Pancreatic medullary carcinoma developed on a pancreatic intraductal papillary mucinous neoplasm with loss of MSH2 and MSH6 expression: a case report

Background Pancreatic medullary carcinoma (PMC) is a rare pancreatic tumor, usually showing the presence of microsatellite instability, mostly MLH1 silencing, and a wild-type KRAS mutation status. We report here a PMC arising from a Pancreatic Intraductal Papillary Mucinous Neoplasm (IPMN), both having KRAS and TP53 mutations. Case presentation We report the case of a 73-year-old woman presenting with right iliac fossa pain. MRI revealed a 16 mm diameter mass in the pancreas, leading to a pancreatic duct stricture and upstream a dilatation of the distal pancreatic duct of Wirsung. A fine needle aspiration was performed, and pathology analysis revealed malignant glandular cells. The patient underwent distal pancreatectomy. Gross examination revealed an12 mm indurated white lesion, adjacent to a cystic lesion extending into the rest of the pancreatic body. Microscopically, the cystic area represented a mixed (gastric-type and pancreatobiliary-type) IPMN, involving the main and secondary pancreatic ducts with low-grade and high-grade dysplasia. In the periphery of this IPMN, a 14mm associated invasive carcinoma was observed, characterized by focal gland formation and by poorly differentiated cells with a syncytial appearance, associated with a dense lymphoplasmocytic and neutrophilic infiltrate. Immunohistochemical analyses showed loss of MSH2 and MSH6 expression. Microsatellite instability was confirmed by molecular test. Molecular analysis was performed both on the invasive carcinoma and on the high-grade dysplasia IPMN, revealing the same mutation profile with KRAS and TP53 mutations. The proposed diagnosis was mixed IPMN with associated invasive medullary carcinoma that presented loss of MSH2 and MSH6 expression. Conclusions The present case reports for the first time, at the best of our knowledge, the coexistence of IPMN lesions and PMC, both having the same molecular alterations. It also describes the second case of PMC with microsatellite instability, MSH2 and MSH6 silenced.

Humoral Predictors of Malignancy in IPMN: A Review of the Literature

Pancreatic cystic lesions are increasingly detected in cross-sectional imaging. Intraductal papillary mucinous neoplasm (IPMN) is a mucin-producing subtype of the pancreatic cyst lesions arising from the pancreatic duct system. IPMN is a potential precursor of pancreatic cancer. The transformation of IPMN in pancreatic cancer is progressive and requires the occurrence of low-grade dysplasia, high-grade dysplasia, and ultimately invasive cancer. Jaundice, enhancing mural nodule >5 mm, main pancreatic duct diameter >10 mm, and positive cytology for high-grade dysplasia are considered high-risk stigmata of malignancy. While increased levels of carbohydrate antigen 19-9 (CA 19-9) (>37 U/mL), main pancreatic duct diameter 5–9.9 mm, cyst diameter >40 mm, enhancing mural nodules <5 mm, IPMN-induced acute pancreatitis, new onset of diabetes, cyst grow-rate >5 mm/year are considered worrisome features of malignancy. However, cross-sectional imaging is often inadequate in the prediction of high-grade dysplasia and invasive cancer. Several studies evaluated the role of humoral and intra-cystic biomarkers in the prediction of malignancy in IPMN. Carcinoembryonic antigen (CEA), CA 19-9, intra-cystic CEA, intra-cystic glucose, and cystic fluid cytology are widely used in clinical practice to distinguish between mucinous and non-mucinous cysts and to predict the presence of invasive cancer. Other biomarkers such as cystic fluid DNA sequencing, microRNA (mi-RNA), circulating microvesicles, and liquid biopsy are the new options for the mini-invasive diagnosis of degenerated IPMN. The aim of this study is to review the literature to assess the role of humoral and intracystic biomarkers in the prediction of advanced IPMN with high-grade dysplasia or invasive carcinoma.

Predictive Factors Involved in Postpartum Regressions of Cytological/Histological Cervical High-Grade Dysplasia Diagnosed during Pregnancy

Objective: The aim of this study was to describe the evolution of high-grade cervical dysplasia during pregnancy and the postpartum period and to determine factors associated with dysplasia regression. Methods: Pregnant patients diagnosed with high-grade lesions were identified in our tertiary hospital center. High-grade lesions were defined either cytologically, by high squamous intraepithelial lesion/atypical squamous cells being unable to exclude HSIL (HSIL/ASC-H), or histologically, with cervical intraepithelial neoplasia (CIN) 2+ (all CIN 2 and CIN 3) during pregnancy. Postpartum regression was defined cytologically or histologically by at least a one-degree reduction in severity from the antepartum diagnosis. A logistic regression model was applied to determine independent predictive factors for high-grade cervical dysplasia regression after delivery. Results: Between January 2000 and October 2017, 79 patients fulfilled the inclusion criteria and were analyzed. High-grade cervical lesions were diagnosed by cytology in 87% of cases (69/79) and confirmed by histology in 45% of those (31/69). The overall regression rate in our cohort was 43% (34/79). Univariate analysis revealed that parity (p = 0.04), diabetes (p = 0.04) and third trimester cytology (p = 0.009) were associated with dysplasia regression. Nulliparity (OR = 4.35; 95%CI = (1.03–18.42); p= 0.046) was identified by multivariate analysis as an independent predictive factor of high-grade dysplasia regression. The presence of HSIL on third-trimester cervical cytology (OR = 0.17; 95%CI = (0.04–0.72); p = 0.016) was identified as an independent predictive factor of high-grade dysplasia persistence at postpartum. Conclusion: Our regression rate was high, at 43%, for high-grade cervical lesions postpartum. Parity status may have an impact on dysplasia regression during pregnancy. A cervical cytology should be performed at the third trimester to identify patients at risk of CIN persistence after delivery. However, larger cohorts are required to confirm these results.

Effect of diminutive adenoma with high-grade dysplasia on surveillance colonoscopy interval

Background Colonoscopy surveillance guidelines set the surveillance schedule based on polyp characteristics. Polyps with high-grade dysplasia (HGD) require 3 years of follow-up regardless of size. However, it is unclear whether patients with diminutive polyps (≤5 mm) with HGD have a higher risk. We evaluated the effect of diminutive adenoma with HGD on adenoma occurrence. Methods From Jan 2015 to Dec 2017, patients who underwent index and surveillance colonoscopy were retrospectively screened. The patients were grouped into no adenoma group, low-risk (patients with ≤2 low-grade dysplasia (LGD)), diminutive HGD and high-risk (HGD >5 mm, ≥3 adenomas) groups according to the index colonoscopy results. Each group was analyzed using logistic analysis. Results The mean follow-up period was 22.47 months. Altogether, 610 (50.45%) patients had LGD and 152 (12.5%) had HGD. Among them, 61(5.0%) patients had a diminutive polyp with HGD. Analysis of the risks of developing advanced adenoma in the surveillance colonoscopy showed that compared to no adenoma group, the diminutive HGD group did not show a significant risk (odds ratio [OR]=1.503 [0.449–5.027], p=0.509), while the high-risk group showed a significant risk (odds ratio [OR]=2.044 [1.015–4.114], p=0.045). Conclusions Diminutive adenoma with HGD increased the risk of adenoma on surveillance colonoscopy, In the case of advanced adenoma, the risk was increased, but it was not statistically significant.

A Promising Diagnostic Role of Immunohistochemical Expression of Insulin-Like Growth Factor II mRNA Binding Protein3 (IMP3) in Pancreatic Lesions Using Endoscopic Ultrasound –Guided –Fine Needle Aspiration (EUS-FNA) Cytology

Background: Poor prognosis and short survival of patients harboring pancreatic cancer emerge how advanced disease it is. In a trial to achieve the earliest and most accurate diagnosis to manage this progressive disease, we proposed that using endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) with an adjuvant diagnostic immunohistochemical marker would give better diagnostic results. IMP3 has gained recently wide attention, as many studies found that IMP3 has not only diagnostic but also prognostic role in different types of malignancies. Aim of the study: this prospective work is to assess the diagnostic role of EUS-FNA combined with the immunohistochemical expression of IMP3 on different benign and malignant pancreatic lesions. Material and Method: the included pancreatic lesions (n=140) were obtained by EUS-FNA technique and stained for IMP3 immunohistochemically. Paraffin blocks from patients who underwent excision (n=92) or core biopsies (n=48) were performed for confirming diagnosis. Results: the combined method for diagnosis showed that IMP3 was positive in 78.7%, 91.7%, 100% PAC, Mucinous neoplasm with high grade dysplasia, IPMN with high grade dysplasia, respectively, while almost all benign lesions showed negative IMP3. Also, this method showed sensitivity (78.26%), specificity (95.83%), and accuracy (84.3%). Conclusion: EUS-FNA cytology with IMP3 could be a reliable diagnostic tool especially for assessment of malignant pancreatic lesions.