Lam‐Himlin, Dora

Background/Objectives: The growing prevalence of metabolic-associated steatotic liver disease (MASLD)/metabolic-associated steatohepatitis (MASH) is forecasted to be over 55% by 2040, representing a significant driver of cirrhosis and highlighting demand for effective therapeutic interventions. The therapeutic landscape is evolving with agents, like glucagon-like peptide-1 receptor agonists (GLP-1 RAs), under active investigation. A common concern across emerging therapies is potentially precipitating decompensation in patients with existing cirrhosis, necessitating careful consideration in this population. Case Presentation: A 46 y.o. female with obesity and cirrhosis from MASH and alcohol who underwent a deceased-donor liver transplant developed steatohepatitis within a year post-transplant after gaining 36 kg. Transient elastography revealed controlled attenuation parameter (CAP) 400 dB/m (S3 steatosis) and liver stiffness measurement (LSM) 61.2 kPa (advanced fibrosis). Follow-up biopsy confirmed severe steatohepatitis (NAS 7/8) and advanced fibrosis (F3), attributed to metabolic dysfunction without evidence of alcohol recurrence. She decompensated with ascites and varices, leading to transplant re-enlistment at MELD-Na 29. Despite two years of intensive lifestyle modification, losing 17 kg, and recompensation, her follow-up elastography showed persistent steatosis (S3) and advanced fibrosis (F4). Subsequent allograft biopsy revealed progression to cirrhosis (F4) with ongoing steatohepatitis (NAS 3/8). Tirzepatide was initiated for the development of type 2 diabetes, attributed to steroids used for immunosuppression. After 2 years on tirzepatide, she lost 43.1 kg. Shockingly, her follow-up elastography demonstrated fibrosis regression with LSM 5.5 kPa (F1) and steatohepatitis resolution with CAP 204 dB/m (S0). Follow-up liver biopsy confirmed fibrosis regression to F2-F3 and steatohepatitis resolution (NAS 1/8). Conclusions: This case challenges the widely accepted dogma that liver MASH cirrhosis is irreversible. Using multiple liver fibrosis monitoring modalities, cirrhosis reversal was demonstrated and attributed to mechanisms of GLP-1/GIP RA therapy. This study suggests that GLP-1/GIP RA may be safe in cirrhosis and may result in fibrosis regression.

ABSTRACT Granulomatosis with polyangiitis (GPA) is a rare small vessel vasculitis that commonly presents with multiorgan involvement of the upper airways, lungs, and kidneys. We report a 55 year-old-man who presented with painful oral ulcers, diffuse joint pain, epistaxis, and intermittent maroon bowel movements. Infectious evaluation was unremarkable. Rheumatologic evaluation demonstrated elevated c-anti-neutrophil cytoplasmic antibody and proteinase 3 antibodies. Colonoscopy with terminal ileum biopsies demonstrated angiocentric inflammatory findings supportive of a diagnosis of GPA. This case was unusual in its presentation with predominately oral manifestations. A diagnosis of GPA should remain on the differential for patients with gastrointestinal bleeding, and these systemic symptoms require a high level of suspicion to lead to timely diagnosis.

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.

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.