology did not reveal a common pathogenetic mechanism. CONCLUSION: Although rare, severe hepatic damage or failure can develop in association with celiac disease. The etiology is varying and multifactorial. Consequently, children with newly onset celiac disease should be routinely checked for liver function and vice versa, children with severe liver damage should be investigated for untreated celiac disease.

Correlation between ultrasound and autopsy findings after 2nd trimester terminations of pregnancy.

OBJECTIVE: To compare ultrasound (US) and fetal autopsy findings in 2(nd) trimester termination of pregnancy because of structural fetal anomalies. METHODS: A total of 112 terminations of pregnancy (TOP) between 1999-2003 were reviewed retrospectively. The cases originated from a secondary and a tertiary Fetal Medicine unit in the south Stockholm area, using a common specialized perinatal pathology service. Karyotype was not known at the time of US examination. The findings were compared and classified into four groups according to the degree of agreement between US and autopsy. RESULTS: In 45% of cases there was total agreement between US and autopsy. In 40%, autopsy confirmed all US findings but provided additional information of clinical importance. Partial or total lack of agreement was noted in 11% and 4% of the cases, respectively. Areas of discrepancy involved mainly CNS- and cardiovascular abnormalities and, to a lesser extent, renal anomalies, abdominal wall defects and hydrops/hygroma. Regarding CNS abnormalities the overall rate of agreement was 62%; it was highest in acrania/anencephaly (92%) and lowest in hydrocephaly (39%). CONCLUSION: We find an overall high degree of agreement between US and autopsy findings. Autopsy often provided additional information of clinical value and it should always follow US examination and TOP. Fixation of CNS is crucial for optimal results. Specific limitations of autopsy, i.e., detection of CNS abnormalities, may be reduced by complementary imaging techniques, such as MRI. The ability of US to detect cardiac anomalies is enhanced with the close contact to specialized fetal cardiology.