Virtual biopsies: Proof of concept for a novel quantitative approach to liver biopsy adequacy and pathology education.

OBJECTIVES: To quantitatively measure liver biopsy adequacy requirements and the effect of a teaching intervention that uses a virtual biopsy platform. METHODS: A library of virtual liver biopsies was created using digital whole-slide, trichrome-stained tissue sections from liver resection material and QuPath image analysis software. Blinded participants staged fibrosis on the virtual biopsies before and after a teaching intervention. RESULTS: This platform both modeled adequacy requirements for cirrhosis diagnosis on biopsy material and measured the effect of a teaching intervention on participant performance. Using this platform, diagnostic accuracy for cirrhosis could be modeled according to the function y = λ(1 ‒ e‒x/γ). The platform demonstrated that the relationship between biopsy size and diagnostic accuracy was statistically significant and that biopsies smaller than 6 mm long and 0.8 mm wide were insufficient to diagnosis cirrhosis. The platform also measured improvement in fibrosis staging accuracy among participants following a teaching intervention. CONCLUSIONS: These results provide proof of concept for a virtual biopsy method by which outstanding questions in anatomic pathology can be addressed quantitatively using open source software. Future work is needed to validate these findings in clinical practice.

Characterization of Amyloidosis in the Gastrointestinal Tract With an Emphasis on Histologically Distinct Interstitial Patterns of Deposition and Misinterpretations.

Amyloidosis can involve the gastrointestinal (GI) tract, and deposition can present with varied histologic patterns that make recognition challenging. This retrospective observational study aimed to characterize the deposition patterns in the GI tract and evaluate key quality metrics, including discrepant cases, to improve recognition and provide insight for accurate diagnosis. Sixty-two patients (195 biopsies) with amyloid involvement of the luminal tract were reviewed. Amyloid subtyping by mass spectrophotometry was available for 59 patients. Immunoglobulin light chain (AL) was the most commonly identified subtype (60%), followed by serum amyloid A (AA; 19%) and transthyretin (ATTR; 16%). 150/195 biopsies (77%) were positive for amyloid deposition, with an average of 2.4 positive biopsies per every 3.1 taken per patient. The sites with the highest yield were duodenum (37/37, 100%) and colon (63/74, 85%). Gastric biopsies were most likely to involve the lamina propria (41/45, 91%, P < 0.001), with the background mucosa showing reactive epithelial changes in almost half of the biopsies (20/45, 44%). Several distinct histologic patterns of interstitial deposition were identified, including muscularis mucosae deposition (n = 40, 27% of positive biopsies), peri-Brunner gland (n = 6, 17% of duodenal biopsies), mass-forming (n = 4, 2.7% of positive biopsies, including 3 suspected cases with localized involvement), collagenous colitis-like (n = 3, 4.8% of positive colonic biopsies), and globular (n = 19, 12.7% of positive biopsies). Congo Red was ordered in 81% of cases in which it was requested clinically, with a positivity rate of 30%. Of the 34 cases in which an amyloid workup was requested (but Congo Red was not performed), 14 were positive on reevaluation. Several missed cases had deposition in multiple biopsies, and almost half were missed by subspecialist GI pathologists. Nine misinterpretations were from the stomach, with seven initially diagnosed as chemical or reactive gastropathy. Additional discrepant cases were identified from the duodenum (n = 2) and colon (n = 3), with the vascular-only deposition pattern (n = 3), muscularis mucosae-only deposition (n = 3), and globular pattern (n = 1) identified. Given the challenges of identifying amyloid on hematoxylin and eosin staining, Congo Red ordering percentage should be 100% in clinically suspicious cases unless deposition is definitively seen on hematoxylin and eosin staining.

Combining clinical and molecular characterization of CDH1: a multidisciplinary approach to reclassification of a splicing variant.

Pathogenic germline variants (PGVs) in the CDH1 gene are associated with diffuse gastric and lobular breast cancer syndrome (DGLBC) and can increase the lifetime risk for both diffuse gastric cancer and lobular breast cancer. Given the risk for diffuse gastric cancer among individuals with CDH1 PGVs is up to 30-40%, prophylactic total gastrectomy is often recommended to affected individuals. Therefore, accurate interpretation of CDH1 variants is of the utmost importance for proper clinical decision-making. Herein we present a 45-year-old female, with lobular breast cancer and a father with gastric cancer of unknown pathology at age 48, who was identified to have an intronic variant of uncertain significance in the CDH1 gene, specifically c.833-9 C > G. Although the proband did not meet the International Gastric Cancer Linkage Consortium (IGCLC) criteria for gastric surveillance, she elected to pursue an upper endoscopy where non-targeted gastric biopsies identified a focus of signet ring cell carcinoma (SRCC). The proband then underwent a total gastrectomy, revealing numerous SRCC foci, but no invasive diffuse gastric cancer. Simultaneously, a genetic testing laboratory performed RNA sequencing to further analyze the CDH1 intronic variant, identifying an abnormal transcript from a novel acceptor splice site. The RNA analysis in conjunction with the patient's gastric foci of SRCC and family history was sufficient evidence for reclassification of the variant from uncertain significance to likely pathogenic. In conclusion, we report the first case of the CDH1 c.833-9 C > G intronic variant being associated with DGLBC and illustrate how collaboration among clinicians, laboratory personnel, and patients is crucial for variant resolution.

Niraparib plus nivolumab or niraparib plus ipilimumab in patients with platinum-sensitive advanced pancreatic cancer: a randomised, phase 1b/2 trial.

BACKGROUND: Establishing alternatives to lifelong chemotherapy for patients with advanced pancreatic cancer has been proposed to address chemotherapy resistance and cumulative toxicity. Poly(ADP-ribose) polymerase (PARP) inhibitors have shown efficacy in this setting, and concurrent immune checkpoint blockade could offer synergistic tumour control. The aim of this study was to test the safety and antitumour activity of maintenance with PARP inhibition combined with immune checkpoint blockade in patients with advanced pancreatic cancer who had a stable response to platinum-based chemotherapy. METHODS: We conducted an open-label, randomised, phase 1b/2 study of niraparib plus anti-PD-1 (nivolumab) or anti-CTLA-4 (ipilimumab) therapy for patients with advanced pancreatic cancer whose cancer had not progressed after at least 16 weeks of platinum-based therapy. Patients were randomly assigned (1:1) via permuted block randomisation (block sizes 2 and 4) to niraparib 200 mg orally per day plus either nivolumab 240 mg intravenously every 2 weeks (later changed to 480 mg intravenously every 4 weeks based on manufacturer update) or ipilimumab 3 mg/kg intravenously every 4 weeks for four doses. The primary endpoints were safety and progression-free survival at 6 months. Treatment groups were not compared for activity, which was assessed in each group against a clinically meaningful progression-free survival at 6 months of 44% (null hypothesis). Superiority of a treatment regimen could be declared if 6-month progression-free survival was 60%, and inferiority if 6-month progression-free survival was 27%. All patients who received at least one dose of study treatment and had at least one post-treatment assessment of response according to Response Evaluation Criteria in Solid Tumours version 1.1 were included in the efficacy population. The safety population consisted of all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03404960, and enrolment is completed and follow-up is ongoing. FINDINGS: 91 patients were enrolled between Feb 7, 2018, and Oct 5, 2021 and were randomly assigned to niraparib plus nivolumab (n=46) or niraparib plus ipilimumab (n=45). Of these patients, 84 were evaluable for the progression-free survival endpoint (niraparib plus nivolumab=44; niraparib plus ipilimumab=40). Median follow-up was 23·0 months (IQR 15·0-31·5). 6-month progression-free survival was 20·6% (95% CI 8·3-32·9; p=0·0002 vs the null hypothesis of 44%) in the niraparib plus nivolumab group; and 59·6% (44·3-74·9; p=0·045) in the niraparib plus ipilimumab group. Ten (22%) of 46 patients in the niraparib plus nivolumab group and 23 (50%) of 45 patients in the niraparib plus ipilimumab group had a grade 3 or worse treatment-related adverse event. The most common grade 3 or worse adverse events in the niraparib plus nivolumab group were hypertension (in four [8%] patients), anaemia (two [4%]), and thrombocytopenia (two [4%]) whereas in the niraparib plus ipilimumab group these were fatigue (in six [14%]), anaemia (five [11%]), and hypertension (four [9%]). There were no treatment-related deaths. INTERPRETATION: The primary endpoint of 6-month progression-free survival was met in the niraparib plus ipilimumab maintenance group, whereas niraparib plus nivolumab yielded inferior progression-free survival. These findings highlight the potential for non-cytotoxic maintenance therapies in patients with advanced pancreatic cancer. FUNDING: Bristol Myers Squibb, GlaxoSmithKline, the Basser Center Young Leadership Council, The Konner Foundation, The Pearl and Philip Basser Innovation Research Award, the Anonymous Foundation, and the US National Institutes of Health.

Gastrointestinal Tract Injury by Yttrium-90 Appears Largely Restricted to Resin Microspheres But Can Occur Years After Embolization.

Radioembolization therapy utilizes yttrium-90 (Y90) impregnated resin (SIR-Spheres) or glass (TheraSpheres) microspheres to selectively target hepatic lesions via transarterial radioembolization. Occasional cases of gastrointestinal tract injury, secondary to nontargeted delivery of microspheres, have been reported, but large descriptive pathology series are lacking. We identified 20 cases of histologically confirmed mucosal injury associated with Y90 from 17 patients and assessed the corresponding clinical and pathologic sequelae. The mucosal biopsies were obtained from 1 to 88 months following Y90 therapy (median: 5 mo). Most cases were gastric (17, 85%), while the remaining were duodenal. Endoscopic ulceration was seen in the majority of cases (16, 80%), and mucosal erythema in the remaining 4. Histologically, a majority (19, 95%) of cases showed rounded, dark blue to purple microspheres measuring 4 to 30 µm, consistent with resin microspheres. A single case with glass microspheres demonstrated 26 µm translucent beads. Histologic evidence of ulceration was appreciated in 14 (70%) cases, and the microspheres were clearly intravascular in 6 (30%). A foreign body giant cell reaction to the microspheres was uncommon (3 cases, 15%). We additionally performed a retrospective review of all gastrointestinal tissue obtained postprocedure from 784 sequential patients treated with Y90 microspheres. Three patients (0.4%) demonstrated the presence of resin microspheres upon histologic examination. No cases involving glass-based Y90 were identified ( P =0.0078), despite the majority of patients having received glass radioembolization (630, 80%). This increased risk of secondary sphere dissemination is likely related to the increased number of particles required per activity for resin versus glass microspheres. We conclude that Y90 microspheres may be encountered in the gastrointestinal tract years after initial liver-targeted therapy and, when present, are often associated with mucosal ulceration. This finding is less likely to be encountered in patients who received Y90 radioembolization utilizing glass microspheres.

A contemporary analysis of xanthogranulomatous cholecystitis in a Western cohort.

BACKGROUND: Xanthogranulomatous cholecystitis is a particularly destructive variant of cholecystitis marked by unique inflammatory changes evident in pathologic specimens. Multiple case series have evaluated this process. However, these often focus on differentiating it from malignancy and have largely been conducted in Asia, where the disease may differ from that seen in the Western hemisphere. This study evaluated surgical outcomes after cholecystectomy for xanthogranulomatous cholecystitis at a high-volume tertiary care institution in the United States. The goal was to determine whether the process can be identified preoperatively and whether modifications should be made to the operative approach in this setting. METHODS: Patients with histopathological confirmation of xanthogranulomatous cholecystitis who underwent cholecystectomy between 2002 and 2019 were identified from an updated institutional database. Data regarding demographics, imaging findings, surgical procedures, and perioperative complications were reviewed retrospectively. A cohort of patients undergoing cholecystectomy for more typical diagnoses was also identified for comparison. RESULTS: Twenty-seven patients with a histopathologic diagnosis of xanthogranulomatous cholecystitis were identified. The median age was 64, and 17/27 (63.0%) were male. The majority of cases were done electively on patients admitted that day (17/27). Seventeen patients were evaluated with diagnostic ultrasonography, 21 with computed tomography scan, and 8 with magnetic resonance imaging; 21/27 patients had multiple modality studies. The most common singular finding was gallbladder wall thickening, but the radiographic findings were otherwise inconsistent. Twenty-five patients had planned laparoscopic cholecystectomies, but only 10 were completed. Only 8 of the 15 converted procedures were completed as simple cholecystectomies. Five patients required subtotal cholecystectomy. Median estimated blood loss was 250 cm3, and the median time of procedure was nearly 3 hours. Eight patients had complications, including 6 severe complications such as intraoperative bile duct injury. CONCLUSION: Xanthogranulomatous cholecystitis unfortunately has a nonspecific presentation, which can make it difficult to recognize preoperatively. It is to be suspected in cases featuring a distended, severely inflamed gallbladder that does not match the benign appearance of the patient. When the diagnosis is suspected, an open approach is justified and patients should be counseled as to the increased likelihood of atypical approaches and elevated risk of complication. Referral to a hepatobiliary specialist is to be considered.

Phase II Study of Maintenance Rucaparib in Patients With Platinum-Sensitive Advanced Pancreatic Cancer and a Pathogenic Germline or Somatic Variant in BRCA1, BRCA2, or PALB2.

PURPOSE: Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi), is approved as maintenance therapy for patients with advanced pancreatic cancer (PC) and a germline BRCA1 or BRCA2 pathogenic variant (PV). This investigator-initiated, single-arm phase II study assessed the role of the PARPi rucaparib as maintenance therapy in advanced PC with germline or somatic PV in BRCA1, BRCA2, or PALB2. PATIENTS AND METHODS: Eligible patients had advanced PC; germline (g) or somatic (s) PVs in BRCA1, BRCA2, or PALB2, and received at least 16 weeks of platinum-based chemotherapy without evidence of platinum resistance. Chemotherapy was discontinued and patients received rucaparib 600 mg orally twice a day until progression. The primary end point was the progression-free survival (PFS) rate at 6 months (PFS6). Secondary end points included safety, ORR, disease control rate, duration of response, and overall survival. RESULTS: Of 46 enrolled patients, 42 were evaluable (27 gBRCA2, seven gBRCA1, six gPALB2, and two sBRCA2). PFS6 was 59.5% (95% CI, 44.6 to 74.4), median PFS was 13.1 months (95% CI, 4.4 to 21.8), and median overall survival was 23.5 months (95% CI, 20 to 27). The PFS at 12 months was 54.8%. ORR of the 36 patients with measurable disease was 41.7% (3 complete responses; 12 partial responses; 95% CI, 25.5 to 59.2), and disease control rate was 66.7% (95% CI, 49.0 to 81.4). Median duration of response was 17.3 months (95% CI, 8.8 to 25.8). Responses occurred in patients with gBRCA2 (41%, 11 out of 27), gPALB2 (50%, 3 out of 6), and sBRCA2 (50%, 1 out of 2). No new safety signals were noted. CONCLUSION: Maintenance rucaparib is a safe and effective therapy for platinum-sensitive, advanced PC with a PV in BRCA1, BRCA2, or PALB2. The finding of efficacy in patients with gPALB2 and sBRCA2 PVs expands the population likely to benefit from PARPi beyond gBRCA1/2 PV carriers.

Vasculitis Involving the Gastrointestinal System Is Often Incidental but Critically Important.

OBJECTIVES: This study was aimed to investigate the significance of unexpected vasculitis identified in gastrointestinal (GI) specimens by determining its prevalence and correlation with clinical outcomes. METHODS: GI specimens with histologic evidence of vasculitis were identified in our pathology database over a 10-year period (January 2008 to August 2018). Clinical history, treatment, and follow-up were reviewed. RESULTS: Of the 131,367 GI pathology cases received over the 10-year study period, 29 (0.02%) cases showed histologic evidence of GI vasculitis. The majority (69%, 20/29) were not clinically suspected. Of these, 20% (4/20) of patients were subsequently diagnosed with systemic vasculitis. During the mean follow-up period of 34.0 months, 24% (4/17) of the patients with this unexpected diagnosis died as the result of direct complications of GI vasculitis. We also found that 95% of cases with unexpected vasculitis in their GI pathology specimens were communicated in a timely manner to the ordering physicians, which necessitated the immediate initiation of additional workups in 85% of these patients. CONCLUSIONS: The GI involvement of vasculitis is rarely encountered by pathologists, but its diagnosis carries tremendous clinical significance with a high mortality rate. Therefore, timely communication is highly recommended for the early diagnosis and treatment of this disease.

Predictors, Presentation, and Treatment Outcomes of Recurrent Hepatocellular Carcinoma After Liver Transplantation: A Large Single Center Experience.

BACKGROUND: Liver transplantation (LT) is an accepted therapeutic option for hepatocellular carcinoma (HCC) in patients with cirrhosis. Despite careful candidate selection, HCC recurrence occurs. We aimed to describe the predictors of recurrence, clinical presentation, and predictors of survival after HCC recurrence post-LT. METHODS: Patients with recurrent HCC after LT between January 1996 and December 2017 were retrospectively reviewed. RESULTS: Of 711 patients, 96 (13.5%) patients had post-LT HCC recurrence. The median time to recurrence was 17.1 months, and the median survival was 10.1 months. Initial recurrence was more often in the graft (34.4%), and most (60.4%) had multiple recurrent lesions, and 26% were in multiple sites. In multivariate analysis, factors associated with shorter survival were poorly differentiated histology in explant (Hazard ratio [HR] = 1.96; p = 0.027), bilirubin ≥1.2 mg/dL (HR = 2.47; p = 0.025), and albumin <3.5 mg/dL (HR = 2.13; p = 0.014) at recurrence, alpha-fetoprotein at recurrence ≥ 1000 ng/mL (HR = 2.96; p = 0.005), and peritoneal disease (HR = 3.20; p = 0.022). There was an increased survival in patients exposed to sirolimus (HR = 0.32; p < 0.0001). CONCLUSIONS: Recurrent HCC after LT is often in extrahepatic sites with a decreased survival in those with poorly differentiated explant pathology, high bilirubin, low albumin, marked elevation of alpha-fetoprotein at recurrence, and peritoneal recurrence. Sirolimus-based immunosuppression may provide benefit.

Helicobacter pylori Antigen But Not the Organism Is Occasionally Present Within Germinal Centers: Implications for Patient Management and Biology.

Helicobacter pylori infection is present in two thirds of the world's population and induces a myriad of human diseases, ranging from gastritis to gastric adenocarcinoma and mucosa-associated lymphoid tissue lymphoma. Detection is critical for treatment and may require immunohistochemical (IHC) staining when organisms are not visible on hematoxylin and eosin. We have encountered cases in which IHC for Helicobacter pylori failed to demonstrate curvilinear or coccoid organisms, but did show a reticular pattern of immunoreactivity involving the underlying germinal centers. We performed a systematic retrospective evaluation of the frequency of H. pylori germinal center immunoreactivity over a 54-month period through evaluation of 367 gastric specimens. H. pylori germinal center immunoreactivity was observed in 5% of cases with germinal centers. Nine of 11 (81%) patients with H. pylori germinal center immunoreactivity had concurrent or recent H. pylori infection, in comparison to 36% of patients with germinal centers present but no immunoreactivity (n=9 of 25 patients, P=0.03). None of the patients with germinal center immunoreactivity developed mucosa-associated lymphoid tissue lymphoma. In situ hybridization for H. pylori performed on 3 cases with positive germinal center IHC was negative for H. pylori nucleic acids within those germinal centers, demonstrating that only the antigen is present. This work demonstrates that H. pylori antigen, but not viable organisms, is present in germinal centers in 5% of gastric specimens, and is associated with recent or concurrent H. pylori infection. We advocate for reporting of all H. pylori germinal center immunoreactivity with a recommendation for ancillary H. pylori testing.

Loss-of-function variants in CTNNA1 detected on multigene panel testing in individuals with gastric or breast cancer.

PURPOSE: CTNNA1 is a potential diffuse gastric cancer risk gene, however CTNNA1 testing on multigene panel testing (MGPT) remains unstudied. METHODS: De-identified data from 151,425 individuals who underwent CTNNA1 testing at a commercial laboratory between October 2015 and July 2019 were reviewed. Tissue α-E-catenin immunohistochemistry was performed on CTNNA1 c.1351C>T (p.Arg451*) carriers. RESULTS: Fifty-two individuals (0.03% tested) had CTNNA1 loss-of-function (LOF) variants and 1057 individuals (0.7% tested) had a total of 302 distinct missense variants of uncertain significance. Detailed history was available on 33 CTNNA1 LOF carriers, with 21 unique CTNNA1 LOF variants. Four (12%) individuals had diffuse gastric cancer and 22 (67%) had breast cancer. Six (21%) and 24 (83%) of the 29 families reported a history of gastric or breast cancer, respectively. The CTNNA1 c.1351C>T nonsense variant was identified in three separate families with early-onset diffuse gastric cancer or breast cancer. Immunohistochemistry showed decreased α-E-catenin expression in gastric cancers. CONCLUSION: CTNNA1 LOF variants are detected on MGPT with a majority of these individuals having gastric or breast cancer. The overall risk of gastric cancer for CTNNA1 LOF carriers may be lower than expected. Given the uncertain phenotype and penetrance, management of individuals with CTNNA1 LOF variants remains challenging.

Brown Bowel Syndrome: A Multi-institutional Case Series.

Brown bowel syndrome (BBS) is a rare condition associated with vitamin E deficiency and defined by prominent lipofuscin deposition in the muscularis propria. Eight unique cases of BBS were identified: 5 men and 3 women (mean age=58.6 y). Pertinent comorbidities included bariatric surgery=2, malnourishment=2, Crohn=2, cystic fibrosis=1, alcohol and cocaine abuse=1, and prior small bowel resections=1. Presenting symptoms included abdominal pain=3, bleeding=1, nausea and vomiting=1, and nonresponsiveness=1. Imaging studies were often abnormal: thickened bowel wall=3 (1 with a mass), small bowel obstruction=2, and edematous and dilated bowel wall=2. Most specimens were surgical resections (n=7, autopsy=1): extended right colectomy=2, small bowel only=5 (terminal ileum=3, jejunum=2). Two specimens were grossly described as mahogany, and 1 case contained a perforation. Histologic sections of all cases showed finely granular, brown cytoplasmic pigment in smooth muscle cells on hematoxylin and eosin. This pigment was most conspicuous in the muscularis propria (small bowel>colon), and it was not identified in the mucosa. The pigment was reactive with Fontana-Masson, carbol lipofuscin, Periodic acid-Schiff, and Periodic acid-Schiff with diastase, and electron microscopy was compatible with lipofuscin. The mean clinical follow-up was 208 weeks: 1 patient died of complications of encephalitis, the others were alive and well. BBS is important to recognize because it is linked with malnutrition, specifically vitamin E deficiency, and it can (rarely) clinically simulate malignancy. The diagnosis is based on the identification of the lipofuscin pigment in the cytoplasm of smooth muscle cells, which is most easily seen in the muscularis propria of the small bowel.

"Homomorphic" Tumor Metastases as an Endodiagnostic Clue: A Case Series of Renal-Cell Carcinoma Metastatic to the Stomach.

Distinguishing between a primary malignancy and a metastasis can be challenging in some cases. Herein, we describe 2 cases of gastric lesions that were endoscopically sampled and ultimately found to be metastatic from a renal-cell carcinoma. In both cases, the gastric metastases were endoscopically homomorphic to the primary organ (the kidney); i.e., grossly resembling and thus providing an endoscopic clue as to the primary tumor source. We report on the evaluation of obscure metastatic gastric involvement of malignancy and present the concept of homomorphism as a potential diagnostic clue in determining the source of unknown and often unsuspected primary malignancy.

Pancreatic schwannoma, an extremely rare and challenging entity: Report of two cases and review of literature.

Pancreatic schwannoma is a rare benign tumor, for which the preoperative and intraoperative definitive diagnosis is quite challenging. We present the clinical, radiological and pathologic features of two primary pancreatic schwannomas identified in our pathology database over a period of 30 years at our tertiary care hospital. To better understand the clinico-pathological and radiological features of this entity, we provide a comprehensive review of 73 cases described in the English literature, along with our two cases. This review will especially focus on preoperative and intraoperative diagnosis to assess their accuracy for pancreatic schwannoma. The three most common preoperative diagnoses based on imaging for pancreatic schwannomas were cystic neoplasm (56%), pancreatic neuroendocrine tumor (29%) and mucinous cystic neoplasm (26%). Imaging could not definitely diagnose pancreatic schwannoma in any of the reported cases. To obtain a definite diagnosis before surgery, 25 cases underwent imaging-guided fine-needle aspiration (FNA)/biopsy, of which 60% were correctly reported as benign with definite diagnosis of pancreatic schwannoma in 48%. A higher diagnostic accuracy was observed in biopsies (71%) than FNA (37%). In addition, an intraoperative frozen section was carried out in 15 cases, and 47% were correctly diagnosed. Despite relatively low accuracy, preoperative histological assessment can be helpful in surgical managment. A core tissue specimen is recommended to improve the diagnostic accuracy in this setting.

The incidence of neoplasia in patients with autoimmune metaplastic atrophic gastritis: a renewed call for surveillance.

BACKGROUND: Autoimmune metaplastic atrophic gastritis (AMAG) is an immune-mediated process that may lead to pernicious anemia (PA) and an increased risk of gastric cancer. Although some literature supports 3- or 5-year endoscopic surveillance for gastric cancer in patients with PA, no formal guidance exists for the general AMAG population. We sought to identify the prevalence and incidence rates of dysplasia or adenocarcinoma in patients with AMAG in order to clarify endoscopic best practices. METHODS: A retrospective study of 150 patients diagnosed with AMAG on endoscopic gastric biopsy between 1/2010 and 11/2015 was performed at a tertiary medical center. Clinical and pathologic data were obtained in order to calculate the prevalence and the incidence rate of dysplasia or adenocarcinoma. RESULTS: The cohort was predominantly female (82%) and white (61%), with median age 64 years. PA was present in 47% of patients. On index endoscopy, the prevalence of adenocarcinoma was 5.3%. A total of 59 patients with AMAG, but without neoplasia on initial biopsy, underwent subsequent endoscopic surveillance. Two patients, both of whom had confirmed PA, developed adenocarcinoma. The incidence rate of adenocarcinoma among this group was 14.2 cases per 1000 person-years, which far exceeds that of the general population (0.073 per 1000 person-years) based on Surveillance, Epidemiology, and End Results data. CONCLUSIONS: AMAG is associated with a high prevalence and incidence of gastric cancer, and endoscopic surveillance should be considered. Prospective cohort studies and cost effectiveness analyses are needed to better estimate cancer risk and recommended endoscopic surveillance intervals in these patients.

Low Referral Rate for Genetic Testing in Racially and Ethnically Diverse Patients Despite Universal Colorectal Cancer Screening.

BACKGROUND & AIMS: Guidelines recommend that all colorectal tumors be assessed for mismatch repair deficiency, which could increase identification of patients with Lynch syndrome. This is of particular importance for minority populations, in whom hereditary syndromes are under diagnosed. We compared rates and outcomes of testing all tumor samples (universal testing) collected from a racially and ethnically diverse population for features of Lynch syndrome. METHODS: We performed a retrospective analysis of colorectal tumors tested from 2012 through 2016 at 4 academic centers. Tumor samples were collected from 767 patients with colorectal cancer (52% non-Hispanic white [NHW], 26% African American, and 17% Hispanic patients). We assessed rates of tumor testing, recommendations for genetic evaluation, rates of attending a genetic evaluation, and performance of germline testing overall and by race/ethnicity. We performed univariate and multivariate regression analyses. RESULTS: Overall, 92% of colorectal tumors were analyzed for mismatch repair deficiency without significant differences among races/ethnicities. However, minority patients were significantly less likely to be referred for genetic evaluation (21.2% for NHW patients vs 16.9% for African American patients and 10.9% for Hispanic patients; P = .02). Rates of genetic testing were also lower among minority patients (10.7% for NHW patients vs 6.0% for AA patients and 3.1% for Hispanic patients; P < .01). On multivariate analysis, African American race, older age, and medical center were independently associated with lack of referral for genetic evaluation and genetic testing. CONCLUSION: In a retrospective analysis, we found that despite similar rates of colorectal tumor analysis, minority patients are less likely to be recommended for genetic evaluation or to undergo germline testing for Lynch syndrome. Improvements in institutional practices in follow up after tumor testing could reduce barriers to diagnosis of Lynch diagnosis in minorities.

Combination of Neoadjuvant Transcatheter Arterial Chemoembolization and Orthotopic Liver Transplantation for the Treatment of Cirrhotomimetic Hepatocellular Carcinoma.

PURPOSE: To examine differences in outcome and response of cirrhotomimetic (CMM) hepatocellular carcinoma (HCC) to a combination of bridging transcatheter arterial chemoembolization and orthotopic liver transplantation (OLT) compared with non-CMM HCC. MATERIALS AND METHODS: All patients with pathologically proven CMM HCC who underwent bridging transcatheter arterial chemoembolization before OLT between 2007 and 2013 (n = 23) were retrospectively compared with a control group of patients with pathologically proven non-CMM HCC (n = 46). RESULTS: There were 29 tumors in the CMM HCC group and 64 tumors in the non-CMM group identified and treated. Objective response rate on MR imaging at 1 and 3 months after transcatheter arterial chemoembolization for CMM HCC tumors (including patients with complete and partial response) was 93.1% and 86.4% compared with 85.2% and 93.2% for non-CMM tumors without statistically significant difference (P = .54 and P = .09, respectively). Pathologic study of liver explants showed complete tumor necrosis in 62.3% of non-CMM tumors (38/61) compared with 10.3% of CMM tumors (3/29) (P < .0001). Overall 2-year survival after transcatheter arterial chemoembolization and OLT was significantly lower for patients with CMM HCC compared with patients non-CMM HCC (65.2% vs 87%, P = .03). Patients with CMM HCC with extranodular tumor extension involving > 50% of liver parenchyma had worse survival with mean 2-year survival of 402 days ± 102 vs 656 days ± 39 for the remaining patients with CMM HCC (P = .02). CONCLUSIONS: Despite similar early imaging response rates, CMM HCC tumors had markedly lower rates of complete pathologic necrosis on liver explants and were associated with reduced survival after OLT compared with conventional HCCs.

Erythropoietic protoporphyria in an adult with sequential liver and hematopoietic stem cell transplantation: A case report.

Erythropoietic protoporphyria (EPP) is a rare inherited disorder of the heme biosynthesis pathway resulting in the accumulation of protoporphyrins in the blood, erythrocytes, and other tissues. Because of a gene mutation in the FECH gene, ferrochelatase, the enzyme involved in the final step of heme synthesis, is deficient in these patients. Although the major symptom of this disorder is photosensitivity, rarely, it can cause progressive liver disease requiring liver transplantation (LT). However, LT is not curative and only bone marrow transplantation (BMT) can correct the underlying enzymatic defect. Because liver disease results from accumulation of protoporphyrin in the liver, LT without hematopoietic stem cell transplantation leaves the new liver at risk for similar EPP-related damage. A handful of pediatric patients undergoing sequential LT and stem cell transplantation have been described in the literature; however, to date none has been described in detail in adults. We report a case of an adult male with EPP and liver failure who successfully underwent a sequential liver and hematopoietic stem cell transplantation (HSCT).