Case records of all patients diagnosed with nasal extranodal NK/T-cell lymphoma, from 1995 to 2007, at the Samsung Medical Center and Korea University Medical Center were consecutively reviewed. Extranodal NK/T-cell lymphoma, nasal type, was diagnosed according to the World Health Organization classification system. Therefore, patients were diagnosed based on the presence of a tumor mass with histological features and immunophenotypes compatible with the NK/T-cell lymphoma (cCD3⁺, CD20^-, CD56⁺, cytotoxic molecules⁺, and EBV [Epstein-Barr virus] in situ hybridization ⁺). Other NHL subtypes, including myeloid/NK cell precursor acute leukemia, blastic NK cell lymphoma/precursor NK cell lymphoblastic leukemia, aggressive NK cell leukemia, and peripheral T-cell lymphoma unspecified were excluded. The selection criteria for cases with an atypical clinical course was repeated relapses (≥3 times) or progression during follow-up, in addition to a longer than 40-month survival, as the longest overall survival median was previously considered at approximately 40 months [2,4]. All relapses were proven by biopsy, and they demonstrated histological similarity to the original disease. Patient treatment at the time of diagnosis and relapse was performed at the attending physician's discretion. Thus, systemic chemotherapy and/or involved field radiation therapy were performed as primary treatment at diagnosis. The primary chemotherapy regimen used was CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or a CHOP-like regimen. The median total radiation dose to the lesion was 40 Gy, and the daily dose for most patients was 2 Gy. After relapse, various salvage chemotherapy regimens were used including SMILE (solumedrol, methotrexate, ifosfamide, L-asparaginase, and etoposide), IMVP-16 (ifosfamide, methotrexate, etoposide, and prednisone), and GDP (gemcitabine, dexamethasone, and cisplatin).

Patient characteristics at the time of diagnosis are summarized in Table 1. All patients presented with localized disease; hence, their International Prognostic Index (IPI) scores were low. The median time to initial relapse was 24 months (20-46 follow-up (Fig. 1). Patient 1 was a 23-year-old man with a mass obstructing the nasal cavity. The nasal mass progressed during chemotherapy and radiation therapy. A new orbital lesion developed 18 months after achieving complete remission (CR) through salvage chemotherapy. However, the patient was alive at the time of the study after the second complete remission (CR2) (Fig. 1). In patient 2 (a 43-year-old man), the leg skin tumor relapsed 46 months after the initial CR (Fig. 1). The patient achieved CR after salvage chemotherapy. However, he refused further treatment such as high-dose chemotherapy with autologous stem cell transplantation that was required to consolidate remission. Three years after CR2, relapse was detected in the chest wall. However, the patient was alive at the time of the study with partial remission, and his survival duration was 86 months (Table 1). Patient 3 was a 75-year-old woman presenting with a left calf muscle mass. She underwent radiation therapy because of her poor performance status, and she achieved CR. However, since her initial relapse in the back muscle, she showed repeated relapses that followed a wandering pattern from back muscle to nasal skin (Fig. 1). The time interval between diagnosis and initial relapse was 33 months. The patient died of disease progression after having survived for 80 months, despite 5 relapses. These 3 patients showed a wandering relapse pattern from nasal cavity to muscle and a long-term survival, in spite of frequent relapses. Cases 4-6 involved patients who had primary lesions of the oral cavity. Their initial relapse, 22-24 months after their initial CR, was followed by 3 other relapses. However, the relapse lesions were confined to the head and neck region, such as the oral and nasal cavities. Interestingly, patient 4, a 38-year-old woman, was alive with stable disease after the initial nasal cavity relapse. During that period, she had not been receiving any treatment (Fig. 1). Patient 5 (41-year-old man) was alive, with the disease, after his third relapse, despite refusing further treatment (Fig. 1). Patient 6 showed 3 relapses in the oral cavity during the 52-month follow-up period, and she was alive at the time of the study with no evidence of relapse. All patient samples were EBV-positive, although the positivity rate varied among the samples. The immunohistochemistry findings of the biopsy specimens collected at the time of diagnosis showed that Ki-67 expression level was less than 50% in 5 of the 6 patients. This indicated a relatively low tumor cell proliferation rate. The re-biopsy samples collected at relapse showed a similar Ki-67 expression pattern. Patient 4's Ki-67 expression level was especially low at relapse (<20%), which was much lower than that observed at diagnosis.