Context.— Immunomarkers with diagnostic, therapeutic, or prognostic values have been increasingly used to maximize the benefits of clinical management of patients with neoplastic diseases of the gastrointestinal tract, liver, biliary tract, and pancreas. Objectives.— To review the characteristics of immunomarkers that are commonly used in surgical pathology practice for neoplasms of the gastrointestinal tract, liver, biliary tract, and pancreas, and to summarize the clinical usefulness of immunomarkers that have been discovered in recent years in these fields. Data Sources.— Data sources include literature review, authors' research data, and personal practice experience. Conclusions.— Immunohistochemistry is an indispensable tool for the accurate diagnosis of neoplastic diseases of the gastrointestinal tract, liver, biliary tract, and pancreas. Useful immunomarkers are available to help distinguish malignant neoplasms from benign conditions, determine organ origins, and subclassify neoplasms that are morphologically and biologically heterogeneous. Specific immunomarkers are also available to help guide patient treatment and assess disease aggressiveness, which are keys to the success of personalized medicine. Pathologists will continue to play a critical role in the discovery, validation, and application of new biomarkers, which will ultimately improve patient care.

- Unusual clinicopathologic features observed in colorectal carcinomas with isolated PMS2 loss are likely related to the high proportion of cases caused by germline mutations. Isolated PMS2-loss tumors may demonstrate more aggressive behavior than other tumors with microsatellite instability, but larger studies are needed to investigate that possibility further.

BackgroundWarthin tumors presenting concomitantly with a lymphoma is vanishingly rare with only 15 reported cases in English literature. Herein, we report an unusual initial presentation of a mantle cell lymphoma involving the lymphoid stroma of a Warthin tumor.Case presentationA seventy-seven year old otherwise healthy gentleman with a 50-pack year smoking history presents with a slowly enlarging left cheek mass. CT scan of the neck demonstrated a left parotid gland tumor measuring 3.4 cm in greatest dimension. He underwent a left superficial parotidectomy, with subsequent histopathologic examination revealing a Warthin tumor with extensive expansion of the lymphoid stroma. Flow cytometric, immunohistochemical, and cytogenetic studies of the stromal component of the tumor confirmed the presence of a mantle cell lymphoma. Clinical staging demonstrated stage IVa disease, and was considered to be at low to intermediate risk due to the slow growth of the parotid lesion. The patient is undergoing close follow up with repeat PET-CT scans at six months.ConclusionTo the best of our knowledge, this is the first well documented collision tumor between mantle cell lymphoma and a Warthin tumor. This case also brings to light the significance of thorough evaluation of the lymphoid component of Warthin tumor.

Malignant mesotheliomas are rather uncommon neoplasms associated primarily with asbestos exposure; however, they may also arise as second primary malignancies after radiation therapy, with a latency period of 15–25 years. Numerous studies have reported an association between pleural malignant mesothelioma and chest radiation performed for other malignancies; on the other hand, post-irradiation mesotheliomas of the pericardium have been reported in only a few published cases to date, and no homozygous deletion of 9p21 has been described in such cases. We report the case of a 48-year-old man with a history of Hodgkin's lymphoma and no prior asbestos exposure who developed pericardial malignant epithelioid mesothelioma. We further discuss the cytologic, histologic, immunophenotypic, and fluorescence in situ hybridization findings in this case. To our knowledge, this is the first well-documented case of post-radiation pericardial malignant mesothelioma showing homozygous deletion of 9p21. Homozygous deletion of 9p21, the locus harboring the p16 gene, is present in post-irradiation pericardial malignant mesothelioma.

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Recent publications have described epithelial cytoplasmic vacuoles and inclusions incidentally noted within gallbladder epithelium and concluded that they represent coccidian parasite infection, in particular, Cystoisospora belli. We identified 8 gallbladder specimens from our institution in the past 3 years in which this diagnosis was suggested or in which similar epithelial alterations were prominent. Molecular analysis was performed on the 8 gallbladder specimens and on 3 positive control specimens: small bowel biopsies from acquired immunodeficiency syndrome patients with diarrhea. Polymerase chain reaction using primers designed to amplify an internal transcribed spacer (ITS2) in the C. belli ribosomal gene cluster was performed on the DNA samples. All 8 gallbladder specimens were negative for amplification, while a product consistent with C. belli was amplified from all 3 positive controls. Histologically, the gallbladder cytoplasmic inclusions stained diffusely positive for Grocott-Gomori's methenamine silver and Periodic acid-Schiff with diastase. In contrast, sections from a positive control small bowel biopsy demonstrated organisms that were negative for Grocott-Gomori's methenamine silver and showed a distinct capsular and punctate internal staining on Periodic acid-Schiff with diastase in various parasite forms. Together, the lack of molecular evidence of C. belli and the distinct morphologic and special staining patterns in these gallbladders compared with positive control small bowel suggest that these epithelial changes do not represent true C. belli infection. Our results suggest that gallbladders of immunocompetent patients may occasionally show epithelial changes that can morphologically mimic C. belli infection. Pathologists should be aware of this histologic variant to minimize unnecessary treatment, testing, and patient anxiety.

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8529 Background: Programmed death ligand 1 (PD-L1) expression is the standard biomarker for PD-L1 inhibitors in advanced non-small cell lung cancer (NSCLC). However, evaluation of PD-L1 tumor proportion score (TPS) by pathologists causes inter-observer variation and demands time to interpret. This study aimed to evaluate the benefit of the artificial intelligence (AI) algorithm in assisting pathologists to determine TPS on PD-L1 immunohistochemistry (IHC) whole-slide images (WSIs) in NSCLC. Methods: Lunit SCOPE PD-L1, an AI-powered PD-L1 TPS analyzer, was developed from 393,565 tumor cells annotated by board-certified pathologists for PD-L1 expression in 802 WSIs stained by 22C3 pharmDx IHC. The AI model was developed based on a region-based convolutional neural network, and the model can detect and count PD-L1 positive or negative tumor cells from WSIs to calculate TPS. Seven independent board-certified pathologists scored ground truth (GT) of PD-L1 TPS from 199 WSI of NSCLC stained by 22C3 pharmDx IHC. TPS from each GT reader was grouped as negative (< 1%), low (1% to 49%), or high (≥ 50%). The GT of each slide was determined by the consensus of GT readers. Another twelve independent board-certified pathologists scored PD-L1 TPS from the same WSIs as observer performance testers (OPT). They scored TPS twice with a washout interval of 4 weeks, with or without AI assistance. TPS accuracy change and reading time of OPT reader according to the presence or absence of AI assistance were analyzed. Results: The standalone accuracy of the AI model was 0.809 (95% CI: 0.690–0.941). With AI assistance, the overall accuracy of TPS had been changed from 0.799 (95% confidence interval [CI]: 0.764–0.836) to 0.832 (95% CI: 0.796–0.869) (P = 0.004). AI assistance increased the accuracy rate in 11 out of 12 OPT readers. The result of the generalized linear mixed model revealed that AI assistance and specimen type affected the probability of correct answer, while the order of reading did not (Table). The mean time to read with AI was 195.4±506.5 (mean±standard deviation) seconds, which was significantly shorter than the mean time to read without AI (285.1±1578.4, P <0.001). Conclusions: This study demonstrates that an AI-powered PD-L1 TPS analyzer can assist board-certified pathologists in evaluating TPS of NSCLC by improving the accuracy of TPS group evaluation and reducing the time to read slides.[Table: see text]