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Objectives The 8th edition American Joint Committee on Cancer (AJCC) staging system for hepatocellular carcinoma (HCC) has been criticized for failing to stratify patients. We aimed to reassess and modify the tumor staging criteria for HCC. Methods Three independent study cohorts were collected and analyzed. Results The initial cohort consists of 103 patients with HCC. By Kaplan-Meier survival analysis, the 8th edition failed to distinguish between T1b and T2. Only tumor size and large vessel invasion, but not small vessel invasion or other histopathologic parameters, predicted HCC survival. We modified the T staging criteria by eliminating small vessel invasion while emphasizing tumor size in the middle categories (T2 and T3), which achieved more even distribution of cases and significantly improved risk stratifications (P Conclusions Our study showed that tumor size, but not small vessel invasion, predicts survival in patients with HCC. We suggest incorporating our modified T staging criteria in future AJCC revisions.

Background Congenital hepatic fibrosis (CHF) is a rare inherited form of ductal plate malformation associated with polycystic kidney disease. The diagnosis requires histopathologic confirmation, but can be challenging to distinguish from other undefined fibrocystic liver diseases. We aimed to describe the clinicopathologic features of congenital hepatic fibrosis (CHF), with comparisons to other entities that may clinically and/or histologically mimic CHF. Methods Nineteen cases that carried a clinical and/or histologic impression of CHF were identified at our institution, of which the histology was reassessed and reappraised into two categories: CHF (n=13) and mimics (n=6). The clinicopathologic features between the two groups were analyzed and compared. Results The CHF group was further sub-classified into those with clinical suspicion (CHF-c, n=8) and those as incidental histology findings (CHF-i, n=5). Patients of CHF-i were much older than CHF-c or mimics (P Conclusions Our study demonstrates classic histology triad of CHF despite a wide spectrum of clinical presentations. HPS is unexpectedly a clinical mimicker of CHF, which can be distinguished histologically.

ObjectivesAutoimmune metaplastic atrophic gastritis (AMAG) is an underrecognized entity, especially in its early stage. This study assessed whether the use of gastrin immunohistochemistry would increase sensitivity for diagnosing early AMAG.MethodsThree-hundred gastric biopsies were prospectively stained for gastrin by immunohistochemistry. Inclusion criteria included well-oriented gastric mucosa with mucus glands and minimal plasma cell infiltrate not suspected to represent pyloric metaplasia. Patient age, sex, designated location of biopsy, presence or absence of intestinal metaplasia, and clinical information were not criteria. Any case with absence of gastrin-positive endocrine cells reflexed to chromogranin immunohistochemistry. Maloriented biopsies or cases with current Helicobacter infection were excluded.ResultsThe 298-patient study cohort comprised 222 females (mean age, 47 years; range, 16-80 years) and 76 males (mean age, 49 years; range, 7-80 years). Biopsies were designated as “antral/antral nodules” (61%), and the rest were labeled “gastric/random stomach” (39%). Nine cases (3%) exhibited absence of gastrin-positive endocrine cells; one of those showed endocrine cell hyperplasia by chromogranin staining.ConclusionsPathologists should be aware of the histologic features of early AMAG and meticulously analyze tissue regardless of specimen labeling. Gastrin immunostain is a supplemental diagnostic tool when encountering inflamed antral-appearing specimens.

Management of anal dysplasia relies upon the accurate diagnosis of anal biopsy specimens. As institutions move towards subspecialty signout (SSSO), decisions must be made regarding whether to assign anal biopsies to the gastrointestinal (GI) or gynaecological (GYN) pathology service.We identified 200 archival tissue biopsies of anal mucosa and circulated them among three GI pathologists and three GYN pathologists. Each pathologist separately scored each biopsy as normal, atypical, low-grade squamous intra-epithelial lesion (LSIL) or high-grade squamous intra-epithelial lesion (HSIL). Every case that was called HSIL by at least one pathologist was stained with p16 immunostain and a 'gold standard' interpretation of whether or not a case represented HSIL was made. The GI pathologists agreed on 97 (49%) cases prior to consensus; the GYN pathologists agreed on 33 (17%). The sensitivities of the three GI pathologists in detecting HSIL against the 'gold standard' were 47, 100 and 21% and for the GYN pathologists the sensitivities were 74, 89 and 84%; the sensitivities of the GI and GYN consensus diagnoses were 74% each. The specificities of the three GI pathologists in detecting HSIL were 99, 90 and 100% and for the GYN pathologists the specificities were 99, 92 and 91%; the specificities of both the GI and GYN consensus diagnoses were 100%.A mild to moderate degree of interobserver variability exists in the diagnosis of anal dysplasia among pathologists. Our study indicates the utility of some form of consensus conference, as overall agreement among GI pathologists and among GYN pathologists improved following in-person consensus.

OBJECTIVES Human epidermal growth factor receptor 2 (HER2) is expressed in some gastric and gastroesophageal junction adenocarcinomas. There were two goals: assess the impact of specimen type on HER2 status and evaluate HER2 concordance with multiple specimens. METHODS All cases were evaluated by immunohistochemistry (IHC) for HER2 and interpreted using established criteria. Fluorescence in situ hybridization (FISH) was performed on a subset. RESULTS Of 460 specimens, 83.9% were IHC negative, 5.4% were equivocal, and 10.7% were IHC positive. Of those with FISH testing, 78.5% were FISH negative, and 21.5% were FISH positive. IHC-FISH concordance for biopsy specimens, resections, and metastases was 82%, 84%, and 86%, respectively. With one vs two vs three or more specimens, the HER2-positive rate increased from 10.5% to 18.1% to 24.1%, respectively. CONCLUSIONS HER2 testing may be performed on biopsy specimens with a relatively high concordance rate with resection specimens, and if multiple samples are analyzed from a single patient, the HER2-positive rate increases over twofold.

Background Histoplasma capsulatum is the most common endemic mycosis in the United States and frequently presents as an opportunistic infection in immunocompromised hosts. Though liver involvement is common in disseminated histoplasmosis, primary gastrointestinal histoplasmosis of the liver in absence of lung involvement is rare. Similarly, cholestatic granulomatous hepatitis in liver histoplasmosis is rarely seen. Case presentation We present a rare case of primary gastrointestinal histoplasmosis manifesting with acute granulomatous hepatitis and cholestasis in a 48-year-old female with psoriatic arthritis, receiving methotrexate and infliximab. The epidemiology, risk factors, clinical presentation, diagnosis, and treatment of histoplasmosis is discussed. Furthermore, we review the published cases of biopsy-proven disseminated histoplasmosis with cholestatic jaundice to highlight histoplasmosis involvement in the liver. Conclusion Histoplasmosis should be considered in immunosuppressed patients with fever, chills, abdominal pain and cholestasis with progressive jaundice, particularly in subjects without evidence of biliary obstruction. Future studies are needed to accurately assess the risk of this fungal infection, specifically in patients on immunomodulatory therapy for autoimmune disease.

Context: Liver cancers (including hepatocellular carcinoma [HCC] and cholangiocarcinoma) are the fifth most common cause of cancer death. The most powerful independent histologic predictor of overall survival after transplantation for HCC is the presence of microscopic vascular invasion (VI). Aims: Given that VI is known to have somewhat high interobserver variability in both HCC and other tumors, we hypothesized that pathologists with special interest and training in liver pathology would be more likely to identify and report VI in HCC than would general surgical pathologists. Settings and Design: We searched our departmental surgical pathology archives for transplant hepatectomies performed for HCC. Subjects and Methods: We identified 143 such cases with available sign-out reports and hematoxylin and eosin-stained slides. Statistical Analysis Used: Kappa results (level of agreement) were calculated. Results: Before surgical pathology subspecialty sign-out (SSSO) implementation, 49 of 88 HCC cases were reported as negative for VI; on rereview, 20 of these had VI. After SSSO implementation, 39 of 55 cases were reported as negative for VI; on our review, 8 of these had VI. Kappa (agreement) between general SO and subspecialty rereview was 0.562 (95% confidence interval [CI] = 0.411–0.714) “weak agreement.” Kappa (agreement) between SSSO and rereview by select liver pathologists was 0.693 (95% CI = 0.505–0.880) “moderate agreement.” Conclusions: Our study is one of only a few so far that have suggested improved accuracy of certain parameters under SSSO.

Microscopic colitis (MC) includes lymphocytic colitis (LC) and collagenous colitis (CC). Microscopic changes are required to establish these diagnoses. While criteria exist, interobserver variability has been reported previously. This has not been evaluated in the context of subspecialty signout (SSSO) or a consensus conference. We identified 133 colon biopsies diagnosed as LC, CC, MC, or normal but with mild changes insufficient for MC. All predated the introduction of SSSO at our institution. They were independently reviewed by three gastrointestinal (GI) pathologists. Cases lacking independent consensus were reviewed by the same pathologists in consensus conference to establish a final diagnosis. Individual diagnoses were compared with the consensus diagnoses, and consensus diagnoses were compared with original diagnoses made by GI and non-GI pathologists. Consensus diagnoses were normal (n = 34), LC (n = 57), and CC (n = 42). “Normal” was the diagnosis most commonly agreed upon independently (27/34 cases, P = 0.0073 versus LC, P = 0.0172 versus CC). The reviewing pathologists independently agreed with 80%, 80%, and 94% of consensus diagnoses (κ = 0.70, 0.69, and 0.91). The group consensus agreed with the diagnoses in 49 of 58 (84%) cases originally signed out by non-GI pathologists (κ = 0.77) and in 44 of 57 (77%) cases originally signed out by GI pathologists (κ = 0.63). Good interobserver agreement exists for MC, though whether GI subspecialty training improves agreement remains unclear. Group consensus may aid in diagnosis of difficult/borderline MC cases.

Objectives Indications for cholecystectomy have changed dramatically over the past three decades. Cystoisospora belli has been reported in cholecystectomy specimens of immunocompetent patients. The present study was designed to determine the prevalence and clinical association of C belli in the gallbladder. Methods The study included retrospective review of cholecystectomy specimens (n = 401) removed for various indications, and a prospective cohort of cholecystectomy specimens (n = 22) entirely submitted for histologic evaluation. Correlations of presence of C belli with age, sex, clinical indication, and abnormalities of preoperative laboratory values were assessed by Fisher exact test. Results C belli was identified in 39/401 (9.7%) of the retrospective cohort, and 6/22 (27.3%) of the entirely submitted specimens. The presence of C belli showed no correlation with age, sex, clinical indication, or laboratory abnormalities. Conclusions C belli resides in a latent state in the gallbladder and may be best considered a commensal organism.

Objectives Biopsies of liver lesions frequently have two goals: confirm malignancy and determine the site of origin. We frequently encounter liver biopsies in patients with pancreatic mass (PM). Given the lack of a specific marker for pancreatic adenocarcinoma, a broad panel of immunohistochemical (IHC) stains is frequently done. In this study, we evaluated the usefulness of IHC staining in the setting of a liver biopsy in the presence of PM. Methods Between 2011 and 2017, 85 cases of liver biopsies or segmental resections with a diagnosis of adenocarcinoma in the presence of PM were retrieved from our archives. Clinical history of other malignancies, any other lesions detected by imaging studies, CA19-9 levels, and reevaluation of the available H&E and IHC slides were performed. Results The patients were divided into four groups: 74.1% with isolated PM on imaging and no previous history of any malignancy, 12.9% with PM on imaging with previous history-proven adenocarcinoma of the pancreas, 7.0% with PM in association with another lesion shown by imaging studies in other organs, and 5 (5.8%) PM on imaging in association with previous history of cancer somewhere else other than pancreas. At least two IHC stains were performed for each case. CK7 was ordered in all the cases and was positive in 100%; CK20 was positive in 35.8%. Interestingly, TTF-1 was positive in only one case, in the absence of discrete lung mass; the patient was treated for pancreatic adenocarcinoma. Conclusion We suggest that in the presence of PM, with liver metastasis of adenocarcinoma morphology on H&E, the metastasis is from the pancreas or upper gastrointestinal primarily and no need for further stains. Although performing IHC is useful sometimes, it should be ordered wisely; this practice will lower costs and result in higher quality care, with more effective use of the lab resources and personnel.

Clinical laboratory testing for human epidermal growth factor receptor-2 (HER2) in patients with newly diagnosed breast and gastric cancer is critically important for therapeutic decisions about adjuvant treatment. The HER2 pathway is a major molecular driver of disease progression in a subset of these solid tumors and the results of HER2 testing determine which patients are likely to respond to an expanding variety of therapies that target this important biologic pathway. Given the significant clinical impact of these test results on patient management and adjuvant treatment decisions, standardization of the assay for HER2 and assured reliability of these results are critical. We review highlights of the clinical rationale that underlies HER2 testing for both breast and gastric carcinomas, and describe some of the challenges associated with ensuring accurate test results.

Eosinophilic esophagitis (EE), initially described in children, is now recognized in adults. The prevalence of EE in adults is largely unknown. Our goals were to determine the prevalence of EE in an adult population undergoing esophagogastroduodenoscopy with biopsy as originally reported and on retrospective review, the rate at which EE was present before this diagnosis was readily appreciated, and whether the prevalence of EE has changed over time. We reviewed esophageal biopsy specimens from 1992 to 2004. If there were more than 15 eosinophils per high-power field and confirmatory clinical information was available, EE was diagnosed. The initial (prereview) prevalence was 1.3%; prevalence on retrospective review was 1.7%. Prevalence was higher in later years (3.8%) compared with early years (0.3%). The demographics of our patients with EE are generally similar to what has been reported. Our results suggest the prevalence of EE is increasing and that pathologists provide accurate diagnoses in the face of changing criteria and significance.

These multimedia modules have been developed to teach senior medical students on their surgical pathology elective the basic microscopic features of common surgical pathology diagnoses. The modules include normal histology and pathology organized into the following organ systems: breast, gastrointestinal, genitourinary, gynecologic, liver, and lung. The first component to this teaching set is a review of normal histology which may serve as a comparison for the histopathology component. A low- and high-power micrograph of each organ is provided. The student is tested with a quiz of micrographs of normal histology where they must identify the organ. Next, students review commonly encountered biopsies in each organ system. Under each diagnosis is listed the definition, etiology, symptoms/indications for biopsy, gross features, microscopic features, and a differential diagnosis. Radiologic features and pertinent additional stains are noted when appropriate. The goal of the surgical pathology rotation at this institution is to allow students to function as junior house officers, actively participating in previewing and sign-out. These teaching modules will provide basic clinical and microscopic descriptions to help the student preview and diagnose biopsy specimens on their own. The clinical implications of certain diagnoses as they pertain to aggressive management in neoplastic disease will also be mentioned. The modules are designed so students can easily navigate between slides, diagnoses, and differentials. Each image is provided with arrows and labels (which may be hidden) to guide the eye of the learner to recognize the patterns of each diagnosis. After completing a module, students will solidify their knowledge with a quiz. We plan to monitor the effectiveness of this assessment by having students take the quiz at the start and end of the rotation to compare the change in their score. These modules will provide an organized foundation on which the student may build his or her knowledge during slide review with senior residents or staff pathologists.

Adenocarcinomas of the esophagus and stomach constitute a substantial number of cancer cases worldwide. Most patients in the United States are diagnosed at an advanced or metastatic stage and, therefore, the prognoses have been poor. New treatments are needed to augment standard surgical and medical management. Recent studies have shown that a subset of esophageal and gastric adenocarcinomas overexpress the HER2 protein, similar to the overexpression seen in breast cancer. Because trastuzumab, a monoclonal antibody to the HER2 receptor, has been used with success in primary and HER2 positive metastatic breast cancers, the phase III ToGA trial was designed to assess the impact of trastuzumab in patients with HER2 positive gastric cancers. They have reported an increase in overall survival time for patients treated with chemotherapy and trastuzumab compared to those treated with chemotherapy alone. They have reported an increase in overall survival time for patients treated with chemotherapy and trastuzumab compared to those treated with chemotherapy alone. This means that accurate HER2 testing in gastric and esophageal carcinomas is necessary. While the breast cancer scoring system can be used to determine HER2 status in most cases, modifications are necessary to accommodate the heterogeneity and incomplete membrane staining that are observed more frequently in gastric cancers. An understanding of the scoring modifications is required for proper stratification of gastric cancer patients for treatment.

The current integrated model of medical student education has the potential to de-emphasize pathology as a crucial discipline. With a move away from traditional lecture-based courses in pathology, an investigation of novel teaching methodologies for pathology education is necessary. To this point we developed a pathology-focused team-based learning (TBL) exercise to supplement clinically based lectures provided by clinicians in the …