Genomic profile analysis of leiomyomas with bizarre nuclei and fumarate hydratase deficient leiomyomas: Strengths, weaknesses, and limitations of array-CGH interpretation.

A close relationship has been demonstrated between genomic complexity and clinical outcome in uterine smooth muscle tumors. We studied the genomic profiles by array-CGH of 28 fumarate hydratase deficient leiomyomas and 37 leiomyomas with bizarre nuclei (LMBN) from 64 patients. Follow-up was available for 46 patients (from three to 249 months, mean 87.3 months). All patients were alive without evidence of disease. For 51 array-CGH interpretable tumors the mean Genomic Index (GI) was 16.4 (median: 9.8; from 1 to 57.8), significantly lower than the mean GI in LMS (mean GI 51.8, p < 0.001). We described three groups: (1) a group with FH deletion (24/58) with low GI (mean GI: 11 vs. 22,4, p = 0.02), (2) a group with TP53 deletion (17/58) with higher GI (22.4 vs. 11 p = 0.02), and (3) a group without genomic events on FH or TP53 genes (17/58) (mean GI:18.3; from 1 to 57.8). Because none of these tumors recurred and none showed morphological features of LMS we concluded that GI at the cut-off of 10 was not applicable in these subtypes of LM. By integration of all those findings, a GI <10 in LMBN remains a valuable argument for benignity. Conversely, in LMBN a GI >10 or alteration in tumor suppressor genes, should not alone warrant a diagnosis of malignancy. Nine tumors were tested with Nanocind CINSARC® signature and all were classified in low risk of recurrence. We propose, based on our observations, a diagnostic approach of these challenging lesions.

The Nanocind Signature Is an Independent Prognosticator of Recurrence and Death in Uterine Leiomyosarcomas.

PURPOSE: Uterine leiomyosarcoma, which accounts for 7% of all soft-tissue sarcomas and 1%-3% of all uterine malignancies, is an aggressive tumor responsible for a significant proportion of uterine cancer-related deaths. While Federation Internationale des Gynaecologistes et Obstetristes (FIGO) stage is the most important prognostic factor, metastatic and relapse rates at stage I exceed 50% so it is currently impossible to predict the clinical outcome of stage I leiomyosarcomas. In 2010, our team published a transcriptomic signature composed of 67 genes related to chromosome biogenesis, mitosis control, and chromosome segregation. It has demonstrated its prognostic value in many cancer types and was recently successfully applied to formalin-fixed, paraffin-embedded sarcomas by NanoCind on NanoString technology, making another step forward toward its use in routine practice. EXPERIMENTAL DESIGN: Sixty uterine leiomyosarcomas at any stage, including 40 localized in the uterus (stage I), were analyzed with the NanoCind (CINSARC with NanoString) signature. Its prognostic value was evaluated for overall survival and relapse-free survival and compared in multivariate analysis with other prognostic markers like FIGO staging and genomic index. RESULTS: The NanoCind signature was able to split the heterogeneous group of uterine leiomyosarcomas of any stage including stage I into two distinct groups with different relapse-free survival and overall survival. These results were validated on an independent cohort of uterine leiomyosarcomas in The Cancer Genome Atlas consortium. CONCLUSIONS: The NanoCind signature is a powerful prognosticator that outperforms FIGO staging and the genomic index. The CINSARC signature is platform independent and "ready to use" and should now be used for randomization in future therapeutic trials.

Clinical application of targeted next-generation sequencing for colorectal cancer patients: a multicentric Belgian experience.

International guidelines made RAS (KRAS and NRAS) status a prerequisite for the use of anti-EGFR agents for metastatic colorectal cancer (CRC) patients. Daily, new data emerges on the theranostic and prognostic role of molecular biomarkers; this is a strong incentive for a validated, sensitive, and broadly available molecular screening test. Next-generation sequencing (NGS) has begun to supplant other technologies for genomic profiling. We report here our 2 years of clinical practice using NGS results to guide therapeutic decisions. The Ion Torrent AmpliSeq colon/lung cancer panel, which allows mutation detection in 22 cancer-related genes, was prospectively used in clinical practice (BELAC ISO 15189 accredited method). The DNA of 741 formalin-fixed paraffin-embedded CRC tissues, including primary tumors and metastasis, was obtained from 14 different Belgian institutions and subjected to targeted NGS. Of the tumors tested, 98% (727) were successfully sequenced and 89% (650) harbored at least one mutation. KRAS, BRAF and NRAS mutations were found in 335 (46%), 78 (11%) and 32 (4%) samples, respectively. These mutation frequencies were consistent with those reported in public databases. Moreover, mutations and amplifications in potentially actionable genes were identified in 464 samples (64%), including mutations in PIK3CA (14%), ERBB2 (0.4%), AKT1 (0.6%), and MAP2K1 (0.1%), as well as amplifications of ERBB2 (0.3%) and EGFR (0.3%). The median turnaround time between reception of the sample in the laboratory and report release was 8 calendar days. Overall, the AmpliSeq colon/lung cancer panel was successfully applied in daily practice and provided reliable clinically relevant information for CRC patients.

Esophagitis dissecans superficialis : a case series of 7 patients and review of the literature.

INTRODUCTION: Esophagitis dissecans superficialis (EDS) is a rare desquamative disorder of the eso-phagus, characterized by sloughing of the superficial mucosa. It is a benign entity of uncertain etiology. Most cases of EDS are idiopathic but can be caused by medications, hot beverages, chemical irritants, celiac disease and many skin conditions. AIM: Knowing that few case series have described this entity, we decided to review all the cases diagnosed in our center to characterize them. METHODS: The pathological institutional database of Erasme University Hospital (Brussels, Belgium) was searched for the diagnosis of EDS. We reviewed retrospectively the clinical and endoscopic findings as well as histological features of all cases of EDS (Table 1). During this period of time, 21497 upper gastrointestinal endoscopies have been performed in our institution. RESULTS: From January 2010 to September 2016, we identified 7 cases of EDS diagnosed in our institution in this time period. During the same period, 21497 upper gastrointestinal endoscopies were performed (incidence 0.03%). Endoscopic findings evoked in 2 patients a suspicion of an esophageal tumor; the first one was described as a raised detached lesion of the distal third of the esophagus with suspicion of squamous cell carcinoma (Fig. 1) and the second as a suspected tumor of the proximal third of the esophagus (Fig. 2). For other patients, EDS was misdiagnosed as unspecific esophagitis in 2, reflux or mycotic esophagitis in 2. Only one patient was suspected to have sloughing esophagitis.Histologic features present in all of those cases were characterized by the presence of a sloughing and necrosis of the superficial layer of the esophageal squamous epithelium with negative anti HSV and anti CMV antibodies, negative periodic acid Schiff stain for fungal infections as well as absence of signs of dysplasia or signs of malignancy. In 2 patients, there was a presence of multiple bacterial colonies on the superficial epithelium. Acute inflammation was reported in 4 of the patients with the presence of eosinophils in the superficial epithelium described in 2 of these patients and of polymorphonuclear leukocytes in 2 other patients (Fig. 3).An endoscopic follow up 2 months after PPI treatment performed in 3 patients, 2 of them had an atypical endoscopic presentation with suspicion of a tumor on endoscopic examination showed a complete resolution of the esophageal lesions was observed in these patients. CONCLUSION: EDS is a rare benign entity that endoscopists must be aware of in order not to mistake it for other entities such as esophagitis or squamous cell carcinoma. The diagnosis is based on biopsies. The prognosis is good after stopping the causative agent.

Disseminated Oligodendroglial-like Leptomeningeal Tumor of Childhood: A Distinctive Entity Revised and Correlated with Pathology.

Disseminated oligodendroglial-like leptomeningeal tumor is a recently acknowledged entity whose radiological characteristics have rarely been discussed before. Typical of the childhood period, it should be differentiated clinically and radiographically from granulomatous or infectious conditions such as tuberculous meningitis, which is more common in this age group. The key to the diagnosis, even at an early stage, might be the presence of tiny T2 hyperintense lesions on the surface of the brain or spine. When suspected, a meningeal biopsy should be performed to confirm the diagnostic.

Clinical Application of Targeted Next Generation Sequencing for Colorectal Cancers.

Promising targeted therapy and personalized medicine are making molecular profiling of tumours a priority. For colorectal cancer (CRC) patients, international guidelines made RAS (KRAS and NRAS) status a prerequisite for the use of anti-epidermal growth factor receptor agents (anti-EGFR). Daily, new data emerge on the theranostic and prognostic role of molecular biomarkers, which is a strong incentive for a validated, sensitive and broadly available molecular screening test in order to implement and improve multi-modal therapy strategy and clinical trials. Next generation sequencing (NGS) has begun to supplant other technologies for genomic profiling. Targeted NGS is a method that allows parallel sequencing of thousands of short DNA sequences in a single test offering a cost-effective approach for detecting multiple genetic alterations with a minimum amount of DNA. In the present review, we collected data concerning the clinical application of NGS technology in the setting of colorectal cancer.