Non-nasal natural killer cell lymphoma: not non-nasal after all

Abstract

Dear Editor, Natural killer (NK) cell lymphoma, or extranodal NK/T-cell lymphoma, nasal type, according to the World Health Organization classification, is a rare neoplasm affecting preferentially Asian and South American populations, being extremely unusual in Western patients [1]. There are two clinical forms, nasal and non-nasal (extranasal) [2]. In nasal NK-cell lymphoma, the nasal and upper aerodigestive areas are initially involved. Dissemination to the skin, gut, testis, salivary glands or marrow occurs in advanced diseases. In non-nasal NK-cell lymphomas, however, the skin, gut, testis, salivary glands or marrow are the primary sites. Non-nasal NK-cell lymphomas have been reported to have a worse prognosis [3]. A 59-year-old man presented with bone pain, jaundice and fever. There were no lymphadenopathy or organomegaly. Investigations showed hemoglobin: 11.4 g/dL, white cell count: 1.4×10/L with no abnormal circulating cells, platelet count: 45×10/L, bilirubin: 67 (7–19) μmol/L, alkaline phosphatase: 510 (49–138) U/L, alanine aminotransferase: 407 (6–53) U/L, aspartate aminotransferase: 336 (13–33) U/L and lactate dehydrogenase (LDH): 1,200 (107– 218) U/L. A positron emission tomography/computerized tomography (PET/CT) showed hyper-metabolic lesions confined exclusively to the bone marrow (Fig. 1a). Histologic examination of the marrow showed diffuse infiltration by medium-sized lymphoid cells with irregular nuclei, clumped chromatin and cytoplasm with fine azurophilic granules, associated with florid hemophagocytosis (Fig. 1b). The neoplastic cells were surface CD3–, CD2+, CD7+, CD56+, and strongly positive for Epstein Barr virus encoded RNA on in situ hybridization (Fig. 1c). A nasal panendoscopy showed normal nasal, nasopharyngeal and oropharyngeal areas. Overall features were consistent with non-nasal NK-cell lymphoma. He was treated with methotrexate 2 g/m (day 1), and ifosamide 1.5 g/m/day, etoposide 100 mg/m/day, dexamethasone 40 mg/day (days 2 to 4) [4]. He responded with normalization of temperature and LDH. On day 8, however, he developed fever, nasal pain and obstruction with epistaxis. A CT scan showed a 2-cm rim-enhancing irregular lesion in the nasopharynx, a site which was uninvolved initially (Fig. 1d). Biopsy of the lesion confirmed NK-cell lymphoma infiltration (Fig. 1e). Treatment with Lasparaginase (6,000U/m/alternate daily×7) induced complete resolution of symptoms. Following normalization of blood counts and liver function, a marrow examination showed complete morphologic remission. Nasal panendoscopy with random nasopharyngeal biopsies also showed normal findings. Although NK-cell lymphomas are considered aggressive [1], stage I/II nasal NK-cell lymphomas have a favorable prognosis with radiotherapy and chemotherapy [5], whereas stage III/IV nasal NK-cell lymphomas fare much worse with few survivors. Conversely, non-nasal NK-cell lymAnn Hematol (2009) 88:185–187 DOI 10.1007/s00277-008-0562-0