A randomized trial evaluating the utility of non-targeted biopsies for colorectal neoplasia detection in adults with inflammatory bowel disease: a pilot study protocol.

BACKGROUND: Persons with inflammatory bowel diseases are at increased risk of developing colorectal cancer and require frequent colonoscopy surveillance. Guidelines recommend taking 30 to 40 non-targeted biopsies throughout the colorectum to detect "invisible" neoplasia in this setting, despite a lack of evidence supporting this practice. We sought to assess the utility of this practice through a randomized controlled trial. We first propose an internal pilot study to assess recruitment potential, protocol adherence and data capture to guide the full trial. METHODS: We have designed a multi-centre, parallel-group, non-inferiority randomized controlled trial to test the utility of non-targeted biopsies as an adjunct to colonoscopy surveillance for neoplasia detection in persons with inflammatory bowel disease involving the colorectum in routine clinical practice. Participants are randomized 1:1, stratified by study site, to either standard of care high-definition white-light colonoscopy with 32 to 40 non-targeted biopsies of non-neoplastic-appearing mucosa along with a sampling of abnormal-appearing mucosa (control group) or modified colonoscopy with targeted sampling alone (intervention group). The primary outcome for the full trial will be the proportion of persons with ≥ 1 neoplastic focus detected during colonoscopy. For the pilot phase, we will assess the feasibility of recruiting a minimum of 15% of the estimated sample size within 1 year, under identical conditions as the full trial, while maintaining ≥ 90-95% rate of protocol adherence and data capture. These participants will contribute data to the full trial. The trial is being conducted at 12 centres across Canada, with a total sample size of 1952 persons. DISCUSSIONS: The trial protocol has been approved by the ethics committees of all participating sites, and the pilot study has received funding through the Canadian Institutes of Health Research (PJT 159607). If feasibility metrics are met during the pilot phase, we will complete the full trial. The trial outcomes will contribute to update the practice guidelines in this area. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04067778.

Interim Analysis of a Trial Evaluating the Utility of Non-Targeted Biopsies for Colorectal Neoplasia Detection in Inflammatory Bowel Disease.

Persons with inflammatory bowel disease (IBD) affecting the colorectum (cIBD) have a 1.5- to 2-fold higher risk of developing colorectal cancer (CRC) relative to age- and sex-matched members of the general population.1 Intensive surveillance colonoscopy is recommended in this population to detect and treat early neoplastic lesions before they evolve to incurable cancers.2 Some societies advocate for widespread non-targeted ("random") biopsies throughout the colorectum to screen for "invisible" neoplastic lesions, in addition to targeted biopsies and/or resection of visible lesions.2 Despite the theoretical value of non-targeted biopsies in this setting, there are no high-quality, controlled data to support this practice. In addition to adding significant time and costs to colonoscopy screening, extensive biopsy sampling may also increase the risk of colorectal bleeding and bowel perforation, particularly in elderly patients and those receiving anticoagulant/antiplatelet therapies. With the widespread adoption of disease-modifying biologic and small molecule therapies,3 mucosal healing as a treatment end point,4 high-definition endoscopes,5 and endoscopy quality standards,6 as well as reports of very low neoplasia yield for non-targeted biopsies (0.1%-0.2% of biopsies),7 many experts have started to question the value of non-targeted biopsies as an adjunct for neoplasia surveillance in persons with cIBD.8 However, a recent large French cohort study reported that non-targeted biopsies still identify up to 20% of all neoplastic foci in persons with cIBD,9 albeit primarily in individuals with other major CRC risk factors.

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.

Histologic Features of Syphilitic Gastritis: A Rare but Resurging Imitator of Common Diseases.

OBJECTIVES: The range of histopathologic features of gastric syphilis is not well described. Here we describe the clinicopathologic findings of eight patients with syphilitic gastritis. METHODS: A search of our Pathology Data System (2003-2022) and multiple other institutions identified eight patients with syphilitic gastritis. Clinical information, pathology reports, and available slides were reviewed. RESULTS: Lesions predominated in middle-aged adults (mean age, 47.2 years; range, 23-61 years) with a propensity for men (n = 7). Three patients had a documented history of human immunodeficiency virus. Clinical presentations included weight loss, abdominal pain, hematochezia, fever, dyspepsia, nausea and vomiting, hematemesis, anemia, and early satiety. Endoscopic findings included ulcerations, erosions, abnormal mucosa, and nodularity. All specimens shared an active chronic gastritis pattern with intense lymphohistiocytic infiltrates, variable plasma cells, and gland loss. Prominent lymphoid aggregates were seen in four specimens. The diagnosis was confirmed either by immunostain for Treponema pallidum (n = 7) or by direct immunofluorescence staining and real-time polymerase chain reaction (n = 1). All patients with available follow-up data showed resolution of symptoms after antibiotic therapy (n = 4). CONCLUSIONS: Recognition of the histologic pattern of syphilitic gastritis facilitates timely treatment, prevents further transmission, and avoids unnecessarily aggressive treatment.

Beyond Neutrophils for Predicting Relapse and Remission in Ulcerative Colitis.

BACKGROUND AND AIMS: This study examines colonic histological features in ulcerative colitis [UC] in endoscopic remission to determine which cell types and biopsy sites best predict a patient's likelihood of remaining in remission. METHODS: This is a retrospective chart, endoscopy and histology review of 166 patients with UC in endoscopic remission followed in a single inflammatory bowel disease practice over a median of 6 years [range, 2-11 years]. Clinical remission was based on global physician assessment and colonoscopy reports, and clinical relapse on chart review. Histological features of previous injury and also number and location of plasma cells and eosinophils were assessed. We evaluated all of these features semi-quantitatively using a standard set of illustrations for the grade to maintain consistency. Multiple logistic regression and survival analyses were used to identify features associated with relapse. RESULTS: Clinical relapse occurred in 44 patients. Ulceration, especially in the left colon, was highly predictive of relapse. In the absence of acute inflammation of ulceration, the variables most predictive of relapse were increased plasma cells in the basal 20% of the lamina propria, and eosinophils in the left colon. The variable most predictive of persistent remission was the presence of intra-epithelial eosinophils whether in the surface epithelium or within crypts, especially in the right colon. Lamina propria eosinophils [grade > 2] throughout the colon predicted relapse. CONCLUSION: In the absence of neutrophils or ulceration, left-sided plasmacytosis in the basal 20% of the lamina propria and increased lamina propria eosinophils provide the best indicators of relapse in UC in clinical and endoscopic remission.

Early Change in Epithelial Neutrophilic Infiltrate Predicts Long-Term Response to Biologics in Ulcerative Colitis.

BACKGROUND & AIMS: The prognostic value of histologic scores, grades, and individual histologic subcomponents, alone or in combination with endoscopy, for predicting endoscopic improvement (EI) and histoendoscopic mucosal improvement (HEMI) during maintenance therapy in ulcerative colitis remains uncertain. METHODS: We performed a post hoc analysis of participants from the VARSITY trial (n = 734 with histology). Receiver operating characteristic and multivariate logistic regression analyses were performed to assess whether baseline and/or week 14 assessments for the Robarts Histopathology Index, Geboes score, individual histologic subcomponents, and baseline disease characteristics, including endoscopic severity and biomarkers, could predict the achievement of EI and HEMI at week 52. RESULTS: Changes in epithelial neutrophil involvement from baseline to week 14 had the best performance for predicting week 52 EI (area under the curve, 0.83; 95 % confidence interval [CI], 0.74-0.91) and HEMI (area under the curve, 0.85; 95 % CI, 0.76-0.94). On multivariate analyses, improvement of neutrophils in the epithelium was the only histologic parameter associated with increased odds of week 52 EI (odds ratio, 3.63; 95 % CI, 1.45-9.08; P = .0059) and HEMI (odds ratio, 6.88; 95 % CI, 3.29-14.36; P < .0001). Patients with more than 50 % of crypts involved with neutrophils at week 14 were significantly less likely to achieve week 52 HEMI irrespective of week 14 Mayo endoscopic scores (week 14 Mayo endoscopic score of 2-3: 9.9 % vs 22.4 %; P = .001; week 14 Mayo endoscopic score of 0-1: 33 % vs 62.4 %; P = .044). CONCLUSIONS: Our results on epithelial neutrophilic infiltrate after induction therapy as the only independent predictor for achievement of maintenance EI or HEMI helps clarify the clinical relevance of measuring histologic disease activity in ulcerative colitis. Epithelial neutrophilic infiltrate poses a means to stratify patients according to their likelihood of response to biologic treatment.

Prognostic and Predictive Value of Tumor Budding in Colorectal Cancer.

BACKGROUND: Tumor budding (TB) is an adverse prognostic factor in colorectal cancer (CRC). International consensus on a standardized assessment method has led to its wider reporting. However, uncertainty regarding its clinical value persists. This study aimed to (1) confirm the prognostic significance of TB, particularly in stage II CRC; (2) to determine optimum thresholds for TB risk grouping; and (3) to determine whether TB influences responsiveness to chemotherapy. METHODS: TB was assessed in CRC sections from 1575 QUASAR trial patients randomized between adjuvant chemotherapy and observation. Optimal risk group cutoffs were determined by maximum likelihood methods, with their influence on recurrence and mortality investigated in stratified log-rank analyses on exploratory (n = 504), hypothesis-testing (n = 478), and final (n = 593) data sets. RESULTS: The optimal threshold for high-grade TB (HGTB) was ≥ 10 buds per 1.23 mm2. High-grade TB tumors had significantly worse outcomes than those with lower TB: 10-year recurrence 36% versus 22% (risk ratio, 2.00 [95% CI, 1.62-2.45]; 2P < .0001) and 10-year mortality 50% vs. 37% (risk ratio, 1.53 [95% CI, 1.34-1.76]; 2P < .0001). The prognostic significance remained equally strong after allowance for other pathological risk factors, including stage, grade, lymphovascular invasion, and mismatch repair status. There was a nonsignificant trend toward increasing chemotherapy efficacy with increasing bud counts. CONCLUSIONS: TB is a strong independent predictor of recurrence. Chemotherapy efficacy is comparable in patients with higher and lower TB; hence, absolute reductions in recurrence and death with chemotherapy should be about twice as large in patients with ≥ 10 than < 10 TB counts.

Russell Body Typhlitis: A Case Report and Literature Review.

Russell bodies are accumulation of immunoglobulin in plasma cells forming intracytoplasmic inclusions. Russell body colitis is rare with only 3 cases described in the English literature up to date. We report a 78-year-old male with cirrhosis showing prominent cecal infiltration of Russell body containing plasma cells. Plasma cells showed no nuclear atypia or mitoses, and no evidence of light chain restriction. In this article, we report a fourth case of Russell body colitis, that is unique in being localized to the cecum in contrast to the other 3, 1 of which was in an inflammatory polyp in the sigmoid colon, 1 in a rectal tubulovillous adenoma and 1 as part of diffuse gastrointestinal disease. This is therefore the first report of localized Russell body typhlitis, occurring in a cirrhotic patient in whom an adjacent erosion was likely nonsteroidal anti-inflammatory drug-associated, a combination that may have facilitated the formation of Russell bodies.

Improving tumor budding reporting in colorectal cancer: a Delphi consensus study.

Tumor budding is a long-established independent adverse prognostic marker in colorectal cancer, yet methods for its assessment have varied widely. In an effort to standardize its reporting, a group of experts met in Bern, Switzerland, in 2016 to reach consensus on a single, international, evidence-based method for tumor budding assessment and reporting (International Tumor Budding Consensus Conference [ITBCC]). Tumor budding assessment using the ITBCC criteria has been validated in large cohorts of cancer patients and incorporated into several international colorectal cancer pathology and clinical guidelines. With the wider reporting of tumor budding, new issues have emerged that require further clarification. To better inform researchers and health-care professionals on these issues, an international group of experts in gastrointestinal pathology participated in a modified Delphi process to generate consensus and highlight areas requiring further research. This effort serves to re-affirm the importance of tumor budding in colorectal cancer and support its continued use in routine clinical practice.

Validation of the 'Inflammatory Bowel Disease-Distribution, Chronicity, Activity [IBD-DCA] Score' for Ulcerative Colitis and Crohn´s Disease.

BACKGROUND AND AIMS: Histological scoring plays a key role in the assessment of disease activity in ulcerative colitis [UC] and is also important in Crohn´s disease [CD]. Currently, there is no common scoring available for UC and CD. We aimed to validate the Inflammatory Bowel Disease [IBD]-Distribution [D], Chronicity [C], Activity [A] score [IBD-DCA score] for histological disease activity assessment in IBD. METHODS: Inter- and intra-rater reliability were assessed by 16 observers on biopsy specimens from 59 patients with UC and 25 patients with CD. Construct validity and responsiveness to treatment were retrospectively evaluated in a second cohort of 30 patients. RESULTS: Inter-rater reliability was moderate to good for the UC cohort (intraclass correlation coefficients [ICCs] = 0.645, 0.623, 0.767 for D, C, and A, respectively) and at best moderate for the CD cohort [ICC = 0.690, 0.303, 0.733 for D, C, and A, respectively]. Intra-rater agreement ranged from good to excellent in both cohorts. Correlation with the Nancy Histological Index [NHI] was moderate and strong with the Simplified Geboes Score [SGS] and a Visual Analogue Scale [VAS], respectively. Large effect sizes were obtained for all three parameters. External responsiveness analysis revealed correlated changes between IBD-DCA score and NHI, SGS and VAS. CONCLUSIONS: The IBD-DCA score is a simple histological activity score for UC and CD, agreed and validated by a large group of IBD specialists. It provides reliable information on treatment response. Therefore, it has potential value for use in routine diagnostics as well as clinical studies.

Most colitis associated carcinomas lack expression of LGR5: a preliminary study with implications for unique pathways of carcinogenesis compared to sporadic colorectal carcinoma.

BACKGROUND: Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), a component of the Wnt receptor complex, is thought to lineage label gastric and intestinal stem cells. LGR5 expression is increased in colorectal carcinoma (CRC) compared to normal tissue. Colitis associated colorectal adenocarcinoma (CAC) often shows distinct morphologic and molecular phenotypes compared to sporadic cases. However, the expression profile of LGR5, and by extension the potential role of an intestinal stem cell phenotype, has not been well described in a series of human CAC. METHOD: RNA in situ hybridization (ISH) for LGR5 expression on 30 CACs (12 cases with conventional morphology and 18 cases with non-conventional type morphology) from 29 inflammatory bowel disease (IBD) patients was performed and compared the expression profile to a control group of 10 sporadic CRCs. Immunohistochemistry for beta-catenin and SATB2 was performed on the 30 CACs. RESULT: LGR5 was positive in 30% (9/30) of CAC cases and 90% (9/10) of sporadic CRCs (p = 0.002). A large majority (89%) of LGR5 positive CACs were of the conventional histologic type, and conventional type CAC showed a significantly higher LGR5 score (median 3.0; interquartile range 1.75-3.25) than non-conventional type CAC (median 1.5; interquartile range 1.00-2.00) (p = 0.034). CAC with conventional morphology did have a lower level of LGR5 expression than sporadic CRC. Sporadic CRCs showed a significantly higher LGR5 level score than non-conventional type CACs (p < 0.001). Nuclear translocation of beta-catenin was strongly associated with LGR5 expression (p = 0.003), however no significant association was identified between SATB2 expression and LGR5 expression status in CACs. CONCLUSION: These findings suggest that the wider spectrum of tumor morphology in CAC may be associated with absence of a LGR5-expressing intestinal stem cell phenotype.

An International Consensus to Standardize Integration of Histopathology in Ulcerative Colitis Clinical Trials.

BACKGROUND & AIMS: Histopathology is an emerging treatment target in ulcerative colitis (UC) clinical trials. Our aim was to provide guidance on standardizing biopsy collection protocols, identifying optimal evaluative indices, and defining thresholds for histologic response and remission after treatment. METHODS: An international, interdisciplinary expert panel of 19 gastroenterologists and gastrointestinal pathologists was assembled. A modified RAND/University of California, Los Angeles appropriateness methodology was used to address relevant issues. A total of 138 statements were derived from a systematic review of the literature and expert opinion. Each statement was anonymously rated as appropriate, uncertain, or inappropriate using a 9-point scale. Survey results were reviewed and discussed before a second round of voting. RESULTS: Histologic measurements collected using a uniform biopsy strategy are important for assessing disease activity and determining therapeutic efficacy in UC clinical trials. Multiple biopsy strategies were deemed acceptable, including segmental biopsies collected according to the endoscopic appearance. Biopsies should be scored for architectural change, lamina propria chronic inflammation, basal plasmacytosis, lamina propria and epithelial neutrophils, epithelial damage, and erosions/ulcerations. The Geboes score, Robarts Histopathology Index, and Nancy Index were considered appropriate for assessing histologic activity; use of the modified Riley score and Harpaz Index were uncertain. Histologic activity at baseline should be required for enrollment, recognizing this carries operational implications. Achievement of histologic improvement or remission was considered an appropriate and realistic therapeutic target. Current histologic indices require validation for pediatric populations. CONCLUSIONS: These recommendations provide a framework for standardized implementation of histopathology in UC trials. Additional work is required to address operational considerations and areas of uncertainty.

An expert consensus to standardise the assessment of histological disease activity in Crohn's disease clinical trials.

BACKGROUND: Targeting histological remission or response in Crohn's disease (CD) is not recommended in clinical practice guidelines or as an outcome in clinical trials due to uncertainties regarding index validity and prognostic relevance. AIMS: To conduct a modified RAND/University of California Los Angeles appropriateness process with the goal of producing a framework to standardise histological assessment of CD activity in clinical trials. METHODS: A total of 115 statements generated from literature review and expert opinion were rated on a scale of 1-9 by a panel of 11 histopathologists and 6 gastroenterologists. Statements were classified as inappropriate, uncertain or appropriate based upon the median panel rating and degree of disagreement. RESULTS: The panellists considered it important to measure histological activity in clinical trials to determine efficacy and that absence of neutrophilic inflammation is an appropriate histological target. They were uncertain whether the Global Histological Activity Score was an appropriate instrument for measuring histological activity. The Geboes Score and Robarts Histopathology Index were considered appropriate. Two biopsies from five segments should be biopsied, and the colon and the ileum should be analysed separately for all indices. Endoscopic mucosal appearance should guide biopsy procurement site with biopsies taken from the ulcer edge, or the most macroscopically inflamed area in the absence of ulcers. CONCLUSION: We evaluated the appropriateness of items for assessing histological disease activity in CD clinical trials. These items will be used to develop a novel histological index.

Beyond Helicobacter: dealing with other variants of gastritis-an algorithmic approach.

In daily practice, the presence of inflammation in gastric biopsies prompts a mental algorithm, an early question being whether the lesion present is Helicobacter-associated. If Helicobacter organisms are not found, then there is a further algorithm, governed by the predominant type of inflammatory cells present, and the presence of other features such as intraepithelial lymphocytosis, a subepithelial collagen band, granulomas, coexisting chronic inflammation, focality, and superimposed reactive changes including erosions and ulcers. Each of these generates its own differential diagnosis. If no inflammation is present, then the two major changes specifically looked for are the changes associated with hypergastrinaemia, by far the most common cause of which is treatment with proton pump inhibitors, and reactive changes. These may be present with and without accompanying inflammation, and, when the epithelial changes dominate, the term gastropathy is preferred. In this article, we present an approach to non-Helicobacter inflammation and gastropathies.

Active Margins, Plexitis, and Granulomas Increase Postoperative Crohn's Recurrence: Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Rates of postoperative Crohn's disease recurrence remain high, although the ability to predict this risk of recurrence remains limited. As such, we aimed to determine the association of histologic features at the time of resection with postoperative recurrence. METHODS: Electronic databases were searched through February 2020 for studies that reported risk of clinical, endoscopic, or surgical postoperative recurrence in patients with positive resection margins, plexitis, or granulomas in the index specimen. Pooled risk ratios (RRs) with 95% CIs were calculated for this risk in patients with and without these histologic features. RESULTS: Twenty-one studies (2481 patients) assessed positive resection margins, 10 studies (808 patients) assessed plexitis, and 19 studies (1777 patients) assessed granulomas. Positive resection margins increased the risk of clinical (RR, 1.26; 95% CI, 1.06-1.49; I2 = 41%) and surgical (RR, 1.87; 95% CI, 1.14-3.08; I2 = 71%) recurrence, with a trend toward endoscopic recurrence (RR, 1.56; 95% CI, 0.79-3.05; I2 = 85%). Granulomas increased the risk of clinical (RR, 1.31; 95% CI, 1.05-1.64; I2 = 36%) and endoscopic (RR, 1.37; 95% CI, 1.00-1.87; I2 = 49%) recurrence, with a trend toward surgical recurrence (RR, 1.58; 95% CI, 0.89-2.80; I2 = 75%). Plexitis increased the risk of endoscopic recurrence (RR, 1.31; 95% CI, 1.00-1.72; I2 = 20%), with a trend toward clinical recurrence (RR, 1.34; 95% CI, 0.95-1.91; I2 = 46%). CONCLUSIONS: Positive resection margins, granulomas, and plexitis are predictive of postoperative Crohn's disease recurrence and should be recorded at the time of index resection.

Alpha-Fetoprotein-Producing Early Gastric Cancer with Intramucosal Hepatoid and Fetal Enteric Differentiation.

Alpha-fetoprotein (AFP)-producing gastric carcinomas (AFPGCs) are relatively rare tumors known to have a poor prognosis and commonly found as advanced lesions. Histologically, AFPGCs have been described as having hepatoid and fetal enteric (enteroblastic) morphology and are associated with conventional adenocarcinomas. Prior studies reported a hepatoid component present only in invasive areas and hypothesized that AFPGCs may develop hepatoid features during the process of tumor invasion. We report three cases of AFP-producing early gastric cancer which had an intramucosal hepatoid component. Immunohistochemistry showed that the hepatoid component was diffusely immunoreactive for SALL4, AFP, arginase-1, and HepPar1, and focally for CDX2 and PDX1. An intramucosal transition between the hepatoid component and conventional intramucosal adenocarcinoma was identified. Two patients also had a coexistent fetal enteric component, which was admixed with a hepatoid component. Although at an early stage one patient subsequently developed liver metastasis and a second patient was suspected of having liver metastasis, these were not biopsy-proven. The latter patient had a previous history of hepatocellular carcinoma (HCC) and SALL4 was used on the HCC to distinguish metastatic/further HCC from a gastric metastatic primary with hepatoid differentiation.

Secondary Involvement of the Uterine Cervix by Nongynecologic Neoplasms: A Detailed Clinicopathologic Analysis.

Secondary involvement of the uterine cervix by nongynecologic neoplasms is rare accounting for <2% of metastases to the gynecologic tract. This study aimed to analyze the clinicopathologic features of cervical involvement by nongynecologic malignancies. A total of 47 cases were identified including 39 (83%) carcinomas, 6 lymphomas (12.8%), and 2 (4.2%) cutaneous malignant melanomas. The most common primary site of origin among carcinomas was the gastrointestinal tract (27, 69.2%), followed by breast and urothelium (5 each, 12.8%), gallbladder, and lung (1 each, 2.6%). The gynecologic tract was involved at the presentation in 16 patients (34%), including 5 (10.6%) with the cervix being the first site, 7 (14.9%) with synchronous involvement of the cervix and other gynecologic sites, and 4 (8.5%) with the involvement of other gynecologic sites before the cervical presentation. Patients with lymphoma were younger compared with those with carcinoma (43.7 vs. >50.5) (P=0.01). Mean time to identification of cervical metastases was <1 year for gallbladder carcinoma, melanomas, and gastrointestinal signet ring cell carcinomas (P=0.03). Features that varied with different types of metastatic tumor included lymphovascular space invasion, depth of stromal invasion, growth pattern (glands lacking architectural complexity, cribriforming, solid), presence of goblet cells, and signet ring cells, degree of cytologic atypia, and overall findings mimicking a benign/noninvasive process (P≤0.027). Six tumors (12.8%) were initially misdiagnosed as cervical primary. Metastatic nongynecologic tumors can mimic primary in situ or invasive neoplasms in both ectocervix and endocervix. In patients with a known prior malignancy, the clinical history with ancillary studies and a high level of suspicion are crucial to ensure accurate diagnosis.

Histological Markers of Clinical Relapse in Endoscopically Quiescent Ulcerative Colitis.

BACKGROUND: In ulcerative colitis (UC) patients who have achieved mucosal healing, active microscopic colonic mucosal inflammation is commonly observed. We aimed to assess the association between histological activity and disease relapse in endoscopically quiescent UC. METHODS: Ulcerative colitis patients with endoscopically quiescent disease and ≥12 months of follow-up were included. Biopsies were reviewed for the presence of basal plasmacytosis (BPC) and active histological inflammation, defined as a Geboes score (GS) ≥3.2. Primary outcome measures were disease relapse at 18 months and time to first relapse after index colonoscopy. RESULTS: Seventy-six UC patients (51% male; mean age, 38.6 years; median follow-up [range], 75.2 [2-118] months) were included. Sixty-two percent had an endoscopic Mayo score of 0 at index colonoscopy. Basal plasmacytosis was present in 46% and active histological inflammation in 30% of subjects. Presence of BPC was associated with a significantly shorter time to disease relapse (P = 0.01). Active histological inflammation was significantly associated with clinical relapse at 18 months (P = 0.0005) and shorter time to clinical relapse (P = 0.0006). Multivariate analysis demonstrated active histological inflammation to be independently associated with clinical relapse at 18 months and time to clinical relapse. CONCLUSIONS: In endoscopically quiescent UC, active histological inflammation and the presence of BPC are adjunctive histological markers associated with increased likelihood of disease relapse. Although prospective studies are required, the presence of these histological markers should be a factor considered when making therapeutic decisions in UC.