Current Management of Nasal NK/T-cell Lymphoma
With better disease definition, staging, and monitoring, treatment of extranodal NK/T-cell lymphoma is becoming more rational. A large proportion of patients with localized nasal disease may enjoy prolonged disease-free survival. On the other hand, early HSCT or novel therapy may be recommended for aggressive extranasal disease.
Nasal natural killer (NK)/T-cell lymphoma-classified as extranodal NK/T-cell lymphoma (ENKTL), nasal type, by the World Health Organization-is a non-Hodgkin lymphoma that is almost always associated with Epstein-Barr virus. Up to 75% of ENKTL cases occur in the upper aerodigestive tract, primarily the nasal cavity. It is the most common type of peripheral T-cell lymphoma in many Asian countries. Histologic diagnosis is essential, and staging consists of bilateral bone marrow biopsy and imaging of the neck, thorax, abdomen, and pelvis. There is a marked dichotomy in treatment and survival between localized and disseminated disease. Since disease incidence is rare even in prevalent areas, experience is limited and most treatment protocols are consensus-guided. ENKTL is both chemosensitive and radiosensitive. Early-stage, localized nasal disease is highly curable with combination therapy, but the optimal dose, combination, and sequence of radiotherapy and chemotherapy are still undefined. For patients with disseminated and extranasal disease, either at initial presentation or at relapse, the prognosis is poor. For disseminated and refractory cases, the 5-year survival rate is below 10%, and better methods of treatment are needed.
Nasal natural killer (NK)/T-cell lymphoma is a unique type of non-Hodgkin lymphoma (NHL) that is almost always associated with Epstein-Barr virus (EBV). The disease predominantly localizes to the upper aerodigestive tract, most commonly in the nose. It is locally angioinvasive and destructive and was previously called lethal midline granuloma. However, up to 25% of patients have primary extranasal disease, without any apparent antecedent or concomitant nasal involvement by radiology, clinical examination, or biopsy.[1] Both categories are grouped together as extranodal NK/T-cell lymphoma (ENKTL), nasal type, in the World Health Organization (WHO) classification.[2]
Although most lesions of this type show an NK lineage (as evident by CD3s-negative, CD56-positive germline T-cell receptor status), some cases may show a cytotoxic T-cell phenotype, and hence, the designation of NK/T-cell lymphoma. Other entities of putative NK lineage but EBV-negative (eg, chronic T- and NK-cell lymphocytosis, plasmacytoid dendritic-cell tumors, and NK/myeloid leukemia) are pathogenetically unrelated.
The disease shows a dramatic ethnic and geographic predilection, accounting for 7% to 10% of NHL cases in Asian and Latin American countries,[3] but only 1% of Caucasian cases.[4,5] It is the most common type of peripheral T-cell lymphoma (20%–30%) in many Asian countries. Hence, most data come from single-center or national series from Asian countries,[6-8] with smaller Caucasian series.[9,10] Large international series of ENKTL patients will also show predominant Asian dominance in terms of case contribution.[1] However, the clinicopathologic features of the disease have appeared the same in different ethnic groups. The persistent higher incidence of ENKTL in Asian people who immigrate to North America suggests a genetic predisposition.[11] However, preliminary epidemiologic studies in endemic areas of ENKTL disease suggest the existence of some environmental factors for local case clustering.[12]
Clinical Presentation
FIGURE 1
Palatal Ulcer in a Patient With Primary Nasal Lymphoma