Abstract
Objectives
We report a case of a 26-year-old man diagnosed with nasal-type extranodal natural killer/T cell lymphoma (ENKTL) extending beyond the nasal cavity. Complete response was achieved after therapy, followed by rapid metastasis to the meningeal nerve fibres. The overall survival (OS) of the patient was 15 months. To better understand ENKTL with meningeal involvement, we summarized the clinical features of the 10 cases involving meningeal metastasis in ENKTL reported in the English literature.
Methods
The patient was admitted for the ENKTL diagnosis, and positron emission tomography-computed tomography showed the disease stage and response. When central nervous system (CNS) infiltration was suspected, magnetic resonance imaging (MRI) of the brain and spinal cord was performed, as well as cerebrospinal fluid (CSF) analysis with flow cytometric immunophenotyping.
Results
MRI of the brain and spinal cord revealed normal results. CSF analysis with flow cytometric immunophenotyping showed NK/T lymphoma cell infiltration.
Conclusion
Meningeal metastasis of ENKTL is rare; when patients present with nervous system symptoms, CNS metastasis should be considered as a possibility, even in the early stage. The OS of our patient was 15 months, which is the longest survival time reported in the literature, probably due to early diagnosis and comprehensive management, including intrathecal therapy, chemotherapy and radiotherapy of the whole brain and spinal cord.
Keywords: NK/T cell, Lymphoma, Metastasis, Meningeal, Central nervous system
A 26-year-old Chinese AIDS-negative man complaining of nasal obstruction and night sweats presented at our hospital, and we conducted a nasal cavity tissue biopsy. The pathological diagnosis was ENKTL. The tumour cells exhibited the following characteristics: CD3ε(+), CD20(−), CD56(+), granzyme B(+), MPO(−), and CD30(−); Ki67 80–90%; and EBER1/2 in situ hybridization (+). TCR-V gene rearrangement (PCR method) did not present clonal rearrangements. Positron emission tomography-computed tomography (PET-CT) indicated local lesions in the bilateral nasal cavity, nasal septum and ethmoid sinus. We provided the patient 4 courses of VDLP (etoposide, dexamethasone, L-asparaginase, cisplatin) chemotherapy, followed by local radiotherapy. One month after PET-CT indicated a complete response (CR), the patient returned with bilateral facial paralysis and difficulty walking, but contrast-enhanced magnetic resonance imaging (MRI) of the brain and spinal cord showed no abnormalities. Cerebrospinal fluid (CSF) analysis with flow cytometric immunophenotyping revealed NK/T lymphoma cells. The patient reported significant improvement in facial paralysis and walking, and no tumour cells were found in the CSF after weekly intrathecal methotrexate, cytarabine and dexamethasone treatment along with oral temozolomide and whole brain and spinal cord radiotherapy (radiotherapy dose, brain 1.6 Gy × 16f, spinal cord 1.6 Gy × 16f). Five months later, the patient presented with headache, limb pain, gradual deterioration of vision and bulging of the left eye, and NK/T lymphoma cells were found in the CSF, but no brain mass was detected. We again treated weekly with intrathecal methotrexate, cytarabine, dexamethasone, and chemotherapy, but the disease progressed rapidly, and the patient died 15 months after diagnosis.
Central nervous system involvement occurs in less than 3% of the ENKTL cases [1]. We searched PUBMED and found 10 cases in the English literature involving meningeal metastasis in ENKTL (Table 1), including 9 patients with secondary ENKTL and 1 patient with primary meningeal ENKTL. For these 10 cases, including the one we present here, the median age was 56 years old, the ratio of females to males was nearly 0.8:1, and 44.4% (4/9) patients showed negative CT or MRI results, but CSF analysis revealed lymphoma cells or autopsy-confirmed disease. The case we present here is the youngest patient among the cases and the first case reported to have received radiotherapy treatment of the whole brain and spinal cord. In cases with meningeal metastasis, the prognosis is very poor. The median overall survival (OS) was 8.9 months for the 8 patients, with a 1-year OS rate of 25%. The OS of our patient was 15 months, most likely due to comprehensive management, including intrathecal therapy, chemotherapy and radiotherapy of the whole brain and spinal cord. In summary, meningeal metastasis of ENKTL is rare; when patients present with nervous system symptoms, CNS metastasis should be considered as a possibility, even in the early stage.
Table 1.
Summary of the reported cases in extranodal NK/T cell lymphoma with meningeal involvement and without parenchymal abnormality
| No. | Age (y), sex | Involved locations | CT or MRI scan | Flow cytometric immunophenotypic studies of NK/T lymphoma cells in the CSF | Therapy | Overall survival | |
|---|---|---|---|---|---|---|---|
| Van Gorp [2] | 1 | 46, F | Meningeal, nasal sinuses | Not mentioned | Not mentioned | RT, CHOP, MTX/DAF/Ara-c | 12 m |
| Kim [3] | 1 | 52, M | Meningeal, testicular, skin | MRI negative | Negative | CHOP, intrathecal methotrexate (MTX) | 8 m |
| Papalkar [4] | 1 | 41, F | Meningeal, right posterior orbit, lungs, pancreas, spleen, uterus, left adrenal gland, heart, pericardium | Not mentioned | Not mentioned | Prednisone | 12 d |
| Dunning [5] | 1 | 67, M | Meningeal, adrenal, bone marrow | MRI positive | Positive | Intravenous dexamethasone | N/A |
| Erős [6] | 2 |
75, M 69, F |
Meninges, skin, bone marrow | CT negative | Positive |
(1) CHOP, cytarabine and etoposide. Intrathecal methotrexate, cytarabine, and dexamethasone (2) Hyper-CVAD,vincristine, etoposide, and dexamethasone. Intrathecal methotrexate, cytarabine, and dexamethasone |
13 m 9 m |
| Hildyard [7] | 1 | 66, F | Pial surfaces of the lower spinal cord | MRI positive | Positive | AspaMetDex, ICE | N/A |
| Cai [8] | 1 | 57, F | Meningeal | MRI positive | Positive | Not mentioned | N/A |
| Shimatani [9] | 1 | 54, M | Meningeal, spinal cord, cauda equina | MRI negative | Positive | Prednisolone | 12 m |
| Zuhaimy [10] | 1 | 56, M | Meningeal, right recti muscles, lacrimal gland, optic nerve sinuses, bone marrow | MRI positive | Not mentioned | Not mentioned | 2 m |
| Present case | 1 | 26, M | Meningeal, nasal cavity, skin, bone, lymphonodal | MRI negative | Positive | VDLP, P-GEMOX, RT, intrathecal methotrexate, cytarabine, and dexamethasone | 15 m |
Compliance with ethical standards
Conflict of interest
All authors declare that they have no potential conflicts of interest to report.
Footnotes
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Contributor Information
Chunli Yang, Email: yangchunli0423@163.com.
Hongyu Zhuo, Email: zhuohongyu_123@163.com.
Liqun Zou, Email: hxlcyxy@163.com.
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