Search

Aims: Since 2020 there has been an increase in the number of polyps removed from patients scoped for the Bowel Cancer Screening Programme (BCSP) of England. General cellular pathology workload also continues to increase disproportionately ahead of consultant pathologist numbers in the United Kingdom. The Optical Diagnosis initiative for BCSP patients has not yet, and may not be, implemented at every hospital in England. The following study therefore aimed to determine whether only a certain number of removed polyps need to be histologically assessed to consistently guide a BCSP patient's post-polypectomy management, and whether all remaining smaller polyps beyond that number could then be discarded., Methods: This retrospective study considered all BCSP specimens/cases submitted to the Cellular Pathology department of a large English teaching hospital from 2016 to 2024. Only cases with six or more resected polyps, for which the endoscopic report stated individual sizes, were included in the final study cohort., Results: Of the 8066 BCSP cases submitted to the aforementioned department, there were six or more polyps for 345 cases. Analysis of the final study cohort of 135 cases showed that assessment of the seven largest polyps measured endoscopically was sufficient to correctly guide follow-up management of the BCSP patient as per the 2020 British Society of Gastroenterology post-polypectomy guidelines., Conclusions: When colonoscopy of a BCSP patient leads to removal of multiple polyps, only the seven largest polyps need to be assessed histologically and the remaining smaller polyps could be discarded with no impact to the patient's BCSP-related management., (© 2024 John Wiley & Sons Ltd.)

Assessing a locally excised colorectal adenoma for malignancy is a common but often challenging scenario. This article outlines a simple, stepwise approach to this diagnostic assessment. The first steps are to assess for high-grade dysplasia and, if present, to determine whether any neoplastic glands lie within the submucosa. If so, a distinction must then be made between epithelial misplacement and adenocarcinoma; this process is aided by certain clinical and endoscopic data together with assessment of six key histological features. If adenocarcinoma is diagnosed, a final step is to report the presence/absence of high-risk features of polyp cancers because this will then determine if further surgical resection is required for that malignancy. Caveats, uncertainties and newly introduced concepts exist at several steps of the assessment pathway presented and are therefore discussed in detail throughout the article., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: British Sarcoma Group guidelines for the management of GIST were initially informed by those published by the European Society of Clinical Oncology. This update was written by a group of experts to includes a discussion of the highlight improvements in our knowledge of the disease and recent treatment developments. The guidelines include sections on Incidence, Aetiology, Diagnosis, including risk assessment, Treatment and Follow-up., Methods: A careful review of the literature was performed to ensure that wherever possible recommendations are supported by the results of clinical trials or substantive retrospective reports. Areas of uncertainty are indicated appropriately., Conclusion: Guidelines represent a consensus view of current best clinical practice. Where appropriate, key recommendations are given and the levels of evidence and strength of recommendation gradings are those used by the European Society for Medical Oncology (ESMO)., (© 2024. The Author(s).)

It is well recognized that the primary KIT or PDGFRA variant of a gastrointestinal stromal tumour (GIST) can predict sensitivity to imatinib. However, these data are currently spread across a wide range of publications and have not been collated as one reference. A broad-ranging literature search was therefore performed to assemble such a database which should help optimize imatinib-based management of GIST patients henceforth. Having excluded wild type GISTs and results for imatinib used as adjuvant therapy, 79 publications (dated August 2001 to March 2022) underwent data extraction. These data on imatinib sensitivity were either derived from in vitro studies, predicted by in silico analysis or based on in vivo clinical patient response. Data interpretation carried some caveats: there was a potential for replication of patient-derived data between older and new publications; only predicted protein sequences were presented; the criteria used to record clinical response were not uniform across all publications; and imatinib dosage could vary between different clinical publications. However, these data showed broad agreement of imatinib sensitivity amongst similar subtypes of KIT or PDGFRA variant. There was also agreement between in vivo versus in vitro/in silico derived sensitivity data for most variants when both data types were available., Competing Interests: Declaration of Competing Interest There are no competing interests or declarations of interest to declare., (Copyright © 2022. Published by Elsevier Inc.)

Aims & Methods: Simple biliary cysts of the liver are described to be lined by biliary epithelium and may be managed nonsurgically or by deroofing only. By contrast, its important differential diagnosis-mucinous cystic neoplasm (MCN)-is at least focally lined by mucinous epithelium, has malignant potential, and therefore should be resected. Following anecdotal observations in routine diagnostic practice, the following case series was assembled to confirm whether simple biliary cysts of the liver can be lined by mucinous epithelium. Detailed clinicoradiological review, including postoperative follow-up, was also completed to assess whether the presence of mucinous epithelium had any associations, including a risk of hepatobiliary neoplasia., Results: Histological review of 21 simple biliary cysts received as surgical specimens over a 3- year period confirmed an absence of ovarian-like stroma in all cases. The lining epithelium of seven cysts showed focal supranuclear/apical mucin, as confirmed histochemically. Cysts with mucinous epithelium were generally larger and more often showed histological evidence of previous haemorrhage than cysts without this epithelium. There were no other statistically-significant differences in clinicoradiological features between cysts with and without mucinous epithelium, including at postoperative radiological follow-up., Conclusions: Focal mucinous epithelium can be present in at least one-third of surgically-managed, simple biliary cysts of the liver. Such epithelium may be metaplastic and should not be misinterpreted to indicate a diagnosis of MCN but, apart from this, appears to have no clinical significance. Ovarian-like stroma may therefore be the only histological feature that reliably distinguishes MCN from simple biliary cyst., (© 2022 John Wiley & Sons Ltd.)

Gastrointestinal (GI) tract pathology represents one of the largest individual specialties within cellular pathology departments globally. As with other specialties, clear communication with clinicians providing primary care for the patient is of utmost importance for optimal management and for appropriate use of resources such as endoscopy. A wide breadth of neoplastic and inflammatory conditions afflicts the GI tract. Here, we aim to illustrate how pathology reporting of GI tract specimens influences patient management and specifically how precise reporting of key parameters in different specimen types and different disease processes can directly impact patient care. We describe the potential clinical relevance of selected pathology data items pertinent to specific conditions and highlight areas of contention with respect to the significance of some pathology features. Recent guidelines are described where a change, for example, in diagnostic criteria for a condition is described, or criteria influencing further management such as endoscopic surveillance. The aim of this review is to focus on the clinical importance of careful written communication between the pathologist and primary clinician, illustrated by selective clinical scenarios involving the upper and lower GI tracts., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Recent data suggest that the incidence of malignant appendiceal tumours is increasing. This study aimed to determine temporal trends in the incidence of malignant appendiceal tumours within England and a possible influence by demographic factors., Methods: All incident cases of appendiceal tumours in patients aged 20 years and above were identified from the National Cancer Registration and Analysis Service database between 1995 and 2016 using ICD-9/10 codes. Cancers were categorized according to histology. Joinpoint regression analysis was used to investigate changes in age-standardized incidence rates by age, sex, histological subtype and index of multiple deprivation quintiles, based on socioeconomic domains (income, employment, education, health, crime, barriers to housing and services and living environment). Average annual per cent changes (AAPCs) were estimated by performing Monte-Carlo permutation analysis., Results: A total of 7333 tumours were diagnosed and 7056 patients were analysed, comprising 3850 (54.6 per cent) neuroendocrine tumours (NETs), 1892 (26.8 per cent) mucinous adenocarcinomas and 1314 (18.6 per cent) adenocarcinoma (not otherwise specified). The overall incidence of appendiceal tumours increased from 0.3 per 100 000 to 1.6 per 100 000 over the study interval. Incidence rate increases of comparable magnitude were observed across all age groups, but the AAPC was highest among patients aged 20-29 years (15.6 per cent, 95 per cent c.i 12.7-18.6 per cent) and 30-39 years (14.2 per cent, 12.2-16.2 per cent) and lowest among those aged 70-79 years (6.8 per cent, 5.7-8.0 per cent). Similar incidence rate increases were reported across all socioeconomic deprivation quintiles and in both sexes. Analysis by grade of NET showed that grade 1 tumours accounted for 63 per cent between 2010 and 2013, compared with 2 per cent between 2000 and 2003., Conclusions: The incidence rate of malignant appendiceal tumours has increased significantly since 1995 and is mainly attributed to an increase in NETs. The increased diagnosis of low-grade NETs may in part be due to changes in pathological classification systems., (© The Author(s) 2022. Published by Oxford University Press on behalf of BJS Society Ltd.)

Aims: The inception of the National Health Service Bowel Cancer Screening Programme in England in 2006 highlighted the fact that the differential diagnosis between the presence of epithelial misplacement and adenocarcinoma occurring in colorectal adenomas is problematic. The pathology Expert Board (EB) was created to facilitate the review of difficult cases by a panel of three experienced gastrointestinal pathologists. This article describes a review of the work of the EB over a 4-year period (2017-2020)., Methods and Results: Four hundred and thirty polyps were referred to the EB from 193 pathologists and 76 hospitals during this time. The EB diagnosis was benign for 67%, malignant for 28%, and equivocal for 2% (with no consensus in the remainder). The most common diagnosis change made by the EB was from malignant to benign-made in 50% of polyps referred with an initially malignant diagnosis. The level of agreement between the individual EB members was 'good' (kappa score of 0.619) but that between the EB and the referring diagnosis was 'poor' (kappa score of 0.149). Data from one EB member indicated that the presence of lamina propria, features of torsion and cytological similarity between the superficial and deep glands were predictors of a benign diagnosis, whereas the presence of irregular neoplastic glands, a desmoplastic reaction and lymphovascular invasion were commonly observed features in polyps with a malignant diagnosis., Conclusion: Diagnostic agreement between EB members is better than that between the EB and referring pathologists. There was a consistent trend for the EB to change diagnoses from malignant to benign., (© 2021 John Wiley & Sons Ltd.)

Aims and Methods: Faecal calprotectin (FCP) measurement is used especially to investigate for inflammatory bowel disease (IBD). To assess the utility of sampling endoscopically normal large bowel among patients first presenting with elevated FCP, this study identified 115 such patients out of 652 patients with elevated FCP from approximately 6000 primary care tests processed over 15 months., Results: 23 cohort patients showed histologically abnormal large bowel biopsies. Only four cases demonstrated acute inflammation and two such patients only showed scattered cryptitis and did not develop IBD. A third patient demonstrated similar histology but, following repeat colonoscopy, her elevated FCP was attributed to small intestinal inflammation. Only the fourth patient's large bowel biopsies showed features suggesting Crohn's disease, but this represented an IBD detection rate out of 115 sets of large bowel biopsies of 0.9%., Conclusions: Sampling of endoscopically normal large bowel among patients first presenting with elevated FCP is not clinically justified., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

The focus on lymph node metastases (LNM) as the most important prognostic marker in colorectal cancer (CRC) has been challenged by the finding that other types of locoregional spread, including tumor deposits (TDs), extramural venous invasion (EMVI), and perineural invasion (PNI), also have significant impact. However, there are concerns about interobserver variation when differentiating between these features. Therefore, this study analyzed interobserver agreement between pathologists when assessing routine tumor nodules based on TNM 8. Electronic slides of 50 tumor nodules that were not treated with neoadjuvant therapy were reviewed by 8 gastrointestinal pathologists. They were asked to classify each nodule as TD, LNM, EMVI, or PNI, and to list which histological discriminatory features were present. There was overall agreement of 73.5% (κ 0.38, 95%-CI 0.33-0.43) if a nodal versus non-nodal classification was used, and 52.2% (κ 0.27, 95%-CI 0.23-0.31) if EMVI and PNI were classified separately. The interobserver agreement varied significantly between discriminatory features from κ 0.64 (95%-CI 0.58-0.70) for roundness to κ 0.26 (95%-CI 0.12-0.41) for a lone arteriole sign, and the presence of discriminatory features did not always correlate with the final classification. Since extranodal pathways of spread are prognostically relevant, classification of tumor nodules is important. There is currently no evidence for the prognostic relevance of the origin of TD, and although some histopathological characteristics showed good interobserver agreement, these are often non-specific. To optimize interobserver agreement, we recommend a binary classification of nodal versus extranodal tumor nodules which is based on prognostic evidence and yields good overall agreement., (© 2021. The Author(s).)

Aims: Because serous cystadenoma (SCA) does not usually require excision, it is critical to distinguish it from differential diagnoses which do, especially neuroendocrine tumour (NET). The gold standard for diagnosing SCA is assessment of endoscopic ultrasound-guided fine needle aspiration/biopsy (EUS-FNAB) material. Inhibin immunohistochemistry aids this assessment, but such positivity is not absolutely sensitive or specific to SCA. The following is the largest known study of SCA EUS-FNAB specimens and the first to compare four potential SCA immunomarkers between themselves and inhibin, compared against NET., Methods and Results: Immunohistochemistry for calponin, mucin 6 (MUC6), glucose transporter 1 (GLUT1) and vascular endothelial growth factor A (VEGFA) was performed on 30 EUS-FNAB and three resection specimens of SCA and 32 EUS-FNAB specimens of NET. GLUT1 and VEGFA were suboptimal as diagnostic immunomarkers of SCA, being expressed by 10 and 44% of NETs, respectively. Further, their expression by cellular constituents of blood which often contaminate EUS-FNAB specimens hampered identification of neoplastic cells, especially in hypocellular samples. While 19% of NETs showed nuclear MUC6 positivity, cytoplasmic expression of the protein showed 100% specificity and sensitivity as an SCA marker. However, assessing MUC6 in EUS-FNAB specimens must also consider the protein's focal expression in physiological pancreatic, gastric or duodenal tissues, which can contaminate these specimens. Calponin was less sensitive (71% versus 100%) but more specific (100% versus 91%) than inhibin, although easier to assess in EUS-FNAB specimens than MUC6., Conclusions: Of the four potential immunomarkers of SCA suggested by the existing literature, calponin and MUC6 are useful complementary studies to inhibin for application to EUS-FNAB specimens., (© 2021 John Wiley & Sons Ltd.)

Aims: The diagnostic and clinical significance of granulomas in gastrointestinal (GI) biopsies from haematopoietic transplant patients remains disputed, especially following the proposal of cord colitis syndrome (CCS) as a new entity. The aim of the following study was to explore this controversy by identifying such biopsies with granulomas and detailing their clinicopathological associations., Methods and Results: Twelve patients with granuloma-containing biopsies were identified from across three scenarios: prospectively during a GI pathologist's routine practice over a period of 5 years; retrospectively from a cohort of transplant patients with clinically validated GI graft versus host disease (GVHD); and retrospectively from a cohort of patients who had received umbilical cord blood (UCB). Their clinicopathological assessments (which included unique long-term patient follow-up) showed that granulomas are only rarely seen across all GI biopsies from haematopoietic transplant patients, and may uncommonly constitute a histological feature of GI GVHD. Granulomas-and especially well-defined, non-cryptolytic ones-are more commonly present in GI biopsies from UCB recipients, but do not show any accompanying histological features that are different from those seen in granuloma-containing biopsies from other patient groups. Furthermore, the three UCB recipients with granuloma-containing biopsies were clinically diagnosed with GVHD rather than CCS. Finally, polymorphic post-transplant lymphoproliferative disorder (PTLD) can present histologically as GI granulomatous inflammation that mimics Crohn's disease., Conclusions: Granulomas in GI biopsies of haematopoietic transplant patients may often indicate a treatable aetiology such as GVHD or PTLD. Granulomas are more commonly seen in GI biopsies from UCB recipients, but do not necessarily indicate a diagnosis of CCS., (© 2020 John Wiley & Sons Ltd.)

Aims: Accurate and consistent pathological staging of colorectal carcinoma (CRC) in resection specimens is especially crucial to guide adjuvant therapy. The aim of this study was to assess whether certain staging scenarios yield discordant opinions in the setting of current international and UK national guidelines., Methods and Results: Members of the UK Gastrointestinal Pathology External Quality Assurance Scheme were invited to complete an anonymous, on-line survey that presented 15 scenarios related to pT or pR staging of CRC, and three questions about the respondent. The survey invitation was e-mailed to 405 pathologists, and 184 (45%) responses were received. The respondents had discordant opinions on whether and how CRC pT or pR staging is affected by: acellular mucin lakes and duration after short-course radiotherapy; the nature of the carcinoma at a resection margin or peritoneal surface; and microscopic evidence of perforation. This discordance was rarely related to the respondent's occupation type, and was not related to duration of work as a consultant or the staging guidelines used., Conclusions: This survey confirms that there remain several clinically critical but unresolved pT and pR staging issues for CRC. These issues therefore deserve attention in future versions of international and national staging guidelines., (© 2020 John Wiley & Sons Ltd.)

Aim: There is no known specific biomarker or genetic signal for quadruple wild-type (qWT) gastrointestinal stromal tumours (GISTs). By next-generation sequencing (NGS) of different GIST subgroups, this study aimed to characterise such a biomarker especially as a potential therapeutic target., Methods and Results: An NGS panel of 672 kinase genes was applied to DNA extracted from 11 wild-type GISTs (including three qWT GISTs) and 5 KIT/PDGFRA mutated GISTs. Short variants which were present in qWT GISTs but no other GIST subgroup were shortlisted. After removing common population variants, in silico-classified deleterious variants were found in CSNK2A1 , MERTK , RHEB , ROCK1 , PIKFYVE and TRRAP . None of these variants were demonstrated in a separate cohort of four qWT GISTs., Conclusions: Short kinase variants which are specific to qWT GISTs are rare and are not universally demonstrated by this whole subgroup. It is therefore possible that the current definition of qWT GIST still covers a heterogenous population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) is the optimal method for sampling lesions of the pancreas. This procedure is being performed at increasing numbers of hospitals and therefore, more and more cellular pathology departments are having to process and report EUS-FNAB specimens. This article outlines the advantages of using tissue/cell block preparation to process these specimens. In particular, such preparation concentrates, conserves and preserves sampled material which is then available for a full array of further analyses. Tissue/cell block preparation also enables EUS-FNAB specimens to be assessed by a wider range of cellular pathologists. This article demonstrates how a tissue/cell block protocol permits the diagnosis of the full range of pancreatic pathologies sampled by EUS-FNAB. The protocol is identical for all these pathologies (including both solid and cystic lesions) and is simple at all stages of the specimen pathway, from collection to processing to assessment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: The cell block technique for assessing endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) specimens from pancreatic mucinous cystic lesions (MCLs) was systematically evaluated for the first time, including comparisons with three traditional methods of assessing such specimens., Methods: The prospective arm comprised EUS-FNA specimens from EUS-suspected pancreatic MCLs. The retrospective arm comprised EUS-FNA specimens from pancreatic MCLs surgically resected before the study start. For each specimen, these data points were collected: macroscopic likelihood of mucin, cyst fluid carcinoembryonic antigen (CEA) level and presence of mucin in air-dried, direct smears and in cell block preparations., Results: The prospective and retrospective arms of the study comprised 80 and 30 EUS-FNA specimens, respectively. Seven prospective cases led to surgical resections during the study, and therefore, 37 EUS-FNA specimens were confirmed to have originated from MCLs. In the prospective arm, macroscopic mucin was suspected, cyst fluid CEA level exceeded 192 ng/mL, mucin was detected in direct smears and cell block preparations in 78%, 30%, 39% and 73% of cases, respectively. Of the 37 specimens confirmed to originate from MCLs, macroscopic mucin assessment, cyst fluid CEA level, direct smear mucin assessment and cell block mucin assessment had sensitivities for diagnosing MCL of 87%, 45%, 45% and 81%, respectively., Conclusions: Cell block preparations are as likely to identify mucin from pancreatic MCLs as macroscopic assessment but are twice as likely to diagnose MCL than direct smears and fluid CEA biochemistry. The cell block technique is easy for sample collection and processing especially because these are identical for solid and cystic pancreatic lesions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: This case series intends to expand currently limited knowledge regarding the existence and diagnostic significance of intramucosal fat in colorectal polyps., Methods: Clinicopathological features of nine such polyps were reported following histopathological review, including S100 and EMA immunohistochemistry., Results and Conclusions: Such review subdivided seven polyps into three groups: (1) mucosal perineurioma/serrated polyps with fat among the perineurial stroma (three cases); (2) submucosal lipomas with adipose tissue extending into the overlying mucosa (two cases) and (3) polyps with intramucosal adipose tissue only, that is, the newly described but less-recognised entity known as intramucosal lipoma (two cases). The two remaining polyps of this series did not include submucosa but, from assessing their muscularis mucosae, were favoured to represent intramucosal lipomas. The first two phenomena are formally described for the first time by this case series. The last of these three diagnoses should prompt investigations for Cowden syndrome, but intramucosal lipomas are more often sporadic/non-syndromic., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

A unique cohort of chemo-naive gastrointestinal stromal tumors (GISTs) with double-primary tyrosine kinase mutations was characterized particularly to determine whether coexistent mutations represent a single mutational event. Up to 2013, 4 UK centers reported 9 GISTs with 2 primary tyrosine kinase mutations. In each of 8 cases validated by next generation sequencing, both mutations were present in the same allele of the same exon (KIT exon 11 or 17, or PDGFRA exon 18). One case showed the second mutation only on some of the mutant alleles. Seven cases showed both mutations in all the reads, but in 2 cases, additional variants were found only in some reads. Clinicopathologic features of the 8 cases were similar to GISTs with single-primary mutations. When GIST genotyping rarely uncovers multiple tyrosine kinase variants in an exon, they occur in the same allele but are likely to represent separate mutational events and lack clinical significance.

Aims: The currently recognised subtypes of anal canal/peri-anal adenocarcinoma are those arising from low rectal mucosa or columnar cuff, fistula-related tumours and anal gland carcinoma. This report presents two examples of a hitherto undescribed subtype of peri-anal adenocarcinoma with an intestinal phenotype., Methods and Results: A 74-year-old man had a peri-anal tumour locally excised, whereas a 73-year-old female underwent an abdominoperineal resection for peri-anal Paget's disease with an underlying carcinoma. Neither patient had a history of perineal fistulae, Crohn's disease or previous gastrointestinal neoplasia, and neither showed clinical, radiological or endoscopic evidence of another abdominal or pelvic tumour. Both resection specimens contained adenocarcinoma, which were similar in demonstrating an intestinal morphology and CDX2 immunopositivity. The man has shown a disease-free outcome thus far, but the woman has suffered with nodal and pelvic recurrence within a few months of surgery., Conclusions: The name 'primary peri-anal adenocarcinoma of intestinal type' is proposed for this previously unrecognised subtype of perineal neoplasia. Awareness of its distinct existence - by recognising its intestinal morphology and immunophenotype while excluding metastasis from the intestinal tract - should help to collate data to determine its specific prognosis and to formulate its best management., (© 2018 John Wiley & Sons Ltd.)

The use of biologics targeted to the human epidermal growth factor receptor 2 (HER2) protein is the latest addition to the armamentarium used to fight advanced gastric or gastro-oesophageal junction adenocarcinoma. The decision to treat with the biologic trastuzumab is completely dependent on HER2 testing of tumour tissue. In 2017, the College of American Pathologists, American Society for Clinical Pathology and the American Society of Clinical Oncology jointly published guidelines for HER2 testing and clinical decision making in gastro-oesophageal adenocarcinoma. The Association of Clinical Pathologists Molecular Pathology and Diagnostics Committee has issued the following document as a commentary of these guidelines and, in parallel, to provide guidance on HER2 testing in National Health Service pathology departments within the UK. This guidance covers issues related to case selection, preanalytical aspects, analysis and interpretation of such HER2 testing., Competing Interests: Competing interests: NACSW has previously received antibodies and immunohistochemistry reagents from Roche Ventana for use in research projects. Other authors have no competing interests to declare., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Aims: CDX2 is widely used as a sensitive and specific immunomarker for colorectal carcinoma (CRC), but neither its sensitivity nor its specificity is absolute. The aim of this study was to compare CDX1 and A33 with CDX2 as immunomarkers for CRC., Methods and Results: As a pilot study, whole sections of 51 cases of liver metastatic carcinoma with different origins-colorectum (n = 32), breast (n = 3), oesophagogastric tract (n = 4), lung (n = 3), pancreas (n = 8), and prostate (n = 1)-were immunostained with CDX1, CDX2, and A33. A33 showed higher sensitivity as a CRC immunomarker, greater interobserver reproducibility for assessment of expression and less background cross-reactivity than CDX1. Therefore, only A33 was compared with CDX2 for a tissue microarray (TMA)-based study of primary adenocarcinomas with different origins: CRC (n = 55), liver deposits of metastatic CRC (n = 60), breast (n = 101), lung (n = 40), oesophagogastric tract (n = 134), ovary (n = 67), pancreas (n = 77), and prostate (n = 56). When the whole section and TMA cases of CRC were combined, A33 had a sensitivity of 95.9% and CDX2 had a sensitivity of 97.2%. When the whole section and TMA cases of non-colorectal carcinomas were combined, A33 had a specificity of 85.4% as a marker of CRC and CDX2 had a specificity of 64.3%. The higher specificity of A33 than of CDX2 as a CRC immunomarker was particularly seen among pancreatic and ovarian carcinomas. Furthermore, unlike what was seen with CDX2, none of the prostatic and lung carcinomas studied showed A33 positivity., Conclusions: A33 shows similar sensitivity to but is more specific than CDX2 as an immunomarker of CRC., (© 2017 John Wiley & Sons Ltd.)