Dysplastic crypt-rings in tandem: A novel histologic parameter in tubular adenomas.

Descriptions of the various dysplastic crypt phenotypes occurring in TA have remained unattended in the literature. Recently, new crypt-phenotypes, characterized by crypt rings in tandem (CRT), and by dysplastic crypt rings in tandem (DCRT) were described in IBD, and in in IBD-associated dysplasia, respectively. Here, we report the occurrence of DCRT in 40.4 % (n = 59) out of 146 consecutive tubular adenomas of the colorectum (TA). The number of DCRT varied: 10 TA had two DCRT, seven TA had three DCRT, two TA, four DCRT and the remaining two TA had ≥ five DCRT. The frequency of DCRT was influenced by TA-size; larger TA (≥ 5 mm) had significantly more DCRT than smaller TA (<5 mm). Conversely, the frequency of TA with DCRT was not influenced by age, gender, or localization. Since only 1 or 2 sections were available per TA, the number of DCRT in the entire TA should be higher than those shown in Results. Historical controls in human and rodent normal colorectum showed no CRT. Moreover, DCRT were not found in 781 historical non-polypoid colorectal adenomas. The present finding might encourage searching for DCRT, the final goal being to achieve a more elaborated microscopic narrative of TA, the most prevalent of all colorectal adenomas.

The frequency of dysplastic branching crypts in colorectal polypoid tubular adenomas.

Dysplastic crypt branching (DCB) was recently found in ulcerative colitis-associated dysplasia. The aim was to assess the frequency and the branching phenotype of DCB in polypoid colorectal tubular adenomas (TA). A total of 3956 DCB were found in the 139 TA: 98% were in asymmetric branching (DCAB) and the remaining 2% in symmetric branching (DCSB). A linear correlation was found between DCB frequency and the increasing digital size in TA (p < .05). Using a digital ruler, adenomas were divided into small TA (<5 mm) and larger TA (≥5 mm). The difference between the frequency of DCB in small TA (n = 75) vs. larger TA (n = 64), was significant (p < .05). DCB frequency was not influenced by age, gender or TA localization. In the normal colorectal mucosa (≈2 m2 ), only occasional CSB is found and no CAB. And yet, multiple DCB (mean 16.7 DCB), mostly DCAB, was found in small TA, occupying <5 mm of the mucosal area. In larger TA, as many as 42.1 DCB (mean), mostly DCAB, occurred in merely 7.8 mm (mean) of the colon mucosa. Thus it is suggested that DCB is a standard histologic element of TA. The natural expansion of the adenomatous tissue in larger TA appears to be follow on from newly produced, mostly DCAB, by DCSB and by the accumulation of their dysplastic offspring's progenies. The findings strongly suggest that DCB is a central microstructure in the histological events unfolding in polypoid colorectal TA.

Branching crypts in inflammatory bowel disease revisited.

Histologic sections from patients with inflammatory bowel disease (IBD) usually exhibit crypts with architectural distortions and branching crypts. It has been postulated that crypt branching should be assessed only in well-oriented, upright crypts. However, those crypts are mostly found in sections from colectomy specimens and colon mucosectomies. Sections from endoscopic biopsies are fortuitously cut in a horizontal plane, a procedure mostly revealing cross-cut crypt rings. In endoscopic biopsies from UC patients we previously detected cross-cut crypts heralding the crest domain of branching crypts. Recently, the scrutiny of biopsies from IBD patients revealed that branching-crest domains concurred either with crypts in symmetric branching, typified by twin, amalgamating back-to-back isometrics crypt-rings, or with crypts in asymmetric branching, characterized by ≥2 amalgamating anisometric crypt-rings; both symmetric and asymmetric branching-crest domains were encased by a thin muscularis mucosae. Quantitative studies in biopsies from Swedish and German patients with IBD showed that crypts in asymmetric branching outnumbered those in symmetric branching. Because crypt-branching seldom occurs in the normal colon in adults and considering that colon crypts typically divide once or twice during a lifetime, the accruing of asymmetric branching crypts in IBD biopsies emerges as a significant histologic parameter. Although the biological significance of asymmetric crypt-branching in IBD remains at present elusive, their occurrence deserves to be further investigated. The future policy will be to include in our pathologic reports, the number of crypts in asymmetric branching, in order to monitor their frequency in prospective surveillance biopsies in patients with IBD.

Two histologic compartments in nonpolypoid conventional colon adenomas.

Two intertwined compartments coexisting in nonpolypoid conventional (i.e. tubular or villous) adenomas are highlighted in this review: one built of dysplastic tissue on top and the other portraying crypts with irregular, corrupted shapes, albeit lined with normal epithelium, below. The latter compartment has remained unattended in the literature. Recently, however, the histologic characteristics of the nondysplastic compartment in nonpolypoid conventional adenomas were closely examined, and some of its biological attributes were unveiled. Studies with the proliferation marker ki67 showed that the crypts with irregular, corrupted shapes in the nondysplastic compartment displayed haphazardly distributed proliferating cell-domains. Given that the proliferating cells are generated by stem cells, the relocation of proliferating cell-domains in those crypts seems to be the result of a reorganization of the stem cells within the crypts. The abnormal distribution of proliferating cells, the finding of p53-upregulated cells, and of crypts in asymmetric fission suggest that the crypts in that compartment are histo-biologically altered, probably somatically mutated. This new information might contribute to unravel the riddle of crypto-histogenesis of nonpolypoid conventional adenomas of the colon. More research along these lines is necessary, before the biology of the crypts in the nondysplastic compartment can be fully translated into molecular terms.

High-Definition Chromoendoscopy Superior to High-Definition White-Light Endoscopy in Surveillance of Inflammatory Bowel Diseases in a Randomized Trial.

BACKGROUND & AIMS: There is debate over the optimal method for colonoscopic surveillance of patients with inflammatory bowel diseases. Guidelines recommend chromoendoscopy, but the value of chromoendoscopy in high-definition colonoscopy has not been proven. Furthermore, the value of random biopsies is controversial. METHODS: We performed a prospective study of 305 patients with ulcerative colitis or Crohn's colitis referred for surveillance colonoscopy at a university hospital in Sweden, from March 2011 through April 2016. Patients randomly assigned to a group that received high-definition chromoendoscopy with indigo carmine (HD-CE; n = 152), collection of 32 random biopsies, and targeted biopsies or polypectomies or to a group that received high-definition white light endoscopy (HD-WLE; n = 153), collection of 32 random biopsies, and targeted biopsies or polypectomies. The primary endpoint was number of patients with dysplastic lesions. RESULTS: Dysplastic lesions were detected in 17 patients with HD-CE and 7 patients with HD-WLE (P = .032). Dysplasias in random biopsies (n = 9760) were detected in 9 patients: 6 (3.9%) in the HD-CE group and 3 (2.0%) in the HD-WLE group (P = .72). Of the 9 patients with dysplasia, 3 patients (33%) had primary sclerosing cholangitis-only 18% of patients (54/305) included in the study had primary sclerosing cholangitis. The number of dysplastic lesions per 10 min of withdrawal time was 0.066 with HD-CE and 0.027 with HD-WLE (P = .056). CONCLUSIONS: In a randomized trial, we found HD-CE with collection of random biopsies to be superior to HD-WLE with random biopsies for detection of dysplasia per colonoscopy. These results support the use of chromoendoscopy for surveillance of patients with inflammatory bowel diseases. ClinicalTrials.gov no: NCT01505842.

Partial to complete abrogation of the subepithelial macrophage barrier against the gut microbiota in patients with ulcerative colitis and Crohn's colitis.

AIMS: The integrity of the band of indigenous macrophages in the subepithelial layer of the lamina propria (SLP) is crucial in preventing the commensal gut microbiota from attacking the host. The breakdown of the SLP macrophage barrier results in microbiota inflow and improper immune responses; this might lead to inflammatory bowel disease (IBD). During inflammation, the SLP macrophage barrier is reinforced by inflammation-elicited macrophages (IEMs), which are derived from blood-circulating monocytes. The aim was to explore the characteristics of the SLP macrophage band in a cohort of biopsies without inflammation, in patients with ulcerative colitis in remission (UCre), and in patients with right-sided Crohn's colitis (RCC). METHODS AND RESULTS: Endoscopic biopsies were taken from endoscopically normal descending colon in 247 patients; 80 with IBD (27 UCre and 53 RCC), and 167 without IBD [90 had colonic diarrhoea, 63 were enrolled in a colorectal cancer (CRC) surveillance programme, seven had microscopic colitis in remission, and seven had miscellaneous colonic ailments]. Sections showed no inflammatory changes; they were immunostained with CD68. Among patients with UCre and RCC, the SLP band of CD68+ macrophages was fragmented or minute in 59% (47/80) and negative in 9% (7/80). In contrast, only 31% (51/167) of the biopsies from control patients had a fragmented/minute SLP band of CD68+ macrophages, and none had a negative SLP band of CD68+ macrophages (IBD versus controls, P < 0.05). CONCLUSIONS: The finding that the SLP macrophage barrier was fragmented to totally abrogated in UCre and RCC patients suggests a longlasting defect in the SLP CD68+ macrophage barrier in these patients. The lack of ongoing inflammation in colonic biopsies should rule out the participation of bone marrow-derived IEMs in the abrogation of the SLP macrophage barrier reported here.

Evaluation of narrow-band imaging signs in eosinophilic and lymphocytic esophagitis.

Background and study aims No specific endoscopic signs for diagnosing eosinophilic esophagitis (EoE) have been described and very few studies have reported endoscopic signs for lymphocytic esophagitis (LyE). This study aimed to assess the utility of narrow-band imaging magnifying endoscopy (NBI-ME) in predicting EoE/LyE diagnosis before histopathological assessment. Patients and methods Adult patients with dysphagia and/or food impaction who underwent esophagogastroduodenoscopy followed by NBI-ME and biopsies were included. Three previously reported NBI-ME signs were studied: beige mucosa, dot-shaped intra-epithelial papillary capillary loop (IPCL), and absent cyan vessels. These signs were compared with the histological diagnosis, and studied in patients with and without EoE or LyE. A predictive model containing the NBI-ME signs was analyzed, based on area under the curve (AUC). Results A total of 137 patients were enrolled. Based on histology 26 were diagnosed with EoE, 26 with LyE, and 85 were control patients with neither diagnosis. Significantly more EoE/LyE patients than control patients showed the NBI signs (P  < 0.001 for all three signs). Absent cyan vessels had the highest accuracy for differentiation (sensitivity 88 %, specificity 92 %). A combination of age, dot IPCLs, and absent cyan vessels was highly predictive of EoE/LyE, with an AUC of 0.952. Conclusions Three NBI-ME signs were found in the majority of patients with EoE/LyE and unlikely to be observed in controls. A combination of two NBI-ME signs and younger age had a higher degree of accuracy. This supports the claim that NBI-ME could be a reliable diagnostic modality for EoE/LyE predictors.

Prediction of Extubation readiness in extremely preterm infants by the automated analysis of cardiorespiratory behavior: study protocol.

BACKGROUND: Extremely preterm infants (≤ 28 weeks gestation) commonly require endotracheal intubation and mechanical ventilation (MV) to maintain adequate oxygenation and gas exchange. Given that MV is independently associated with important adverse outcomes, efforts should be made to limit its duration. However, current methods for determining extubation readiness are inaccurate and a significant number of infants fail extubation and require reintubation, an intervention that may be associated with increased morbidities. A variety of objective measures have been proposed to better define the optimal time for extubation, but none have proven clinically useful. In a pilot study, investigators from this group have shown promising results from sophisticated, automated analyses of cardiorespiratory signals as a predictor of extubation readiness. The aim of this study is to develop an automated predictor of extubation readiness using a combination of clinical tools along with novel and automated measures of cardiorespiratory behavior, to assist clinicians in determining when extremely preterm infants are ready for extubation. METHODS: In this prospective, multicenter observational study, cardiorespiratory signals will be recorded from 250 eligible extremely preterm infants with birth weights ≤1250 g immediately prior to their first planned extubation. Automated signal analysis algorithms will compute a variety of metrics for each infant, and machine learning methods will then be used to find the optimal combination of these metrics together with clinical variables that provide the best overall prediction of extubation readiness. Using these results, investigators will develop an Automated system for Prediction of EXtubation (APEX) readiness that will integrate the software for data acquisition, signal analysis, and outcome prediction into a single application suitable for use by medical personnel in the neonatal intensive care unit. The performance of APEX will later be prospectively validated in 50 additional infants. DISCUSSION: The results of this research will provide the quantitative evidence needed to assist clinicians in determining when to extubate a preterm infant with the highest probability of success, and could produce significant improvements in extubation outcomes in this population. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01909947 . Registered on July 17 2013. Trial sponsor: Canadian Institutes of Health Research (CIHR).

Colonoscopy findings in high-risk individuals compared to an average-risk control population.

BACKGROUND AND AIMS: There is clear evidence of reduced morbidity and mortality from regular colonoscopy programs in patients with Lynch syndrome (LS). Today, also individuals with empirically increased risks of colorectal cancer (CRC) are offered colonoscopic surveillance. The aim was to compare the findings at the first screening colonoscopy in LS carriers, and individuals with an increased risk of bowel cancer due to family history of CRC with a control population. METHODS: Altogether 1397 individuals with an increased risk for CRC were divided in four risk groups: one with LS carriers and three groups with individuals with different family history of CRC. The findings were compared between the different risk groups and a control group consisting of 745 individuals from a control population who took part in a population-based colonoscopy study. RESULTS: In LS, 30% of the individuals had adenomas and 10% advanced adenomas. The corresponding figures in the other risk groups were 14-24% and 4-7%, compared with 10% and 3% in the control group. The relative risk of having adenomas and advanced adenomas was, compared to controls, significantly higher for all risk groups except the group with the lowest risk. Age was a strong predictor for adenomas and advanced adenomas in both risk individuals and controls. CONCLUSIONS: Individuals with a family history of CRC have a high prevalence and cumulative risk of adenomas and advanced adenomas, and screening is motivated also in this risk group.

Pediatric Crohn's disease from onset to adulthood: granulomas are associated with an early need for immunomodulation.

OBJECTIVE: Childhood onset Crohn's disease (CD) is considered more aggressive than adult onset disease. Epithelioid cell granulomas in intestinal biopsies are one, non-obligate, criterion of CD. We investigated granulomas as markers of CD severity in children followed to adulthood. MATERIAL AND METHODS: Forty-five individuals with childhood onset CD were studied from diagnosis until attainment of final height, with data on disease location, medical and surgical management and with detailed growth data analyses. A blinded review of diagnostic biopsies was also performed. RESULTS: We found granulomas in 22/45 (49%) children at diagnosis, altogether in 28/45 (62%) patients during the disease course (median overall follow-up - 12.3 years, range 9.3-18). Granulomas were found in 9/11 (82%) with upper gastrointestinal involvement (cumulatively 17/20, 85%) (p = 0.017 and p = 0.006, respectively). The time from diagnosis to initiating immune modulating treatment (median 4.5 months, range 0-75) was shorter in the granuloma-positive group (16/22) compared to the granuloma-negative group (18/23) (median 33 months, range 2-105; p = 0.01). The median standard deviation score height at diagnosis and final adult height (both adjusted for target height) did not correlate to findings of granulomas. CONCLUSIONS: Epithelioid cell granulomas were associated with a shorter time to initiating immune modulating drugs, as a possible sign of more severe disease, but growth was not affected.

Paucity of synaptophysin-expressing cells in Barrett's mucosa.

AIMS: To assess synaptophysin expression in columnar-lined oesophageal mucosa showing either goblet cells, known as intestinal metaplasia, or with accompanying oxyntic glands or pyloric glands. METHODS AND RESULTS: Of 159 biopsies, 53 were oesophageal (19 had intestinal metaplasia, 13 oxyntic glands, and 21 pyloric glands), 77 gastric (12 had goblet cells and 27 no goblet cells) and 29 duodenal. Synaptophysin-positive goblet cells were found in all biopsies from the normal duodenum, in 53% of the oesophageal biopsies showing intestinal metaplasia, but only in 8% of gastric biopsies showing intestinal metaplasia. Synaptophysin-positive Paneth cells occurred in all duodenal biopsies, and in nine of the gastric biopsies showing intestinal metaplasia, but in only one of the oesophageal biopsies showing intestinal metaplasia. A continuous synaptophysin-positive neck cell zone was found in all biopsies from the normal antrum, but in none of the oesophageal biopsies with pyloric glands or with chronic antritis. CONCLUSIONS: The paucity or absence of synaptophysin-positive cells in all three phenotypes of Barrett's mucosa might mirror a sequela of chronic inflammation caused by the particular pathogenic bacteria present in the immediate oesophageal microenvironment.

Novel histological repertoire of crypt-associated anomalies in inflamed colon mucosa.

AIMS: Studying crypt branching in ulcerative colitis (UC) and in infectious colitis (IC), we detected previously unreported crypt-associated anomalies (CAAs). The objective was to describe, illustrate and assess the frequency of CAAs in inflamed colon mucosa in patients with UC and IC. METHODS: Sections from 100 consecutive biopsies with UC, in 50 with IC and in 27 with UC in remission (UCR) were reviewed. The following CAAs were identified: crypt eosinophilia, intracryptal epithelial hyperplasia, intracryptal epithelial budding, intracryptal supernumerary crypts, intracryptal epithelial bridges, crypt rings in rows and off-centre epithelial budding. RESULTS: The frequency of crypts with extensive crypt eosinophilia and with intracryptal epithelial budding was significantly higher in UC than in IC and UCR (p<0.05); the frequency in the remaining histological parameters was similar in UC, IC and UCR. CONCLUSIONS: CAAs were found interspersed with branching crypts. CAAs persisted in long-lasting UC mucosal inflammation, but declined when the inflammation waned. Since similar anomalies are not present in normal colon mucosa, the results suggest that CAAs had been boosted by the ongoing mucosal inflammation. The development of these previously unreported CAAs in the colon mucosa with inflammation might embody pathological aberrations of cryptogenesis.

Crypt-rings in tandem detected in infectious colitis, in IBD and in IBD-associated noninvasive neoplasia.

AIMS: Recently, eight novel histologic structures in colon mucosa with inflammation were described. Here, we assessed the frequency of one of them: crypt rings in tandem (CRT), in patients with infectious colitis (IC), IBD (ulcerative colitis; UC or Crohn colitis; CrC) and UC in remission (UCR). In addition, the frequency of dysplastic CRT (DCRT) in IBD-associated noninvasive neoplasia (IBDNIN) were also calculated. METHODS: Colon biopsies in 578 cases were reviewed: 42 cases with IC, 280 with IBD (180 UC and 100 CrC), 100 UCR and the remaining 156, IBDNIN. RESULTS: The proportions of CRT in IC was 16.7%, in IBD 14.3% %, in UCR 3%, and of DCRT in IBDNIN, 20%. No differences were recorded between the proportions of CRT in IC, UC and CrC. Conversely, the difference in CRT frequency between UC and UCR, and between CRT and DCRT were significant (P = 0.006, and p = 0.05, respectively). CONCLUSIONS: CRT evolved in IC and in IBD. The finding of CRT in IC strongly suggest that those characteristic crypts were shaped at the early stages of mucosal inflammation. CRT persisted in IBD with protracted inflammation but plummeted in UCR, that is when the mucosal inflammation waned. The proportion of DCRT was significantly higher than that of CRT. It is submitted that DCRT might had developed in IBDNIN using CRT as scaffolds. This is the first study in which a characteristic pathologic aberration of cryptogenesis was tracked in colon biopsies from patients with IBD and with IBD-associated neoplastic transformation.

Sporadic Colorectal Tubular Adenomas Thrive in Symbiosis With Underlying Nondysplastic Branching Crypts.

BACKGROUND/AIM: Nondysplastic crypt branching (NDCB), mostly asymmetric branching (NDCAB), was previously found beneath the dysplastic epithelium of colorectal tubular adenomas (TA) in Swedish patients. This study examined the frequency of NDCB and NDCAB beneath the dysplastic epithelium of TA, in German patients. PATIENTS AND METHODS: From a collection of 305 TA, 121 TA fulfilled the prerequisites for inclusion. All NDCB were registered. RESULTS: Of 673 NDBCs, 572 (85%) NDCABs and 101 (15%) NDCSs, were found beneath the neoplastic tissue in the 121 TA. When the frequency of NDCB was challenged against the TA size, a linear correlation was found in the 121 TA (p<0.05, p=0.020172). Most NDCB were NDCAB (p<0.05, p=0.00001). The frequency of NDCB correlated with increasing TA size, implying that the higher frequency of both NDCB, dysplastic crypt branching, and their dysplastic offspring crypts were the most probable sources of TA enlargement. The frequency of NDCB underneath TA was not influenced by increasing age, sex or TA localization. CONCLUSION: Similar findings as those reported here were previously found in TA in Swedish patients. The similarity between these two populations, located in disparate geographical areas and subjected to dissimilar microenvironmental conditions suggests that NDBC in TA might be a ubiquitous unreported phenomenon. According to the literature, normal colon cells often harbor somatic mutations. Consequently, NDCB underneath TA may be mutated nondysplastic branching crypts upon which the dysplastic epithelium in TA eventually develops.

The Number of Colon Crypts in Digital Mucosal Samples: A New Independent Parameter for Diagnosing Ulcerative Colitis.

Background/Aim: It has been demonstrated that most routine biopsies from the colon and rectum display cross-cut crypts (CCC). The aim was to assess the number of CCC in microscopic isometric digital samples (0.500 mm2) from routine colon biopsies. Patients and Methods: Colon biopsies from 224 patients were investigated: 99 in patients with ulcerative colitis (UC), 31 UC in remission (UCR), 28 infectious colitis (IC), 7 resolved IC (RIC), 19 diverticular sigmoiditis (DS), and 40 normal colon mucosa (NCM). Results: A total of 8,024 CCC were registered: 2,860 (35.6%) in UC, 1,319 UCR (16.4%), 849 (10.6%) in IC, 340 (4.2%) in RIC, 795 (9.9%) in DS, and 1,861 (23.2%) in NCM. The CCC frequencies in UC and IC were significantly lower (p<0.05) than those in UCR, RIC, DS, and NCM. Conclusion: By the simple algorithm of counting CCC in standardized isometric microscopic digital circles measuring 0.500 mm2, it was possible to differentiate between UC (long-lasting inflammation) and IC (short-lasting inflammation) on the one hand, and UCR, RIC, DS (persistent inflammation), and NCM, on the other. The counting of CCC in the algorithm by five pathologists working in three disparate European Countries, was found to be reproducible.

Colorectal dysplasia in chronic inflammatory bowel disease: a contemporary consensus classification and interobserver study.

The clinical management of patients with dysplasia in chronic inflammatory bowel disease (IBD) is currently guided by Riddell et al.'s grading system (negative, indefinite, low grade, high grade) from 1983 which was based primarily on nuclear cytoarchitectural characteristics. Although most dysplasia in IBD resembles sporadic adenomas morphologically, other distinctive potential cancer precursors in IBD have been described over time. Recognizing the need for a updated comprehensive classification for IBD-associated dysplasia, an international working group of pathologists with extensive clinical and research experience in IBD devised a new classification system and assessed its reproducibility by having each participant assess test cases selected randomly from a repository of electronic images of potential cancer precursor lesions. The new classification system now encompasses three broad categories and nine sub-categories: 1) intestinal dysplasia (tubular/villous adenoma-like, goblet cell deficient, crypt cell, traditional serrated adenoma-like, sessile serrated lesion-like and serrated NOS), 2) gastric dysplasia (tubular/villous and serrated), and 3) mixed intestinal-gastric dysplasia. In the interobserver analysis, 67% of the diagnoses were considered definitive and achieved substantial inter-rater agreement. The key distinctions between intestinal and gastric lesions and between serrated and non-serrated lesions achieved substantial and moderate inter-rater agreement overall, respectively, however, the distinctions among certain serrated sub-categories achieved only fair agreement. Based on the Riddell grading system, definite dysplasia accounted for 86% of the collective responses (75% low grade, 11% high grade). Based on these results, this new classification of dysplasia in IBD can provide a sound foundation for future clinical and basic IBD research.

Morphological subtypes of colorectal low-grade intraepithelial neoplasia: diagnostic reproducibility, frequency and clinical impact.

AIMS: Special histomorphological subtypes of colorectal low-grade intraepithelial neoplasia (LGIN) with variable prognostic impact were recently described in patients with inflammatory bowel disease (IBD) referred to as non-conventional dysplasia. However, they can also be found in patients without IBD. We aimed to analyse the reproducibility, frequency and prognostic impact of non-conventional colorectal LGIN in patients with and without IBD. METHODS: Six pathologists evaluated 500 specimens of five different LGIN-cohorts from patients with and without IBD. Non-conventional LGIN included hypermucinous, goblet cell-deficient, Paneth cell-rich and crypt cell dysplasia. A goblet cell-rich type and non-conventional LGIN, not otherwise specified were added. Results were compared with the original expert-consented diagnosis from archived pathology records. RESULTS: Four or more pathologists agreed in 86.0% of all cases. Non-conventional LGIN was seen in 44.4%, more frequently in patients with IBD (52%; non-IBD: 39.3%, p=0.005). In patients with IBD non-conventional LGIN associated with more frequent and earlier LGIN relapse (p=0.006, p=0.025), high-grade intraepithelial neoplasia (p=0.003), larger lesion size (p=0.001), non-polypoid lesions (p=0.019) and additional risk factors (p=0.034). Results were highly comparable with expert-consented diagnoses. In patients without IBD, non-conventional LGIN may indicate a higher risk for concurrent or subsequent colorectal carcinoma (CRC, p=0.056 and p=0.061, respectively). Frequencies and association with high-grade intraepithelial neoplasia or CRC varied between the different LGIN subtypes. CONCLUSIONS: Non-conventional histomorphology in colorectal LGIN is frequent and highly reproducible. Our results indicate an increased risk for CRC in patients with non-conventional LGIN, probably independent of IBD. We recommend reporting non-conventional LGIN in routine pathology reports.

Dysplastic Crypts in Asymmetric Branching in Ulcerative Colitis: A Preliminary Report.

AIM: To report the detection of dysplastic crypts in asymmetric branching (DCAB) in biopsies from patients with ulcerative colitis (UC). PATIENTS AND METHODS: One hundred consecutive endoscopic biopsies from patients with UC undergoing surveillance were reviewed. RESULTS: Three biopsy/cases showed DCAB. The frequency of DCAB varied from two in one case, three in another case, and five in the remaining case. CONCLUSION: The final outcome of DCAB is to generate two or more dysplastic asymmetric offspring-crypts. Repeated DCAB offspring formation, together with new DCAB, would boost the pool of dysplastic crypts, resulting in an exponential expansion of the mucosal area occupied by dysplasia in UC.

Diagnostic and Prognostic Impact of Crypt Branching in Patients With Ulcerative Colitis: A Validation Study.

BACKGROUND/AIM: This study aimed to validate the inter-rater agreement of the assessment of crypt branching (also called crypt fission) in patients with ulcerative colitis (UC) and to elucidate its potential diagnostic and prognostic impact. PATIENTS AND METHODS: A total of 100 biopsies from patients with UC were analyzed. Two cohorts of 50 patients each served as controls [infectious controls/controls with low grade intraepithelial neoplasia (LGIN) in UC alio loco]. Three pathologists scored the number of total crypts in fission as well as the number of crypts in symmetric (CSF) and asymmetric fission (CAF). RESULTS: Inter-rater agreement ranged from good to excellent in the study cohort. The number of crypts in fission correlated significantly with UC-activity (p=0.001; p<0.001). The study cohort showed higher mean counts of crypts in fission and significant more total and CAF than the infectious controls (p=0.007 and p=0.008), especially in male patients (p<0.001) The LGIN-control cohort showed significant more CSF (p=0.012). CONCLUSION: Inter-rater agreement for crypt branching was reliable in the study cohort. Crypt branching proved as an additional histologic feature to distinguish active UC against infectious colitis. Higher amounts of CSF may help identifying patients at higher risk for neoplasia.