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Item Human papillomavirus-related cancer risk for solid organ transplant recipients during adult life and early prevention strategies during childhood and adolescence(Wiley, 2022-11) Nailescu, Corina; Ermel, Aaron C.; Shew, Marcia L.; Pediatrics, School of MedicineMalignancies are among the top three causes of patient death in pediatric and adult kidney transplant (KT) recipients. Solid organ transplant (SOT) recipients, including KT individuals, experience more cancer compared with the general population, including human papillomavirus (HPV)-related anogenital and oropharyngeal cancers. This article describes the epidemiology, pathophysiology and natural history of the HPV infection in both the general population and in SOT recipients, as well as its role in the development of HPV-related pre-cancerous lesions and cancers. Emphasis is given to the primary prevention strategy, HPV vaccination in SOT recipients, and its particularities compared with the general population. Secondary prevention strategies in SOT recipients are discussed and compared with the general population, highlighting cervical cancer screening needs within SOT populations. The article emphasizes how these primary and secondary HPV prevention strategies applied during childhood and adolescence by the pediatric transplant professionals, can lower the burden of HPV-related cancers for SOT recipients in subsequent years, during their adult life.Item Integrated molecular pathology accurately determines the malignant potential of pancreatic cysts(Thieme, 2015-02) Al-Haddad, Mohammad A.; Kowalski, Thomas; Siddiqui, Ali; Mertz, Howard R.; Mallat, Damien; Haddad, Nadim; Malhotra, Nidhi; Sadowski, Brett; Lybik, Mark J.; Patel, Sandeep N.; Okoh, Emuejevoke; Rosenkranz, Laura; Karasik, Michael; Golioto, Michael; Linder, Jeffrey; Catalano, Marc F.; Department of Medicine, IU School of MedicineBackground and study aims: Current diagnostic testing is inadequate to determine the malignant potential of pancreatic cysts, resulting in overcautious patient management. Integrated molecular pathology (IMP) testing combines molecular analysis with first-line test results (cytology, imaging, and fluid chemistry) to assess the malignant potential of pancreatic cysts. This multicenter study aimed to determine the diagnostic accuracy of IMP for pancreatic adenocarcinoma, and the utility of IMP testing under current guideline recommendations for managing pancreatic cysts. Patients and methods: Patients who had undergone previous IMP testing as prescribed by their physician and for whom clinical outcomes were available from retrospective record review were included (n = 492). Performance was determined by correlation between clinical outcome and previous IMP diagnosis (“benign”/“statistically indolent” vs. “statistically higher risk [SHR]”/ “aggressive”) or an International Consensus Guideline (Sendai 2012) criteria model for “surveillance” vs. “surgery.” The Cox proportional hazards model determined hazard ratios for malignancy. Results: Benign and statistically indolent IMP diagnoses had a 97 % probability of benign follow-up for up to 7 years and 8 months from initial IMP testing. SHR and aggressive diagnoses had relative hazard ratios for malignancy of 30.8 and 76.3, respectively (both P < 0.0001). Sendai surveillance criteria had a 97 % probability of benign follow-up for up to 7 years and 8 months, but for surgical criteria the hazard ratio was only 9.0 (P < 0.0001). In patients who met Sendai surgical criteria, benign and statistically indolent IMP diagnoses had a > 93 % probability of benign follow-up, with relative hazard ratios for SHR and aggressive IMP diagnoses of 16.1 and 50.2, respectively (both P < 0.0001). Conclusion: IMP more accurately determined the malignant potential of pancreatic cysts than a Sendai 2012 guideline management criteria model. IMP may improve patient management by justifying more relaxed observation in patients meeting Sendai surveillance criteria. IMP can more accurately differentiate between the need for surveillance or surgery in patients meeting Sendai surgical criteria.Item Is it time to extend synoptic reporting to include potentially preneoplastic oral epithelial and lichenoid lesions?(Elsevier, 2017-08) Edwards, Paul C.; Department of Oral Pathology, Medicine and Radiology, School of DentistryItem Mucinous intrahepatic cholangiocarcinoma: a distinct variant(Elsevier, 2018) Chi, Zhikai; Bhalla, Amarpreet; Saeed, Omer; Cheng, Liang; Curless, Kendra; Wang, Hanlin L.; Patil, Deepa T.; Lin, Jingmei; Pathology and Laboratory Medicine, School of MedicineMucinous variant of intrahepatic cholangiocarcinoma (iCC) is rare, and its clinicopathological features and prognosis are far less clear. Six patients who had iCCs with more than 50% of mucinous component and 79 conventional iCCs were included in the study. The mean size of mucinous and conventional iCCs was 6.2 cm and 6.0 cm, respectively. The majority of patients (83%) with mucinous iCC presented at T3 stage or above, compared to 28% of the conventional group (p < 0.01). Three patients with mucinous iCC (50%) died within 1 year. The average survival time of patients with mucinous iCCs was significantly reduced compared to that of conventional group (9 months vs 2 years; P < .001). Immunohistochemistry was performed on 6 mucinous and 12 conventional iCCs with matched age, sex and stage, which revealed positive immunoreactivity in MUC1 (83% vs 58%), MUC2 (33% vs 17%), MUC5AC (100% vs 42%), MUC6 (50% vs 0), CK7 (83% vs 83%), CK20 (0 vs 17%), and CDX2 (17% vs 0) in mucinous and conventional iCCs, respectively. Molecular studies showed one mucinous iCC with KRAS G12C mutation and no BRAF or IDH1/2 mutations. Mucinous iCC is a unique variant that constitutes 7.2% of iCCs. It is more immunoreactive for MUC1, MUC2, MUC5AC and MUC6. Unlike adenocarcinomas of colorectal primary, mucinous iCCs are often CK7+/CK20-/CDX2- and microsatellite stable. Patients with mucinous iCC likely present at advanced stage upon diagnosis with shorter survival time compared to the conventional counterparts.