LAG3 is an independent prognostic biomarker and potential target for immune checkpoint inhibitors in malignant pleural mesothelioma: a retrospective study.

BACKGROUND: Lymphocyte-activation gene 3 (LAG3) is an immune checkpoint receptor; novel LAG3 immune checkpoint inhibitors (ICIs) exhibit therapeutic activity in melanoma. The role of LAG3and ICIs of LAG3 are unknown in malignant pleural mesothelioma (MPM). This study aimed to uncover the prognostic landscape of LAG3 in multiple cancers and investigate the potential of using LAG3 as an ICIs target in patients with MPM. METHODS: We used The Cancer Genome Atlas (TCGA) cohort for assessing mRNA expression and our cohort for immunohistochemical expression. TCGA cohort were analyzed using the Wilcoxon rank-sum test to compare mRNA expression between normal and tumor tissues in multiple cancers. We used 86 MPM cases from TCGA and 38 MPM cases from our cohort to analyze the expression of LAG3 in tumor-infiltrating lymphocytes. The mean LAG3 mRNA expression was set as the cut-off and samples were classified as positive/negative for immunohistochemical expression. Overall survival (OS) of patients with MPM was determined using the Kaplan-Meier method based on LAG3 mRNA and immunohistochemical expression. OS analysis was performed using the multivariate Cox proportional hazards model. The correlation of LAG3 expression and mRNA expression of tumor immune infiltration cells (TIICs) gene markers were estimated using Spearman correlation. To identify factors affecting the correlation of LAG3 mRNA expression, a multivariate linear regression model was performed. RESULTS: LAG3 mRNA was associated with prognosis in multiple cancers. Elevated LAG3 mRNA expression was correlated with a better prognosis in MPM. LAG3 expression was detected immunohistochemically in the membrane of infiltrating lymphocytes in MPM. LAG3 immunohistochemical expression was correlated with a better prognosis in MPM. The multivariate Cox proportional hazards model revealed that elevated LAG3 immunohistochemical expression indicated a better prognosis. In addition, LAG3 mRNA expression was correlated with the expression of various gene markers of TIICs, the most relevant to programmed cell death 1 (PD-1) with the multivariate linear regression model in MPM. CONCLUSIONS: LAG3 expression was correlated with prognosis in multiple cancers, particularly MPM; LAG3 is an independent prognostic biomarker of MPM. LAG3 regulates cancer immunity and is a potential target for ICIs therapy. PD-1 and LAG3 inhibitors may contribute to a better prognosis in MPM. TRIAL REGISTRATION: This study was registered with UMIN000049240 (registration day: August 19, 2022) and approved by the Institutional Review Board (approval date: August 22, 2022; approval number: 2022-0048) at Tokyo Women's Medical University.

Expression of T-cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif domains (TIGIT) in anaplastic thyroid carcinoma.

BACKGROUND: Immune checkpoint proteins have not been fully examined in follicular cell-derived thyroid carcinoma and medullary thyroid carcinoma (MTC). Anaplastic thyroid carcinoma (ATC) is one of the most aggressive carcinomas. Even multimodal treatment does not result in favorable clinical outcomes for patients with ATC. Anti-tumor immunity has therefore been highlighted as having therapeutic promise for ATC. METHODS: We examined a novel immune checkpoint receptor, T-cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif domains (TIGIT), in variable thyroid lesions: adenomatous goiter, follicular adenoma, and thyroid carcinoma (TC) using immunohistochemistry (IHC). RESULTS: Our IHC results showed that TIGIT expression was detected in cancer cells of MTC and high-grade TC: poorly differentiated thyroid carcinoma (PDTC) and ATC. Neoplastic cells were positive for TIGIT in four of five MTCs (80.0%), 17 of 31 ATCs (54.8%) and in 3 of 12 PDTCs (25.0%). TIGIT was not detected in any adenomatous goiters, thyroid benign tumors, or differentiated thyroid carcinoma (DTCs). Intriguingly, ATC cells showing pleomorphic/giant cell features were positive for TIGIT, while ATC cells with other cell morphologies lacked the immunoreactivity. Intra-tumoral immune cell was inclined to be enriched in TIGI-positive ATC. Although coexisting papillary thyroid carcinoma (PTC) components demonstrated high-grade microscopic features, neither the PTC nor follicular thyroid carcinoma (FTC) components expressed TIGT in any composite ATCs. CONCLUSION: TIGIT was immunohistochemically found in MTC with high frequency and partially in high-grade TC. TIGIT expression in cancer cells may be beneficial for a potential utility in MTC and a subset of high-grade TC, especially ATC therapy.

Membranous HEG1 expression is a useful marker in the differential diagnosis of epithelioid and biphasic malignant mesothelioma versus carcinomas.

Sialylated HEG1 has been reported as a highly specific and sensitive mesothelioma marker but a comprehensive evaluation of its expression in carcinomas in different organs, various sarcomas and reactive mesothelial proliferations has not been reported. The aim of this study was to evaluate the clinical applicability of HEG1 as a marker in the diagnosis of mesothelioma. HEG1 immunoreactivity was evaluated in whole sections of 122 mesotheliomas, 75 pulmonary carcinomas, 55 other carcinomas, 16 mesenchymal tumors, and 24 reactive mesothelial proliferations and in tissue microarrays containing 70 epithelioid (EM), 36 biphasic (BM), and 2 sarcomatoid mesotheliomas (SM). In whole sections and tissue microarrays, respectively, membranous HEG1 was expressed in 93.0% and 85.5% of EM, 81.3% and 69.4% of BM, 0% and 0% of SM. HEG1 was not expressed in pulmonary adenocarcinomas. HEG1 was expressed as cytoplasmic immunoreactivity in pulmonary squamous cell carcinomas (21.7%). Membranous HEG1 staining was seen in ovarian carcinomas (66.7%), thyroid carcinomas (100%), reactive conditions (16.7%), and mesenchymal tumors (18.8%). The sensitivity of membranous HEG1 expression to distinguish EM/BM from all carcinomas was 88.8%. The specificity for the differential diagnosis between EM/BM and all carcinomas and pulmonary carcinomas was 92.3% and 98.7%, respectively.

CLINICAL IMPACT OF NON-INVASIVE FOLLICULAR THYROID NEOPLASM WITH PAPILLARY-LIKE NUCLEAR FEATURES ON THE RISK OF MALIGNANCY IN THE BETHESDA SYSTEM FOR REPORTING THYROID CYTOPATHOLOGY: A META-ANALYSIS OF 14,153 RESECTED THYROID NODULES.

Objective: It is still controversial as to how the reclassification of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) affects the risk of malignancy (ROM) in The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). This meta-analysis was aimed to investigate the impact of NIFTP on the ROM in each TBSRTC category. Methods: We accessed three electronic databases including PubMed, Web of Science, and Scopus to search for relevant data from January, 2016 to July, 2018. Relative risk and meta-analysis of proportions using the DerSimonian-Laird method, and each corresponding 95% confidence interval (CI) was pooled using a random-effect model. Results: A total of 14 studies consisting of 14,153 resected nodules were included for meta-analyses. Overall, there was a significant reduction in ROM in all TBSRTC categories following the NIFTP reclassification, except TBSRTC category I. The largest absolute and relative decrease in ROM was observed in TBSRTC category V (16%; 95% CI = 8 to 24) and category III (32%; 95% CI = 24 to 39), respectively. There was a positive correlation between the rate of NIFTP and resection rate (r = 0.83; P = .02). The decreases in ROM were more prominent in Western than in Asian cohorts. Conclusion: We confirmed the decrease in ROM due to the NIFTP reclassification for most of TBSRTC categories, which was more significant in Western than in Asian practice. The incidence of NIFTP was higher in institutions where surgical resection rates were high in patients with indeterminate cytology nodules. Abbreviations: AUS/FLUS = atypia of undetermined significance/follicular lesion of undetermined significance; CI = confidence interval; FNA = fine-needle aspiration; FN/SFN = follicular neoplasm/suspicious for follicular neoplasm; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; NI-FVPTC = noninvasive follicular variant of papillary thyroid carcinoma; ROM = risk of malignancy; RR = relative risk; SM = suspicious for malignancy; TBSRTC = The Bethesda System for Reporting Thyroid Cytopathology.

High expression of CD10 in anaplastic thyroid carcinomas.

AIMS: CD10 is an endopeptidase that degrades various bioactive peptides in the extracellular matrix. In addition to enzymatic degradation, it affects multiple intracellular signal transduction pathways. CD10 expression has been extensively studied in human epithelial cancers of numerous organs and sites. However, its presence in thyroid carcinomas, especially in anaplastic thyroid carcinoma (ATC), has not been fully determined. An actual CD10 expression in thyroid lesions including a large series of ATC was evaluated. METHODS AND RESULTS: We examined CD10 by immunohistochemistry (IHC) in 152 thyroid lesions: nine adenomatous goitres (AGs) and 143 tumours, including 47 anaplastic carcinomas. IHC showed diffuse and strong positivity for CD10 in the epithelial components of almost all ATCs. However, epithelia with squamous metaplasia and oncocytic change from AGs, follicular adenomas and differentiated carcinomas had focal CD10 reactivity. Some papillary thyroid carcinomas (PTCs), along with the PTC components of some ATCs, showed CD10 positivity in fibroblast-like stromal cells and fibrous material. CONCLUSION: Our results imply that the CD10 expression pattern depended on the histotypes of thyroid lesions. When possible metastatic tumours and non-epithelial tumours are excluded, high CD10 expression may be useful in determining whether a primary thyroid carcinoma includes an anaplastic component.

Magnetic resonance elastography is as accurate as liver biopsy for liver fibrosis staging.

BACKGROUND: Liver MR elastography (MRE) is available for the noninvasive assessment of liver fibrosis; however, no previous studies have compared the diagnostic ability of MRE with that of liver biopsy. PURPOSE: To compare the diagnostic accuracy of liver fibrosis staging between MRE-based methods and liver biopsy using the resected liver specimens as the reference standard. STUDY TYPE: A retrospective study at a single institution. POPULATION: In all, 200 patients who underwent preoperative MRE and subsequent surgical liver resection were included in this study. Data from 80 patients were used to estimate cutoff and distributions of liver stiffness values measured by MRE for each liver fibrosis stage (F0-F4, METAVIR system). In the remaining 120 patients, liver biopsy specimens were obtained from the resected liver tissues using a standard biopsy needle. FIELD STRENGTH/SEQUENCE: 2D liver MRE with gradient-echo based sequence on a 1.5 or 3T scanner was used. ASSESSMENT: Two radiologists independently measured the liver stiffness value on MRE and two types of MRE-based methods (threshold and Bayesian prediction method) were applied. Two pathologists evaluated all biopsy samples independently to stage liver fibrosis. Surgically resected whole tissue specimens were used as the reference standard. STATISTICAL TESTS: The accuracy for liver fibrosis staging was compared between liver biopsy and MRE-based methods with a modified McNemar's test. RESULTS: Accurate fibrosis staging was achieved in 53.3% (64/120) and 59.1% (71/120) of patients using MRE with threshold and Bayesian methods, respectively, and in 51.6% (62/120) with liver biopsy. Accuracies of MRE-based methods for diagnoses of ≥F2 (90-91% [108-9/120]), ≥F3 (79-81% [95-97/120]), and F4 (82-85% [98-102/120]) were statistically equivalent to those of liver biopsy (≥F2, 79% [95/120], P ≤ 0.01; ≥F3, 88% [105/120], P ≤ 0.006; and F4, 82% [99/120], P ≤ 0.017). DATA CONCLUSION: MRE can be an alternative to liver biopsy for fibrosis staging. LEVEL OF EVIDENCE: 3. Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1268-1275.

Clinicopathological Risk Factors for Distant Metastasis in Differentiated Thyroid Carcinoma: A Meta-analysis.

INTRODUCTION: Distant metastasis (DM) is not a frequent event in differentiated thyroid carcinoma (DTC) but has an adverse impact on mortality of patients with DTC. In the current study, we aimed to conduct a comprehensive systematic review and meta-analysis to investigate the risk factors for DM in DTCs and for each histological subtype. METHODS: Five electronic databases were searched from inception to December 2016 for relevant articles. Pooled odd ratios and 95% confidence interval were calculated using random-effect model. RESULTS: Thirty-four articles with 73,219 patients were included for meta-analyses. In DTCs, male gender, age ≥45 years, tumor size ≥4 cm, multifocality, vascular invasion (VI), extrathyroidal extension (ETE), lymph node metastasis (LNM), and lateral LNM were demonstrated to be associated with significant risks for DM. In addition, several clinicopathological factors such as age ≥45 years, VI, ETE, and LNM were shown to be significant risk factors for DM in both PTC and FTC subgroups. CONCLUSION: Our study demonstrated the promising value of several clinicopathological factors such as male gender, older age, VI, ETE, and LNM in predicting DM in PTCs and FTCs. Our study affirms the value of the selected clinicopathological factors for tumor risk stratification and assessment of patients' prognosis.

[A Case of Triple Negative Breast Cancer Successfully Treated with S-1].

A 73-year-old woman noticed a mass in her right breast about 1 year ago and consulted our hospital for an enlarged mass of about 10 cm in diameter.She was diagnosed with locally advanced triple negative breast cancer, and we initiated S-1 treatment as neoadjuvant chemotherapy.After 4 chemotherapy courses, computed tomography showed that the primary tumor had shrunk.Therefore, right mastectomy and axillary dissection were performed, and UFT was administered after surgery.She is currently alive with no recurrence 18 months after surgery.

[Case of main duct-intraductal papillary mucinous carcinoma (pancreatobiliary type) causing 4-mm dilatation of the pancreatic duct].

A 77-year-old woman with mild dilatation (4mm) of the main pancreatic duct was referred to our hospital. Contrast-enhanced computed tomography revealed segmental dilatation of the main pancreatic duct in the pancreatic tail, but no mass was noted in the pancreas. Endoscopic ultrasonography showed low papillary lesions in the dilated pancreatic duct. Cytological analysis of the pancreatic juice revealed adenocarcinoma. Distal pancreatectomy was performed for a diagnosis of main duct-intraductal papillary mucinous cancer (MD-IPMC) of the pancreatic tail. Histological findings indicated pancreatobiliary (PB)-type non-invasive IPMC. Although the patient did not meet the diagnostic criteria for intraductal papillary mucinous neoplasms (IPMNs), her final diagnosis was PB-type non-invasive IPMC. Because PB-type IPMNs display poor mucin production, pancreatic duct dilatation is sometimes mild and requires careful assessment for accurate diagnosis.

Molecular alterations of coexisting thyroid papillary carcinoma and anaplastic carcinoma: identification of TERT mutation as an independent risk factor for transformation.

Thyroid papillary carcinoma is the most common endocrine neoplasm and generally carries a favorable prognosis. However, a small subset of papillary carcinomas transforms into anaplastic carcinoma, an undifferentiated cancer with a dismal prognosis. Recent studies using next-generation sequencing revealed the genomic landscape of papillary carcinoma and anaplastic carcinoma. However, risk factors for anaplastic transformation in papillary carcinoma remain obscure. In the present study, we investigated molecular alterations of papillary carcinoma and anaplastic carcinoma components in 27 tumors in which anaplastic carcinoma coexisted with antecedent papillary carcinoma. We conducted direct sequencing for BRAF, TERT promoter and PIK3CA, and immunohistochemistry for p53, TTF-1 and subunits of the SWI/SNF complex (ARID1A, ARID1B, ATRX, SMARCA2, SMARCA4, SMARCB1, and PBRM1). BRAFV600E and TERT promoter mutated at the rate of 90% and 95%, respectively, and these mutational statuses were almost identical between the papillary carcinoma and anaplastic carcinoma components. PIK3CA mutation was positive in 33% of our samples with a heterogeneous mutation pattern of the papillary carcinoma and anaplastic carcinoma components. Aberrant expression of p53 and loss of TTF-1 were present in 63 and 59%, respectively, and these two alterations were confined to the anaplastic carcinoma components. There was a loss of the SWI/SNF complex in a subset of the tumors with a heterogeneous pattern of the papillary carcinoma and anaplastic carcinoma components: SMARCA4 in 4% and PBRM1 in 4%. In a multivariate comparison between the antecedent papillary carcinoma components and control papillary carcinomas without anaplastic transformation, TERT promoter mutation was independently associated with anaplastic transformation. Collectively, papillary carcinoma-derived anaplastic carcinomas are characterized by BRAF and TERT promoter mutations, and these mutations occur prior to anaplastic transformation. Alterations of PIK3CA and the SWI/SNF complex are relatively rare and temporally heterogeneous. Of note, a papillary carcinoma harboring TERT promoter mutation is at higher risk for anaplastic transformation.

Paediatric follicular thyroid carcinoma - indolent cancer with low prevalence of RAS mutations and absence of PAX8-PPARG fusion in a Japanese population.

AIMS: Paediatric follicular thyroid carcinomas are uncommon, and their clinicopathological features and molecular profiles are still unknown. In the present study, we aimed to investigate the clinicopathological aspects of a large series of follicular thyroid carcinomas (FTCs) in paediatric patients and to analyse the point mutations in codons 12, 13 and 61 of NRAS, HRAS and KRAS genes and the rearrangements of PAX8-PPARG. METHODS AND RESULTS: A total of 41 paediatric FTCs less than 21 years of age were enrolled into the present study. We used direct sequencing and reverse transcription-polymerase chain reaction (RT-PCR) to detect RAS mutations and PAX8-PPARG fusions, respectively. The paediatric FTCs were 6:1 in a female to male ratio, with a mean tumour size of 52.7 mm. Distant metastasis was found in one case at the time of presentation. During a median follow-up time of 69 months, two cases had lung metastasis and all patients were alive. Histologically, all cases were minimally invasive FTCs and varied in growth patterns: microfollicular (39%), follicular (14.6%), solid/trabecular (6%), oncocytic (4.9%) and mixed patterns (26.8%). The mean Ki67 index was 5.7% and it was not statistically different among the growth patterns. NRAS mutations were found in five cases (12.2%) and associated significantly with small tumour size (P = 0.014). PAX8-PPARG fusion was not detected in our series. CONCLUSION: Paediatric FTCs are indolent in clinical course in spite of their large tumour size and have a distinct genetic background. RAS mutations and PAX8-PPARG fusions may not play major roles in the tumorigenesis of paediatric FTCs.

Role of molecular markers to predict distant metastasis in papillary thyroid carcinoma: Promising value of TERT promoter mutations and insignificant role of BRAF mutations-a meta-analysis.

The presence of distant metastasis is associated with an adverse outcome in papillary thyroid cancer. We performed a meta-analysis to investigate the role of molecular markers as predictors for distant metastasis in papillary thyroid cancer. Four electronic databases including PubMed, Web of Science, Scopus, and Virtual Health Library were searched, and odds ratio and its 95% confidence interval concerning the association of BRAF, RAS, and TERT promoter mutations and RET/PTC rearrangements with distant metastasis were calculated using random-effects model. In total, 42 studies with 11,109 papillary thyroid cancers were included for meta-analyses. Overall, the presence of TERT promoter (odds ratio = 5.95; 95% confidence interval = 2.95-11.99), RAS mutations (odds ratio = 2.5; 95% confidence interval = 1.00-6.22), and RET/PTC rearrangements (odds ratio = 1.92; 95% confidence interval = 1.03-3.56) were found to be associated with a significantly increased risk for distant metastasis. BRAF mutations were not associated with an elevated risk for distant metastasis (odds ratio = 0.79; 95% confidence interval = 0.54-1.16). In conclusion, our study demonstrated the promising value of few molecular biomarkers, especially TERT promoter mutations in predicting distant metastasis in papillary thyroid cancers, while BRAF mutations showed no association with distant metastasis. Our study affirms the value of selected mutations for tumor risk stratification and assessment of patients' prognosis.

[Adaptation of Anti-PD-1/Anti-PD-L1 Antibody from the Viewpoint of Analysis of Tumor Microenvironment].

The response rate of anti-PD-1/anti-PD-L1antibody alone is about 20 to 30%and the development of biomarker for them is important to know their indication. Based on previous reports and our research results, we suggested that basic candidates of biomarker for anti-PD-1/anti-PD-L1antibody are the expression of PD-L1and HLA class I on cancer cells and the invasion of CD8 positive T cells in tumor microenvironment. Furthermore, in addition to these conditions, regulatory T cells and immune cells expressing PD-L1in tumor microenvironment, and microsatellite instability of cancer cells will be considered in the future.

Hepatitis activity should be considered a confounder of liver stiffness measured with MR elastography.

PURPOSE: To evaluate the effect of hepatitis activity on liver stiffness measurements and the role of serum alanine aminotransferase (ALT) in liver fibrosis staging by MR elastography (MRE). MATERIALS AND METHODS: We measured liver stiffness (kPa) in 135 patients by MRE and histologically assessed fibrosis and hepatitis activity within 2 months. Stepwise multiple linear regression was performed to determine the maximum adjusted R(2) against liver stiffness, after adjusting for nothing (model 1), ALT/upper limit of normal categories (model 2), and hepatitis activity (A grade) by METAVIR (model 3). Logistic regression was used to identify independent factors associated with pathologically proven cirrhosis. RESULTS: Platelet count and METAVIR F score were strongly associated with liver stiffness. The adjusted R(2) value of model 3 (0.7026) was higher than those of models 1 (0.6472) and 2 (0.6564), showing that hepatitis activity affected liver stiffness measurement. High ALT levels (odds ratio, 0.0066; P = 0.0003) as well as MRE (odds ratio, 9.91; P < 0.0001) were independently associated with cirrhosis. CONCLUSION: Hepatitis activity may be a confounder of liver stiffness measurement during liver fibrosis staging using MRE. MRE can potentially make an overdiagnosis of liver cirrhosis if the patient has high ALT levels.

Subcutaneous porocarcinoma clinically presenting as a soft tissue tumor.

Porocarcinoma is a rare malignancy with glandular adnexal differentiation. A 38-year-old Japanese man noticed a subcutaneous mass in right inguinal region about 20 years prior to being examined. Radiological examinations demonstrated the mass, 11 × 10 cm in size, was in the subcutaneous fat tissue. Recently, the mass grew rapidly, and it was biopsied by an orthopedist based on clinical diagnosis of primary soft tissue tumor. Histopathological examination of the resected specimens also revealed that the tumor lacked involvement to the skin. Microscopically, the tumor was mainly composed of poroid cells with partially obvious squamous differentiation, accompanied by focal ductal structures immunoreactive for CEA and EMA. The tumor contained a low-grade area consisting of poroid cells and high-grade area with squamous differentiation. This histopathological heterogeneity suggested malignant transformation from poroma. The patient had the tumor in almost same size over the period of 20 years, which is the longest in the previous reports. This unique case of subcutaneous porocarcinoma is reported.

High prevalence of the MYD88 mutation in testicular lymphoma: Immunohistochemical and genetic analyses.

The activating mutation of MYD88 has been identified in diffuse large B-cell lymphoma (DLBCL). We investigated the mutational status and both the gene amplification and protein expression of MYD88 in 23 cases of testicular DLBCL. To detect the MYD88 mutations, we employed the allele-specific PCR and Sanger sequencing. MYD88 gene amplification and protein expression were analyzed by quantitative PCR and by immunohistochemistry, respectively. There were 17 cases of primary testicular DLBCL: 94% (16/17) exhibited a non-Germinal center B-cell (non-GCB) subtype, 82% (14/17) showed the MYD88 L265P, and 65% (11/17) had intense expression of MYD88. When compared with normal lymph nodes, the MYD88 is significantly amplified in primary testicular DLBCL. However, the amplification status showed no correlation with its mutational status or protein expression. Moreover, neither the MYD88 mutational status nor the expression pattern affected overall survival. Six cases were secondary testicular DLBCL with an 83% (5/6) and an 80% (4/5) incidence of the non-GCB subtype and of the MYD88 L265P, respectively. In conclusion, we demonstrated a high prevalence of the non-GCB subtype and the common MYD88 L265P in both primary and secondary testicular DLBCL. Our data suggest that the MYD88 mutation is a fairly consistent genetic feature in testicular DLBCL.

Low frequency of PAX8-PPARγ rearrangement in follicular thyroid carcinomas in Japanese patients.

Paired-box gene 8 (PAX8)-peroxisome proliferator-activated receptor-γ (PPARγ) gene fusion has been identified at significant frequency in follicular thyroid carcinomas (FTCs) with cytogenetically detectable translocation t(2;3)(q13;p25). This represents a possible specific molecular marker for follicular carcinoma. In this study, we examined PAX8-PPARγ rearrangement in 24 FTC samples from Japanese patients by reverse transcribed-polymerase chain reaction (RT-PCR) using two upstream PAX8 primers located in exons 7 and 8 and a downstream primer in exon 1 of PPARγ. The fusion gene was detected in only one of 24 FTCs (4%). The FTC with PAX8-PPARγ rearrangement from a 56-year-old man showed a product consistent with fusion between exon 8 of PAX8 and exon 1 of PPARγ. It was confirmed by direct sequencing. This FTC was histologically encapsulated, composed of trabeculae and small follicles and had complete penetration of the capsule by tumor tissues (minimally invasive type). The frequency of the fusion gene in this study was much lower than the 29-63% noted in reports from other countries suggesting that FTCs in Japanese patients may have a special genetic background, and that the high iodine intake from a typical Japanese diet might influence the frequency of the fusion gene in FTCs.

Typical fibrolamellar hepatocellular carcinoma in a Japanese boy: report of a case.

We report a case of typical fibrolamellar hepatocellular carcinoma (FL-HCC) in a 16-year-old Japanese boy. This is very rare malignancy in Japan. The patient was referred for investigation of a large hepatic tumor and the results of tests for hepatitis B virus surface antigen and hepatitis C virus antibody were negative. Liver function test results and serum alpha-fetoprotein (AFP) levels were normal; however, the prothrombin induced by vitamin K absence/antagonist II was elevated. Computed tomography (CT) showed a large lobulated heterogeneously enhanced tumor in the posterior section of the liver. We diagnosed FL-HCC and performed posterior sectionectomy of the liver. The resected specimen contained a light brown and green tumor with a central fibrous scar, 10.0 cm in diameter. Microscopic and electron microscopic examinations revealed the typical features of FL-HCC. Immunohistochemically, the tumor cells were positive for cytokeratin (CK) 7, but negative for CK19 and AFP. The patient was alive without recurrence 48 months after surgery. Following this case report, we summarize the clinical features of the Japanese cases documented in the literature.

Gastric metastasis of renal cell carcinoma treated with endoscopic resection: A case report.

Gastric metastasis of renal cell carcinoma (RCC) is rarely encountered. The time interval between the primary diagnosis of RCC and the occurrence of gastric metastasis tends to occur after more than 10 years. Clinicians should be diligent in checking the general symptoms of patients for more than 10 years.