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The intraductal oncocytic papillary neoplasm (IOPN) of the pancreas has been recognized by WHO classification as a unique intraductal papillary mucinous neoplasm (IPMN) category. IOPN is composed of oxyphil cells, usually expressing MUC5AC, MUC6, and Hep Par-1, and harboring PRKACA/B fusion genes as their genetic hallmark. Although IOPNs are associated with an infiltrative adenocarcinoma in up to 30% of cases, the survival rate after surgical resection approaches 100%. This highlights the importance of the correct IOPN diagnosis, above all in cases with an associated invasive component. In this study, the immunohistochemical expression of CD117 was investigated in 111 IPMNs, including 17 oncocytic, 45 gastric, 20 pancreatico-biliary, and 29 intestinal IPMNs. We also tested the expression of MUC5AC, MUC6, and Hep Par-1 in the IOPN cohort. CD117 positivity was significantly more frequent in IOPNs compared to the other IPMN subtypes (p &lt, 0.0001). Furthermore, within IOPN, a lower or absent CD117, MUC5AC, MUC6, and Hep Par-1 expression tended to be associated with the presence of an infiltrative component. Our findings shed light into the biology of these complex lesions, which are confirmed to be a distinctive IPMN subtype, notably, CD117 emerged as a potential, additional tool in the differential diagnosis of IPMNs.

CD200 has been recently indicated as a robust marker of well-differentiated neuroendocrine neoplasms. Here, we evaluate its role in differential diagnosis of solid pancreatic neoplasms. We immunostained for CD200 22 solid pseudopapillary neoplasms (SPNs), 8 acinar carcinomas (ACs), 2 pancreatoblastomas (PBs), 138 neuroendocrine tumors (PanNETs), and 48 ductal adenocarcinomas. All SPNs showed strong cytoplasmic and membranous staining for CD200, while only one case of AC had focal positivity. The two PBs showed focal CD200 positivity, mainly located in squamoid nests. The vast majority of PanNETs (96%) showed strong cytoplasmic and membranous staining for CD200, whereas all PDACs were negative. As both PanNETs and SPNs express CD200, it has no role in the differential diagnosis between these two entities.

We investigated the usefulness of interphase fluorescence in situ hybridization (FISH) analysis to differentiate between 11 chromophobe renal carcinomas and 12 renal oncocytomas, showing different clinical outcomes, when compared with conventional metaphase cytogenetics by karyotyping. Karyotypically, 3 chromophobe renal cell carcinomas showed losses of chromosomes, 3 were polyploid, 1 was normal, and 4 failed to grow. Of 12 oncocytomas, 5 showed a normal numeric karyotype and 6 additional structural rearrangements. FISH on chromophobe renal cell carcinomas showed a high percentage of cases (10/11 [91%]) with multiple numeric losses among chromosomes 1, 2, 6, 10, and 17; this interphase pattern was observed irrespective of the 3 different metaphase karyotypes. Of 12 oncocytomas, 11 (92%) revealed a normal numeric chromosomal status showing at least 2 chromosomes without aneusomy by interphase FISH. The study demonstrates that indeed FISH performed on formalin-fixed, paraffin-embedded tissue can provide clinically useful information more reliably than karyotyping of most of these tumors.

Introduction The epithelial to mesenchymal transition, a well-known and re-emerging model in pathology, has not been completely investigated in the field of gestational pathology. This study aims at improving the comprehension of this process in molar disease, even looking for new possible immunohistochemical markers. Materials and methods We have analysed the immunohistochemical expression of Twist1 and Snai2, two of the most important transcription factors involved in epithelial to mesenchymal transition, in formalin-fixed paraffin-embedded samples of 23 spontaneous abortive pregnancies, 22 molar pregnancies (10 partial and 12 complete) and 7 term placentas. Results Twist1 and Snai2 were highly expressed in stromal villi cells of molar disease. Particularly, Twist1 was highly expressed in complete moles compared to both abortive pregnancies (p < 0.001) and partial moles (p < 0.05). Also Snai2 was more expressed by complete moles, differentiating them from non-molar abortions (p < 0.05). Discussion On the basis of the known cadherins and claudins expression in these pathologies, our new findings reinforce the hypothesis of the involvement of epithelial to mesenchymal transition in early molar pregnancies and above all in complete moles. Furthermore, we highlighted that in molar disease not only the trophoblast, but even the villi stromal cells, are involved. Thanks to their specificity, furthermore, these Twist1 and Snai2 could be used as additional immunohistochemical tool in the diagnosis of complete molar disease, with Twist1 as the first choice. © 2015 Elsevier Ltd. All rights reserved.

Transferrin receptor/CD71 is a membrane protein expressed on nucleated red blood cells (NRBCs) and trophoblasts. Here, we propose the first study to evaluate the usefulness of CD71 immunolabeling in the main fields of gestational pathology. To this aim, formalin-fixed, paraffin-embedded samples of 45 orthotopic (23 spontaneous abortive and 22 molar pregnancies) and 11 ectopic pregnancies were immunostained for CD71. NRBCs were morphologically evident in 23 cases: 12/23 abortive, 4/11 ectopic, and 7/10 partial molar pregnancies. CD71 immunolabeling detected NRBCs in all 23 previous cases and in 8 new cases: 2 partial moles and 6 spontaneous abortive pregnancies. No NRBCs were detected in complete moles by means of either morphology or immunohistochemistry (IHC). In 4 cases with extensive necrotic changes, CD71 marked NRBCs and a few ghost villi, which were not certainly identifiable with standard histological evaluation. Furthermore, there was an inversely proportional relationship between total percentage of CD71-positive NRBCs and gestational age (R=0.69; P

Purpose: There is evidence that Hodgkin Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL) could display some molecular and morphologic markers of cellular senescence (CS). We hypothesized that CS mechanisms may have potential prognostic relevance in cHL and investigated whether the expression of the well-established CS biomarkers p21CIP1/WAF1 and p16INK4a by HRS cells might be predictive of the probability of event-free survival (EFS). Experimental Design: The study analyzed a retrospective cohort of 147 patients and the results were validated on a cohort of 91 patients independently diagnosed and treated in a different institution. p16INK4a and p21CIP1/WAF1 were categorized as dichotomous variables (< or ≥ 30% of HRS cells at diagnosis) and evaluated in univariate and multivariate analysis. Results: Both molecules were independent prognostic factors. A positive staining of one of the two molecules in more than 30% HRS cells predicted a better EFS (P < 0.01). p16INK4a/p21CIP1/WAF1 together as a unique categorical variable (both Conclusions: These findings point to (i) the relevance of CS-related mechanisms in cHL, and to (ii) the prognostic value of a simple, reproducible, and low-cost immunohistochemical evaluation of p16INK4a and p21CIP1/WAF1 expression. Clin Cancer Res; 21(22); 5164–72. ©2015 AACR.

To assess the clinical validity of renal resistive index (RI) to determine prognosis and guide therapy over a long-term follow-up in patients with chronic nephropathies and to verify the commonly used threshold value of 0.70.Of patients referred to the nephrology center since 1995, 177 were initially enrolled and 86 were followed up for RI and renal function annually for 2-11 years (mean, 5.93 years +/- 2.92 [standard deviation]). All patients gave informed consent for the institutional review board-approved study. Correlations were determined between initial RI and age, estimated glomerular filtration rate (eGFR), proteinuria, hematuria, blood pressure, and biopsy scores. The sample was categorized in four groups on the basis of whether initial values of RI and eGFR were normal, and progression to renal failure was compared. With grouping of the sample by using initial RI (or =0.61, 0.62-0.69, andor =0.70), Kaplan-Meier analysis was used to obtain survival curves.Initial RI correlated with final eGFR (R = -0.4, P.001), systolic blood pressure (R = 0.39, P.001), proteinuria (R = 0.28, P = .009), and age (R = 0.28, P = .007). In stepwise multiple regression analysis, RI emerged as the only independent risk factor for the progression to renal failure (P.001). Among the four groups of patients with different initial RIs and eGFRs, the group with an initial RI of 0.70 or higher showed a worse outcome, independent of initial eGFR. In the Kaplan-Meier analysis by using initial RI, only the group with a value of 0.70 or higher showed a rapid decline of renal function (50% decrease in eGFR in 6 years).An RI of 0.70 or higher is predictive of an unfavorable outcome in patients with chronic nephropathies.

Over-expression of P53-related protein detected by immunohistochemistry (IHC) and absence of p21waf1— expression, the main downstream target following P53 activation, are useful surrogate markers in identifying diffuse large B-cell lymphoma (DLBCL) patients with mutated P53-gene. Following recent studies on gene expression, tissue micro-array technology has been shown to represent a reliable technique in discriminating DLBCL with germinal center B-cell like (GC), or post- germinal center (non-GC) origin. We analyzed 80 consecutive patients with de-novo DLBCL, homogeneously treated with cure-intent (CHOP-like regimens +/− Rituximab) in a single Institution, for expression of p53/p21waf1—, with regard to the expression of GC (CD10+, bcl-6+/mum-1−/CD138−), and post-germinal center (CD10−, mum-1+, CD138+) IHC markers. Cases with 50% or more p53-positive neoplastic cells were defined as p53+++. All patients were provided with complete clinical information. Median age of our patients was 50 years, AAS was III or IV in half of patients, IPI was high or int/high in 36%. Median follow-up for survivors was 77 months. A p53+++/p21waf1— phenotype (corresponding to loss of function of the P53-gene) was detected in 19 of 80 patients (23%), while a GC phenotype characterized 42 patients (52%). Patients with P53+++/p21waf1— phenotype were more frequently resistant to induction therapies (p Our results strongly point to the usefulness of a combined molecular and clinical approach for prognostic considerations in DLBCL, and should be validated in larger series.

The occurrence of the nephrotic syndrome in 3 patients treated for 1–8 months with 2-mercapto-propionyl-glycine (Thiola) (at doses ranging from 0.750 to 2.000 g/day) is reported. The drug had been administered for chronic active hepatitis in 1 patient and for cystinuria in the remaining patients. Percutaneous renal biopsies, obtained in all patients and examined at light microscopy, immunofluorescence and electron microscopy, showed ‘minimal change’ nephropathy in 2 patients and membranous glomerulonephritis in the 3rd patient. In all patients, complete remission of the nephrotic syndrome and, eventually, disappearance of proteinuria were observed 15–120 days after discontinuation of Thiola. It is suggested that this drug may act either through an antigenie mechanism, akin to that of penicillamine, or through a sensitization mechanism, both of them being able to cause the nephrotic syndrome.