Anti-N-Methyl-D-Aspartate Receptor (NMDAR) Encephalitis Associated With Mediastinal and Ovarian Teratomas: A Case Report.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common type of autoimmune encephalitis. Approximately 80% of patients with anti-NMDAR encephalitis are women. Tumors are detected in approximately 50% of female patients with anti-NMDAR encephalitis, of which 96% are ovarian teratomas. We describe the case of a 28-year-old woman diagnosed with anti-NMDAR encephalitis with mediastinal and bilateral ovarian teratomas in July 2019. The patient recovered following surgical management of the mediastinal mass and both ovarian teratomas, and immunotherapy. This case shows that teratomas can be found at multiple sites other than ovaries. Therefore, detecting teratomas using whole-body evaluation may be helpful for diagnosis and treatment.

Ultrahigh-field cardiovascular magnetic resonance T1 and T2 mapping for the assessment of anthracycline-induced cardiotoxicity in rat models: validation against histopathologic changes.

BACKGROUND: Chemotherapy-induced cardiotoxicity is a well-recognized adverse effect of chemotherapy. Quantitative T1-mapping cardiovascular magnetic resonance (CMR) is useful for detecting subclinical myocardial changes in anthracycline-induced cardiotoxicity. The aim of the present study was to histopathologically validate the T1 and T2 mapping parameters for the evaluation of diffuse myocardial changes in rat models of cardiotoxicity. METHODS: Rat models of cardiotoxicity were generated by injecting rats with doxorubicin (1 mg/kg, twice a week). CMR was performed with a 9.4 T ultrahigh-field scanner using cine, pre-T1, post-T1 and T2 mapping sequences to evaluate the left ventricular ejection fraction (LVEF), native T1, T2, and extracellular volume fraction (ECV). Histopathological examinations were performed and the association of histopathological changes with CMR parameters was assessed. RESULTS: Five control rats and 36 doxorubicin-treated rats were included and classified into treatment periods. In the doxorubicin-treated rats, the LVEF significantly decreased after 12 weeks of treatment (control vs. 12-week treated: 73 ± 4% vs. 59 ± 9%, P = 0.01).  Increased native T1 and ECV were observed after 6 weeks of treatment (control vs. 6-week treated: 1148 ± 58 ms, 14.3 ± 1% vs. 1320 ± 56 ms, 20.3 ± 3%; P = 0.005, < 0.05, respectively). T2 values also increased by six weeks of treatment (control vs. 6-week treated: 16.3 ± 2 ms vs. 10.3 ± 1 ms, P < 0.05). The main histopathological features were myocardial injury, interstitial fibrosis, inflammation, and edema. The mean vacuolar change (%), fibrosis (%), and inflammation score were significantly higher in 6-week treated rats than in the controls (P = 0.03, 0.03, 0.02, respectively). In the univariable analysis, vacuolar change showed the highest correlation with native T1 value (R = 0.60, P < 0.001), and fibrosis showed the highest correlation with ECV value (R = 0.78, P < 0.001). In the multiple linear regression analysis model, vacuolar change was a significant factor for change in native T1 (P = 0.01), and vacuolar change and fibrosis were significant factors for change in ECV (P = 0.006, P < 0.001, respectively) by adding other histopathological parameters (i.e., inflammation and edema scores) CONCLUSIONS: Quantitative T1 and T2 mapping CMR is a useful non-invasive tool reflecting subclinical histopathological changes in anthracycline-induced cardiotoxicity.

Clinicopathological and Preclinical Findings of NUT Carcinoma: A Multicenter Study.

BACKGROUND: NUT carcinoma is a rare aggressive disease caused by BRD4/3-NUT fusion, and C-MYC upregulation plays a key role in the pathogenesis. Here, we report on the clinicopathological characteristics of Korean patients with NUT carcinoma and the in vitro efficacy of MYC-targeting agents against patient-derived NUT carcinoma cell lines. MATERIALS AND METHODS: Thirteen patients with NUT carcinoma were evaluated for p53, C-MYC, epidermal growth factor receptor (EGFR), HER2, and programmed cell death ligand 1 (PD-L1) by immunohistochemistry. The half maximal inhibitory concentration (IC50) values of NUT carcinoma cell lines (SNU-2972-1, SNU-3178S, HCC2429, and Ty-82) were determined using MYC-targeting agents, including bromodomain and extraterminal (BET) inhibitors (I-BET, OTX-015, AZD5153) and histone deacetylase (HDAC) inhibitors (vorinostat, romidepsin, panobinostat, CUDC-907). RESULTS: Primary tumor sites included head and neck (n = 9) and lung (n = 4). The patient age ranged from 8 to 73 years with the male/female ratio of 1.2:1. Nine patients died at 3-23.6 months (median, 10.6) after diagnosis. Eight patients had been misdiagnosed initially with other diseases. One patient with metastatic NUT carcinoma who received mass excision plus metastasectomy followed by chemoradiotherapy was a long-term survivor (>27 months). Although expressions of C-MYC (8/12, 73%) and p53 (12/12, 100%) were commonly observed, EGFR, HER2, and PD-L1 expressions were observed in 2 of 7 (29%), 2 of 8 (25%), and 1 of 12 (8.3%) patients, respectively. BET and HDAC inhibitors showed variable but limited in vitro efficacy. However, a dual HDAC/PI3K inhibitor, CUDC-907, was most potent against NUT carcinoma cells, with an IC50 of 5.5-9.0 pmol/L. Consistent with these findings, kinome short interfering RNA screening showed a positive hit for PI3KCA in NUT carcinoma cells. Panobinostat (IC50, 0.4-1.3 nmol/L) and a bivalent BET inhibitor, AZD5153 (IC50, 3.7-8.2 nmol/L), also showed remarkable efficacies. CONCLUSION: East Asian patients with NUT carcinoma showed dismal survival outcomes like Western patients, and CUDC-907 might be promising in NUT carcinoma treatment. IMPLICATIONS FOR PRACTICE: NUT carcinoma (NC) is a disease caused by BRD-NUT fusion leading to C-MYC upregulation. NC is often misdiagnosed and very aggressive, requiring development of effective therapeutic strategy. This article presents the clinicopathological features of the largest series of NCs in East Asians and preclinical sensitivities to MYC-targeting agents in NC cell lines. Patients with NC had grave outcomes and poor response to treatment. Among MYC-targeting agents, including BET and HDAC inhibitors, CUDC-907 (a dual PI3K/HDAC inhibitor) was most effective against NC cells, followed by panobinostat (an HDAC inhibitor) and AZD5153 (a bivalent BET inhibitor). CUDC-907 might be promising in NC treatment.

Lung Adenocarcinoma Invasiveness Risk in Pure Ground-Glass Opacity Lung Nodules Smaller than 2 cm.

BACKGROUND: We aimed to identify clinicopathologic characteristics and risk of invasiveness of lung adenocarcinoma in surgically resected pure ground-glass opacity lung nodules (GGNs) smaller than 2 cm. METHODS: Among 755 operations for lung cancer or tumors suspicious for lung cancer performed from 2012 to 2016, we retrospectively analyzed 44 surgically resected pure GGNs smaller than 2 cm in diameter on computed tomography (CT). RESULTS: The study group was composed of 36 patients including 11 men and 25 women with a median age of 59.5 years (range, 34-77). Median follow-up duration of pure GGNs was 6 months (range, 0-63). Median maximum diameter of pure GGNs was 8.5 mm (range, 4-19). Pure GGNs were resected by wedge resection, segmentectomy, or lobectomy in 27 (61.4%), 10 (22.7%), and 7 (15.9%) cases, respectively. Pathologic diagnosis was atypical adenomatous hyperplasia, adenocarcinoma in situ, minimally invasive adenocarcinoma (MIA), or invasive adenocarcinoma (IA) in 1 (2.3%), 18 (40.9%), 15 (34.1%), and 10 (22.7%) cases, respectively. The optimal cutoff value for CT-maximal diameter to predict MIA or IA was 9.1 mm. In multivariate analyses, maximal CT-maximal diameter of GGNs ≥10 mm (odds ratio, 24.050; 95% confidence interval, 2.6-221.908; p = 0.005) emerged as significant independent predictor for either MIA or IA. Estimated risks of MIA or IA were 37.2, 59.3, 78.2, and 89.8% at maximal GGN diameters of 5, 10, 15, and 20 mm, respectively. CONCLUSION: Pure GGNs were highly associated with lung adenocarcinoma in surgically resected cases, while estimated risk of GGNs invasiveness gradually increased as maximal diameter increased.

Spontaneous remission of advanced progressive poorly differentiated non-small cell lung cancer: a case report and review of literature.

BACKGROUND: Spontaneous remission (SR) of cancer is a very rare phenomenon of unknown mechanism. In particular, SR of non-small cell lung cancer (NSCLC) has been scarcely reported. We present the case of a 74-year-old woman with advanced, poorly differentiated NSCLC (highly expressing programmed death ligand-1 [PD-L1]) that progressed despite multiple lines of chemotherapy but then spontaneously remitted. CASE PRESENTATION: The patient presented with hemoptysis and was diagnosed with stage IIIA poorly differentiated NSCLC via bronchoscopic biopsy. She had an unremarkable medical history and moderate performance status. The initial treatment plan was surgery after neoadjuvant chemotherapy. Despite conventional chemotherapy, follow-up chest computed tomography (CT) showed gradual tumor progression and she decided against further treatment after fifth-line chemotherapy. However, the size of lung mass was markedly decreased on follow-up chest CT one year after ceasing chemotherapy. Also, follow-up positron emission tomography images showed decreased metabolic activity in the lung mass and a percutaneous biopsy specimen from the diminished lung mass revealed no viable tumor cells. A diagnosis of SR of NSCLC was confirmed, and the patient was without tumor progression on follow-up nine months later. Later, PD-L1 immunostaining revealed high positivity (> 99%) in initial tumor cells. CONCLUSION: Our case showing SR of poorly advanced NSCLC refractory to multiple lines of chemotherapy suggested the association between immunity and tumor regression.

Genetic heterogeneity of actionable genes between primary and metastatic tumor in lung adenocarcinoma.

BACKGROUND: Biopsy for lung cancer diagnosis is usually done at a single site. But it is unclear that genetic information at one biopsy site represents that of other lesions and is sufficient for therapeutic decision making. METHODS: Non-synonymous mutations and insertions/deletions of 16 genes containing actionable mutations, and intron 2 deletion polymorphism of Bcl2-like11 were analyzed in 41 primary tumor and metastatic lymph node (L/N) matched, pStage IIA ~ IIIA non-small cell lung cancer (NSCLC) samples using a next generation sequencing based technique. RESULTS: A total of 249 mutations, including 213 non-synonymous mutations, 32 deletions, and four insertions were discovered. There was a higher chance of discovering non-synonymous mutations in the primary tumors than in the metastatic L/N (138 (64.8%) vs. 75 (35.2%)). In the primary tumors, 106 G > A:C > T transitions (76.8%) of 138 non-synonymous mutations were detected, whereas in the metastatic L/N, 44 (58.7%) of 75 were discovered. A total 24 (11.3%) out of 213 non-synonymous mutations were developed in the context of APOBEC signature. Of those, 21 (87.5%) was detected in the primary tumors and 4 (16.7%) was detected in the metastatic L/N. When the mutation profiles between primary tumor and metastatic L/N were compared, 13 (31.7%) of 41 cases showed discrepant mutation profile. There were no statistically significant differences in disease free survival and overall survival between groups showing identical mutation profiles and those with discrepancy between primary and metastatic L/N. CONCLUSIONS: Genetic heterogeneity between the primary and L/N metastatic lesions is not infrequent finding to consider when interpreting genomic data based on the result of one site inspection. A large prospective study may be needed to evaluate the impact of genetic heterogeneity on the clinical outcomes of NSCLC patients.

Effect of preoperative colonoscopic tattooing on lymph node harvest in T1 colorectal cancer.

OBJECTIVE: This study aimed to identify the impact of preoperative colonoscopic tattooing (PCT) on lymph node harvest in T1 colorectal cancer patients. MATERIAL AND METHODS: One hundred and forty-three patients were included who underwent curative resection and were diagnosed with T1 colorectal cancer. These patients were categorized into the tattooing group and the non-tattooing group depending on whether preoperative India ink tattooing was done. Clinicopathological findings and lymph node harvest were compared between the two groups. RESULTS: The median number of lymph nodes examined was 18 in the tattooing group and 13 in the non-tattooing group (p < 0.001). The rate of adequate lymph node harvest (retrieval of more than 12 lymph nodes) was higher in the tattooing group than that in the non-tattooing group (83.7 vs. 58.5 %, p = 0.002). The PCT was significantly associated with adequate lymph node harvest in multivariate analysis (hazard ratio, 3.8; 95 % confidence interval, 1.5-9.2; p = 0.003). Among the 40 patients who showed at least one carbon particle-containing lymph nodes, the positive lymph node rate was not different between carbon-containing LNs (0.9 %) and non-carbon-containing LNs (1.7 %). CONCLUSIONS: PCT was associated with higher lymph node yield in T1 colorectal cancer. It is questionable if tattooing has additional detection power as a sentinel lymph node mapping tool in T1 colorectal cancer.

High EGFR gene copy number predicts poor outcome in triple-negative breast cancer.

Epidermal growth factor receptor (EGFR) is frequently overexpressed in triple-negative breast cancer and is emerging as a therapeutic target. EGFR gene copy number alteration and mutation are highly variable and scientists have been challenged to define their prognostic significance in triple-negative breast cancer. We examined EGFR protein expression, EGFR gene copy number alteration and mutation of exon 18 to 21 in 151 cases of triple-negative breast cancer and correlated these findings with clinical outcomes. In addition, intratumoral agreement of EGFR protein overexpression and gene copy number alteration was evaluated. EGFR overexpression was found in 97 of 151 cases (64%) and high EGFR gene copy number was detected in 50 cases (33%), including 3 gene amplification (2%) and 47 high polysomy (31%). Five EGFR mutations were detected in 4 of 151 cases (3%) and included G719A in exon 18 (n=1), V786M in exon 20 (n=1), and L858R in exon 21 (n=3). One case had two mutations (G719A and L858R). High EGFR copy number, but not EGFR mutation, correlated with EGFR protein overexpression. Intratumoral heterogeneity of EGFR protein overexpression and EGFR copy number alteration was not significant. In survival analyses, high EGFR copy number was found to be an independent prognostic factor for poor disease-free survival in patients with triple-negative breast cancer. Our findings showed that EGFR mutation was a rare event, but high EGFR copy number was relatively frequent and correlated with EGFR overexpression in triple-negative breast cancer. Moreover, high EGFR copy number was associated with poor clinical outcome in triple-negative breast cancer, suggesting that evaluation of EGFR copy number may be useful for predicting outcomes in patients with triple-negative breast cancer and for selecting patients for anti-EGFR-targeted therapy.

18F-FDG PET/CT features of pulmonary sclerosing hemangioma.

BACKGROUND: Pulmonary sclerosing hemangioma (PSH) has been reported to show increased FDG uptake and be potential false-positives on 18F-FDG PET/CT examination. However, it is still unclear whether the previously-reported high FDG uptake is a universal characteristic of PSH, and furthermore, there have been no investigations on what kind of radiologic or histologic features may have been related with its FDG uptake values. PURPOSE: To investigate the 18F-FDG PET/CT features of pulmonary sclerosing hemangiomas (PSHs), and to evaluate the relating factors with their FDG uptake values. MATERIAL AND METHODS: We identified 10 PSHs in eight patients who had a pathologic diagnosis and available antecedent 18F-FDG PET/CT images. 18F-FDG PET/CT images were investigated both qualitatively and quantitatively, along with their histopathologic features. Correlation between 18F-FDG PET features and radiologic as well as histopathologic features were also evaluated. RESULTS: Mean diameter of the 10 PSHs in our study was 16.9 mm ± 6.26 (range 5-25 mm). Four tumors showed intense uptake, and four tumors showed moderate uptake on 18F-FDG PET/CT scans. In the remaining two tumors, there were no significant FDG uptakes. The SUVmax of tumors ranged from 0.60-4.7 (median 2.30; 2.51 ± 1.42), and was significantly correlated with the tumor size (r = 0.754, P = 0.012) and three out of four tumors ≥2 cm (75%) showed intense FDG uptake and their SUVmax values were greater than 2.5. Immunohistochemical results for GLUT-1, GLUT-4, and Ki-67 and other pathologic features were not correlated with the tumors' FDG uptake. CONCLUSION: The majority of PSHs show increased FDG uptakes, and their SUVmax values are significantly correlated with their tumor size. PSH ≥2 cm can frequently be falsely interpreted as malignancy in FDG-PET/CT. Further studies with large study population are warranted to confirm our observations.

Rhabdomyomatous mesenchymal hamartoma of nasal vestibule.

Rhabdomyomatous mesenchymal hamartoma is a rare congenital tumor and usually occurring in the head and neck. Characteristically, this tumor is composed of various mesenchymal elements such as adipose tissue, blood vessels, collagen fibers, elastic fibers, and peripheral nerves in random orientation. We present a 7-year-old boy with an intranasal mass developed after the trauma and who had a diagnosis of rhabdomyomatous mesenchymal hamartoma.

Intraosseous hemangioma as a rare differential diagnosis of intranasal bony tumor.

Intraosseous hemangioma is a benign vascular tumor of the bone. The most common site of this tumor is the vertebral body, followed by calvarial bones. Intraosseous hemangioma of the nasal cavity is extremely rare. This lesion had en bloc been resected through the endoscopic approach without preoperative embolization, significant intraoperative bleeding, and postoperative events. We report a rare case of intraosseous hemangioma of the nasal cavity with distinctive radiologic findings. Clinicians should be well familiar with the radiologic findings and clinical features of this tumor, which would be helpful in making a correct diagnosis and management plan.

The Effect of Complete Prostate Examination of Radical Cystoprostatectomy Specimen on the Final Stage of Urothelial Carcinoma of the Urinary Bladder and the Detection of Prostate Cancer.

CONTEXT.­: The prostate sampling methods for radical cystoprostatectomy (RCP) specimens may affect pathologic results. OBJECTIVE.­: To investigate the impact on the tumor stage and clinicopathologic features according to the prostate sampling method for RCP specimens. DESIGN.­: From 2016 to 2017, the prostate in RCP was minimally and conventionally embedded (group 1, n = 98). From 2017 to 2018, it was completely embedded (group 2, n = 102). RESULTS.­: Group 2 was more likely to have prostatic ducts or acini involvement by urothelial carcinoma in situ component (27% versus 10%, P = .002) and prostate involvement (30% versus 13%, P = .003) than group 1. Although there were cases with prostatic stromal invasion in group 2 (14% versus 7%, P = .13), this was not statistically significant. In all, 6 cases were upstaged by subepithelial prostatic stromal invasion through intraurethral extension according to the 8th edition of the American Joint Committee on Cancer (AJCC) staging system. Tumor location and the presence of concurrent carcinoma in situ were strongly associated with prostate involvement of urothelial carcinoma. Prostatic adenocarcinoma (PA) was incidentally identified in 47 cases (23.5%). Incidental PA and clinically significant PA were more often identified in group 2 than group 1 (38% versus 8%, P < .01 and 15% versus 6%, P = .048, respectively). CONCLUSIONS.­: A complete prostate examination in RCP specimens can be suggested, since the final pathologic stage can be changed through a thorough prostate examination especially in accord with the AJCC staging manual 8th edition. In addition, the complete prostate analysis could detect more incidental and clinically significant PA.

Comparative analyses of overall survival in patients with anaplastic lymphoma kinase-positive and matched wild-type advanced nonsmall cell lung cancer.

BACKGROUND: The purpose of this study was to investigate the overall survival (OS) of patients with advanced ALK-positive nonsmall cell lung cancer (NSCLC) who were managed in the pre-ALK inhibitor era and to compare their survival with that of a matched case cohort of ALK wild-type (WT) patients. METHODS: Data from 1166 patients who had stage IIIB/IV NSCLC with nonsquamous histology were collected from the NSCLC database of Seoul National University Hospital between 2003 and 2009. ALK fluorescence in situ hybridization (FISH) was used to analyze 262 patients who either had the WT epidermal growth factor receptor (EGFR) or were nonresponders to previous EGFR tyrosine kinase inhibitor (TKI) therapy. Overall survival (OS) was compared between 3 groups: 1) ALK-positive patients, 2) EGFR mutation-positive patients, and 3) ALK-WT/EGFR-WT patients. Progression-free survival (PFS) after first-line chemotherapy and EGFR TKIs also was analyzed. RESULTS: Twenty-three patients were ALK-positive according to FISH analysis and did not receive ALK inhibitors during follow-up. The median OS for ALK-positive patients, EGFR mutation-positive patients, and WT/WT patients was 12.2 months, 29.6 months, and 19.3 months, respectively (vs EGFR mutation-positive patients, P = .001; vs WT/WT, P = .127). The PFS after first-line chemotherapy for the 3 groups was not different. However, the PFS for patients who received EGFR TKIs was shorter in ALK-positive patients compared with the other 2 groups (vs EGFR mutation-positive patients, P < .001; vs WT/WT, P < .021). CONCLUSIONS: In the pre-ALK inhibitor era, ALK-positive patients experienced the shortest survival, although it did not differ statistically from that of WT/WT patients. Although their responses to platinum-based chemotherapy were not different from comparator groups, ALK-positive patients were even more resistant to EGFR TKI treatment than WT/WT patients.

Treatment response and long term follow-up results of nonspecific interstitial pneumonia.

The purpose of this study was to investigate the long-term clinical course of non-specific interstitial pneumonia (NSIP) and to determine which factors are associated with a response to steroid therapy and relapse. Thirty-five patients with pathologically proven NSIP were included. Clinical, radiological, and laboratory data were reviewed retrospectively. The male-to-female ratio was 7:28 (median age, 52 yr). Thirty (86%) patients responded to steroid therapy, and the median follow-up was 55.2 months (range, 15.9-102.0 months). Five patients (14%) showed sustained disease progression and three died despite treatment. In the five with sustained disease progression, NSIP was associated with various systemic conditions, and the seropositivity of fluorescent antinuclear antibody was significantly associated with a poor response to steroids (P = 0.028). The rate of relapse was 25%, but all relapsed patients improved after re-treatment. The initial dose of steroids was significantly low in the relapse group (P = 0.020). In conclusion, progression is associated with various systemic conditions in patients who show progression. A low dose of initial steroids is significantly associated with relapse.

Pulmonary Multinodular Epithelioid Hemangioendothelioma with Mixed Progression and Spontaneous Regression during a 7-Year Follow-Up: A Case Report and Review of Imaging Findings.

Pulmonary epithelioid hemangioendothelioma (PEH) is a rare vascular tumor of borderline or low-grade malignancy, and its prognosis is unpredictable. Herein, we describe the case of a 47-year-old asymptomatic female with a diagnosis of multinodular PEH. During a 7-year follow-up, the nodules with large size and high 18F-fluorodeoxyglucose uptake in the initial study showed progression with increasing sizes; however, most small nodules (size < 1 cm) demonstrated spontaneous regression with peripheral rim or nodular calcification. The patient underwent surgical resection for an enlarged nodule. Of note, it is unusual for an individual to have mixed progression and regression concomitantly, which may be helpful in predicting the prognosis.

A novel FLCN gene mutation causing Birt-Hogg-Dubé syndrome in a Korean family.

Spontaneous pneumothorax is a common manifestation of Birt-Hogg-Dubé (BHD) syndrome, an inherited disorder caused by mutation of the folliculin (FLCN) gene. A 44-year-old female with a history of breast cancer was diagnosed with recurrent pneumothorax. Chest CT showed multiple cysts with left lung pneumothorax, and she received surgery for the diagnosis. Because the patient also had a family history of spontaneous pneumothorax, a FLCN genetic examination was conducted. A novel heterozygous, likely pathogenic variant (NM_144997.5:c.779+2T > C) was detected in the proband, her mother, and aunt. This is the first report of a new mutation of FLCN gene in a BHD syndrome patient.

Gene expression profiling of metaplastic lineages identifies CDH17 as a prognostic marker in early stage gastric cancer.

BACKGROUND & AIMS: Intestinal metaplasia (IM) and spasmolytic polypeptide-expressing metaplasia (SPEM) are precursors to gastric carcinogenesis. We sought to identify molecular biomarkers of gastric metaplasias and gastric cancer by gene expression profiling of metaplastic lesions from patients. METHODS: Complementary DNA microarray analysis was performed on IM and SPEM cells isolated from patient samples using laser capture microdissection. Up-regulated transcripts in metaplastic lesions were confirmed by immunostaining analysis in IM, SPEM, and gastric cancer tissues. Proteins that were highly expressed specifically in gastric cancer tissues were analyzed for their association with survival in a test set (n = 450) and a validation set (n = 502) of samples from gastric cancer patients. RESULTS: Compared with normal chief cells, 858 genes were differentially expressed in IM or SPEM samples. Immunostaining was detected for 12 proteins, including 3 new markers of IM (ACE2, LGALS4, AKR1B10) and 3 of SPEM (OLFM4, LYZ, DPCR1). Of 13 proteins expressed in IM or SPEM, 8 were expressed by 17%-50% of human gastric cancer tissues (MUC13, OLFM4, CDH17, KRT20, MUC5AC, LGALS4, AKR1B10, REG4). Expression of CDH17 or MUC13 correlated with patient survival in the test and validation sets. Multivariate analysis showed that CDH17 was an independent prognostic factor in patients with stage I or node-negative disease. CONCLUSIONS: We identified several novel biomarkers for IM, SPEM, and gastric cancer using gene expression profiling of human metaplastic lesions. Expression of CDH17 and MUC13 was up-regulated in gastric cancer tissues. CDH17 is a promising prognostic marker for early stage gastric cancer.

Determination of the cutoff value of the proportion of cystic change for prognostic stratification of clear cell renal cell carcinoma.

PURPOSE: Cystic renal cell carcinoma has more favorable biology than noncystic renal cell carcinoma. Recently cystic change detected grossly or by low power microscopy was found to be a good prognostic factor for clear cell renal cell carcinoma. We assessed the optimal cutoff value of the proportion of cystic change with prognostic significance for clear cell renal cell carcinoma. MATERIALS AND METHODS: We identified 223 patients with clear cell renal cell carcinoma who underwent partial or radical nephrectomy between 2001 and 2003. The cystic proportion of the tumor cut surface was calculated objectively and its prognostic significance was evaluated. RESULTS: The ROC curve showed that a cystic percent of between 6% and 10% was appropriate to detect patients with renal cell carcinoma at low risk for cancer mortality and progression. A cutoff of 6% was adopted as a break point of cystic change for patient stratification. We analyzed the records of 87 patients (39.0%) with tumors with a cystic proportion of greater than 5%, that is 6% or greater. They had significantly lower stage and lower Fuhrman nuclear grade than patients with tumors with a cystic change of 5% or less (each p<0.0001). On multivariate analysis a cystic proportion of more than 5% was a good prognostic indicator of cancer specific and progression-free survival (HR 0.221, p=0.044 and HR 0.214, p=0.004, respectively). CONCLUSIONS: In patients with clear cell renal cell carcinoma a cystic change comprising more than 5% of the tumor is a good independent predictor of survival.

Sarcomatoid urothelial carcinoma arising in the female urethral diverticulum.

A sarcomatoid variant of urothelial carcinoma in the female urethral diverticulum has not been reported previously. A 66-year-old woman suffering from dysuria presented with a huge urethral mass invading the urinary bladder and vagina. Histopathological examination of the resected specimen revealed predominantly undifferentiated pleomorphic sarcoma with sclerosis. Only a small portion of conventional urothelial carcinoma was identified around the urethral diverticulum, which contained glandular epithelium and villous adenoma. The patient showed rapid systemic recurrence and resistance to immune checkpoint inhibitor therapy despite high expression of programmed cell death ligand-1. We report the first case of urethral diverticular carcinoma with sarcomatoid features.