Upper respiratory tract carcinoma with chromosomal translocation 15;19: evidence for a distinct disease entity of young patients with a rapidly fatal course

Abstract

Background: Carcinoma of the upper respiratory tract is rare in childhood, and cytogenetic aberrations have not been characterized in this population. The chromosomal translocation 15;19 has been reported four times previously. All patients were young and had tumors arising in the thorax. The three reports that provide clinical follow-up all describe superior vena cava syndrome and death soon after presentation. All tumors were diagnosed as carcinoma (three undifferentiated, one mucoepidermoid), and the authors suggested thymus, lung, or germ cell origin.

Methods: The authors investigated the clinical and pathologic findings in two patients with poorly differentiated carcinoma showing evidence of t(15;19). This included a 13-year-old girl with a rapidly growing epiglottic mass, leading to superior vena cava syndrome and death and a 12-year-old girl with an aggressive nasopharyngeal mass showing intracranial extension.

Results: The laryngeal tumor was poorly differentiated, with vesicular nuclei, prominent nucleoli, extensive necrosis, and a lymphoplasmacytic infiltrate; cells were positive for cytokeratin and negative for lymphoma, melanoma, germ cell, and endocrine markers. Electron microscopy showed rare intermediate junctions and basal lamina. The nasopharyngeal tumor was poorly differentiated with areas of obvious squamous differentiation observed histologically, immunophenotypically, and ultrastructurally. Cytogenetic and fluorescent in situ hybridization studies were consistent with t(15;19)(q13;p13.1) in both cases. Both children received chemo- and radiotherapy. The first child died of disease after 36 weeks; autopsy revealed tumor in the larynx with spread to the skin/subcutis (neck and thorax) and lymph nodes (cervical, subcarinal, and pulmonary hilar). The second child developed widespread bony metastases and died of disease after 13 weeks.

Conclusions: In conjunction with previous reports, the authors' findings show that t(15;19) is part of a distinct clinicopathologic entity characterized by young age, midline carcinoma of the neck or upper thorax, and a rapidly fatal course. Female gender and superior vena cava syndrome are common. The histogenesis of these distinctive tumors is unknown. The authors' findings suggest origin in the upper airway, perhaps from submucosal glands.