Necrotizing sialometaplasia: a malignant masquerade but questionable precancerous lesion, report of four cases.

BACKGROUND: Necrotizing sialometaplasia (NSM) is an extremely rare benign lesion with an uncertain pathogenesis. The differential diagnosis of this lesion is challenging due to little familiarity with this entity and histologic similarity with carcinomas, especially mucoepidermoid carcinoma (MEC). The purpose of this study is to raise awareness about NSM, which is often overlooked or misdiagnosed as malignancy in a small biopsy. METHODS: We reviewed all biopsy materials taken from the oral cavity in a single institution in Korea from 2012 to 2018 and found 4 cases of NSM out of 726. Clinicopathologic characteristics and comparison with other lesions were discussed. RESULTS: Unlike previous reports, patients in our series were relatively young, and NSM was not related to smoking and not associated with malignancies, although one patient was misdiagnosed with MEC on the basis of the initial biopsy. High-grade squamous dysplasia was observed in one patient; however, all four patients showed excellent prognoses without further management. CONCLUSIONS: A conservative approach is recommendable for necrotizing lesions of the palate in young adults to avoid unnecessary treatment. However, careful monitoring is also required due to uncertainty of premalignant potential.

Utility of a formatted pathologic reporting system in thyroid core needle biopsy: A validation study of 1998 consecutive cases.

OBJECTIVE: Thyroid core needle biopsy (CNB) is increasingly being used as a tool for evaluating thyroid nodules; thus, standardization of its diagnostic terminology is called for. We aimed to analyse the pathologic reporting system of thyroid CNB based on the recently proposed protocol by the Korean Endocrine Pathology Thyroid Core Needle Biopsy Study Group and evaluate its usefulness. DESIGN/METHODS: A total of 1998 consecutive cases of thyroid CNBs were reviewed and divided into six categories according to the protocol. Malignancy rate in each category and the diagnostic performance of thyroid CNB were calculated using 705 resected cases. RESULTS: Thyroid CNB yielded 132 nondiagnostic (6.6%), 791 benign (39.6%), 328 indeterminate (16.4%), 227 follicular neoplasm (11.4%), 69 suspicious for malignancy (3.5%) and 451 malignant lesions (22.6%). In resected specimens, all of the cases designated as suspicious for malignancy and malignant categories in CNB were proven to be true malignant lesions. Lesions diagnosed with follicular neoplasm in CNB were identified as malignant lesions in 57.0%. Malignancy rate was significantly higher in indeterminate lesions with nuclear atypia compared to those with architectural atypia (80.0% vs 28.2%). When CNB diagnoses of indeterminate lesions or higher categories were considered positive, the sensitivity and positive predictive value for final malignant diagnoses were 99.2% and 81.3%, respectively. CONCLUSIONS: CNB is an accurate method of evaluating thyroid nodules and can serve as an alternative to fine needle aspiration when it is used and reported according to standardized diagnostic categories.

Primary lymphomatoid granulomatosis in the central nervous system: A report of three cases.

Lymphomatoid granulomatosis (LYG) is a rare lymphoproliferative disorder characterized by infiltration of Epstein-Barr virus (EBV)-positive large atypical B-cells in an angiocentric fashion in a mixed inflammatory background. The histologic spectrum of LYG ranges from reactive proliferation to diffuse large B-cell lymphoma according to the number of EBV+ B-cells. It is known that virtually all patients have pulmonary involvement, whereas primary LYG of the other organs has been rarely reported. Herein, we describe three cases of primary LYG of the central nervous system (CNS) without pulmonary lesions, and this is the first collection to be reported in Korea. All of the cases revealed multifocal enhancing necrotic brain lesions masking as metastatic tumors, infection or vasculitis. These patients were successfully managed by corticosteroids and immunomodulating agents without chemotherapy against malignant lymphoma even in grade 3 LYG. We assume that primary CNS LYG might be less aggressive and more controllable than pulmonary LYG. The clinicopathologic characteristics of the cases with a special regard to the differential diagnosis and clinical courses are discussed in combination with an overview of the literature.

Invasion Depth Measured in Millimeters is a Predictor of Survival in Patients with Distal Bile Duct Cancer: Decision Tree Approach.

BACKGROUND: AJCC staging system is unreliable for predicting survival in distal bile duct (DBD) cancer patients, due to inter-observer variation. Measured depth of invasion (DOI) is suggested to be more accurate to predict patients' clinical outcome in extra-hepatic cholangiocarcinomas, but its significance in DBD cancer and cutoff values are still debatable. This study aimed to identify the optimal cutoff value of DOI in relation to prognosis in DBD cancer patients. METHODS: Data of 179 patients with DBD adenocarcinoma treated in three institutions were investigated. Under microscopic review, DOI was measured. The relationships between the clinicopathological parameters and the groups based on DOI (≤3; 3-10; >10 mm) were evaluated, and the survival times of each group based on DOI and T classification were compared. RESULTS: Deeply invading tumors exhibited a greater tendency toward the infiltrative type, high histological grade, AJCC stage, and pancreatic, duodenal, lymphovascular and perineural invasion. The measured DOI was significantly correlated with worse relapse-free and overall survival (all p < 0.05). In multivariate analyses, the DOI remained as one of the prognostic factors (all p < 0.05), while T classification was not a significant prognostic factor. The new prognostic models (low, intermediate, and high risk) that applied DOI and nodal metastasis showed significant difference in recurrence and survival rate (all p < 0.05). CONCLUSIONS: On the basis of the proposed cutoff value, the DOI could be clear and meaningful, overcoming the vagueness of the T classification for predicting clinical outcomes in patients with DBD carcinoma.

PELI1 expression is correlated with MYC and BCL6 expression and associated with poor prognosis in diffuse large B-cell lymphoma.

PELI is a family of E3 ubiquitin ligases that regulate protein activity through a post-translational modification, ubiquitination. While PELI1 has been found to play a pivotal role in inflammatory processes through the activation of Toll-like receptor signaling and the NF-kB pathway, the role of PELI1 in oncogenesis has not been the subject of much investigation. We aimed to explore PELI1 expression in various malignant lymphomas and identify clinicopathologic significance. Immunohistochemistry for PELI1 was performed on a total of 502 cases, including 406 B-cell, 76 T or NK-cell, and 20 Hodgkin lymphomas. High expression of PELI1 was found in high-grade B-cell lymphoma cases such as diffuse large B-cell lymphoma, Burkitt lymphoma, and plasmablastic lymphoma, whereas low-grade B-cell lymphoma, T/NK-cell lymphoma, and Hodgkin lymphoma cases showed very low levels of expression. In vitro cell line studies, the results of western blot, and RT-PCR were concordant with those of the immunohistochemical results; RL7, Pfeiffer, SUDHL-2, DOHH2, and Ramos cell lines showed high levels of PELI1 protein and mRNA expression. In 182 diffuse large B-cell lymphoma, PELI1 expression was positively correlated with the expression of MYC, BCL6, BCL2, and MUM1 (Spearman's ρ=0.427, 0.507, 0.246, and 0.137, respectively; P<0.001, <0.001, 0.001, and 0.066, respectively). In diffuse large B-cell lymphoma, high expression of PELI1 was associated with frequent bone marrow involvement (P=0.013) and shorter relapse-free survival (P=0.002). Our results suggest that PELI1 might participate in B-cell maturation or oncogenic activation of aggressive B-cell lymphomas, both during and after germinal center stages.

MYC overexpression correlates with MYC amplification or translocation, and is associated with poor prognosis in mantle cell lymphoma.

AIMS: We aimed to investigate MYC expression and chromosomal aberration in mantle cell lymphoma (MCL), and the clinical significance of these factors. METHODS AND RESULTS: Sixty-five patients with MCL, including 54 classic, nine blastoid and two pleomorphic variants, were enrolled. Expression of MYC, Ki67 and p53 was assessed by immunohistochemistry. MYC amplification or translocation was examined by fluorescence in-situ hybridization. MYC expression was higher in blastoid/pleomorphic MCL variants (mean, 19.0%) than in classic MCL (mean, 1.9%; P < 0.001). Expression of p53 and Ki67 was also significantly higher in these variants. MYC amplification was found in two of 53 cases tested, both of which were blastoid variants with high MYC expression (29.7% and 20.4%). MYC translocation was found in two of 52 cases tested, both of which were pleomorphic variants with remarkably high MYC expression (68.5% and 71.0%). High MYC or p53 expression was significantly associated with shortened overall survival and progression-free survival in univariable and multivariable analyses (all P < 0.05). CONCLUSIONS: MYC overexpression is a negative predictor of MCL patient outcomes. MYC gene amplification or translocation might be related to the pathogenesis of MCL, particularly in blastoid/pleomorphic variants.

Expression of hypoxic signaling markers in head and neck squamous cell carcinoma and its clinical significance.

Hypoxia is a consistent finding in fast-growing tumors; it contributes to tumor progression and therapeutic responses. We explored the expression of hypoxia-associated biomarkers in head and neck squamous cell carcinoma (HNSCC) to assess their relationship with clinical factors in HNSCC. In total, 90 patients with HNSCC were enrolled. Expression of HIF-1α, HSP70, HSP90, VEGF, IGF-1R, and P16 was investigated by immunohistochemistry. Their correlations with clinical factors, including location of primary sites, T stage, N stage, M stage, HPV status, primary treatment success/failure, recurrences, disease-free survival (DFS), and overall survival, were analyzed. HIF-1α, HPS70, HPS90, VEGF, and IGF-1R were positive in 33 of 89 (37.1 %), 62 of 87 (71.3 %), 83 of 89 (93.3 %), 41 of 87 (47.1 %), and 50 of 56 (89.3 %) cases, respectively. Expression levels of some of these markers were correlated. High HIF-1α or HSP 70 correlated with poor DFS, and expression of HSP70 correlated with LN metastasis. HPV-related carcinomas showed high HSP 70 and IGF-1R expression. Hypoxia-associated proteins were highly expressed and associated with aggressive clinical features in HNSCC. Expression of HIF-1α or HSP70 can be considered poor prognostic indicator in HNSCC. Our results suggest that hypoxic signaling is activated in HNSCC, especially in HPV-related tumors.

Indoleamine 2,3-dioxygenase (IDO) is frequently expressed in stromal cells of Hodgkin lymphoma and is associated with adverse clinical features: a retrospective cohort study.

BACKGROUND: Regulation of tumor microenvironment is closely involved in the prognosis of Hodgkin lymphoma (HL). Indoleamine 2,3-dioxygenase (IDO) is an enzyme acting as immune modulator through suppression of T-cell immunity. This study aims to investigate role of IDO in the microenvironment of HL. METHODS: A total of 121 cases of HL were enrolled to do immunohistochemistry for IDO, CD163, CD68, CD4, CD8, and FoxP3. Positivity was evaluated from area fractions or numbers of positive cells using automated image analyzer. Correlations between IDO expression and various cellular infiltrates and clinicopathologic parameters were examined and survival analyses were performed. RESULTS: IDO was expressed in histiocytes, dendritic cells and some endothelial cells with variable degrees, but not in tumor cells. IDO positive cells were more frequently found in mixed cellularity type than other histologic types, and in cases with EBV+, high Ann Arbor stages, B symptoms, and high IPS (all p < 0.05). High IDO expression was associated with inferior survival (p < 0.001) and reflects an independent prognostic factor in nodular sclerosis HL. CONCLUSIONS: This is the first study suggesting that IDO is the principle immunomodulator and is involved to adverse clinical outcomes of HL.

Clinicopathologic Significance of Quaking Expression in Hepatocellular Carcinoma.

BACKGROUND/AIM: The RNA binding protein quaking (QKI) is associated with the development and progression of tumor suppressors in various cancers. However, the clinical implications of QKI expression have not yet been fully elucidated. In this study, we aimed to investigate the clinicopathological and prognostic significance of QKI expression in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: We performed QKI, Zinc finger E-box-binding homeobox 1 (ZEB1), E-cadherin, and glutathione peroxidase 4 (GPX4) immunohistochemical staining on 166 HCC patient tissue samples. X-tile bioinformatics software was used to set the cut-off value for high QKI expression. Correlations between QKI expression and various clinicopathological parameters were assessed. RESULTS: The best cut-off value for high QKI expression was 12.5. High QKI expression was observed in 28 of 166 patients (16.9%) and was an independent prognostic factor for inferior recurrence-free survival (RFS). In addition, high ZEB1 and GPX4 expression correlated with high QKI expression, but not with the loss of E-cadherin expression. CONCLUSION: High QKI expression was identified in HCCs and associated with poor RFS. QKI might be a prognostic biomarker of HCCs associated with epithelial-to-mesenchymal transition and a potential candidate therapeutic target.

High expression of Sonic hedgehog signaling proteins is related to the favorable outcome, EGFR mutation, and lepidic predominant subtype in primary lung adenocarcinoma.

BACKGROUND: Dysregulation of the Sonic hedgehog (SHH) signaling pathway has been identified in many human malignancies. However, it remains unclear whether this pathway is activated in human lung adenocarcinoma. METHODS: We investigated the expression of the SHH ligand and its downstream molecules, such as glioma-associated oncogene homologue (GLI)-1, GLI-2, GLI-3, and ATP-binding cassette G2 (ABCG2), in 166 cases of surgically resected lung adenocarcinoma by immunohistochemistry. Correlations between the expression of SHH-related proteins and clinicopathologic parameters, histologic subtypes, and prognostic significance were statistically analyzed. RESULTS: SHH was highly expressed in the 36.1 % (60/166), GLI-1, GLI-2, and ABCG2 were found in 90/164 (54.9 %), 26/166 (15.7 %), and 139/165 (84.2 %), respectively, and GLI-3 was positive in all cases. SHH was more frequently highly expressed in nonsmokers, patients with no recurrences, lepidic predominant subtype, and with EGFR mutation (p < 0.05, respectively). The high expression of SHH and GLI-1 was related to better overall survival and progression-free survival (p < 0.05). CONCLUSIONS: The SHH signaling pathway is frequently up-regulated in a subset of lung adenocarcinoma and is significantly associated with EGFR mutation and lepidic subtype. Although SHH signaling protein expression is not an independent prognostic marker, the expression of these proteins can predict a better prognostic outcome.

Inflammatory pseudotumor-like follicular dendritic cell sarcoma of the spleen: a report of six cases with increased IgG4-positive plasma cells.

Inflammatory pseudotumor (IPT)-like follicular dendritic cell (FDC) sarcoma is a rare neoplasm typically occurring in the spleen or liver. We present six cases of EBV(+) IPT-like FDC sarcoma of the spleen among Koreans along with their clinicopathologic features and IHC results. Most patients presented with an asymptomatic, incidentally detected single splenic mass and were successfully managed by splenectomy alone. Concomitant disease was found in one case, showing EBV(+) gastric carcinoma with lymphoid-rich stroma. Histologic features showed fibro-inflammatory lesions that were often accompanied by necrosis and epithelioid histiocytic collection, which are barely distinguishable from IPT. Tumor cells did not frequently express conventional FDC markers, including CD21 (3/6 positive cases), clusterin (4/6), and D2-40 (2/6), but showed uniform positivity for smooth muscle actin (SMA). Noticeably, significant numbers of IgG4(+) plasma cells were found within all six tumors. We suggest that the diagnosis of IPT-like FDC sarcoma should be made by the application of a panel of FDC markers, and CD21 negativity or SMA positivity cannot be the criterion for exclusion of IPT-like FDC sarcoma. Relationship of IPT-like FDC sarcoma of the spleen and IgG4-related sclerosing disease should be investigated in further studies.

Comparison between Two-Dimensional and Point Shear Wave Elastography Techniques in Evaluating Liver Fibrosis Using Histological Staging as the Reference Standard: A Prospective Pilot Study.

Evaluation of hepatic fibrosis is essential to prevent liver-related morbidity and mortality. Although various types of ultrasound shear wave elastography (SWE) have been used and validated, there are limited studies on the relatively newer technique, two-dimensional SWE (2D-SWE). Therefore, this study aimed to compare the diagnostic performances of 2D-SWE and point SWE (p-SWE) for evaluating liver fibrosis using histology as the reference standard. To measure liver stiffness (LS) values, 87 patients underwent 2D-SWE and p-SWE using the same machine. Technical failures and unreliable measurements were also evaluated. The diagnostic performances of 2D-SWE and p-SWE were compared using area under the receiver operating characteristic (AUROC) curve analysis. No technical failures were observed in either method; however, unreliable measurements were less frequent in 2D-SWE (1/87 [1.1%]) than in p-SWE (8/87 [9.2%]) (p < 0.001). The AUROC of the LS values of 2D-SWE were significantly higher than those of p-SWE for diagnosing significant fibrosis (0.965 vs. 0.872, p = 0.022) and cirrhosis (0.994 vs. 0.886, p = 0.042). In conclusion, 2D-SWE is more reliable and accurate than p-SWE for diagnosing hepatic fibrosis.

Expression of Peptidyl Arginine Deiminase 2 Is Closely Associated with Recurrence in Patients with Hepatocellular Carcinoma.

Peptidyl arginine deiminases (PAD) enzymes have been investigated in various cancers. Recently, PAD enzyme, in particular PAD2, has been further implicated in cancers. Although the expression of PAD2 was significantly higher in hepatocellular carcinoma (HCC) tissue, its diagnostic or prognostic role of PAD2 in HCC patients is unknown. This study investigated whether the expression of PAD2 affects recurrence and survival in HCC patients who underwent hepatic resection. One hundred and twenty-two HCC patients after hepatic resection were enrolled. The median follow-up was 41 months (range 1-213 months) in enrolled patients. To investigate an association between PAD2 expression level and the clinical characteristics of enrolled patients, the recurrence of HCC following surgical resection and survival of the patients were examined. Ninety-eight cases (80.3%) of HCC demonstrated a higher expression of PAD2. The expression of PAD2 was correlated with age, hepatitis B virus positivity, hypertension, and higher alpha-fetoprotein level. There was no association between PAD2 expression and sex, diabetes mellitus, Child-Pugh class, major portal vein invasion, HCC size or number. The recurrence rates in patients with lower PAD2 expression were higher than those with higher PAD2 expression. The cumulative survival rates of patients with higher PAD2 expression were better than those of patients with lower PAD2 expression, but it was not statistically significant. In conclusion, PAD2 expression is closely associated with recurrence of HCC patients following surgical resection.

Ultra-low-dose radiation treatment for early-stage ocular adnexal MALT lymphoma.

PURPOSE: To investigate the long-term outcomes of ultra-low-dose (4 Gy) radiation treatment (RT) in patients with early-stage ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: This retrospective case series includes eight patients with ocular adnexal MALT lymphoma who received ultra-low-dose RT at a single tertiary referral center between March 2016 and February 2018. Response to treatment and the time taken to respond were analyzed. RESULTS: Of the eight patients (three men, five women), seven patients had conjunctival lymphoma (T1N0M0), and one patient had orbital lymphoma (T2N0M0). Six patients with T1 disease showed complete response (CR), and the median time to CR was 4.5 months (range 2-5). Partial response was achieved in the remaining two patients (one each with T1 and T2). During the median follow-up period of 44 months (range 30-54), none of the patients had a relapse or needed additional treatment. RT was well-tolerated in all patients with no ocular complications, including cataracts and dry eye. CONCLUSION: This case series suggests that ultra-low-dose RT is effective and well-tolerated in patients with early-stage ocular adnexal MALT lymphoma. Further studies with a larger sample size and long-term follow-up are needed to evaluate the local control rate and disease-free survival precisely.

Cellular Prion Protein Is Closely Associated with Early Recurrence and Poor Survival in Patients with Hepatocellular Carcinoma.

The cellular prion protein (PrPC) is known to play a role in cancer proliferation and metastasis. However, the role of PrPC expression in hepatocellular carcinoma (HCC) is unknown. This study investigated whether overexpression of PrPC affects recurrence after surgical resection and survival in HCC. A total of 110 HCC patients who underwent hepatic resection were included. They were followed up for a median of 42 months (range 1-213 months) after hepatectomy. The relationships between PrPC expression and the HCC histologic features, recurrence of HCC following surgical resection, and survival of the patients were examined. Seventy-one cases (64.5%) of HCC demonstrated higher expression of PrPC. The expression of PrPC was only correlated with diabetes mellitus. There was no association between PrPC expression and age, sex, hypertension, hepatitis B virus positivity, alcohol consumption, Child-Pugh class, major portal vein invasion, serum alpha-fetoprotein, and HCC size or number. The 1-year recurrence rates in patients with higher PrPC expression were higher than those with lower PrPC expression. The cumulative survival rates of patients with higher PrPC expression were significantly shorter than those of patients with lower PrPC expression. In conclusion, PrPC expression is closely associated with early recurrence and poor survival of HCC patients following surgical resection.

Clinical prognostic significance of cancer stem cell markers in patients with papillary thyroid carcinoma.

The recent development of the cancer stem cell (CSC) model has been heralded as a new era in thyroid cancer research. The aim of this study was to evaluate the presence of CD44+ and CD24- tumor cells in papillary thyroid carcinoma (PTC) as markers of aggressiveness and poor prognosis. Patients with PTC, who underwent successful surgical resections between January 2003 and December 2012 at a single tertiary hospital, were included in this study. Tissue arrays were prepared from 454 primary tumor tissues. Immunohistochemistry (IHC) was performed to detect the CSC markers CD24 and CD44 on the tissue arrays. IHC was graded using a semi-quantitative histology scoring system based on the extent and intensity of staining. Subsequently, the association between IHC results and clinicopathological characteristics and recurrence-free survival (RFS) was analyzed. In 454 patients, 39 cases recurred during the 70-month median follow-up period, with some patients exhibiting multiple sites of relapse. The results of a Kaplan-Meier survival analysis and univariate log-rank test demonstrated that sex (P=0.008), age (P=0.002), cN1b, defined as metastasis to unilateral, bilateral, or contralateral neck lymph nodes or retropharyngeal lymph nodes (P<0.001), pN1, defined as pathologically proven lymph node metastasis >5 (P<0.001), tumor size >2 cm (P<0.001), extrathyroidal extension (P=0.001) and CD24- (P<0.001) were prognostic factors for RFS. CSC marker combinations (CD44+/CD24-) also exhibited statistical significance in the log-rank test. In conclusion, expression of the CSC markers CD44+ and CD24- in PTC tissue samples was associated with RFS. The combination of CD44+ and CD24- exhibited a statistically significant negative association with RFS and a strong association with gross extra-thyroidal extension.

Preoperative diagnostic categories of fine needle aspiration cytology for histologically proven thyroid follicular adenoma and carcinoma, and Hurthle cell adenoma and carcinoma: Analysis of cause of under- or misdiagnoses.

Cytologic diagnosis of thyroid follicular adenoma and carcinoma, and Hurthle cell adenoma and carcinoma (FACHAC) is challenging due to cytomorphologic features that overlap with other follicular-patterned lesions. This study was designed to analyze diagnostic categories (DCs) of preoperative fine needle aspiration cytology (FNAC) of histologically proven thyroid FACHACs to evaluate under- or misdiagnoses in FNAC and elucidate potential causes for such phenomena. A total of 104 thyroid nodules with preoperative FNAC which were diagnosed as FACHAC in resection specimens were included in this study. Of these, 66 cases had also undergone thyroid core needle biopsy (CNB); FNAC and CNB DCs were compared in these cases. Various cytologic and histologic parameters were compared between the nodules with different FNAC DCs. After a review of FNAC slides, DCs were re-assigned in 20 (19.2%) out of the 104 cases. Of the 66 cases with CNB diagnoses which were mostly classified as lower DCs in FNAC, 31 (47.0%) were diagnosed as suspicious for a follicular neoplasm in CNB. Cases which were underdiagnosed in FNACs were associated with lower cellularity, predominant macrofollicular pattern, absence of microfollicles arranged in trabecular pattern, and absence of transgressing vessels in cytology smears. High cellularity, microfollicles arranged in trabecular pattern, nucleolar prominence, and large cell dysplasia were more frequently found in malignancy than in benign neoplasm. In conclusion, thyroid FACHACs seem to be under- and misdiagnosed in preoperative FNAC. Innate characteristics of the nodules were associated with under-diagnosis as well as the quality of the FNAC specimens. Certain cytomorphologic features can be helpful in differentiating malignancy among FACHACs.

Comparison of point and 2-dimensional shear wave elastography for the evaluation of liver fibrosis.

PURPOSE: This study aimed to assess the technical performance of ElastQ Imaging compared with ElastPQ and to investigate the correlation between liver stiffness (LS) values obtained using these two techniques. METHODS: This retrospective study included 249 patients who underwent LS measurements using both ElastPQ and ElastQ Imaging equipped on the same machine. The applicability, repeatability (coefficient of variation [CV]), acquisition time, and LS values were compared using the chi-square or Wilcoxon signed-rank tests. In the development group, the correlation between the LS values obtained by the two techniques was assessed with Spearman correlation coefficients and linear regression analysis. In the validation group, the agreement between the estimated and real LS values was evaluated using a Bland-Altman plot. RESULTS: ElastQ Imaging had higher applicability (94.0% vs. 78.3%, P<0.001) and higher repeatability, with a lower median CV (0.127 vs. 0.164, P<0.001) than did ElastPQ. The median acquisition time of ElastQ Imaging was significantly shorter than that of ElastPQ (45.5 seconds vs. 96.5 seconds, P<0.001). The median LS value obtained using ElastQ Imaging was significantly higher than that obtained using ElastPQ (5.60 kPa vs. 5.23 kPa, P<0.001). The LS values between the two techniques exhibited a strong positive correlation (r=0.851, P<0.001) in the development group. The mean difference and 95% limits of agreement were 0.0 kPa (-3.9 to 3.9 kPa) in the validation group. CONCLUSION: ElastQ Imaging may be more reliable and faster than ElastPQ, with strongly correlated LS measurements.

CT and MR imaging findings of ocular adnexal mucosa-associated lymphoid tissue lymphoma associated with IgG4-related disease: multi-institutional case series.

AIM: To report CT and MR imaging findings of ocular adnexal mucosa-associated lymphoid tissue lymphoma associated with IgG4-related disease (IgG4-MALT lymphoma), a rare but clinically important complication of ocular adnexal IgG4-related disease. METHODS: We retrospectively reviewed all cases of histologically confirmed ocular adnexal IgG4-related disease at three tertiary and one secondary referral centers, between February 2003 and December 2016. Seven cases of histopathologically diagnosed IgG4-MALT lymphoma were identified. CT and MR images were analyzed by consensus of two experienced head and neck radiologists. RESULTS: Lacrimal glands were the main site of involvement in all seven patients. The lesions typically showed well-demarcated margins, iso- to hyperattenuation on precontrast CT, T2 hypo- to isointensity, T1 isointensity, and homogenous internal architecture with homogenous enhancement pattern. Lesions were mostly hyperdense and isointense to normal extraocular muscles on postcontrast CT and MR images, respectively. CONCLUSION: Unlike in typical ocular adnexal IgG4-related disease, T2 isointensity and hyperattenuation on precontrast CT images were noted in some IgG4-MALT lymphoma cases. Although the findings may be nonspecific, the possibility of accompanying MALT lymphoma may need to be considered, when ocular adnexal lesions in patients clinically suspected of having IgG4-related disease are refractory to glucocorticoids and show T2 isointensity and hyperattenuation on precontrast CT for the optimal management of the patients. However, this is a case series of a very rare complication of ocular adnexal IgG4-related disease, and thus caution is warranted to generalize the conclusion.

Significance of druggable targets (PD-L1, KRAS, BRAF, PIK3CA, MSI, and HPV) on curatively resected esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) still remains intractable disease with few therapeutic options. Programmed death-ligand 1 (PD-L1), which is essential for immune evasion, is involved in the pathogenesis of ESCC and thus is a potential therapeutic target. PIK3CA, KRAS, and BRAF mutations, microsatellite instability (MSI) caused by deficient mismatch repair (dMMR), and human papillomavirus (HPV) can potentially upregulate PD-L1 expression, which might contribute to the clinical outcome of patients with ESCC. METHODS: We investigated the significance of the present druggable markers [PD-L1, PIK3CA, KRAS, and BRAF mutations, MSI caused by deficient dMMR, and HPV] in 64 curatively resected ESCCs, using immunohistochemistry (PD-L1 and MMR protein expression), direct sequencing (KRAS, BRAF, and PIK3CA mutations), real-time PCR (HPV infection), and MSI using quasi-monomorphic markers. RESULTS: PD-L1 expression, PIK3CA mutation, and MSI/dMMR were detected in 35.9, 12.5, and 17.2% of ESCCs, respectively. HPV was rarely detected (1.6%) (high-risk HPV68), whereas KRAS and BRAF mutations were not detected in ESCCs. PD-L1-positive tumors were not correlated with PIK3CA mutation or MSI/dMMR (all P > 0.05). PD-L1, PIK3CA mutation, and MSI/dMMR characterized the patients associated with light smoking, female and younger age, and younger age and well-differentiated tumors, respectively (all P < 0.05). In multivariate analysis, only PD-L1-positivity was an independent favorable prognostic factor for overall survival (OS) and disease-free survival (DFS) (P = 0.023, P = 0.014). In the PD-L1-negative ESCCs, PIK3CA mutation had a poor prognostic impact on both OS and DFS (P = 0.006, P = 0.002). CONCLUSIONS: PIK3CA mutation may be an alternative prognostic biomarker in PD-L1-negative curatively resected ESCCs that can be optional to identify high-risk patients with worse clinical outcome who require more intensive therapy and follow-up.