A case report of primary unilateral adrenal NK/T cell lymphoma: good clinical outcome with trimodality treatment

There have been seven reported cases of NK/T cell lymphoma involving adrenal masses worldwide [1‐7]. Among them, only one was primary adrenal NK/T cell lymphoma [2]. There have been no reported cases of the primary adrenal NK/T-cell lymphoma in China. Anatomically, it usually originates in the nasal cavity/nasopharynx and invades the surrounding tissues. Sometimes, it can arise in other organs including the skin, spleen/liver, or the gastrointestinal tract [8]. Here, we report a primary unilateral adrenal NK/T cell lymphoma with subsequent management. Although the longest survival was reported to be 90 days for adrenal NK/T cell lymphoma, our patient has been disease-free for 26 months.

Primary adrenal lymphoma or lymphoma involving mainly the adrenal gland without the regional lymph node involvement is a very rare extra-nodal lymphoma. Patients with adrenal lymphoma may present with systemic symptoms including fever, fatigueand weight loss [9‐11]. Primary adrenal lymphoma can be discovered incidentally on abdominal imaging. Differential diagnoses include cortical adenoma, pheochromocytoma, metastatic-disease, and adrenocorticotropic hormone (ACTH) dependent Cushing’s syndrome [12, 13]. The definitive diagnosis of primary adrenal lymphoma is made by an image-guided percutaneous biopsy, surgical exploration, or a postmortem examination [1, 2, 14]. Histopathologically, the most common type of primary adrenal lymphoma is B-cell type, mainly diffuse large B-cell lymphoma. Although involvement of the adrenal glands can be seen in disseminated disease, primary NK/T cell lymphoma in the adrenal gland as an initial presentation is extremely rare. The NK/T cell lymphomas are aggressive lymphoproliferative disorders derived from either activated NK cells or cytotoxic T cells. The 2008 World Organization classification system categorized NK–cell malignancies into three types: extra-nodal NK/T-cell lymphoma (nasal and non-nasal), aggressive NK-cell leukemia and chronic lymphoproliferative disorder of NK cells [15]. NK/T-cell lymphomas demonstrate vascular destruction with prominent necrosis. Immunophenotypically, they express CD2 and CD56. NK/T-cell lymphomas are strongly associated with Epstein-Barr virus (EBV), suggesting a pathogenic role of this virus [16, 17]. In this case, the patient’s tumor was positive for CD2, CD56 and EBER.

NK/T cell lymphoma is an extra-nodal lymphoma with predilection for the nasal cavity, nasopharynx, skin, and the other extra-nodal sites. The primary adrenal NK/Tcell lymphoma is exceedingly uncommon. In the review of the literature, we found only seven reported cases of NK/T cell lymphoma presenting as adrenal masses. Among these cases, the adrenal mass was the only involved site in one case [9]. The rest involved multiple organs, including central nervous system (CNS), paranasal sinus, kidney, bone marrow, etc. [1, 3‐7]. Tissue diagnosis was made from the adrenal mass in four cases through adrenalectomy, CT-guided biopsy and autopsy specimen [1‐3, 16], from cervical lymph nodes or nasal mass in two cases. There was no pathologic diagnosis in one case (the diagnosis was made per imaging study). The ages of the patients ranged from 17 to 76. Among these cases, the highly aggressive nature of the lymphoma and its rapid clinical progression were reported and the long-term prognosis has not been observed (Table. 1).

Because of the rarity of this disease, the standard therapies have not been defined. The treatments have included various combinations of surgery, chemotherapy, and radiation. In the reported cases, four patients received chemotherapy, one patient received surgery and chemotherapy; one patient received high dose intravenous dexamethasone, and one patient received immunosuppression therapy. CHOP was the most common used chemotherapy regimen in these reported cases. The longest reported survival was 90 days in a patient who received surgery and chemotherapy. Our patient underwent surgery, postoperative chemotherapy with 4 cycles of CHOP followed by radiotherapy. Two more cycles of CHOP were administered afterwards. It should be noted that the surgery was performed prior to the patient’s visit at our hospital. If a biopsy sufficed, then surgery would not be necessary, given that these tumors are generally sensitive to chemotherapy and radiation therapy. Because of the residual tumor at the left side of the retroperitoneum, postoperative radiation therapy was recommended. In terms of chemotherapy regimen, SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase and etoposide) is a standard chemotherapy regimen for NK/T lymphoma patients in the western countries. However, there was a shortage of L-asparaginase in our province in the end of 2013, when this patient was first treated. Therefore, this patient was treated with CHOP according to the previous case reports [2, 5, 7]. As a side note, SMILE has been used for NK/T lymphoma patients in our province since mid-2014.

Our patient remains disease-free with a follow up of over two years. We list three possible reasons for the longer disease-free survival for our patient: (1) the NK/T cell lymphoma only involved one adrenal gland; (2) the NK/T cell lymphoma did not involve other organs, except for the adjacent kidney; and (3) the utilization of trimodality therapy.

In conclusion, primary adrenal NK/T cell lymphoma is an exceedingly uncommon neoplasm and the outcomes for it are generally poor. We present the first case of a primary adrenal NK/T cell lymphoma in China with over 2-year disease-free survival treated with trimodality therapy. NK/T cell lymphoma should be considered in the differential diagnosis of a rapidly enlarging adrenal mass. As reports of such cases increase and our understanding of the disease improves, we anticipate more effective treatment for these patients.