Histologic Features of Mycobacterial Spindle Cell Pseudotumors: A Multi-institutional Clinicopathologic Analysis of 14 Cases.

Mycobacterial spindle cell pseudotumors (MSPs) are a rare and diagnostically challenging manifestation of non-tuberculous mycobacterial (NTM) infections. Proper recognition of these pseudotumors is important because they are treatable and benign. In this study, we evaluated the morphologic patterns of MSPs to improve their pathologic identification. Clinical and morphologic features of 14 MSPs were analyzed. Histologic factors evaluated included the architectural growth pattern of spindled or epithelioid macrophages, granulomas and their location within the lesion, neutrophilic microabscesses, multinucleated giant cells, necrosis, and effacement of background tissue. The composition of inflammatory infiltrates, organism density by acid-fast staining, and stromal changes were also assessed. In addition, 8 of 14 cases underwent molecular microbiology identification by a clinical amplicon-sequencing assay for non-tuberculous mycobacteria. MSP sites included 2 bowel, 10 lymph nodes, 1 liver, and 1 extremity. Cases with available clinical history (n=10) all occurred in immunocompromised patients. All demonstrated effacement of normal structures with spindled cells arranged in a storiform or fascicular architectural pattern. In addition, all cases showed lymphocytic inflammation, with prominent concurrent neutrophilic inflammation in 50% (7/14) of cases. Other morphologic findings included foamy histiocytes (64%, 9/14), peripherally situated granulomas (21%, 3/14), and neutrophilic microabscesses (21%, 3/14). All tested cases were positive for NTM by PCR methods. Mycobacterium avium was the most commonly isolated pathogen (6/8). Mycobacterial spindle cell pseudotumors show predominantly spindled morphology that may be mistaken as a neoplasm. Surgical pathologists who evaluate lymph nodes, soft tissue, and gastrointestinal tissues should be aware of this spindled tumefactive phenomenon in the setting of immunocompromised patients. Recognition of key morphologic features of neutrophilic inflammation, peripheral granulomas, or foamy histiocytes within a spindled lesion can help guide the pathologist to a correct diagnosis of an inflammatory process secondary to infection rather than a spindle cell neoplasm. Accurate diagnosis to facilitate appropriate antimicrobial and/or surgical therapy requires a comprehensive evaluation combining clinical, histopathologic, and microbiological findings.

Nonspecificity of Immunohistochemistry for Mycobacteria Species Using a Rabbit Polyclonal Antibody.

CONTEXT.­: Recent publications have featured immunohistochemistry (IHC) as a sensitive tool for detecting Mycobacterium tuberculosis and nontuberculous mycobacteria, but performance is limited to cases suspected to have mycobacterial infection. OBJECTIVE.­: To examine cross-reactivity of a polyclonal antimycobacterial antibody with various types of pathogens, tissues, and inflammatory patterns. DESIGN.­: Surgical pathology files during a period of 6 years were searched, and 40 cases representing a variety of pathogens, tissue types, and inflammatory responses were retrieved. Cases were stained with a rabbit polyclonal antimycobacterial antibody (Biocare Medical, Pacheco, California). The cases and associated histochemical stains, culture, and molecular results were reviewed by 3 pathologists. RESULTS.­: All 8 cases of mycobacterial infection previously diagnosed by other methods were positive for mycobacteria by IHC. In addition, multiple bacterial and fungal organisms and 1 case of Leishmania amastigotes were also immunoreactive with the mycobacterial IHC. CONCLUSIONS.­: Although highly sensitive for mycobacteria, the polyclonal antibody shows significant cross-reactivity with other organisms. This is a sensitive but nonspecific stain that can be used as an alternative confirmation method for mycobacteria, but attention should be paid to inflammatory reaction and organism morphology when IHC is positive to avoid misdiagnosis.

Infectious Disease Pathology of the Gastrointestinal Tract: Diagnosing the Challenging Cases.

Infectious diseases of the GI tract mimic a variety of other GI diseases, including chronic idiopathic inflammatory bowel disease and ischemia. It can be challenging to identify pathogens in tissue sections as well, as many trainees are not exposed to infectious disease pathology other than in the context of microbiology. Our ability to diagnose infections in formalin fixed, paraffin embedded material has grown exponentially with the advent of new histochemical and immunohistochemical stains, as well as more options for molecular testing. Correlating these diagnostic techniques with morphology has led to increasing understanding of the histologic patterns that are associated with specific pathogens.

Crohn's Disease Features in Anastomotic Biopsies from Patients With and Without Crohn's Disease: Diagnostic and Prognostic Value.

Endoscopic evidence of disease activity is a critical predictor of clinical relapse in patients with Crohn's disease (CD), and histologic disease activity is evolving as a similarly important end point for patient management. However, classical morphologic features of CD may overlap with postoperative inflammatory changes, confounding the evaluation of anastomotic biopsies. There is a clear unmet need for better characterization of diagnostic and clinically significant histologic features of CD in these surgically altered sites. We evaluated ileocolonic and colocolonic/rectal anastomotic biopsies performed at 3 academic institutions in patients with and without CD. The biopsies were blindly assessed for CD histologic features and correlated to clinical and endoscopic characteristics. In CD patients, the presence of each feature was correlated with the subsequent clinical exacerbation or relapse. We obtained anastomotic biopsies from 208 patients, of which 109 were operated on for CD and 99 for another indication (neoplasia [80%], diverticular disease (11%), and other [9%]). Mean time since surgery was 10 years (0-59; 14 years for CD [1-59], 6 years for non-CD [0-33]). Endoscopic inflammation was noted in 52% of cases (68% for CD and 35% for non-CD). Microscopic inflammation was present in 74% of cases (82% for CD and 67% for non-CD). Only discontinuous lymphoplasmacytosis (P < .001) and pyloric gland metaplasia (P = .04) occurred significantly more often in CD patients. However, none of the histologic features predicted clinical disease progression. In subset analysis, the presence of histologic features of CD in nonanastomotic biopsies obtained concurrently in CD patients was significantly associated with relapse (P = .03). Due to extensive morphologic overlap between CD and postoperative changes and the lack of specific histologic features of relapse, biopsies from anastomotic sites are of no value in predicting clinical CD progression. Instead, CD activity in biopsies obtained away from anastomotic sites should be used for guiding endoscopic sampling and clinical management.

A Pattern-Based Approach to Hepatic Infections.

The evaluation of liver biopsies for infection can be a challenging and frustrating situation for diagnostic pathologists as well as clinicians. Patients often present with nonspecific symptoms, such as fever and elevated transaminases, leading to a broad differential diagnosis that typically includes malignancy and noninfectious inflammatory diseases in addition to infections. A pattern-based histologic approach can be extremely helpful in both making a diagnosis and guiding the next steps for the evaluation of the pathology specimen as well as the patient. This review discusses several of the more commonly encountered histologic patterns associated with hepatic infectious diseases, the most common pathogens with which they are associated, and helpful ancillary studies.

Gastroblastoma of the Pylorus: A Case Report and Review of the Literature.

Gastroblastoma is an extremely rare biphasic tumor that typically occurs in the stomach in patients between the ages of 10 and 30. Only 16 cases have been reported previously. These tumors are important to diagnose and distinguish from more aggressive neoplasms; although numbers are small, prognosis appears excellent overall with complete excision, with only occasional metastasis and/or local recurrence. We report a case of gastroblastoma in a 26-year-old male arising from the pylorus and extending through the first and second portions of the duodenum. This is the first case to be reported from this specific location.

Histologic Features of Syphilitic Gastritis: A Rare but Resurging Imitator of Common Diseases.

OBJECTIVES: The range of histopathologic features of gastric syphilis is not well described. Here we describe the clinicopathologic findings of eight patients with syphilitic gastritis. METHODS: A search of our Pathology Data System (2003-2022) and multiple other institutions identified eight patients with syphilitic gastritis. Clinical information, pathology reports, and available slides were reviewed. RESULTS: Lesions predominated in middle-aged adults (mean age, 47.2 years; range, 23-61 years) with a propensity for men (n = 7). Three patients had a documented history of human immunodeficiency virus. Clinical presentations included weight loss, abdominal pain, hematochezia, fever, dyspepsia, nausea and vomiting, hematemesis, anemia, and early satiety. Endoscopic findings included ulcerations, erosions, abnormal mucosa, and nodularity. All specimens shared an active chronic gastritis pattern with intense lymphohistiocytic infiltrates, variable plasma cells, and gland loss. Prominent lymphoid aggregates were seen in four specimens. The diagnosis was confirmed either by immunostain for Treponema pallidum (n = 7) or by direct immunofluorescence staining and real-time polymerase chain reaction (n = 1). All patients with available follow-up data showed resolution of symptoms after antibiotic therapy (n = 4). CONCLUSIONS: Recognition of the histologic pattern of syphilitic gastritis facilitates timely treatment, prevents further transmission, and avoids unnecessarily aggressive treatment.

Towards high reliability in national pathology education: Evaluating the United States and Canadian Academy of Pathology educational product.

The United States and Canadian Academy of Pathology (USCAP) leadership undertook a high level, global review of educational product outcomes data using high reliability organization (HRO) principles: preoccupation with failure; reluctance to simplify; sensitivity to operations; commitment to resilience; and deference to expertise. HRO principles have long been applied to fields such as aviation, nuclear power, and more recently to healthcare, yet they are rarely applied to the field that underpins these-and many other-complex systems: education. While errors in education are less calamitous than in air travel or healthcare delivery, USCAP's educational products impact over 15,000 learners a year, and thus have important implications for the future practice of pathology. Here we report USCAP's experiences using HRO principles to evaluate our keystone educational product, the "USCAP Short Course." Following this novel method of data review, USCAP leadership was able to better understand diverse learner needs based on practice venue, training level, and course topic. Unexpected lessons included the identification of specifically challenging educational topics, such as molecular pathology, and a need to focus more resources on emerging fields such as quality and patient safety. The results allow USCAP to assess educational product performance using HRO tools, and provide strong data-driven decision support for future national pathology education strategy.

Gastrointestinal, hepatic, and pancreatobiliary involvement by plasma cell neoplasms: clinicopathologic correlations in a retrospective cohort of 116 cases.

AIMS: Plasma cell neoplasms (PCNs) may involve the gastrointestinal (GI) tract in two forms: plasmacytoma (PC), an isolated lesion that lacks marrow involvement, and extramedullary myeloma (EMM). However, previous literature on PCNs involving the GI tract, liver, and pancreas is limited. We evaluated the clinicopathologic features of the largest series of GI PCNs to date. METHODS AND RESULTS: Six institutional archives were searched for GI, liver, and pancreas cases involved with PCNs. Medical records were reviewed for clinical and imaging features. Histopathologic features evaluated included involved organ, tumor grade, and marrow involvement. Overall, 116 cases from 102 patients were identified. The tumors most presented as incidental findings (29%). The liver was most involved (47%), and masses/polyps (29%) or ulcers (21%) were the most common findings. Most cases had high-grade morphology (55%). The majority (74%) of GI PCNs were classified as EMM due to the presence of marrow involvement at some point during the disease course, occurring within a year of marrow diagnosis in 46% of patients. PC was classified in 26% of patients due to the lack of marrow involvement. Most (70%) patients died from disease within 10 years (median 14.1) of diagnosis and more than half (58%) died within 6 months. CONCLUSION: PC and EMM involving the GI tract, liver, and pancreas have a wide range of clinicopathologic presentations. Tumors may occur virtually anywhere in the GI tract or abdomen and may precede the diagnosis of marrow involvement. Both GI PC and EMM are associated with a poor prognosis.

Pronounced squamous cell contamination in biliary tract cytology: A diagnostic pitfall.

Squamous cells are rarely found in biliary tract cytology specimens, and when present are typically scant in quantity. Over an 8-year time period, two cases at our institution reporting abundant squamous cells were identified. Both patients underwent endoscopic retrograde cholangiopancreatography with bile duct brushings and removal of a migrated biliary stent. The migrated stents were retrieved using rat toothed forceps and required removal of the endoscope through the esophagus with the stent exposed to esophageal and oral mucosa outside of the endoscope. Cytologic examination of the accompanying biliary stent material accordingly revealed abundant benign squamous cells. However, bile duct brushings showed benign ductal epithelial cells without squamous cells. Prior and subsequent cytology and bile duct surgical pathology specimens did not show squamous metaplasia. Migrated biliary stents that require endoscopic withdrawal increase the risk of contaminating samples with squamous cells. Recognition of this unique scenario is important, as the differential diagnosis includes squamous metaplasia and squamous neoplasia.

Histologic and Clinical Correlates of Multiplex Stool Polymerase Chain Reaction Assay Results.

CONTEXT.­: Multiplex stool polymerase chain reaction tests (SPTs) simultaneously test for many enteric pathogens. However, the clinical significance of a positive result, particularly in the context of chronic gastrointestinal disease, remains controversial. OBJECTIVE.­: To determine whether SPT results correlate with findings on colon biopsies obtained within a week of SPT or with clinical features. DESIGN.­: We reviewed 261 colon biopsies during a 15-month period that were obtained within a week of SPT, along with available clinical information, from patients with and without chronic idiopathic inflammatory bowel disease (CIIBD). Statistical analysis was used to test associations between SPT result, histologic features, and clinical variables. RESULTS.­: The most commonly detected pathogens were Clostridium difficile, enteropathogenic Escherichia coli, and norovirus. The presence of underlying CIIBD did not correlate with a positive SPT result or with a specific pathogen. Positive SPT result was significantly associated with neutrophilic activity, pseudomembranes, and increased intraepithelial lymphocytes. In addition, the presence of C difficile on SPT was significantly associated with pseudomembranes and neutrophilic activity. There were no other statistically significant relationships between SPT result and any other histologic abnormality. Only about half of SPT positive results were acted on clinically, and most patients with CIIBD were managed as having a presumed IBD flare. CONCLUSIONS.­: SPTs have many advantages; however, interpretation of results, particularly in the background of chronic gastrointestinal disease, remains a challenge. Therapeutic decisions influenced by a positive SPT result should integrate biopsy findings, clinical data, and other laboratory testing to avoid inappropriate treatment.

Measuring the Submucosal Depth of Invasion in Endoscopic Mucosal Resections for Barrett-associated Adenocarcinoma: Practical Issues and Relevance for the Decision for Esophagectomy.

CONTEXT.­: Endoscopic mucosal resection (EMR) has made it possible for Barrett esophagus patients with superficial cancers to be treated without esophagectomy. Recent guidelines recommend measuring depth of invasion (DOI) in submucosal cancers based on reports that in low-risk cancers, submucosal invasion 500 µm or less is associated with low nodal metastasis rates. However, pathologists face challenges in reproducibly measuring DOI. OBJECTIVE.­: To determine how often DOI measurements could impact treatment and to evaluate reproducibility in measuring submucosal DOI in EMR specimens. DESIGN.­: Consecutive adenocarcinoma EMR cases were identified, including cases of "low histologic risk" submucosal cancer, as follows: those with negative deep margins, no high-grade histology (G3), and no lymphovascular invasion. Submucosal DOI was measured by 7 pathologists according to guidelines. RESULTS.­: Of 213 cancer EMR cases, 46 were submucosa invasive and 6 cases were low histologic risk submucosal cancers for which measurement could impact decision-making. Of these low histologic risk cases, 3 were categorized as superficial, indicating that measurement would be a clinically actionable decision point in only 1.4% of adenocarcinoma EMRs. Interobserver agreement for in-depth categorization between 7 pathologists was moderate (κ = 0.42), and the range of measurements spanned the 500-µm relevant threshold in 40 of 55 measured samples (72.7%). CONCLUSIONS.­: While therapeutic decisions would rarely have depended on DOI measurements alone in our cohort, interobserver variability raises concerns about their use as a sole factor on which to offer patients conservative therapy. Responsibly reporting and clinically using submucosal DOI measurements will require practical experience troubleshooting common histologic artifacts, as well as multidisciplinary awareness of the impact of variable specimen-handling practices.

Adenomatoid tumours of the gastrointestinal tract - a case-series and review of the literature.

AIMS: Adenomatoid tumours are mesothelial-derived benign neoplasms with a predilection for the genital tract. Extragenital sites are rare and can cause significant diagnostic challenges. Herein, we describe the clinicopathological features of a cohort of adenomatoid tumours involving the gastrointestinal tract and liver in order to more clearly characterise their histological findings and aid in diagnosis. METHODS AND RESULTS: The pathology databases at four institutions were searched for adenomatoid tumours involving the gastrointestinal tract or liver, yielding eight cases. Available clinicoradiological and follow-up data were collected from the medical records. Six tumours were incidentally discovered during imaging studies or at the time of surgical exploration for unrelated conditions; presenting symptoms were unknown in two patients. Histologically, the tumours were well-circumscribed, although focal ill-defined borders were present in four cases. No infiltration of adjacent structures was identified. Architectural heterogeneity was noted in five (63%) tumours; an adenoid pattern often predominated. The neoplastic cells were flattened to cuboidal with eosinophilic cytoplasm. Cytoplasmic vacuoles mimicking signet ring-like cells were present in five (63%) cases. Three (38%) cases showed involvement of the mesothelium with reactive mesothelial hyperplasia. Cytological atypia or increased mitotic activity was not identified. The surrounding stroma ranged from oedematous/myxoid to densely hyalinised. Immunohistochemistry confirmed mesothelial origin in all cases evaluated. No patients developed recurrence of disease. CONCLUSIONS: The current study evaluates the clinicopathological findings in a collective series of gastrointestinal and hepatic adenomatoid tumours, correlating with those described in individually reported cases. We highlight common histological features and emphasise variable findings that could mimic a malignant neoplasm.

Intramural Ova of Enterobius vermicularis in the Appendix-An Egg-Topic Location!

We report an unusual case of appendicitis in a 9-year-old girl in whom the wall of the appendix contained necrotizing granulomas, as well as eggs of Enterobius vermicularis. Although luminal E vermicularis adult parasites are commonly identified in the appendix and luminal eggs are occasionally seen, intramural worms and eggs are rare. We are unaware of earlier reports of ectopic intramural eggs in the appendix. It is important to and make a correct diagnosis, as both, the patient, as well as the family should be treated for enterobiasis.

Usefulness of Controlled Attenuation Parameter and Liver Stiffness Measurement for the Identification of Extended-criteria Donors and Risk-assessment in Liver Transplantation.

BACKGROUND: Controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) are noninvasive surrogates for hepatic steatosis and fibrosis, respectively, and could help identify extended criteria donors in liver transplantation (LT). We aimed to determine the accuracy of CAP/LSM in deceased donors along with post-LT changes. METHODS: Accuracy of preprocurement CAP/LSM to grade/stage steatosis/fibrosis was determined using liver biopsy as reference. Transplant outcomes, including primary nonfunction (PNF) and early allograft dysfunction, were recorded. Recipients underwent CAP/LSM as outpatients. Areas under the receiver operating characteristic curve and regression models were constructed to analyze data. RESULTS: We prospectively evaluated 160 allografts (138 transplanted). Same-probe paired baseline/post-LT CAP was 231 dB/m (181-277)/225 (187-261) (P = 0.61), and LSM 7.6 kPa (6.3-10.8)/5.9 (4.6-8.7) (P = 0.002), respectively. CAP reading was affected by BMI and LSM by ALT, race and bilirubin. Although CAP did not correlate with steatosis from frozen sections (ρ = 0.08, P = 0.47), it correlated with steatosis from permanent sections (ρ = 0.32, P < 0.001) and with oil red O histomorphometry (ρ = 0.35, P = 0.001). CAP identified moderate-to-severe steatosis with an areas under the receiver operating characteristic curve curve of 0.79 (0.66-0.91), for a negative predictive value of 100% at a cutoff value of 230 dB/m. LSM correlated with fibrosis staging (ρ = 0.22, P = 0.007) and it identified discarded allografts with advanced fibrosis/cirrhosis. Patients with no to minimal fibrosis had an LSM of 7.6 (6-10.1) kPa. CONCLUSIONS: Our results are proof-of-concept of the utility of CAP/LSM during organ procurement. Establishing the precise role of these noninvasive tools in the organ allocation process mandates confirmatory studies.

Metallothionein immunohistochemistry has high sensitivity and specificity for detection of Wilson disease.

Diagnosis of Wilson disease (WD) can be difficult because of its protean clinical presentations, but early diagnosis is important because effective treatment is available and can prevent disease progression. Similarly, diagnosis of WD on liver biopsy specimens is difficult due to the wide range of histologic appearances. A stain that could help identify WD patients would be of great value. The goal of this study was to use mass spectrometry-based proteomics to identify potential proteins that are differentially expressed in WD compared to controls, and could serve as potential immunohistochemical markers for screening. Several proteins were differentially expressed in WD and immunohistochemical stains for two (metallothionein (MT) and cytochrome C oxidase copper chaperone (COX17)) were tested and compared to other methods of diagnosis in WD including copper staining and quantitative copper assays. We found diffuse metallothionein immunoreactivity in all liver specimens from patients with WD (n = 20); the intensity of the staining was moderate to strong. This staining pattern was distinct from that seen in specimens from the control groups (none of which showed strong, diffuse staining), which included diseases that may be in the clinical or histologic differential of WD (steatohepatitis (n = 51), chronic viral hepatitis (n = 40), autoimmune hepatitis (n = 50), chronic biliary tract disease (n = 42), and normal liver (n = 20)). COX17 immunostain showed no significant difference in expression between the WD and control groups. MT had higher sensitivity than rhodanine for diagnosis of WD. While the quantitative liver copper assays also had high sensitivity, they require more tissue, have a higher cost, longer turnaround time, and are less widely available than an immunohistochemical stain. We conclude that MT IHC is a sensitive immunohistochemical stain for the diagnosis of WD that could be widely deployed as a screening tool for liver biopsies in which WD is in the clinical or histologic differential diagnosis.

Hepatic Secondary Syphilis Can Cause a Variety of Histologic Patterns and May Be Negative for Treponeme Immunohistochemistry.

The rate of syphilis in the United States has been increasing steadily in the past decade, but it remains an uncommon diagnosis in tissue biopsies. Most of the pathology literature on hepatic syphilis consists of older series or case reports. This study aimed to systematically characterize the histologic spectrum of hepatic syphilis in a contemporary cohort. Clinicopathologic features of 14 hepatic syphilis cases between 2012 and 2018 were analyzed to characterize the broad spectrum of histologic changes. Thirteen patients were men (age range: 19 to 59 y); 6 had known human immunodeficiency virus, 7 were men known to have sex with men, and no patient had known prior syphilis. Hepatic syphilis was the primary clinical suspicion in only 1 patient. Common symptoms included jaundice, rash, and abdominal pain. Thirteen had elevated transaminases, and 12 had elevated alkaline phosphatase. Pathologic changes were grouped into 5 histologic patterns: biliary-pattern injury (n=5), acute hepatitis (n=4), autoimmune hepatitis-like (n=1), fibroinflammatory mass-forming lesion (n=2), and no particular pattern (n=2). Nearly all showed portal and lobular lymphocytes and plasma cells; 12 had prominent histiocytes/Kupffer cells, 9 had ductular reaction, and 7 had duct inflammation. Occasional focal findings included dropout (n=7), phlebitis (n=7), and loose granulomata (n=5). Treponeme immunohistochemistry was positive in 10 and negative in 4, though treatment was given before biopsy in 3 of those 4. Thirteen patients had rapid plasma reagin testing either before or after biopsy, with 1:64 or higher titer. All patients who received treatment recovered. Hepatic syphilis is rare but likely underrecognized. It exhibits a variety of histologic appearances and therefore should be considered in several hepatic differential diagnoses, especially in men who have sex with men. Kupffer cells, granulomata, and phlebitis may suggest the diagnosis regardless of predominant histologic pattern. Negative treponeme immunohistochemical staining does not exclude the diagnosis, including in untreated patients.

NCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Colorectal, Version 1.2021.

Identifying individuals with hereditary syndromes allows for timely cancer surveillance, opportunities for risk reduction, and syndrome-specific management. Establishing criteria for hereditary cancer risk assessment allows for the identification of individuals who are carriers of pathogenic genetic variants. The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Colorectal provides recommendations for the assessment and management of patients at risk for or diagnosed with high-risk colorectal cancer syndromes. The NCCN Genetic/Familial High-Risk Assessment: Colorectal panel meets annually to evaluate and update their recommendations based on their clinical expertise and new scientific data. These NCCN Guidelines Insights focus on familial adenomatous polyposis (FAP)/attenuated familial adenomatous polyposis (AFAP) syndrome and considerations for management of duodenal neoplasia.

De Novo Inflammatory Bowel Disease Rarely Occurs During Posttransplant Immunosuppression.

OBJECTIVES: De novo chronic idiopathic inflammatory bowel disease (CIIBD) is reported to occur at higher rates in posttransplant patients than that of the general population. The previous reports, however, included patients with primary sclerosing cholangitis (PSC), a known association with CIIBD. Hence, we investigated how often posttransplant de novo CIIBD occurs in the absence of PSC. METHODS: We identified 185 posttransplant adults without a history of PSC or CIIBD, who had undergone colonoscopy between July 2013 and June 2020. Biopsies were reviewed and clinical data were gathered. RESULTS: CIIBD-like colitis accounted for 1.1% (2/185) of our cohort. The 2 affected patients were already taking multiple immunosuppressive therapies. They were initially placed on standard CIIBD maintenance therapy, but then required escalation therapy. One patient had persistent active colitis despite escalation therapy, while the other subsequently had resolution of symptoms and developed quiescent disease. CONCLUSIONS: The incidence of CIIBD-like colitis in our study population was lower than what has been previously described. Both patients had a poor response to standard CIIBD therapy, raising the question whether their diagnosis is truly de novo CIIBD or another immunologic process.

Diagnostic challenges of focal nodular hyperplasia: interobserver variability, accuracy, and the utility of glutamine synthetase immunohistochemistry.

AIMS: The diagnosis of focal nodular hyperplasia (FNH) and the interpretation of glutamine synthetase (GS) staining can be challenging on biopsies. We aimed to evaluate the reproducibility of needle biopsy diagnosis of FNH, the effect of GS immunohistochemistry on FNH diagnosis, and which histological features are most useful for the diagnosis of FNH. METHODS AND RESULTS: The study included virtual needle biopsies generated from 75 resection specimens (30 FNHs, 15 hepatocellular adenomas, 15 hepatocellular carcinomas, and 15 non-lesional liver specimens). Pathologists were reasonably accurate (83.1%) in the diagnosis of FNH with haematoxylin and eosin alone. Ductular reaction and nodularity had the highest sensitivity for a diagnosis of FNH (88.1% and 82.2%, respectively), whereas central scar was the most specific feature (90.6%). The presence of two or more of the classic histological features had 89.6% sensitivity and 86.2% specificity for a diagnosis of FNH. Diagnostic accuracy was significantly higher with the addition of a GS stain. A map-like GS staining pattern was highly specific (99.3%) for FNH. However, GS staining was interpreted as non-map-like in 14.4% of reviews of true FNH cases, and overall interobserver agreement for interpretation of the GS staining pattern was only moderate (kappa = 0.42). CONCLUSIONS: Pathologists are reasonably accurate in the diagnosis of FNH on virtual biopsies, and GS staining improves accuracy. However, a subset of FNH cases remain challenging. Steatosis and a pseudo-map-like GS staining pattern were associated with increased difficulty. Therefore, although a map-like GS staining pattern is useful for confirmation of a diagnosis, the lack of a map-like GS staining pattern on needle biopsy does not necessarily exclude a diagnosis of FNH.