INTRODUCTION:We aim to evaluate our experience of tonsil biopsies in the investigation of patients presenting with asymmetrical tonsils.METHODS:A two-centre retrospective analysis of all patients who underwent histology sampling of the palatine tonsils between 1 January 2013 and 31 December 2018 was completed. Data collected included patient demographics, method of obtaining tonsil tissue, histological diagnosis and need for repeat tissue sampling. A follow-up period of 36 months was allowed to establish whether any patients re-presented with missed diagnoses.RESULTS:In total, 937 patients were included for analysis: 375 (40.0%) had a biopsy, of which 191 (50.9%) were performed in clinic. The mean duration from initial appointment with the ear, nose and throat clinic to tissue sample collection was 17.6 days (range 0-327 days) for all biopsies, reducing to 0.2 days (range 0-17 days) for biopsies performed in clinic. This was significantly shorter than for tonsillectomies (mean 38.9 days, range 0-444 days; p<0.05). Of the patients who underwent tonsil biopsy, six (1.6%) had malignancy that was not unequivocally diagnosed on initial biopsy. In all six patients, prior clinical suspicion was high, and repeat tissue sampling was undertaken on receipt of negative histology results.CONCLUSIONS:Tonsil biopsy is a viable alternative to tonsillectomy for histology in the assessment of tonsil asymmetry. Tonsil biopsy in the outpatient setting has reduced surgical morbidity, significantly less delay in diagnosis, less inconvenience for patients and lower healthcare costs compared with formal tonsillectomy. Although tonsil biopsies should not be used in isolation, they can be useful in the investigation of patients presenting with tonsillar asymmetry.

Gastric heterotopia can occur in any part of the gastrointestinal tract but is rare in the rectum. This case of rectal gastric heterotopia is novel as the heterotopic mucosa contained fundic gland polyps, and there were histological changes in the gastric glands characteristic of proton pump inhibitor-related changes. These changes included apocrine-like luminal cytoplasmic protrusions in cystically dilated oxyntic gland parietal cells. These are well described in the native stomachs of PPI treated patients, but this is the first report of these changes in heterotopic gastric mucosa to our knowledge. The lesion was removed via transanal endoscopic operation (TEO) without prior biopsy due to its unusual irregular nodular appearance mimicking a high-risk rectal neoplasm.

Objective Coeliac disease (CD) diagnosis generally depends on histological examination of duodenal biopsies. We present the first study analysing the concordance in examination of duodenal biopsies using digitised whole-slide images (WSIs). We further investigate whether the inclusion of immunoglobulin A tissue transglutaminase (IgA tTG) and haemoglobin (Hb) data improves the interobserver agreement of diagnosis.Design We undertook a large study of the concordance in histological examination of duodenal biopsies using digitised WSIs in an entirely virtual reporting setting. Our study was organised in two phases: in phase 1, 13 pathologists independently classified 100 duodenal biopsies (40 normal; 40 CD; 20 indeterminate enteropathy) in the absence of any clinical or laboratory data. In phase 2, the same pathologists examined the (re-anonymised) WSIs with the inclusion of IgA tTG and Hb data.Results We found the mean probability of two observers agreeing in the absence of additional data to be 0.73 (±0.08) with a corresponding Cohen’s kappa of 0.59 (±0.11). We further showed that the inclusion of additional data increased the concordance to 0.80 (±0.06) with a Cohen’s kappa coefficient of 0.67 (±0.09).Conclusion We showed that the addition of serological data significantly improves the quality of CD diagnosis. However, the limited interobserver agreement in CD diagnosis using digitised WSIs, even after the inclusion of IgA tTG and Hb data, indicates the importance of interpreting duodenal biopsy in the appropriate clinical context. It further highlights the unmet need for an objective means of reproducible duodenal biopsy diagnosis, such as the automated analysis of WSIs using artificial intelligence.

We often associate nasal olfaction with desirable sensations, but the nose and paranasal sinuses also have an important role in filtration, detection and inactivation of particulate, chemical and biological irritants or toxins. The delicate mucosal lining of the sinonasal tract can be damaged by these external insults, and mutations affecting its diverse cellular components can result in an abundance of histological tumour types. While these are too numerous to catalogue in this short article, we have chosen a "fragrant pot pourri" of tumour types that have caused these authors diagnostic difficulties in the past and should therefore be of interest to the specialist trainee and jobbing histopathologist. While most are rarely encountered in general diagnostic practice, they can all initially present with non-specific symptoms, and feasibly reach the microscope of a general histopathologist as a seemingly innocuous nasal polyp. We highlight potential diagnostic pitfalls of this group of "sinonasal stinkers" in the hope of clarifying diagnostic terminology and highlighting some of the unique anatomical, morphological, molecular and biological characteristics of these lesions at this site.

Background: This article describes how a simple slide scanner with remote viewing software enabled a remote "nomadic" pathologist to continue his role as specialist lead for a regional gastrointestinal multidisciplinary team meeting (MDTM) after relocating to another site in the 5 hospital Southwest UK Peninsula cancer network just prior to the COVID-19 pandemic. Materials and methods: The author used digital pathology (DP) to supplement a conventional workflow as a way of minimising delay in reporting and reviewing slides for a regional specialist Oesophagogastric MDTM (the OGSMDT). The specialist centre at University Hospital Plymouth (UHP) is 58 miles from the author's new workplace at Royal Cornwall Hospital (RCHT). Slides from the 44 cases (10% of this specialist annual workload) in this validation study were reported or reviewed digitally using the slide scanner. All were listed for the OGSMDT due to being clinically suspicious for upper gastrointestinal malignancy, having been processed at UHP, or one of the other hospitals in the cancer network. Results: The scanner allowed the author who was only on site at UHP 1 day per week to prevent delays in reporting/reviewing glass slides, using remote DP. Confidence in digital diagnosis was assessed using the Royal College of Pathologists recommendations. The author was the primary pathologist signing out 31, and second opinion for the remaining 13 cases. These comprised a mixture of biopsies as well as endoscopic and surgical excision specimens. The DP system enabled the author to report the cases digitally with an equivalent degree of confidence to glass slides and no significant discrepancies were identified between the author's digital and final glass slide diagnosis. Conclusions: The scanner was found to be safe and effective for remote reporting and review for OGSMDT cases. It was recognised that DP was advantageous to enable this role to continue remotely but that a fully integrated digital reporting system capable of high-capacity scanning would be preferable to the simple system used.

Accurate assessment of lymph node involvement is vital in the staging and prognostication of oesophagogastric cancers. Radiological lymph node size is an established criterion for metastatic involvement. Enlarged lymph nodes are generally interpreted as metastatic. However, there is little data on the correlation between lymph node size and metastatic infiltration confirmed on histopathology. This study aims to correlate lymph node size in oeosphageal cancer resection specimens with frequency of metastatic involvement. Regional lymph nodes from oesophagectomy specimens of 32 consecutive patients who had pathologically confirmed N1 disease were analysed from May 2019 to May 2021. The number of positive and negative lymph nodes for each patient were counted. The largest diameter of each positive and negative lymph node was measured. The frequency of metastatic involvement was then calculated and correlated to lymph node size. A total of 956 lymph nodes from 32 patients were analysed. Median age was 73.5 (48-80) years, there were 28 male and 4 female patients and 30 of them had adenocarcinoma with the remaining 2 reported as squamous cell carcinoma. Of 956 nodes, 94 (9.8%) were found to have metastatic involvement. The median size for the positive lymph nodes was 4.16 mm compared to 3.15 mm for the negative nodes (p=0.20). Ninety two percent of involved nodes were less than 10 mm diameter. Ninety four percent of the reactive nodes also measured less than 10mm (p=0.347). There was no significant difference in size between metastatic and reactive lymph nodes with the majority of nodes with metastatic infiltration in oesophageal cancer resection specimens measuring less than 10 mm in diameter. Lymph node size is not a reliable indicator of metastatic involvement in patients with oesophageal cancer.

We report a patient with carbamazepine-induced drug reaction with eosinophilia and systemic symptoms (DRESS), who developed painful dysphagia in the follow-up period. Gastrointestinal, including oesophageal, complications are rarely reported following DRESS, and we wish to highlight this possibly under-reported phenomenon.

A 77-year-old male presented with a progressively enlarging midline neck mass. On further investigation he was found to have synchronous thyroglossal duct cyst and extranodal mantle cell lymphoma (MCL) localized to the base of tongue. Both pathologies were managed simultaneously with a surgical approach and the patient remained in clinical remission at the time of publication without indication for systemic oncological treatment. Histology revealed primary extranodal nonblastoid MCL forming a base of tongue mass, with colonization of the thyroglossal duct cyst. Lymphoma was also found in the epithelium of a crypt-like tract traversing one of the tongue base tumor sections. This tract was anatomically and histologically consistent with documented descriptions of the foramen cecum. This case report illustrates a previously undescribed temporal, clinical, and histological association between a base of tongue MCL and symptomatic thyroglossal duct cyst. We provide evidence for a potential causal relationship for the presentation of the thyroglossal duct cyst as a result of oropharyngeal MCL, in the absence of clinical and histological evidence of disseminated disease, directly infiltrating from its tongue base origin to the infrahyoid neck region, potentially via an embryologic foramen cecum remnant. We also highlight the crucial role of the histopathologist in multidisciplinary clinicopathological discussion in demonstrating how fundamental embryological and microanatomical relationships can unite apparently separate diseases.

We present the case of a 33 year-old male presenting with a white lesion within the left oral commissure. The lesion was initially regarded as either smoker's keratosis or verrucous hyperplasia and was biopsied to exclude a neoplasm. Histology revealed squamous epithelial hyperplasia, plasmacytic inflammation and neuritis. Treponema immunohistochemistry demonstrated the presence of spirochetes and subsequent serology confirmed the diagnosis as syphilis. The oral commissure is an unusual site for secondary syphilis (condylomata lata). The clinical resemblance of condylomata lata to other oral cavity lesions may lead to biopsy, as it did in this case. This presents a diagnostic challenge for pathologists since the features of syphilis are non-specific. Associated features that raise suspicion include: epithelial hyperplasia; granulomatous inflammation; endarteritis; and florid plasma cell inflammation with neuritis. Morphology should be corroborated with immunohistochemistry and serological testing. Prompt communication with clinical colleagues facilitates timely treatment and contact tracing.

Phyllodes tumors (PTs) represent a spectrum of rare, fibroepithelial neoplasms of the breast, which can be subcategorized as benign, borderline, or malignant based on their histological appearance. Accessory breast tissue may present anywhere along the embryological mammary ridge, and at distant locations as aberrant breast tissue. We present the case of a 56-year-old lady with an umbilical mass, thought to represent a strangulated hernia. Sections showed a fibroepithelial tumor with leaf-like ducts, conspicuous mitotic activity (up to 8 per 10 high-power fields), and focal infiltration into fat. Immunohistochemical studies showed diffuse positivity of epithelial cells for estrogen receptor, mammaglobin, GCDFP-15, and CK7. These findings were consistent with a borderline PT. This is the first case report of PT presenting as an umbilical mass, and the first extramammary borderline PT described.

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.

Bile duct hamartomas are typically small benign liver lesions that can radiologically mimic metastases on ultrasound and computed tomography, as well as macroscopically. We present a rare and interesting case and review the relevant literature. A 49-year-old woman underwent ultrasound investigation for right upper quadrant pain, which revealed diffuse liver lesions. In the setting of her previous vulval cancer, it was suspected that she had hepatic metastases. This was strongly reinforced with computed tomography and elevated CA 19-9 levels. A liver biopsy revealed diffuse and multifocal bile duct hamartomas and positron emission tomography was negative for metastases or features of cancer recurrence. A diagnosis of diffuse liver hamartomatosis was made. In view of the continuing clinical and laboratory picture, she required regular follow-up. The collective features of this case are unique, as the isolated characteristics of particular interest have not been previously described in the context of a single case. Bile duct hamartomas should be included in the differential diagnosis of multiple liver lesions. CA 19-9 is not a reliable marker for differential diagnosis of this entity.

Histopathology departments have adapted to the challenges posed by the COVID-19 pandemic by a variety of changes including working pattern alterations, technology adoptions and incorporation of techniques.This article summarizes these adaptations and provides references to guide pathologists through the continuing pandemic.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) and primary cutaneous mucinous carcinoma (PCMC) are both uncommon low-grade cutaneous adnexal tumors with predilection for the eyelids of elderly women. Their clinical appearance is nonspecific, typically presenting as a slowly growing poorly circumscribed papule, nodule, plaque, or swelling. Histological features of EMPSGC include a lobulated dermal neoplasm with bland cytology and an invasive mucinous component in up to half of the cases. PCMC exhibits tumor nests suspended in abundant pools of mucin with focal strands or nests of tumor cells infiltrating the dermis. Because of their rarity and banal cytological features, both entities pose a risk for misdiagnosis with other benign/malignant cutaneous adnexal neoplasms. Histomorphological features can suggest a diagnosis of EMPSGC or PCMC, but immunohistochemistry is necessary for confirmation. A review of the literature showed variable results of antigens present in EMPSGC, and many of the positive markers only show sparse or focal immunoreactivity of tumor cells. As a result, diffusely positive markers play a crucial role in identification of these tumors, particularly with initial superficial biopsies. We present 9 cases of EMPSGC and 5 cases of PCMC with strong and diffuse immunoreactivity to renal cell carcinoma antigen. This novel finding can be useful in the diagnosis of EMPSGC and PCMC in combination with other known positive markers to differentiate them from other cutaneous neoplasms. In addition, it provides further evidence that EMPSGC could be a precursor lesion to PCMC with both existing on a spectrum.

Duplication cysts are an uncommon finding. Majority of these cases are found in the region of the midgut, and many have been reported in literature. However, there has been only one previous case of a midgut duplication cyst lined by respiratory epithelium. This is a rare pathology, of which very little is known about. The pathophysiology of these cases is also difficult to explain. We aim to present a case of a midgut duplication cyst in a paediatric patient, who had other abnormalities as well. We also aim to offer a hypothesis for this case.

INTRODUCTION:Accuracy of locoregional staging in patients with oesophageal cancer is critical in determining operability and the need for neoadjuvant treatment. Imaging technology has advanced significantly in recent years but it is not known whether this translates to improved staging accuracy. This study investigates staging accuracy in relation to CT, EUS, PET-CT and final pre-operative stage. It specifically addresses the accuracy of staging with respect to the threshold for administering neoadjuvant therapies.MATERIALS AND METHODS:Pre-operative staging according to CT, EUS, PET-CT and final pre-operative stage were compared to the postoperative histological staging in 133 patients undergoing potentially curative surgery (without neoadjuvant therapy) for oesophageal cancer between January 2010 and January 2015. T and N stage accuracies were reported separately for each imaging modality. Patients were also divided into two groups depending on whether the final pre-operative stage was below (≤T2, N0, early tumours) or above (≥T3 and/or ≥N1, locally advanced tumours) the threshold for offering neoadjuvant therapy. Accuracy of pre-operative staging was then analysed with respect to identification of patients below/above this threshold. The additional benefit offered by EUS for this purpose was investigated.RESULTS:T stage accuracies were 72.6%, 76.7% and 79.3% for CT, EUS and final pre-operative stage respectively. N stage accuracies were 75.6%, 77.2%, 74.5% and 78.6% for CT, EUS, PET-CT and final pre-operative stage respectively. Staging accuracy with respect to threshold for neoadjuvant treatment showed 62.0% early tumours were correctly staged and 80.5% advanced tumours were correctly staged. Whether or not patients underwent EUS did not affect the staging accuracy with respect to neoadjuvant treatment threshold.CONCLUSIONS:Staging accuracy with respect to the threshold for treatment with neoadjuvant therapy is poor, leading to potential over/under treatment. Predicting individual response to neoadjuvant therapy would provide a better way to determine which patients should receive this additional treatment.

This article reports differences between the properties of extravascular carcinoma, which generally forms the vast bulk of a tumor, and those of intravascular carcinoma, at both primary and metastatic lymph node sites. In a morphological and immunohistochemical study of 19 diffuse gastric adenocarcinomas, we report that in comparison to extravascular carcinoma, the intravascular tumor compartment showed frequent and profound phenotypic change, including increased tumor cell cohesion, differentiation and cadherin/catenin expression. For example, greatest cohesion was seen at the intravascular site in 78% (P = .00006) of primary cancers and in 84% (P = .000015) of their lymph node metastases. Pan cadherin showed a statistically significant increase at the intravascular metastatic site (P = .031). We suggest that this change from an extravascular isolated cell phenotype to an intravascular cohesive phenotype represents reversal of the epithelial to mesenchymal transition. Since this proposed reversal of epithelial to mesenchymal transition in intravascular carcinoma is frequently conspicuous in routine histological sections of many types of cancer, as our previous publications have indicated, this process is likely to have widespread significance for the biology of metastasis.

Can scanning and storing the contents of microscope slides simplify the logistical challenges faced by pathologists today?

Introduction The advantages of neoadjuvant therapy (NAT) in oesophago-gastric (OG) cancer have been proven in randomised trials. Benefits are modest and likely to be restricted to patients who respond well to therapy. The risks may outweigh benefits in earlier stages of disease. This study explores the risks associated with NAT, analyses which patients benefit and investigates whether there is a need for a change in NAT treatment strategy. Method All patients planned for surgical resection of OG cancer in this unit between 01/2010 and 12/2014 were identified. Part a) patients were divided according to pre-operative stage. Within each stage, survival was compared in patients undergoing NAT and those undergoing surgery alone. Similar comparisons were made with the NAT group further divided into histological responders and non-responders. Part b) from the cohort, patients undergoing NAT were identified. Adverse effects (AE) were recorded and graded according to the Common Terminology Criteria for Adverse Events v3.0. The relationships between the presence of AE and a range of variables were investigated along with survival. Survival analyses were undertaken by plotting Kaplan-Meier curves. Groups were compared using the Log Rank (Mantel-Cox) test. Results 587 patients were identified from the database. Part a) only stage III patients had improved survival with NAT vs. surgery alone (P = 0.02). Those in stage II with a histological response to treatment showed a trend towards better survival vs. surgery alone (P = 0.058). In all patients above the threshold for offering NAT (≥stage II), survival was no different in non-responders vs. those having surgery alone. Age and performance status were lower in the NAT group vs. the surgery only group and were both associated inversely with survival. This could mean NAT effects are overestimated and true survival in non-responders to NAT may be poorer than in patients having surgery alone. Part b) 376 patients received NAT and 88 (23.4%) suffered AE. 69% of these were severe, life-threatening or fatal. NAT course completion rate was lower in patients suffering AE vs. those not (P = 0.003). 20.5% patients with AE did not proceed to resection vs. 6.4% without AE (P = 0.001). Survival was better in patients without AE vs. with AE (P = 0.02) and was better in those undergoing resection (P Conclusion Efficacy of NAT is dependent on cancer stage and histological response to NAT. AE are common, often severe and associated with a reduced resection rate and survival. Identifying a means of predicting response to NAT is of great importance and should be used to guide treatment alongside/instead of disease stage. Disclosure of interest None Declared.