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Background Inhibition of the interaction of programmed death 1 with programmed death ligand 1 and 2 has been used successfully for treatment of multiple advanced cancers, but expression has not been studied in adrenocortical carcinoma. In this study, we investigated programmed death ligand 1 and 2 expression in adrenocortical carcinoma to determine the potential usefulness of checkpoint inhibitors in these malignant neoplasms. Methods A total of 56 tissue samples from patients with adrenocortical carcinoma (34) and benign adrenal tissues (22) were identified. Immunohistochemistry was performed for programmed death ligand 1, programmed death ligand 2, and CD8 and scored for membranous staining on adrenal and stromal tissue according to the immunoreactive score and absolute percentage, respectively. Descriptive statistics, a Mann-Whitney U test, and Fisher exact tests were calculated. Results In total, 15 adrenocortical carcinoma (44%) stained positive for programmed death ligand 2 and 1 adrenocortical carcinoma for programmed death ligand 1 (P = .03). Adrenocortical carcinoma samples were more likely to express programmed death ligand 2 on tumor cells or in stromal tissues than benign samples (OR = 2.3, P = .03). There was no relationship between programmed death ligand 2 and CD8 expression (P = .08). There were also no relationships between programmed death ligand 2 or CD8 expression and tumor characteristics. Conclusion Programmed death ligand 2, but not programmed death ligand 1, is expressed commonly in adrenocortical carcinoma samples. The utility of certain checkpoint inhibitors should, therefore, be evaluated in further studies.

Background. Altered miRNA expression and down-regulation of Dicer has been shown in various cancers. We investigated Dicer expression and global miRNA environment in correlation with malignant features of thyroid tumors. Methods. Dicer gene expression was assessed for 22 normal thyroids, 16 follicular adenomas, 28 papillary thyroid cancers (PTCs), 10 tall-cell variants of PTC, 11 follicular variants of PTC, as well as the four thyroid cell lines BCPAP, TPC1, KTC1, and TAD2 via quantitative polymerase chain reaction. BRAF (V600E) mutation screening was completed for 31 neoplasms. Next-generation sequencing was performed on a subset of PTC and normal thyroid. Protein levels were assessed via Western blotting and immunohistochemistry. Results. Dicer mRNA was down-regulated in malignant thyroid samples and cell lines compared with normal tissues, benign neoplasms, and the fetal cell line TAD2. Decreased Dicer gene expression in malignant tissues was correlated greatly with aggressive features: extrathyroidal extension, angiolymphatic invasion, multifocality, lymph node and distant metastasis, recurrence, and BRAF (V600E) mutation. Conversely, increased levels of Dicer protein were observed in malignant tissues and cell lines. Sequencing yielded 19 differentially expressed miRNAs. Eight samples had a nonsignificant a global down-regulation in malignant tissues. Conclusion. Dysregulation of Dicer and possibly altered expression of miRNAs are associated with aggressive features in thyroid cancers. These findings suggest that disruption in normal miRNA processing involving Dicer may play a role in thyroid cancer progression. (Surgery 2014;156:1342-50.)

Background The tall cell (TC) variant of papillary thyroid carcinoma (PTC) is more aggressive than classic PTC, but the percentage of TC necessary to diagnose this variant has been debated. We aimed to better determine what percentage of TC correlates with a more aggressive phenotype. Methods Cases from 2005 to 2010 that were the TC variant of PTC or PTC with TC features were identified and compared with classic PTCs. All cases were reviewed to determine what percent, if any, of the tumors consisted of TC. Results One hundred forty-one cases of PTC were reviewed. Eighty-three cases had some TC component, and 58 cases had none. There were no differences in patient demographics. Tumors with ≥10% TC had more extrathyroidal extension, angiolymphatic invasion, positive surgical margin, and lymph node involvement than classic PTC. There were more recurrences in patients with ≥10% TC, but this was not significant. Similar findings were also observed with increasing percentages of TC. Conclusion The aggressive features conferred by the presence of TC in PTCs occur with as little as 10% TC and are maintained with increasing percentages. Therefore, TC in a PTC should be reported if they comprise at least 10% of the tumor.

Extrathyroidal extension (ETE) is a risk factor for recurrence of papillary thyroid carcinoma (PTC). Although initial data supporting this was based on gross ETE noted at surgery, current treatment regimens group patients with microscopic ETE-identified only on histopathology-similarly to those with macroscopic (gross) ETE. This study was designed to assess the influence of microscopic ETE on disease recurrence.Retrospective analysis of 212 patients undergoing thyroidectomy for PTC between 1995 and 2004 with minimum 3-year follow-up was conducted.Of 212 patients, 71 had ETE; 32% were macroscopic and 68% microscopic. Patient demographics, tumor variables, and adjuvant therapy were similar between both ETE groups. Recurrence rates were 52% for macroscopic ETE, 21% for microscopic ETE, and 13% without ETE. On multivariate analysis, patients with macroscopic ETE had a 6.4-fold increased relative risk of recurrence compared with patients with microscopic ETE (P.02; 95% confidence interval, 1.6-25.9) and a significantly decreased disease-free survival (DFS). Furthermore, patients with microscopic ETE had neither a significantly increased risk of recurrence nor different DFS compared with patients without ETE.Macroscopic ETE has a higher incidence of disease recurrence than microscopic ETE, implying they should be considered separately when devising adjuvant treatment regimens. The significance of microscopic ETE is undetermined.