Advanced Non-small Cell Lung Cancer: EGFR Mutation Analysis Using Pyrosequencing and the Fully Automated qPCR-Based IdyllaTM System.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutation status is of a major clinical significance in non-small cell lung cancer (NSCLC) management, as it guides therapeutic decision making to target patients for a better response to therapy. This implicates the introduction of EGFR mutation analysis as the standard of care for Moroccan NSCLC patients, which in itself entails the implementation of targeted methods for routine EGFR mutation analysis in our laboratories. In this study, we aimed to present 2 targeted methods for EGFR mutation identification and to determine the prevalence and spectrum of EGFR mutations in NSCLC Moroccan patients. METHODS: A retrospective investigation of a cohort of 340 patients was undertaken to analyze somatic EGFR mutations in exons 18 to 21 using pyrosequencing and the IdyllaTM system. RESULTS: Of the enrolled patients, 70.9% were males and 29.1% were females. Predominately, 92% of cases had adenocarcinoma, and 53.7% of patients self-reported a history of smoking. Overall, 73 patients (21.7%) harbored an EGFR mutation, the most prevalent of which were the exon 19 deletions (53.4%) followed by exon 21 substitutions (31%). Exon 18 mutations and exon 20 alterations occurred in 8.1% and 6.7% of the positive EGFR mutation cases, respectively. Of the analyzed cases, all of the EGFR-mutated patients had adenocarcinoma. EGFR mutation prevalence was significantly higher in females (females vs males: 38.4% vs 14.5%, P < .001) and non-smokers (non-smokers vs non-smokers: 36% vs 10.3%, P < .001). The featured pyrosequencing and the IdyllaTM system are targeted methods endowed with high sensitivity and specificity as well as other compelling characteristics which make them great options for routine EGFR mutation testing for advanced NSCLC patients. CONCLUSION: These findings underline the imperious need for implementing quick and efficient targeted methods for routine EGFR mutation testing among NSCLC patients, which is particularly useful in determining patients who are more likely to benefit from targeted therapy.

Frequency and types of EGFR mutations in Moroccan patients with non-small cell lung cancer.

BACKGROUND: Mutations in the epidermal growth factor receptor (EGFR) gene are commonly observed in non-small cell lung cancer (NSCLC), particularly in adenocarcinoma histology. The frequency of EGFR mutations is ethnicity-dependent, with a higher proportion reported in Asian populations than Caucasian populations. There is a lack of data on these mutations in north Africa. METHODS: Tumor specimens from Moroccan patients with NSCLC were collected from five pathology laboratories between November 2010 and December 2017 to determine frequency and types of EGFR mutations. Tumors were tested in a reference center for EGFR by polymerase chain reaction and sequencing of exons 18, 19, 20, and 21. RESULTS: A total of 334 patients were enrolled: 242 (72.5%) males and 92 females (27.5%). A total of 56.9% had a history of smoking. EGFR testing of the 334 lung adenocarcinoma samples demonstrated a wild-type EGFR in 261 (78.1%) and mutated EGFR in 73 (21.9%). Mutations were mainly detected in the exon 19 deletion (65.8%), followed by exon 21 L858 (17.8%) and other exon 21 codon mutations (5.5%) and exon 18 (6.8%), whereas primary mutations of exon 20 were less frequent (4.1%). In patients with advanced NSCLC, the detection of EGFR mutation was independently associated with sex (41.3% female vs 14.5% male; p < 0.001) and smoking status (34.8% nonsmokers vs 12.9% active smokers; p < 0.001). The mean age was significantly different between the two groups (p = 0.041). CONCLUSION: Our findings confirm the genetic heterogeneity of NSCLC worldwide, reporting frequency of EGFR mutations in Moroccan patients with NSCLC between those of Asian and Caucasian populations.

Malignant transformation of a spiradenoma with blaschkoïd pattern.

Eccrine spiradenoma is a benign and rare adnexal tumor originating from cutaneous eccrine sweat glands. It usually presents as a solitary lesion. It can have different presentations, including a blaschkoid arrangement which is rare. Malignant transformation is possible and usually occurs after a long period of latency in multifocal types.

A Case of Well-Differentiated Papillary Mesothelioma of the Male Peritoneum: Successful Treatment by Systemic Chemotherapy.

Well-differentiated papillary mesothelioma of the peritoneum (WDPMP) is a rare subtype of epithelioid mesothelioma, which is usually seen in young women without a history of asbestos exposure, and generally, has an indolent course. The relative rarity of this neoplasm in males prompted us to report this case of a well-differentiated papillary mesothelioma of the peritoneum in a 36-year-old man. The patient, who had no history of asbestos exposure, presented with abdominal pain and ascites of unknown etiology. Computed tomography showed abundant ascites with nodules of the peritoneal cavity. Laparoscopic examination revealed a large number of white miliary nodules diffusely covering the peritoneum. Pathology revealed a diagnosis of well-differentiated papillary mesothelioma of the peritoneum, based on histomorphology and immunohistochemistry. The patient started chemotherapy with cisplatin and pemetrexed. After six cycles of chemotherapy, the effectiveness of this chemotherapy was checked by only the computed tomography. PET scan was not used because it is not routinely recommended in WDPMP. Few data are currently available in the literature regarding the performance of the PET scan in WDPMP. Nine months later, the patient was free of symptoms. Based on reviewing the literature and our observations in this case, consultation of other pathologists is highly recommended to discern WDPMP from other disseminated peritoneal diseases, in order to offer the most effective and safe therapeutic strategy. Chemotherapy should be strongly considered if the tumor is unresectable and accompanied by symptoms. Cisplatin and pemetrexed chemotherapy could be a promising therapeutic choice.

Pegylated interferon alfa-2b vs standard interferon alfa-2b, plus ribavirin, for chronic hepatitis C in HIV-infected patients: a randomized controlled trial.

CONTEXT: Treatment of chronic hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected patients is a growing concern. Most data on the virologic efficacy and safety of the combination of peginterferon alfa-2b and ribavirin in coinfected patients come from uncontrolled studies. OBJECTIVE: To study the safety and efficacy of peginterferon alfa-2b plus ribavirin vs standard interferon alfa-2b plus ribavirin in HIV-HCV coinfected patients. DESIGN AND SETTINGS: A multicenter, randomized, parallel-group, open-label trial. Patients were enrolled from February 2000 to February 2002 and followed up for 72 weeks. PATIENTS: Four hundred twelve HIV-HCV coinfected patients with detectable serum HCV-RNA, abnormal liver histology, a CD4 cell count of at least 200 x 10(6)/L, and stable plasma HIV-RNA. INTERVENTION: Treatment with ribavirin 400 mg twice a day, orally, plus either peginterferon alfa-2b (1.5 microg/kg subcutaneous injection once a week) or standard interferon alfa-2b (3 million units of subcutaneous injection 3 times a week) for 48 weeks. MAIN OUTCOME MEASURES: Sustained virologic response, defined by undetectable serum HCV-RNA at week 72. RESULTS: More patients had sustained virologic responses in the peginterferon group than in the standard interferon group (27% vs 20%, P = .047). This difference between the treatments was found in patients with HCV genotype 1 or 4 infection (17% for peginterferon vs 6% for standard interferon, P = .006) but was not found in patients with HCV genotype 2, 3, or 5 (44% for peginterferon vs 43% for standard interferon, P = .88). Together, a decline in HCV-RNA of less than 2 log10 from baseline and detectable serum HCV-RNA at week 12 predicted 99% of treatment failures. Histologic activity diminished and fibrosis stabilized in virologic responders. The 2 regimens showed similar tolerability although dose modifications for clinical and biological events were more frequent with peginterferon. Eleven cases of pancreatitis or symptomatic hyperlactatemia were observed, all in patients receiving didanosine-containing antiretroviral regimens. CONCLUSION: In combination with ribavirin, treatment with peginterferon alfa-2b is more effective than standard interferon alfa-2b for HCV infection in HIV-infected patients.

Telangiectatic focal nodular hyperplasia: a variant of hepatocellular adenoma.

BACKGROUND & AIMS: "Telangiectatic focal nodular hyperplasia" designate atypical lesions considered as variants of focal nodular hyperplasia (FNH). However, because "telangiectatic FNH" share several morphologic patterns with hepatocellular adenomas, classification of such lesions deserve further clarification. Therefore, the aim of the present study was to reconsider the classification of telangiectatic FNH with the help of a molecular approach. METHODS: Ten telangiectatic FNH, 6 typical FNH, and 6 hepatocellular adenomas were studied. DNA, RNA, and protein from each lesion were extracted. Clonality was assessed by the study of the X chromosome inactivation pattern (HUMARA assay). Angiopoietin (ANGPT-1 and ANGPT-2) mRNA, genes the expression of which is typically modified in FNH, were quantified by a real-time RT-PCR procedure. Protein profiles were analyzed by SELDI-TOF PROTEINCHIP (Cyphergen Biosystem, Inc., Fremont, CA) technology. RESULTS: Although all informative cases of FNH (5 of 6) and hepatocellular adenomas (6 of 6) were polyclonal and monoclonal, respectively, clonal analysis showed a nonrandom pattern of X chromosome inactivation consistent with a monoclonal lesion in 6 of 8 cases of telangiectatic FNH. The mean value of the ANGPT-1/ANGPT-2 mRNA ratio was 21.4 in FNH, 2.6 in adenomas, and 2.1 in telangiectatic FNH (P