A rare epidermal growth factor receptor (EGFR) gene mutation in small cell lung carcinoma patients.

AIM: Activating mutations in the epidermal growth factor receptor (EGFR) are predominantly detected in pulmonary adenocarcinoma and have been reported in small cell lung cancer (SCLC) for decades. This retrospective single-center study aimed to determine the frequency and types of EGFR mutations in SCLC in Taiwan. METHODS: This study comprises a consecutive cohort of 161 patients histologically diagnosed with SCLC between January 1992 and August 2014 at the Department of Pathology in Keelung Chang Gung Memorial Hospital, Taiwan. Archived formalin-fixed paraffin-embedded sections from 71 patients were eligible for molecular analysis. EGFR mutation analysis was performed using a fully-automated IdyllaTM EGFR Mutation Test and confirmed a comparable result through Qiagen Therascreen® EGFR RGQ PCR. In addition, EGFR gene copy number was assessed in EGFR-mutated tumors by fluorescence in situ hybridization (FISH). RESULTS: Mutational status of the EGFR gene was successfully analyzed in 63 specimens by both IdyllaTM and Qiagen platforms. Both methods detected L858R point mutation in exon 21 in an 81-year-old female and a 47-year-old male non-smoker. Both tumors show no concurrent EGFR gene amplification. The overall agreement between results obtained with the Idylla™ EGFR Mutation Test and Qiagen Therascreen® EGFR RGQ PCR was 100% Conclusions. Our results showed that EGFR mutation is a rare mutation type in a consecutive series of de novo SCLC. Furthermore, the performance of Idylla™ EGFR Mutation Test and Qiagen Therascreen® EGFR RGQ PCR on archived paraffin sections of limited quantities is available with the high agreement of results.

A Retrospective Cohort Study of Oral Leukoplakia in Female Patients-Analysis of Risk Factors Related to Treatment Outcomes.

BACKGROUND: The aim of this study was to make a comparison of clinicopathological characteristics of oral leukoplakia between male and female patients following carbon dioxide laser excision for oral leukoplakia and analyze the factors associated with the treatment outcomes in female patients. METHODS: Medical records of patients with oral leukoplakia receiving laser surgery from 2002 to 2020 were retrospectively reviewed and analyzed statistically. RESULTS: A total of 485 patients were enrolled, including 412 male (84.95%) and 73 female (15.05%). Regarding the locations, the predilection site of oral leukoplakia in male patients was buccal mucosa (p = 0.0001) and that for women patients was tongue (p = 0.033). The differences of recurrence and malignant transformation between both sexes were not significant (p > 0.05). Among female patients, area of oral leukoplakia was the risk factor related to recurrence (p < 0.05). Clinical morphology and postoperative recurrence were the risk factors related to malignant transformation (p < 0.05). CONCLUSIONS: In comparison with male patients, there was no significant difference of the postoperative recurrence and malignant transformation of oral leukoplakia in female patients. Among the female patients, clinicians should pay more attention to large-sized and non-homogeneous leukoplakia, and postoperative recurrent lesions.

Warthin's tumor with necrotizing tuberculous granulomatous inflammation causing severe facial nerve adhesion in parotid gland: A case report and literature review.

RATIONALE: Warthin's tumor is the second most common tumor arising from the parotid gland, but it rarely occurs concomitantly with tuberculous granulomatous inflammation with only 13 documented case reports in the English literature. PATIENT CONCERNS: An 82-year-old woman had a left infraauricular mass for approximately 3 years that had significantly increased in size over the previous 1 month. DIAGNOSES: A diagnosis of Warthin's tumor was made by ultrasonography (US)-guided core needle biopsy. Pathological examinations of the specimen obtained by total extirpation confirmed that the tumor was superimposed with tuberculous granuloma. INTERVENTIONS: The core biopsy wound did not heal and there was formation of a skin fistula tract with persistent discharge. During the operation with en bloc resection of the necrotic parotid tumor, adhesion between the branches of the facial nerve was too tight to allow preservation. OUTCOMES: A diagnosis of necrotic Warthin's tumor superimposed with tuberculous granuloma was made. Due to the high-clinical suspicion of tuberculosis (TB) due to Mycobacterium tuberculosis infection, anti-TB chemotherapy was given. LESSONS: Poor wound healing from a core biopsy and formation of a skin fistulous tract with persistent discharge should raise concern regarding potential extrapulmonary tuberculous infection. Although very rare, tuberculous granuloma concomitant with Warthin's tumor should be considered in the differential diagnosis of a parotid mass lesion. Adhesion of branches of the facial nerve should be expected, and sacrifice of the nerve may be planned. This consideration can be explained to the patient in preoperative counseling and planning. Anti-TB chemotherapy should be given in cases with a definite pathological report associated with speculative clinical presentation.

Clincopathological characteristics and treatment outcomes of oral leukoplakia by carbon dioxide laser excision in the elderly patients.

BACKGROUND: Older age is one of the factors associated with malignant transformation of oral leukoplakia (OL). The purpose of this study is to analyze the clincopathological features and treatment outcomes of OL in the elderly patients. METHODS: The demographic data and histopathological results of the patients (age ≥ 65) who received carbon dioxide laser surgery for OL from 2002 to 2017 were analyzed statistically. RESULTS: There were 53 males and 16 females, with a mean age 71.2 ± 4.9. The follow-up time was 42.5 ± 35.2 months. In the univariate analysis, morphology, pathology, and area were found to be factors associated with postoperative recurrence. Among these factors, pathology and area were the independent predictive factors for recurrence in the multivariate logistic regression model. Malignant transformation occurred in 8 of 69 patients (11.6%). CONCLUSIONS: The pathological high-risk dysplasia and area of OL were the two prognostic factors for postoperative recurrence.

Detection of common diarrhea-causing pathogens in Northern Taiwan by multiplex polymerase chain reaction.

Conventional methods for identifying gastroenteritis pathogens are time consuming, more likely to result in a false-negative, rely on personnel with diagnostic expertise, and are dependent on the specimen status. Alternatively, molecular diagnostic methods permit the rapid, simultaneous detection of multiple pathogens with high sensitivity and specificity. The present study compared conventional methods with the Luminex xTAG Gastrointestinal Pathogen Panel (xTAG GPP) for the diagnosis of infectious gastroenteritis in northern Taiwan. From July 2015 to April 2016, 217 clinical fecal samples were collected from patients with suspected infectious gastroenteritis. All specimens were tested using conventional diagnostic techniques following physicians' orders as well as with the xTAG GPP. The multiplex polymerase chain reaction (PCR) approach detected significantly more positive samples with bacterial, viral, and/or parasitic infections as compared to conventional analysis (55.8% vs 40.1%, respectively; P < .001). Moreover, multiplex PCR could detect Escherichia coli O157, enterotoxigenic E coli, Shiga-like toxin-producing E coli, Cryptosporidium, and Giardia, which were undetectable by conventional methods. Furthermore, 48 pathogens in 23 patients (10.6%) with coinfections were identified only using the multiplex PCR approach. Of which, 82.6% were from pediatric patients. Because the detection rates using multiplex PCR are higher than conventional methods, and some pediatric pathogens could only be detected by multiplex PCR, this approach may be useful in rapidly diagnosing diarrheal disease in children and facilitating treatment initiation. Further studies are necessary to determine if multiplex PCR improves patient outcomes and reduces costs.

The ratio of thioredoxin/Keap1 protein level is a predictor of distant metastasis in colorectal cancer.

AIM: Thioredoxin can reduce the cysteine group of Keap1 which could induce proteasome degradation of Nrf2, PGAM5 and Bcl-xL. Nrf2 regulates redox balance and Bcl-xL is anti-apoptotic and both are important in tumor progression. METHODS: The protein levels of Keap1, thioredoxin, PGAM5 and Bcl-xL in the normal and tumor tissues of 64 subjects with colorectal cancer (CRC) were determined by western blot. RESULTS: The tumor had higher Keap1 but lower PGAM5s and Bcl-xL protein expression than the normal tissue. The ratio of thioredoxin/Keap1 protein level in the normal (OR: 0.12; 95% CI: 0.02-0.83) or tumor tissue (OR: 0.17; 95% CI: 0.03-0.89) was a negative predictor for distant metastasis in CRC. CONCLUSION: Keap1-mediated degradation of PGAM5 and Bcl-xL may be active in CRC. The ratio of thioredoxin/Keap1 protein level may be useful for suggesting distant metastasis in CRC.

Amplification of HER2 and TOP2A and deletion of TOP2A genes in a series of Taiwanese breast cancer.

BACKGROUND: The prognostic relevance of topoisomerase II alpha (TOP2A) copy number change remains not well established. This study is aimed to investigate the frequency and pattern of TOP2A aberrations; to correlate TOP2A alterations with human epidermal growth factor receptor 2 (HER2) status and clinicopathological parameters, and further to explore prognostic value of TOP2A and HER2 status in breast cancer in Taiwan. METHODS: We analyzed tissue samples from 311 invasive carcinomas in tissue microarrays for TOP2A and HER2 status by fluorescent in situ hybridization. RESULTS: TOP2A copy number change is an infrequent genetic event (9.8% amplification and 2.7% deletion) and is present in both HER2-amplified and nonamplified tumors. TOP2A amplification is statistically associated with age >50 at diagnosis (P = 0.016) and HER2 amplification (P < 0.001). HER2 amplification, but not TOP2A amplification, is a predictor of unfavorable prognosis (P = 0.002). Univariate and multivariate analysis showed that higher histologic grading, positive nodal involvement, and HER2 positivity were associated with poorer overall survival. Cytogenetically, double minutes-type amplification is the predominant pattern for both genes (HER2: 64% and TOP2A: 93.1%). Homogeneous staining region-type signals of both genes are resistant to RNase digestion, supporting that these were not nuclear accumulation of mRNA transcripts. CONCLUSION: Our results demonstrate the prognostic value of tumor grading, nodal involvement, and HER2 status in Taiwanese breast cancer. TOP2A aberrations are an infrequent event independent of HER2 status, and TOP2A amplification carries no prognostic value. The predictive value of TOP2A aberrations in patients of breast cancer taking athracycline-containing treatment in Taiwan remains to be determined in prospectively well-designed clinical trials.

The Ratio of Hmox1/Nrf2 mRNA Level in the Tumor Tissue Is a Predictor of Distant Metastasis in Colorectal Cancer.

Heme oxygenase 1 (Hmox1) plays an important role in the growth and spread of tumor, and its expression is regulated positively by Nrf2 [nuclear factor (erythroid-derived 2)-like 2; NFE2L2] and negatively by kelch-like ECH-associated protein 1 (Keap1) and by BTB and CNC homology 1 (Bach1). Both Hmox1 and Nrf2 contribute to distant metastasis of cancer. The mRNA levels of Hmox1, Nrf2, Keap1, and Bach1 in the tumor and normal tissues of 84 subjects with colorectal cancer (CRC) were determined by real-time polymerase chain reaction. The tumor had lower Hmox1 but higher Bach1 mRNA levels than the normal tissue. The correlations of Hmox1 with components of the Nrf2 pathway were not significant in the tumor tissue of CRC subjects with distant metastasis. The ratio of Hmox1/Nrf2 mRNA level (by percentage) in the tumor tissue was lower in the subjects with distant metastasis (97.4% (84.4-111.1%)) than in those without (101.0% (92.7-136.5%)) and was a predictor for distant metastasis in CRC (odds ratio: 0.83; 95% confidence interval: 0.68-0.97) along with serum carcinoembryonic antigen (1.0027, 1.006-1.064). The mRNA level of Hmox1 in the tumor tissue of CRC is not correlated with that of the Nrf2 pathway molecules, and its ratio to the Nrf2 level may be useful for suggesting distant metastasis in CRC.

Cutaneous syncytial myoepithelioma: A case report with emphasis on the differential diagnosis of problematic dermal tumors.

Cutaneous myoepithelioma is a peculiar and recently recognized neoplasm exhibiting purely myoepithelial differentiation. These lesions affect different areas of the body, and are characterized by heterogenous morphological and immunophenotypical features. The majority of cutaneous myoepitheliomas behave in a benign fashion, however, the risk for local recurrence is higher with incomplete resection. A relatively newly described variant of myoepithelioma exhibits syncytial cytological features. The current study reports a case of cutaneous syncytial myoepithelioma presenting as a painless and papular skin lesion. The presence of the Ewing sarcoma RNA-binding protein 1 gene rearrangement in the present case supported the diagnosis of a myoepithelial tumor. The patient subsequently underwent local excision of the tumor and was followed up twice in the year after surgery. At the time of writing, the patient was alive and no recurrences had been identified. Furthermore, the current study discusses how this myoepithelial neoplasm may be distinguished from other problematic spindle or epithelioid cell tumors, particularly superficial dermal lesions.

Clinical characteristics of narrow-band imaging of oral erythroplakia and its correlation with pathology.

BACKGROUND: To analyze the clinical application of endoscope with narrow-band imaging (NBI) system in detecting high-grade dysplasia, carcinoma in situ, and carcinoma in oral erythroplakia. METHODS: The demographic, histopathological data, and NBI vasculature architectures of patients receiving surgical intervention for oral erythroplakia were retrospectively reviewed and analyzed statistically. RESULTS: A total of 72 patients, including 66 males and 6 females, with mean age of 54.6 ± 11.2 years, were enrolled. The odds ratio of detecting high-grade dysplasia, carcinoma in situ, and carcinoma by twisted elongated morphology and destructive pattern of intraepithelial microvasculature was 15.46 (confidence interval 95%: 3.81-72.84), and the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 80.95%, 78.43%, 60.71%, 90.91%, and 79.17%, respectively, which were significantly better than other two established NBI criteria (p < 0.001). CONCLUSIONS: Twisted, elongated, and destructive patterns of intraepithelial papillary capillary loop of NBI images are indicators for high-grade dysplasia, carcinoma in situ, and invasive carcinoma in oral erythroplakia.

IFNAR1 is a predictor for overall survival in colorectal cancer and its mRNA expression correlated with IRF7 but not TLR9.

Toll-like receptor (TLR) 9 plays a role in intestinal inflammation that, in turn, is related to the tumorigenesis of colorectal cancer. Nuclear factor κB (NFκB), and interferon regulatory factor (IRF) 5 and IRF7 can be activated by TLR9 and induce the production of proinflammatory cytokines and type I interferon, respectively. This study investigated the mRNA expressions of TLR9 and its downstream signaling molecules in both the tumor and the normal tissues of colorectal cancer. Eighty-four subjects with colorectal cancer were consecutively recruited at a community-based hospital, and the mRNA expression of TLR9, NFκB, IRF5, IRF7, interleukin 6 (IL6), and interferon α/ß/ω receptor 1 (IFNAR1) in the tumor and normal tissue were determined by real-time reverse transcription polymerase chain reaction using TaqMan FAM-labeled MGB probes (Life Technologies, Carlsbad, CA). The tumor had higher percentages of detection of TLR9, IFNAR1, and IL6 mRNA expressions than normal tissue. The absence of detectable TLR9 mRNA expression was associated with an absence of significance in the correlation between IL6 and NFκB or IRF5, but not that between IRF7 and IFNAR1 in both the tumor and the normal tissues. An absence of detectable IFNAR1 mRNA expression in the tumor (hazard ratio: 3.77; 95% confidence interval: 1.22-11.60) and advanced stage (stages III and IV, 7.86; 1.76-35.40) were significant predictors for overall survival. IFNAR1 is a predictor for overall survival and mRNA expression is correlated to IRF7, but not TLR9 in colorectal cancer. The results cast doubt on the usefulness of TLR9 agonist in treating colorectal cancer.

A retrospective review of the prognostic value of ALDH-1, Bmi-1 and Nanog stem cell markers in esophageal squamous cell carcinoma.

Stem cell markers are upregulated in various cancers and have potential as prognostic indicators. The objective of this study was to determine the expression of three stem cell markers, aldehyde dehydrogenase 1 (ALDH-1), B cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1), and Nanog, in esophageal squamous cell carcinoma (ESCC) tissues. Immunohistochemistry was used to measure the expression of ALDH-1, Bmi-1, and Nanog in ESCC tissues from 41 patients who received pre-operative chemoradiation. We evaluated the relationship between expression of these markers, and clinicopathological features, tumor regression grade (TRG), and 5-year overall survival (OS). There were no significant associations of ALDH-1 or Bmi-1 expression with age, gender, clinical stage, and treatments (p>0.05). However, patients with Nanog-positive tumors were significantly older than those whose tumors were Nanog-negative (p = 0.033). TRG after treatment was significantly associated with expression of ALDH-1 (p = 0.001), Bmi-1 (p = 0.004), and Nanog (p<0.001). Although OS was significantly better in patients with low TRGs (p = 0.001), there were no significant correlations between ALDH-1, Bmi-1, or Nanog with OS. Expression of ALDH-1, Bmi-1, and Nanog correlated with TRG, but not OS. Further large studies are necessary to fully elucidate the prognostic value of these stem cell markers for ESCC patients.

Absence of estrogen receptor alpha (ESR1) gene amplification in a series of breast cancers in Taiwan.

Immunohistochemical expression of ERα, encoded by the ESR1 (estrogen receptor 1) gene located at 6q25.1, is the most important determinant of responsiveness to endocrine therapy in breast cancer. The prevalence and significance of ESR1 amplification in breast cancer remain controversial. We set out to assess ESR1 status and its relevance in breast cancer in Taiwan. We tested tissue samples from 311 invasive carcinomas in a tissue microarray for ESR1 status by fluorescent in situ hybridization (FISH) and chromogenic in situ hybridization (CISH). In order to examine its association with ERα and ESR1 status, HER2 status was determined by FISH. Of the carcinomas, 58.8 % (183/311) was ERα positive. None of the carcinomas showed amplification of ESR1 by either method, whereas 24.1 % (75/311) of the carcinomas harbored HER2 amplification. Of the carcinomas, 9.6 % (26/301) showed ESR1 gain (1.3 ≤ ratio ESR1/chromosome 6 < 2) by FISH and 10 % (24/299) by CISH. FISH and CISH results showed a good correlation (κ-coefficient = 0.786). ESR1 gain by FISH and CISH was significantly associated with high-grade (P = 0.0294 and 0.0417, respectively) but not with ERα expression, HER2 status, or overall survival. ERα positivity was significantly associated with better overall survival (P = 0.039). HER2 amplification was significantly related with poor overall survival (P = 0.002). Our data confirm that in breast cancer, HER2 amplification is a frequent genetic aberration and a negative prognostic factor, and show that ESR1 amplification is not a key genetic abnormality in the tumorigenesis of breast cancer in Taiwan.

Use of endoscopy with narrow-band imaging system in detecting squamous cell carcinoma in oral chronic non-healing ulcers.

OBJECTIVES: This study seeks to analyze the factors associated with the occurrence of squamous cell carcinoma in oral non-healing ulcers for more than 3 weeks and investigate the role of endoscopy with narrow-band imaging system (NBI) in detecting carcinoma in these lesions. METHODS: The demographic and clinicopathological data of patients receiving surgical interventions for chronic oral non-healing ulcers, and the intraepithelial papillary capillary loop patterns shown by NBI were retrospectively reviewed and analyzed. RESULTS: A total of 63 patients (41 males and 22 females) with mean age of 57.9 ± 16.7 years were enrolled. In univariate analysis, ulcers with induration, history of oral cancer, and intraepithelial microvasculature of NBI were factors associated with the occurrence of squamous cell carcinoma in oral non-healing ulcers. Multivariate analysis showed that the intraepithelial microvasculature of NBI was the only independent factor predicting the occurrence of carcinoma in oral chronic non-healing ulcers with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 93.75 %, 91.49 %, 78.95 %, 97.73 %, and 92.06 %, respectively. CONCLUSIONS: Morphology of intraepithelial microvasculature of NBI, or twisted, elongated, and destructive pattern of intraepithelial papillary capillary loop, is the only independent factor associated with the occurrence of squamous cell carcinoma in oral chronic non-healing ulcers. Endoscope with NBI is a rapid, safe, and promising tool in detecting squamous cell carcinoma in oral chronic non-healing ulcers.

Immunohistochemical study of the Nrf2 pathway in colorectal cancer: Nrf2 expression is closely correlated to Keap1 in the tumor and Bach1 in the normal tissue.

Oxidative stress is a contributing factor in the carcinogenesis of colorectal cancer. The Nrf2 [nuclear factor (erythroid-derived 2)-like 2; NFE2L2] pathway is one of the major cellular defense mechanisms against oxidative stress. This study investigated the expression of the Nrf2 pathway in colorectal cancer. Formalin-fixed paraffin-embedded tissue arrays consisting of the tumor, adjacent normal, and distant normal tissues from the resected specimens of 83 colorectal cancer patients were subjected to immunohistochemical (IHC) staining with antibodies against Nrf2, kelch-like ECH-associated protein 1 (Keap1), p21, P62, Parkinson protein 7 (Park7), prohibitin, BTB and CNC homology 1 (Bach1), CD34 and 8-hydroxy-2'-deoxyguanosine (8-OHdG). The mean IHC density of each IHC staining was digitally analyzed. The results showed that molecules of the Nrf2 pathway were actively expressed, with different expression profiles among the tumor and normal tissues. The oxidative stress, represented by the mean IHC staining density of 8-OHdG, did not differ but was correlated with the expressions of different Nrf2 pathway molecules to a varied extent in tumor and normal tissues of colorectal cancer. Keap1 [estimate, 0.49; 95% confidence interval (CI), 0.19-0.79] and Bach1 (estimate, 0.24; 95% CI, 0.11-0.38) were significant predictors for the expression of 8-OHdG and had the closest proximity to Nrf2 in the cluster dendrogram of the tumor and distant normal tissues, respectively. Advanced stage (estimate, 14.9; 95% CI, 2.99-26.8) and current smoker (estimate, 15.6; 95% CI, 1.92-29.3) were significant predictors with high estimates for Bach1 in the adjacent and distant normal tissues, respectively. In colorectal cancer, the molecules of the Nrf2 pathway have different expression profiles and a difference in their importance, especially Keap1 and Bach1, related to Nrf2 and oxidative stress among tumor and normal tissues.

Diagnostic significance of narrow-band imaging for detecting high-grade dysplasia, carcinoma in situ, and carcinoma in oral leukoplakia.

OBJECTIVES/HYPOTHESIS: To investigate the diagnostic accuracy of the established patterns of intraepithelial microvasculature of narrow-band imaging (NBI) in diagnosing upper aerodigestive tract neoplasm of the squamous epithelium for detecting high-grade dysplasia, carcinoma in situ, and carcinoma in oral leukoplakia. STUDY DESIGN: Retrospective case-control study. METHODS: Using histopathological findings as the standard, clinical diagnosis of oral leukoplakia and 3 different but established NBI criteria were compared and evaluated statistically. RESULTS: A total of 414 patients, including 365 males and 49 females, with mean age of 52.15 ± 10.75 years, were enrolled. The odds ratio of detecting high-grade dysplasia and carcinomatous lesions by twisted elongation of intraepithelial papillary capillary loop (IPCL) and IPCL pattern destruction was 95.53 (confidence interval 95%: 42.19-216.29), and the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 84.62%, 94.56%, 74.32%, 97.06%, and 93.0%, respectively, which were significantly better than the other two established NBI criteria (p < 0.001). CONCLUSIONS: The NBI images of twisted elongation of IPCL and IPCL pattern destruction are indicators of high-grade dysplasia or carcinomatous lesions in oral leukoplakia.

Liver angiosarcoma, a rare liver malignancy, presented with intraabdominal bleeding due to rupture--a case report.

Liver angiosarcoma is a rare disease, however it still ranks as the third of most common primary liver maligancies. The prognosis of liver angiosarcoma is very poor with almost all patients with this kind of disease die within 2 years after diagnosis. No specific symptoms and signs are closely associated with this disease. Here, we report a case presenting shock status at first due to rupture of liver angiosarcoma- induced internal bleeding. After emergent transarterial embolization (TAE), she received partial hepatectomy two weeks later. 4 months after operation, she is still with a good performance status without obvious recurrence or metastasis identified.

Use of endoscopy with narrow-band imaging system in evaluating oral leukoplakia.

BACKGROUND: The purpose of this study was to analyze the relationship between clinical features of oral leukoplakia using endoscopy with broadband white light, narrow-band imaging (NBI) illumination, and histopathology, and to discuss the clinical relevance of the NBI system. METHODS: Clinicopathologic data of patients receiving biopsy or excision after endoscopic examination for leukoplakia from April 2009 to December 2010 were reviewed and analyzed statistically. RESULTS: A total 154 patients, 130 men and 24 women (average age, 52.60 ± 10.86 years) were enrolled. The correlation between intraepithelium papillary capillary loop (IPCL) classification and stepwise increased severity of pathology (Pearson's r = .88, R(2) = 0.78) was significantly better than that of broadband white light images (p < .001). CONCLUSIONS: Flexible endoscopy can enhance detailed inspection of oral cavity mucosa and can be a powerful tool for examining oral leukoplakia. The IPCL patterns shown by NBI system can be helpful in detecting oral leukoplakia with higher grade dysplasia or invasive carcinoma.

Dual-colour chromogenic in-situ hybridization is a potential alternative to fluorescence in-situ hybridization in HER2 testing.

AIM: Dual-colour chromogenic in-situ hybridization (dc-CISH) is an emerging methodology for characterizing genomic alterations. This study was aimed at evaluating the performance of a dc-CISH kit (ZytoVision) in determining human epidermal growth factor receptor 2 (HER2) status in breast cancer. METHODS AND RESULTS: Two hundred and twenty-eight invasive breast carcinomas arranged in tissue microarrays were analysed in parallel with dc-CISH, fluorescence in-situ hybridization (FISH), and immunohistochemistry. Of 227 tumours with available FISH and dc-CISH results, HER2 amplification and non-amplification were detected in 49 (21.6%) and 178 (78.4%) tumours, respectively, by both assays. The concordance between dc-CISH and FISH results showed 100% agreement (κ-coefficient=1.00). Immunohistochemically, 162 (71%), 25 (11.0%) and 41 (18%) tumours were scored 0/1+, 2+, and 3+, respectively. The corresponding results with both FISH and dc-CISH demonstrated HER2 amplification in two (3.2%), nine (36%) and 38 (93%) tumours, respectively. Complete consensus among these three methods was observed in 197 cases, representing 98% of all 3+ and 0/1+ tumours (κ-coefficient=0.92). Confirmatory testing of 25 2+ tumours showed complete consensus between FISH and dc-CISH. CONCLUSIONS: dc-CISH is a promising alternative to FISH in HER2 testing, and the single-institute incidence of HER2 amplification in breast cancer in Taiwan is 21.2%.

De novo malignant solitary fibrous tumor of the kidney.

The kidney is a relatively infrequent site for solitary fibrous tumor (SFT). Among the previously reported cases, only two cases of malignant renal SFT developing via dedifferentiation from a pre-existing benign SFT have been reported. Here we reported a case of de novo malignant renal SFT clinically diagnosed as renal cell carcinoma in a 50-year-old woman. The tumor was circumscribed but unencapsulated and showed obvious hemorrhagic necrosis. Microscopically, the tumor was composed of patternless sheets of alternating hypercellular and hypocellular areas of spindle cells displaying mild to moderate nuclear atypia, frequent mitoses up to 8 per 10 high power fields, and a 20% Ki-67 proliferative index. Immunohistochemical studies revealed reactivity for CD34, CD99 and vimentin, with no staining for all other markers, confirming the diagnosis of SFT. No areas of dedifferentiation were seen after extensive sampling. Based on the pathologic and immunohistochemical features, a diagnosis of de novo malignant renal SFT was warranted. Our report expands the spectrum of malignant progression in renal SFTs. Even though this patient has been disease-free for 30 months, long-term follow-up is still mandatory.