ABSTRACT
Anaplastic lymphoma kinase (ALK) break-apart fluorescent in situ hybridization (FISH) is currently used in diagnostics for the selection of non-small cell lung cancer (NSCLC) patients to receive crizotinib. We evaluated ALK status in NSCLC with a novel ALK mRNA test based on the break-apart FISH concept, which we called break-apart transcript (BAT) test. ALK5' and ALK3' transcript patterns were established with qPCR for ALK-expressing controls including fusion-negative neuroblastomas, as well as fusion-positive anaplastic large cell lymphomas and NSCLC. The BAT test was evaluated on 271 RNA samples from routinely processed paraffin NSCLC tissues. Test results were compared with ALK FISH (n=121), immunohistochemical (IHC) analysis (n=86), and automated quantitative analysis (AQUA, n=83). On the basis of the nonoverlapping ALK BAT patterns in ALK-expressing controls (P<0.0001), 8/174 adenocarcinomas (4.6%) among 259 informative NSCLC were predicted as fusion positive. Overall concordance for paired method results was high (94.1% to 98.8%) but mainly concerned negative prediction because of the limited availability of positive-matched cases. Tumors with 100% cytoplasmic IHC staining of any intensity (n=3) were positive for AQUA, FISH, and BAT test; tumors with lower IHC positivity and different staining patterns were AQUA-negative. Upon multiple reevaluations, ALK gene status was considered as originally misinterpreted by FISH in 3/121 cases (2.5%). Tumors with >4 ALK gene copies were associated with longer overall survival upon first-line chemotherapy. In conclusion, application of the ALK BAT test on routinely processed NSCLC tissues yields the same fusion partner independent information as ALK break-apart FISH but is more robust and cost-effective. The BAT concept may be considered for the development of further drug-predictive translocation tests.
Subject(s)
Carcinoma, Non-Small-Cell Lung/diagnosis , Lung Neoplasms/diagnosis , Oncogene Proteins, Fusion/genetics , RNA, Messenger/analysis , Receptor Protein-Tyrosine Kinases/genetics , Aged , Anaplastic Lymphoma Kinase , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/mortality , Crizotinib , Diagnostic Errors , Female , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence/methods , Lung Neoplasms/drug therapy , Lung Neoplasms/mortality , Male , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Prognosis , Pyrazoles/therapeutic use , Pyridines/therapeutic use , Survival Analysis , Translocation, Genetic/geneticsABSTRACT
INTRODUCTION: Although central giant-cell granulomas of the jaws (CGCG) tend to appear more often in children and young adults, most studies include patients of all ages. AIM: Aim of this study was to present and discuss the characteristics, the selected treatment pattern and the outcome of central giant-cell granulomas of the jaws exclusively in children up to 13 years old, during a 10 years period. MATERIAL AND METHOD: Twelve young patients, 5-13 years old were included in the study. CGCGs were surgically removed in toto by enucleation followed by curettage of the bone. Repair of the remaining bone defect was performed at the same operation in five cases. RESULTS: All patients healed uneventfully and had prosthetic and/or orthodontic rehabilitation applied post-operatively. Regular long-lasting follow-ups were scheduled. Recurrence occurred in two cases (16.7%), it was small in size and was surgically treated again. CONCLUSIONS: Conservative surgery, without extensive bone removal, for CGCGs of the jaws in children was successful in our cases. Additional repair of the osseous defect when needed and teeth rehabilitation as soon as possible are essential in children population. Follow-up needs to be long-lasting, to secure bone healing and unaffected jaw growth. Findings in children population of the present study were similar to those of adults or adolescent populations, although a rather low recurrence rate has been noticed.
Subject(s)
Granuloma, Giant Cell/surgery , Mandibular Diseases/surgery , Maxillary Diseases/surgery , Patient Care Planning , Adolescent , Bone Plates , Bone Screws , Bone Transplantation/methods , Child , Child, Preschool , Curettage/methods , Female , Follow-Up Studies , Humans , Imaging, Three-Dimensional/methods , Male , Plastic Surgery Procedures/methods , Recurrence , Reoperation , Retrospective Studies , Surgical Flaps , Tomography, X-Ray Computed/methods , Treatment OutcomeABSTRACT
Myxomas of the maxillofacial region are neoplastic entities of mesenchymal origin most often associated with odontogenic origin; sinonasal myxoma is rare, located in the nasolabial region and originating from the sinonasal tract. The aim of the current study was to report a well-documented case of sinonasal myxoma in a 12-month-old boy, initially presenting with obliteration of his left nasolacrimal duct. A soft-tissue mass of the nasobuccal groove, firmly attached to the underlying bone, was revealed. After biopsy where benign fibroblastic elements were found, the tumor was removed surgically in wide margins, whereas great care was taken to reconstruct the involved adjacent anatomic structures and preserve facial aesthetics. Histopathologic findings were compatible with an extragnathic, nonodontogenic sinonasal myxoma originating from the nasolacrimal duct. The clinical significance of the case presented was its rather rare location and origin. Three and a half years postoperatively, functional and aesthetic results were satisfactory with no sign of recurrence. To the authors' knowledge, this is the second youngest reported case in the literature.
