Voltaggio, Lysandra

This review, based on the content of the 2020 US Gastrointestinal Pathology Society’s Rodger Haggitt Lecture, concerns an array of tubular gastrointestinal tract dysplastic or possible “predysplastic lesions” with an almost purely morphologic focus based on our collaborative efforts over the past few years. These processes include esophageal epidermoid metaplasia, Barrett esophagus-associated dysplasia, polypoid gastric dysplastic lesions, small intestinal dysplasia, and the ability of metastases to mimic it, the controversial “serrated epithelial change” encountered in the setting of long-standing ulcerative and Crohn colitis, and recently described anal columnar human papilloma virus-associated neoplasms.

INTRODUCTION: Ablation of Barrett's esophagus (BE) is the preferred approach for the treatment of neoplasia without visible lesions. Limited data on cryoballoon ablation (CBA) suggest its potential clinical utility. We evaluated the safety and efficacy of CBA in a multicenter study of patients with neoplastic BE. METHODS: In a prospective clinical trial, 11 academic and community centers recruited consecutive patients with BE of 1–6 cm length and low-grade dysplasia, high-grade dysplasia (HGD), or intramucosal adenocarcinoma (ImCA) confirmed by central pathology. Patients with symptomatic pre-existing strictures or visible BE lesions had dilation or endoscopic mucosal resection (EMR), respectively, before enrollment. A nitrous oxide cryoballoon focal ablation system was used to treat all visible columnar mucosa in up to 5 sessions. Study end points included complete eradication of all dysplasia (CE-D) and intestinal metaplasia (CE-IM) at 1 year. RESULTS: One hundred twenty patients with BE with ImCA (20%), HGD (56%), or low-grade dysplasia (23%) were enrolled. In the intention-to-treat analysis, the CE-D and CE-IM rates were 76% and 72%, respectively. In the per-protocol analysis (94 patients), the CE-D and CE-IM rates were 97% and 91%, respectively. Postablation pain was mild and short lived. Fifteen subjects (12.5%) developed strictures requiring dilation. One patient (0.8%) with HGD progressed to ImCA, which was successfully treated with EMR. Another patient (0.8%) developed gastrointestinal bleeding associated with clopidogrel use. One patient (0.8%) had buried BE with HGD in 1 biopsy, not confirmed by subsequent EMR. DISCUSSION: In patients with neoplastic BE, CBA was safe and effective. Head-to-head comparisons between CBA and other ablation modalities are warranted (clinicaltrials.gov registration NCT02514525).

Malakoplakia is an inflammatory process related to defective macrophage response to bacterial infection. To further characterize the clinicopathologic manifestations of gastrointestinal malakoplakia, 26 cases were identified from 6 institutions. Hematoxylin and eosin-stained slides and available stains were reviewed, and pertinent clinicopathologic features analyzed. Sixteen patients were women (62%). Mean patient age was 64 (range: 24 to 83). Sites included the colorectum (n=23), appendix (n=1), and stomach (n=2). Clinical indications for tissue procurement included screening (n=14), tumor resection (n=5), diarrhea (n=1), adenoma surveillance (n=1), ulcerative colitis flare (n=1), abdominal pain (n=1), and appendicitis (1). All cases featured histiocytes with abundant, pale, eosinophilic cytoplasm focally containing Michaelis-Gutmann bodies. The process frequently involved the mucosa (n=19), with architectural distortion in 13 cases. Lymphoid aggregates were present in 18 cases, which were prominent or obscuring in 11 (all colon biopsies) and provoked concern for lymphoma in 2. Associated findings included adenocarcinoma (n=5), adenoma (n=2), gastric hyperplastic polyps (n=1), chemical gastritis (n=1), collagenous colitis (n=1), and active chronic colitis (n=2). In cases with available stains, Michaelis-Gutman bodies were highlighted by Periodic Acid-Schiff with diastase, Von Kossa, and iron stains. Although 2 cases were positive for Tropheryma whipplei antibody, no T. whipplei transcripts were detected on real-time polymerase chain reaction. All patients with available follow-up are alive and well with no additional instances of malakoplakia. Malakoplakia of the gastrointestinal tract is a benign, incidental finding. Although histologic features in the stomach and colon resections are similar to those at other sites, exuberant lymphocytic response in colon biopsies and immunoreactivity with T. whippleii antibody may provoke initial confusion and lead to unnecessary time and resource investment.

Selective internal radiation therapy with 90Y-TheraSphere or 90Y-SIRSphere is used in the treatment of unresectable hepatic malignancies. To the best of our knowledge, this is the first 90Y-TheraSpheres series. BTG International Canada Inc. provided nonradiated microspheres from the Nordion manufacturer. The histologic processed microspheres were colorless, refractile, polarizable, 20 to 30 μm in diameter, and an occasional internal bulls’-eye seen with the condenser out and an internal cross seen with polarized light. Identical microspheres were identified in 15 hepatectomy specimens from four centers between February 2016 and March 2018. The patients were usually male (male=10, female=5) with a mean age of 59 years. All patients had a prior diagnosis of hepatocellular carcinoma (HCC) and documented 90Y-TheraSphere (mean duration from last deployment=32 wk). All surgical pathology specimens in these 15 patients were reviewed, but the microspheres were only identified in the hepatectomy specimens. During manuscript preparation, one case of 90Y-TheraSpheres gastritis was prospectively identified from a separate patient with a history of HCC and 90Y-TheraSpheres. In conclusion, recognition of 90Y-TheraSpheres is important so that one may consider the possibility of a nearby malignancy and or establish the cause of the background inflammatory or radiation-related injury. These structures can be easy to miss because the subtle morphology is distinct from previously reported 90Y-SIRSphere. Clues to the diagnosis include a history of HCC and background radiation change. We report the characteristic morphology as microspheres that overlap in size with 90Y-SIRSphere, but can be differentiated based on 90Y-TheraSpheres’ colorless appearance with occasional internal bulls’-eyes with the condenser out and an internal cross with polarized light.

AimsInverted appendices are rare, but have the potential to cause diagnostic confusion among endoscopists and pathologists. The aim of this study was to describe the clinicopathological features of inverted appendices seen at our institution over the last 30 years.Methods and resultsTwenty‐one inverted appendices were identified and the clinical and pathological features reviewed. Patients were predominantly middle‐aged women. Most cases were detected incidentally on colonoscopy. Endoscopically, inverted appendices appeared polypoid in the proximal caecum. All resections featured associated pathological processes, including endometriosis (n = 3), inflammatory mucocoele (n = 1), low‐grade appendiceal mucinous neoplasm (n = 2), traditional serrated adenoma (n = 1) and inflammatory fibroid polyp (n = 1). Five cases were endoscopically mischaracterised as caecal polyps and removed via polypectomy; initial pathological impressions were erroneous in most cases. All polypectomies featured a dome‐like configuration covered by mucosa on the convex surface; the majority had aggregates of ganglion cells and neural plexi embedded in muscularis propria. The vast majority of cases, regardless of the procedure, showed lymphoid aggregates. Among post‐polypectomy patients with follow‐up, none experienced perforation‐associated morbidity despite the histological presence of muscularis propria.ConclusionsThe diagnosis of an inverted appendix should be considered in polypectomy specimens from the caecum or appendiceal orifice with (i) dome‐like tissue configuration covered by mucosa on the convex surface, (ii) a deep, robust smooth muscle component with ganglion cells (muscularis propria) and (iii) associated lymphoid aggregates. Prompt recognition on H&E will avoid unnecessary time and resource investment.

AimsGastric heterotopia (GH) has been described throughout the gastrointestinal tract. However, the colorectal region is an extremely rare location for it. We describe the clinicopathological features of GH of the colon, rectum and anus.Methods and resultsWe identified 33 cases in 20 males and 13 females (median age = 54 years; range = 4 months–73 years). Sites included the rectum (n = 26), anus (n = 4), ileocaecal junction (n = 1), ascending colon (n = 1) and descending colon (n = 1). Presenting symptoms (n = 27) included haematochezia (41%) and altered bowel habits (4%); 15 patients (55%) were asymptomatic. On colonoscopy (n = 31), all appeared as solitary lesions (median size = 6.5 mm, range = 2–55 mm), either as polyps (61%), raised erythematous patches (23%), an ulcer (10%), within a rectal diverticulum (3%) or a haemorrhoid (3%). Patients were managed by polypectomy. One with an associated carcinoma in the area of GH underwent resection. No morbidity related to GH itself was reported following excision. Histologically, heterotopic gastric mucosa was oxyntic (85%), mixed oxyntic and non‐oxyntic (12%) and not specified (3%) types. In five patients a pyloric gland adenoma (PGA) arose from heterotopic gastric mucosa, two of which contained a focus of invasive adenocarcinoma. One case had associated surface foveolar‐type low‐grade dysplasia. Another had associated adenocarcinoma arising from the heterotopic mucosa. One example harboured Helicobacter pylori organisms.ConclusionsWe highlight the features of GH in the distal GIT – the ‘outlet patch’. Association with PGA, surface dysplasia and adenocarcinoma suggests that lower tract GH can undergo neoplastic transformation.

Medication injury in the gastrointestinal tract (GIT) is a rapidly evolving topic. Increasing endoscopy together with an ageing population, polypharmacy, and a burgeoning drug industry offer heightened opportunities to observe the unintended side effects of therapeutic ingestants. In this review, we emphasise the most commonly encountered medication injuries involving the GIT, as well as emerging agents and mimics. While topics are organised by organ system, the reader should keep in mind that injury patterns are generally not site-specific. As such, awareness of these major morphologic patterns can be translated to multiple tissue sites to more broadly facilitate the diagnostic process.