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Aims We sought to determine if non-terminal respiratory unit (TRU) type adenocarcinoma of lung with invasive mucinous adenocarcinoma (IMA) morphology shows gastric differentiation. Methods and results We reviewed whole-section images of 489 cases of lung adenocarcinoma from The Cancer Genome Atlas (TCGA). TCGA data were classified into 426 TRU type adenocarcinoma, 49 IMA and 14 unclassifiable. Their RNA sequencing data was analysed by DESeq2 and WGCNA R packages. Gene expression in patients' samples was measured by NanoString assay. Overexpression of genes including REG4, TFF2, MUCL3, FER1L6, B3GALT5, ANXA10 was observed by TCGA analysis in IMA compared to TRU type adenocarcinoma. Many of these genes are those expressed in normal gastric glands and selected for NanoString experiment on 14 IMA and 10 TRU type adenocarcinoma cases. The expression of genes, including ANXA10, FER1L6, HNF4a, MUC5AC, REG4, TFF1, TFF2 and VSIGI, was increased> 15-fold in IMA. Immunohistochemistry of ANXA10, TFF2 and FER1L6 performed on 31 IMA and 135 TRU type adenocarcinomas showed a predominant expression in IMA, but are not in TRU type adenocarcinoma. Conclusion Our results showed the level of genes expressed in stomach mucosa was increased in IMA compared to TRU type adenocarcinoma, supporting gastric differentiation of IMA. This finding may help the understanding of the pathogenesis of IMA and discovery of therapeutic targets.

Aims Interaction between programmed death-1 ligand (PD-L1) and its receptor programmed death 1 (PD-1) on T cells inactivates antitumour immune responses. PD-L1 expression has been associated with poor prognosis in renal cell carcinoma (RCC) and predicts adverse outcome. This study was designed to evaluate the impact of PD-L1 expression and the immune microenvironment on the clinical outcome in Xp11 translocation renal cell carcinoma (TRCC) and, therefore, their potential relevance as prognostic biomarkers. Methods and results The present retrospective analysis investigated expression of PD-L1 and immune cells CD8, CD4, CD3, forkhead box protein 3 (FoxP3) and PD-1 in TRCC compared to other types of RCC. FFPE specimens were collected between 2011 and 2017 from 311 patients who underwent nephrectomy at our institution for RCC. Specimens were immunostained for PD-L1, CD8, CD4, CD3, FoxP3 and PD-1, and an outcome analysis was conducted. PD-L1 expression rate was highest in TRCC (68%, 16 of 25), followed by mucinous tubular and spindle cell RCC and collecting duct carcinoma (33%, one of three), papillary RCC (27%, seven of 26), clear cell RCC (16%, 29 of 233), chromophobe RCC (11%, two of 18) and multilocular cystic RCC (0%, none of three). In TRCC, PD-L1 expression was associated with poor recurrence-free survival (RFS) (P = 0.041). The CD4high and FoxP3high groups showed a significantly shorter RFS (P = 0.05 and P = 0.031, respectively) compared to CD4low and FOXPlow groups. Conclusion PD-L1 expression was higher in TRCC than in other types of RCC. High PD-L1 tumour cell expression and tumour infiltration by CD4+ and FoxP3+ immune cells were associated with poor RFS in TRCC.

BACKGROUND A wide range of specificity values for the differentiation of benign and malignant soft-tissue tumors show the limitations of conventional MRI features. The data obtained by quantitative analysis of diffusion-weighted image (DWI) and dynamic contrast-enhanced (DCE) MRIs would provide more objective results, especially in terms of cellularity and perfusion. PURPOSE To evaluate the diagnostic efficacies of DWI and DCE MRI for the differentiation of malignant and benign soft-tissue tumors. STUDY TYPE Retrospective. SUBJECTS In all, 136 patients (68 females, 68 males; age range 18-86 years, mean age 57.2 years) with soft-tissue tumors. FIELD STRENGTH/SEQUENCE 3 T, DWI, DCE. ASSESSMENT Tumor sizes, margins, locations, the presence of involvement in bone or neurovascular bundle, peritumoral edema, heterogeneity, and tumor necrosis were investigated on conventional MR images. On DWIs, visual signal drops were assessed and ADC (apparent diffusion coefficient) values were measured. Ktrans , Kep , Ve , and iAUC values, and time-concentration curve (TCC) types were determined using DCE images. STATISTICAL TESTS The data were statistically analyzed to determine the abilities to differentiate benign and malignant tumors using the chi-square test, two-sample t-test, and receiver operating characteristic (ROC) analysis. RESULTS Seventy-three cases were malignant and 63 benign. Age (mean ages of benign/malignant tumors, 51.75/61.86 years; P = 0.0002) and gender (F:M = 40:23 [benign], F:M = 28:45 [malignant], P = 0.003) influenced the distinction between benign and malignant. Sizes, margins, neurovascular bundle involvement, peritumoral edema, and heterogeneity of the tumors on conventional MR images and DCE parameters (Ktrans , Kep , Ve , and iAUC, and TCC plots) obtained from focal region of interest within a narrow volume of interest significantly differentiated benign and malignant lesions (all P < 0.0001, except Ve [P = 0.0004]). For DWI with ADC mapping, all ADC values and visually signal drops were also significant (P < 0.0001). DATA CONCLUSION DWI and DCE-MRI and derived variables were significantly helpful in discriminating benign and malignant soft-tissue tumors complementary to conventional MRI. LEVEL OF EVIDENCE 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:798-809.

Background and aim The biologic behavior of gastrointestinal stromal tumors (GIST) is a topic of continuing controversy. The assessment of accurate mitotic figures is known to be one of the major indicators for patients with GIST. However, it is not always easy to search for mitotic figures (MFs) and count them accurately on hematoxylin and eosin stained (H&E) slides. Methods In this study, phopho-histone H3 (PHH3), which is a recently described specific mitosis marker, was immunohistochemically examined and compared to the mitotic count on H&E sections (H&E-MI) and Ki-67 expression (Ki-67 PI). A hundred cases of histologically confirmed GISTs were reviewed based on counting MF on H&E slides. PHH3 positive MFs (PHH3-MI) were counted in the same way, and the Ki-67 PI was calculated for each case. Results A strong correlation was found between PHH3-MI and H&E-MI. Recurrence-free survival was correlated with risk category by National Institutes of Health (NIH) consensus criteria (P = 0.017), mucosal invasion (P = 0.005), H&E-MI (P = 0.002), Ki-67 PI (P = 0.005), and PHH3-MI (P = 0.000). None of these factors was an independent prognostic factor. Conclusions Among GISTs, PHH3 staining was primarily found to support grading by facilitating mitotic counting, and it might have a prognostic value in GISTs.

Aim: The aim of this study was to evaluate O6-methyguanine-DNA methyltransferase (MGMT) promoter hypermethylation, MGMT expression and microsatellite instability (MSI), as well as to elucidate their correlation with clinical and pathological parameters in epithelial ovarian cancer. Methods: Ovarian cancer tissue specimens (n = 86) were obtained after a staging operation. The MGMT gene was investigated by methylation-specific polymerase chain reaction (MSP) and MGMT expression status was analyzed using immunohistochemistry. MSI status was examined by the fluorescence-based PCR using five National Cancer Institute markers. Results: Negative MGMT expression was detected in 12 of 86 (14.0%) epithelial ovarian cancers. In 34 cases where MSP results were available, MGMT promoter hypermethylation was detected in five cases (14.7%) with mucinous or clear cell carcinomas, but not in any of other histological types (P = 0.031). Five out of six cases with negative MGMT expression showed MGMT promoter hypermethylation, whereas all of the 28 cases that retained expression of MGMT were unmethylated at the MGMT CpG island (P

Background and aims: Precise pathological diagnosis is essential for optimal treatment of thyroid tumors. Ancillary diagnostic markers may be helpful in some cases. The purpose of this study was to compare and evaluate the diagnostic value of CD56, cytokeratin 19 (CK19), and galectin-3 immunohistochemical stainings in distinguishing between papillary carcinoma (PC) and other thyroid malignancies and benign lesions. Methods: The expressions of the three markers were evaluated in PC (n= 67), follicular carcinoma (FC, n= 23), medullary carcinoma (MC, n= 18), anaplastic carcinoma (AC, n= 4), follicular adenoma (FA, n= 15), and nodular hyperplasia (NH, n= 21). Results: Statistical analysis showed significantly different expressions of CD56, galectin-3, and CK19 in PC versus other lesions of the thyroid gland, with the exception of AC. Especially, the sensitivity and specificity of CD56 for diagnosing PC were 92.5% and 86.4%, respectively. The diagnostic specificity of CD56 was higher than that of galectin-3 or CK19 in differentiating PC from other lesions of the thyroid gland. However, its sensitivity was lower than that of galectin-3 or CK19. Conclusion: CD56 turns out to be a good negative marker for diagnosing PC. We suggest that immunohistochemical panels directed at the diagnosis of PC should include CD56 together with galectin-3 and CK19.

Background and aim: The objective of this study was to evaluate the relationship between preoperative cervical cytology and clinicopathologic factors associated with prognosis in endometrial carcinoma. Methods: We reviewed all Pap smears and histologic sections from 108 patients who underwent hysterectomy for endometrial carcinomas. Abnormal cervical cytology was defined as the presence of atypical cells and malignancy. Results: Forty-one patients (38%) had abnormal cervical cytology on preoperative Pap smears, and 67 patients (62%) had normal cytology. Abnormal cervical cytology was statistically correlated with higher FIGO grade, advanced FIGO stage, myometrial invasion, lymphovascular invasion, cervical involvement, polypoid growth pattern, non-endometrioid histology, and tumor size. Tumor grade, stage, histologic type, cervical involvement, lymph node metastasis, and serosal involvement were associated with survival. Multivariate analysis showed that lymph node metastasis was related to survival. However, abnormal cervical cytology was not an independent prognostic indicator for survival. Conclusion: Abnormal preoperative cervical cytology is associated with poor prognostic factors. However, cervical cytology itself neither influences treatment decision nor predicts poor prognosis in endometrial carcinoma.

Background: The management of cystic thyroid nodules has not been standardized with respect to an initial fine-needle aspiration cytology (FNAC) cystic change result, which is defined as fluid aspiration and a smear with numerous macrophages but scant or no follicular cells. In the present study the physical characteristics of cystic thyroid nodules predictive of the pathology were investigated, and recommendations made on their management. Methods: The aspiration results of 1436 thyroid nodules managed between 1998 and 2000 were investigated. A total of 157 patients who had a subsequent operation or follow-up data with reaspiration were the subjects of the present study. Age, sex, nodule characteristics and others were examined as possible predictors of cancer risk. Results: The malignancy rate was 8.9%. Ten cases (71%) of malignancy were not cytologically diagnosed. Male sex and a nodule size of ≥4 cm were found to be statistically significant predictors of malignancy. The malignancy rate was highest (100%) when a cystic lesion had malignant cytology on reaspiration and local invasion on radiology. Conclusions: When a cystic change is observed by initial FNAC of thyroid nodules, nodules of ≥4 cm must be reaspirated and a firm cytologic diagnosis made to rule out malignancy. Nodules should be considered for surgery having taken into account other characteristics, in particular male sex and radiologic findings of local invasion.

Background and aim: With the increasing therapeutic use of endoscopic resection for intestinal early gastric cancer (EGC), it is very important to predict biological behaviors of intestinal type EGC prior to endoscopic resection. On this background, we tried to elucidate the presumptive clinicopathologic factors and biologic markers to predict submucosal invasion and lymph node metastasis based on mucin expression in EGCs. Methods: One hundred and thirty cases of intestinal EGCs were divided as EGCs with intestinal mucin phenotypes (EGC-IPs) and EGCs with gastric mucin phenotypes (EGC-GPs) based on mucin expression. The expressions of mucins (Muc2, Muc5Ac, Muc6, CD10), other protein markers (p53, CDX2, beta-catenin, E-cadherin, Smad4) by immunohistochemistry were studied. Results: EGC-IPs showed significantly increased p53 expression, CDX2 expression and beta-catenin delocalization than EGC-GPs. Using binary logistic regression analysis, expression of both gastric mucin and nuclear beta-catenin expression could be independent predictive factors of lymph node metastasis and submucosal invasion in intestinal EGCs. Lymphovascular emboli, and size of lesion could be clinicopathological independent predictive factors of lymph node metastasis and submucosal invasion in intestinal EGCs, respectively. Conclusions: Taken together, we suggest that beta-catenin expression based on mucin phenotype might be used to predict biologic behavior prior to endoscopic mucosal resection in intestinal EGC.

It usually presents as apolypoid mass in the superior nasal cavity, including thecribriform plate, superior turbinate, and superior portion ofthe nasal septum. ONB outside of the region where olfac-tory epithelium exists is exceedingly rare. ONB has beenreported to arise from the maxillary sinus, inferior meatus,and sphenoid sinus