CD, or not CD, that is the question: a digital interobserver agreement study in coeliac disease.

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.

The Nomadic Digital Pathologist. Validation of a simple, dual slide scanner with remote reporting for a regional upper gastrointestinal specialist multidisciplinary meeting.

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.

Eosinophilic infiltration of oesophagus following carbamazepine-induced drug reaction with eosinophilia and systemic symptoms: an under-reported sequel?

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.

Symptomatic Thyroglossal Duct Cyst Presenting With Synchronous and Localized Tongue Base Extranodal Mantle Cell Lymphoma. A Unique Case Report Demonstrating Lymphoma Colonization of Cyst Wall, Potentially Relating to a Persistent Embryological Foramen Cecum Remnant.

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.

Histopathology during the COVID-19 pandemic: resilience through adaptation and innovation.

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.

Extramammary Borderline Phyllodes Tumor Presenting as an Umbilical Mass.

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.

Current dilemmas in the pathological staging of colorectal cancer: the results of a national survey.

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.

Renal Cell Carcinoma Antigen Expression in Primary Cutaneous Endocrine Mucinous Carcinomas: A Case Series of 14 Patients and Review of the Literature.

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.

A Midgut Duplication Cyst Lined by Respiratory Epithelium.

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.

Loco-regional staging accuracy in oesophageal cancer-How good are we in the modern era?

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.

Diffuse Gastric Carcinoma Undergoes Characteristic Phenotypic Changes in the Intravascular Environment: Evidence for a Reversal of the Epithelial-Mesenchymal Transition in Lymphovascular Metastasis.

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.

Nodular 'fasciitis' presenting as a cutaneous polyp.

A polypoid cutaneous variant of 'nodular fasciitis' presenting on the upper arm of an 8-year-old girl is described. Nodular fasciitis is a reactive myofibroblastic proliferation that can be mistaken clinically as sarcoma, given its rapid growth. As its name implies, nodular fasciitis was originally described involving the fascia. Although rare dermal cases have been described, this is the first report of a dermal polypoid variant known to us, thus extending the presentations of this condition.

Cerebral infarction following thrombolysis for massive pulmonary embolism.

A 29-year-old male developed a fatal stroke 6 h after successful thrombolysis for massive pulmonary embolism. Autopsy showed thrombus protruding through a patent foramen ovale (PFO). A strand of thrombus extended from the aortic arch into the left common carotid artery. The brain showed extensive infarction of the left fronto-parietal area. Thrombolysis caused initial disintegration of the embolism. It is likely that thrombolysis caused fragments of clot to later break lose and embolise into the cerebral circulation. We discuss the need for risk stratification in patients who present with massive pulmonary embolism and PFO.