Solitary Extramedullary Plasmacytoma of the Sphenoid Sinus: A Case Report.

Solitary extramedullary plasmacytomas are rare, discrete mass of neoplastic monoclonal plasma cells in the soft tissue with no evidence of multiple myeloma. They constitute 3 % of all plasma cell tumors and less than 1 % of head and neck malignancies. A 43 year old lady presented to our clinic with complains of diplopia and headache for 4 weeks. Computed Tomography scan showed a mass lesion in the sphenoid sinus eroding the sinus floor, right wall, basisphenoid and parasellar area. A biopsy of the mass reported as plasmacytoma. Systemic examination revealed no evidence of dissemination of the disease confirming the diagnosis of a solitary extramedullary plasmacytoma. The patient was subjected to 25 fractions of radiotherapy. Here, we report a rare case of solitary extramedullary plasmacytoma of the sphenoid sinus.

Exome Sequencing Identifies Potentially Druggable Mutations in Nasopharyngeal Carcinoma.

In this study, we first performed whole exome sequencing of DNA from 10 untreated and clinically annotated fresh frozen nasopharyngeal carcinoma (NPC) biopsies and matched bloods to identify somatically mutated genes that may be amenable to targeted therapeutic strategies. We identified a total of 323 mutations which were either non-synonymous (n = 238) or synonymous (n = 85). Furthermore, our analysis revealed genes in key cancer pathways (DNA repair, cell cycle regulation, apoptosis, immune response, lipid signaling) were mutated, of which those in the lipid-signaling pathway were the most enriched. We next extended our analysis on a prioritized sub-set of 37 mutated genes plus top 5 mutated cancer genes listed in COSMIC using a custom designed HaloPlex target enrichment panel with an additional 88 NPC samples. Our analysis identified 160 additional non-synonymous mutations in 37/42 genes in 66/88 samples. Of these, 99/160 mutations within potentially druggable pathways were further selected for validation. Sanger sequencing revealed that 77/99 variants were true positives, giving an accuracy of 78%. Taken together, our study indicated that ~72% (n = 71/98) of NPC samples harbored mutations in one of the four cancer pathways (EGFR-PI3K-Akt-mTOR, NOTCH, NF-κB, DNA repair) which may be potentially useful as predictive biomarkers of response to matched targeted therapies.

Integrated pathway analysis of nasopharyngeal carcinoma implicates the axonemal dynein complex in the Malaysian cohort.

Nasopharyngeal carcinoma (NPC) is an epithelial squamous cell carcinoma on the mucosal lining of the nasopharynx. The etiology of NPC remains elusive despite many reported studies. Most studies employ a single platform approach, neglecting the cumulative influence of both the genome and transcriptome toward NPC development. We aim to employ an integrated pathway approach to identify dysregulated pathways linked to NPC. Our approach combines imputation NPC GWAS data from a Malaysian cohort as well as published expression data GSE12452 from both NPC and non-NPC nasopharynx tissues. Pathway association for GWAS data was performed using MAGENTA while for expression data, GSA-SNP was used with gene p values derived from differential expression values from GEO2R. Our study identified NPC association in the gene ontology (GO) axonemal dynein complex pathway (pGWAS-GSEA = 1.98 × 10(-2) ; pExpr-GSEA = 1.27 × 10(-24) ; pBonf-Combined = 4.15 × 10(-21) ). This association was replicated in a separate cohort using gene expression data from NPC and non-NPC nasopharynx tissues (pAmpliSeq-GSEA = 6.56 × 10(-4) ). Loss of function in the axonemal dynein complex causes impaired cilia function, leading to poor mucociliary clearance and subsequently upper or lower respiratory tract infection, the former of which includes the nasopharynx. Our approach illustrates the potential use of integrated pathway analysis in detecting gene sets involved in the development of NPC in the Malaysian cohort.

Clinical significance of plasma Epstein-Barr Virus DNA loads in a large cohort of Malaysian patients with nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is an Epstein-Barr Virus (EBV)-associated cancer that is the fifth most common cancer in Malaysia. Early and accurate diagnoses are critical for patient prognosis. Unfortunately, early detection of NPC is still a challenge and the cost of more accurate imaging protocols is prohibitive in developing countries like Malaysia. OBJECTIVES: To evaluate the clinical values of pre-treatment plasma EBV DNA levels in Malaysian NPC patients. STUDY DESIGN: Plasma EBV DNA levels were measured by quantitative PCR (Q-PCR) in a large and multi-ethnic cohort of Malaysian patients with NPC (n=459) and 72 control subjects. RESULTS: We show for the first time that, compared to controls, NPC patients with stage I disease had significantly higher levels of EBV DNA (p<0.001). Further, the median level of plasma EBV DNA in stage IV patients with distant metastasis was >9-fold higher than those without systemic spread (p=0.001), suggesting plasma EBV DNA measurement could aid in the diagnosis of metastatic disease in advanced cases. Further, using a cut-off value of 8000 copies/mL, we demonstrate that EBV DNA level is a strong predictor for overall survival of NPC patients. CONCLUSIONS: Our data show that pre-treatment plasma EBV DNA is a potential biomarker for early stage and metastatic NPC. We conclude that the quantification of plasma EBV DNA is a useful tool in developing countries to stratify patients for MRI or PET/CT scans where such imaging protocol is not routinely applied.

Successful treatment of tracheal stenosis by rigid bronchoscopy and topical mitomycin C: a case report.

Tracheal stenosis is a known complication of prolonged intubation. It is difficult to treat and traditional surgical approach is associated with significant risk and complications. Recurrent stenosis due to granulation tissue necessitates repeated procedures. We describe a case of short web-like tracheal stenosis (concentric membranous stenosis less than 1 cm in length without associated cartilage damage) managed by a minimally invasive thoracic endoscopic approach. Topical application of Mitomycin C, a potent fibroblast inhibitor reduces granulation tissue formation and prevents recurrence.