Melanotic Neuroectodermal Tumor of Infancy: Case Report and Review of Management.

Melanotic neuroectodermal tumor of infancy (MNTI) is a rare pigmented tumor of the head and neck, which most commonly presents during the first year of life. Most cases present in the bones of the craniofacial region, including the maxilla (60.3%), skull (18.1%), and mandible (10.3%). The alveolar crest of the anterior maxilla is the most common site. MNTIs are locally aggressive, but benign, lesions derived from neural crest cells. However, they have a high rate of recurrence, and ≤6.5% of cases will demonstrate metastasis to lymph nodes or distant organs. They present clinically as an expansile pigmented mass. Radiographically, these lesions are often intraosseous expansile lytic lesions that can envelope or displace teeth. Extraosseous components might be better visualized on magnetic resonance imaging, demonstrating an enhancing iso- or hypointense mass on T1- and/or T2-weighted imaging. MNTIs have a distinctive biphasic cell population composed of large pigmented epithelial cells and small blue neuroblastic cells. Many immunohistochemical markers have also been identified. The large cell population often expresses cytokeratins, HMB-45, and vimentin; S100 is much less common. The small cell population typically expresses synaptophysin but will be negative for another neuroendocrine marker, chromogranin A. Rarely, patients will have elevated levels of urine vanillylmandelic acid, similar to findings from other tumors of neuroectodermal origin, such as neuroblastomas. First-line treatment of these lesions should be surgery with the goal of complete local excision. Radiotherapy and chemotherapy have been described but have been largely used as adjuvant or neoadjuvant therapy and for metastatic disease. We present a case of MNTI in an 8-week-old male, who had presented with a nonpigmented mass of the mandible associated with a pathologic fracture. In addition to a review of the data, our case serves to highlight potential prognostic factors, current clinical management, and local complications of this rare tumor.

Molecular basis for decreased folylpoly-gamma-glutamate synthetase expression in a methotrexate resistant CCRF-CEM mutant cell line.

A CCRF-CEM mutant, CEM-p, has been shown to exhibit resistance to methotrexate due to decreased methotrexate polyglutamate accumulation. To ascertain the mechanism(s) responsible for this phenotype, we analyzed FPGS and SLC19A1 mRNA expression, examined FPGS promoter activity, and determined nucleotide sequence of the FPGS promoter and full length cDNA from CCRF-CEM and CEM-p cells. We identified in FPGS from CEM-p cells three amino acid substitutions that altered the ATP binding P-loop, glutamate/folate binding, and a conserved domain located at the carboxyl-terminal. Our data demonstrated for the first time the importance of the highly conserved domain (VTGSLHLVGGV) located at the carboxyl-terminal for FPGS activity.