Measuring depth of invasion of submucosa - invasive adenocarcinoma in oesophageal endoscopic specimens: how good are we?

AIMS: Emerging data support that submucosa-invasive (pT1b) esophageal adenocarcinomas are cured via endoscopic resection, provided that invasion measures ≤500 µm, they lack other histological features predictive of nodal metastasis and have negative margins. Hence, pathologists' measurement of the depth of submucosal invasion in endoscopic resections may dictate further management (i.e. endoscopic follow-up versus oesophagectomy). In this study, we assessed the interobserver agreement in measuring the depth of submucosal invasion in oesophageal endoscopic resections. METHODS AND RESULTS: Six subspecialised gastrointestinal (GI) pathologists from five academic centres independently measured the depth of submucosal invasion in µm from the deepest muscularis mucosae on 37 oesophageal endoscopic resection slides (round 1 scoring). A consensus meeting with a systematic approach for measuring and discussion of pitfalls was undertaken and remeasuring (round 2 scoring) was conducted. Interobserver agreement was assessed by the intraclass correlation coefficient (ICC) and Cohen's kappa statistics. A lack of agreement was seen among the six reviewers with a poor ICC for both rounds: 1 [0.40, 95% confidence interval (CI) = 0.26-0.56] and 2 (0.49, 95% CI = 0.34-0.63). When measurements were categorised as < or >500 µm, the overall agreement among the six reviewers was only fair for both rounds: 1 (kappa = 0.37, 95% CI = 0.22-0.53) and 2 (kappa = 0.29, 95% CI = 0.12-0.46). CONCLUSIONS: Our study shows a lack of agreement among gastrointestinal pathologists in measuring the depth of submucosal invasion in oesophageal endoscopic resections despite formulating a consensus approach for scoring. If important management decisions continue to be based upon this parameter, more reproducible and concrete guidelines are needed.

Goblet Cell Carcinoid/Carcinoma: An Update.

Goblet cell carcinoid (GCC) or goblet cell carcinoma is a unique mixed endocrine-exocrine neoplasm that is almost exclusively seen in the appendix. The hallmark of GCC is the concentric infiltration of the appendiceal wall by small tight clusters, nests or cords of tumor cells that exhibit a goblet cell morphology with a small compressed nucleus and conspicuous intracytoplasmic mucin. The coexistence of high-grade adenocarcinoma with GCC has been increasingly recognized as a common finding, which has been called adenocarcinoma ex GCC or mixed GCC-adenocarcinoma. A number of studies have shown that it is the high-grade adenocarcinomatous component that dictates the prognosis. Several histologic classification/grading systems have been proposed, which correlate with overall patient survival. Treatment options are primarily based on tumor stage and the presence or absence of a high-grade adenocarcinomatous component.

Herbal hepatitis due to use of alternative medicines for Lyme disease.

Lyme disease often leaves patients with chronic symptoms of fatigue, easy confusion, and even cardiac arrhythmias. We report a case in which Lyme disease was treated with an herbal mixture due to protracted symptoms despite intravenous antibiotics. This mixture was associated with hepatotoxicity. General providers should be aware of the fact that homeopathic remedies may be associated with hepatotoxicity, and herbalists need better understanding of the safety risks of the individual components in remedy mixtures.

Interobserver Variability in Assessment of Depth of Submucosal Invasion for Colonic Endoscopic Resections Among Subspecialized Gastrointestinal Pathologists.

CONTEXT.­: Recent data support that low-risk submucosally invasive (pT1) colonic adenocarcinomas (ie, completely resected tumors that lack high-grade morphology, tumor budding, and lymphovascular invasion) are considered cured via endoscopic resection, provided that the submucosal invasion is less than 1000 µm. Hence, the pathologists' assessment of depth of submucosal invasion may guide further management (ie, surveillance versus colectomy). OBJECTIVE.­: To assess interobserver concordance among gastrointestinal pathologists in measuring submucosal depth of invasion in colonic endoscopic resections. DESIGN.­: Six gastrointestinal pathologists from 5 academic centers independently measured the greatest depth of submucosal invasion in micrometers on 52 hematoxylin-eosin-stained slides from colonic endoscopic specimens with pT1 adenocarcinomas, per published guidelines (round 1 scoring). Two separate measurements (round 2 scoring) were subsequently performed by each pathologist following a consensus meeting, (1) from the surface of the lesion and (2) from the muscularis mucosae, and pathologists were asked to choose their (3) "real-life (best)" assessment between the first 2 measurements. Interobserver agreement was assessed by the intraclass correlation coefficient (ICC) and Cohen κ statistics. RESULTS.­: Round 1 had poor ICC (0.43; 95% CI, 0.31-0.56). Round 2 agreement was good when measuring from the surface (ICC = 0.83; 95% CI, 0.76-0.88) but moderate (ICC = 0.59; 95% CI, 0.47-0.70) when measuring from the muscularis mucosae and became poor (ICC = 0.49; 95% CI, 0.36-0.61) for the best-assessment measurement. CONCLUSIONS.­: Our findings indicate that clearer and reproducible guidelines are needed if clinical colleagues are to base important management decisions on pathologists' estimate of the depth of submucosal invasion in colonic endoscopic resections.

Lifting Agent Granuloma: Histologic Findings Following Use of ORISE Gel for Endoscopic Resections in the Gastrointestinal Tract

OBJECTIVES: Histologic findings after endoscopic resection using submucosal lifting agents Eleview and ORISE gel are described. METHODS: Four cases were identified based on the histologic presence of ORISE gel. Cases were selected to illustrate the histologic appearance of the lifting agent immediately after injection (day 0) and after an interval of approximately 2 months. RESULTS: Immediately after injection, the gel had an appearance similar to acellular mucin on H&E stain and showed mucicarmine positivity but was negative for periodic acid-Schiff stain and Alcian blue. At 2 months, the appearance changed drastically and was characterized by a hard, homogenous eosinophilic quality and elicited a robust foreign body-type giant cell reaction; we have proposed the name lifting agent granuloma for this histologic appearance. The aged material may be mistaken for amyloid or a pulse (legume) granuloma; however, the material was negative on Congo red stain and had a different clinical history and distribution in the tissue from those of a pulse granuloma. CONCLUSIONS: It is important to take note of the histologic appearance of these new submucosal lifting agents over a varying time interval, as outlined here, so that they are readily recognized and not mistaken for other entities.

The Morphologic Features of Primary Epstein-Barr Virus Infection in the Gastrointestinal Tract: An Approach to Correct Diagnosis.

Epstein-Barr virus (EBV) is a herpes virus that has been shown to contribute to the development of multiple tumor types. There are isolated reports on EBV infection in the gastrointestinal tract, but, notably, there are none with detailed descriptions of the morphologic features. It is believed to be difficult to generalize the histologic features, as EBV does not cause viral inclusions in infected cells. This study was aimed at describing the pathologic changes of nonlymphomatous gastrointestinal EBV lymphoproliferative diseases in both immunocompetent and immunocompromised settings; the former was focused on chronic active EBV infection, and the latter was about the infection in posttransplantation patients. A retrospective search identified a total of 26 cases of EBV lymphoproliferative disease in the gastrointestinal tract-8 in immunocompetent patients and 18 in immunocompromised patients. We found that there was no difference in pathologic findings in immunocompetent and immunocompromised patients, which ranged from essentially subtle to severe mucosal architectural distortion with prominent lymphoid aggregates. Most cases showed either focal or diffuse lymphocytic infiltration comprised of small to intermediate-sized lymphocytes with a round shape and increased cytoplasm when compared with mature small lymphocytes. Focal lymphoepithelial lesions and karyorrhexis can be seen. Although gastrointestinal primary EBV lymphoproliferative diseases are not common, the mortality is high. Awareness of the potential histologic features combined with suspicion of EBV infection from clinical presentation, radiographic findings, and/or EBV serologies can aid in the diagnosis of primary EBV infection in the gastrointestinal tract.

Virtual histological staining of unlabelled tissue-autofluorescence images via deep learning.

The histological analysis of tissue samples, widely used for disease diagnosis, involves lengthy and laborious tissue preparation. Here, we show that a convolutional neural network trained using a generative adversarial-network model can transform wide-field autofluorescence images of unlabelled tissue sections into images that are equivalent to the bright-field images of histologically stained versions of the same samples. A blind comparison, by board-certified pathologists, of this virtual staining method and standard histological staining using microscopic images of human tissue sections of the salivary gland, thyroid, kidney, liver and lung, and involving different types of stain, showed no major discordances. The virtual-staining method bypasses the typically labour-intensive and costly histological staining procedures, and could be used as a blueprint for the virtual staining of tissue images acquired with other label-free imaging modalities.