Primary Natural Killer/T-cell Lymphoma Presenting as Leptomeningeal Disease Bing Liao, Carlos Kamiya-Matsuoka, Yun Gong, Merry Chen, Brian A. Wolf, Nathan H. Fowler PII: DOI: Reference:
S0022-510X(14)00305-0 doi: 10.1016/j.jns.2014.05.015 JNS 13192
To appear in:
Journal of the Neurological Sciences
Received date: Revised date: Accepted date:
11 January 2014 29 April 2014 6 May 2014
Please cite this article as: Liao Bing, Kamiya-Matsuoka Carlos, Gong Yun, Chen Merry, Wolf Brian A., Fowler Nathan H., Primary Natural Killer/T-cell Lymphoma Presenting as Leptomeningeal Disease, Journal of the Neurological Sciences (2014), doi: 10.1016/j.jns.2014.05.015
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Primary Natural Killer/T-cell Lymphoma Presenting as Leptomeningeal Disease Bing Liao*, M.D., M.Sc. (1,2), Carlos Kamiya-Matsuoka*, M.D. (1), Yun Gong, M.D. (3), Merry
RI P
T
Chen, M.D. (1), Brian A. Wolf, M.D. (5) Nathan H. Fowler, M.D. (4)
1, Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center
SC
(BL, CK-M, MC)
NU
Mailing Address: 1400 Holcombe Boulevard, Room FC7.3000, Unit 431, Houston, Texas 77030
MA
2, Department of Neurology, The University of Texas Medical Branch (BL)
ED
Mailing Address: 301 University Boulevard, Room JSA 9.128, Galveston, Texas 77555
PT
3, Department of Pathology, The University of Texas MD Anderson Cancer Center (YG)
CE
Mailing Address: 1515 Holcombe Boulevard, Office G3.3775, Houston, Texas 77030
Center (NHF)
AC
4, Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer
Mailing Address: 1515 Holcombe Boulevard, R6.1617, Houston, Texas 77030
5, Department of Neurology, Baylor College of Medicine (BAW) Mailing Address: 6501 Fannin Street, NB320, Houston, Texas 77030
*These authors contributed equally to this study
1
ACCEPTED MANUSCRIPT Correspondence to: Dr. Bing Liao
T
Phone: 1-409-772-8058 (O)
RI P
Email: [email protected]
NU
SC
Running Title: Leptomeningeal Natural Killer/T-cell Lymphoma
Disclosure/Conflict of Interest
AC
CE
PT
ED
MA
The authors report no disclosure. This study does not involve use of any grant funds.
2
ACCEPTED MANUSCRIPT KEYWORDS CNS lymphoma
T
Leptomeningeal disease
RI P
Natural Killer/T-cell lymphoma
AC
CE
PT
ED
MA
NU
SC
Epstein-Barr virus
3
ACCEPTED MANUSCRIPT ABSTRACT
T
INTRODUCTION: Primary central nervous system natural killer/T-cell lymphoma (primary-
RI P
CNS-NK/TCL) is a rare non-Hodgkin’s lymphoma. To our knowledge, only five patients have been described previously, all of whom were male, with brain parenchymal involvement and
SC
previous Epstein-Barr virus infection, it has never been reported to present as leptomeningeal
NU
disease as our case. Our objective is to report a rare case of primary-CNS-NK/TCL presenting as
MA
leptomeningeal disease and to share our diagnostic/therapeutic approach to this rare disease.
METHODS: We report a rare case of primary-CNS-NK/TCL presenting as leptomeningeal
ED
disease. The patient was diagnosed and treated at The University of Texas MD Anderson Cancer
PT
Center.
CE
RESULTS: The patient presented with multiple cranial neuropathies and gait ataxia. Brain and
AC
spinal cord magnetic resonance imaging demonstrated leptomeningeal enhancement of the cerebellar folia/vermis, spinal cord dura, and both temporal lobes as well as adjacent brain parenchymal disease. Cerebrospinal fluid (CSF) revealed atypical lymphoma cells of NK/T-cell lineage by flow cytometric immunophenotyping. Molecular analysis using real-time quantitative polymerase chain reaction did not detect Epstein-Barr virus DNA in the lymphoma cells. Bone marrow biopsy revealed no morphologic, flow cytometric, or immunohistochemical evidence of B-, T- or NK-cell lymphoma. Slit-lamp examination demonstrated no evidence of intraocular lymphoma. Whole-body PET scan showed no evidence of malignancy other than CNS disease. The patient was given systemic chemotherapy with high-dose methotrexate, vincristine, and
4
ACCEPTED MANUSCRIPT procarbazine, along with intrathecal therapy with free cytarabine. The patient showed
T
clinicoradiographic improvement and CSF cytology became negative.
RI P
CONCLUSION: This case highlights an atypical presentation of primary-CNS-NK/TCL with a
AC
CE
PT
ED
MA
NU
SC
potentially successful treatment regimen.
5
ACCEPTED MANUSCRIPT INTRODUCTION Natural killer/T-cell lymphomas (NK/TCLs) are a group of rare non-Hodgkin’s lymphomas from
T
post-thymic T-cells. The World Health Organization classifies NK/T-cell tumors into three types:
RI P
extranodal NK/TCLs (nasal and non-nasal), NK-cell leukemias, and blastic NK/TCL.1,2 NK/TCL is an aggressive entity that almost always shows an extranodal presentation and most frequently
SC
affects Asian and South American populations. In 2009, the International Peripheral T-cell
NU
Lymphoma Project reviewed 1,314 cases and reported a four-fold higher relative frequency of extranodal NK/TCL among cases of lymphoma in Asian countries than in Western countries
MA
(22% vs 5%).3 Extranodal NK/TCL is characterized by vascular damage and destruction, prominent necrosis, a cytotoxic phenotype, and association with Epstein-Barr virus (EBV)4 that
ED
may be directly involved in lymphomagenesis. The sites most commonly involved are the upper
PT
aerodigestive tract (80%), and extra-nasal sites such as skin, soft tissue, gastrointestinal tract, and testis make up to 10% of the cases. Bone marrow and central nervous system (CNS) involvement
AC
CE
at presentation are rare,
S0022-510X(14)00305-0 doi: 10.1016/j.jns.2014.05.015 JNS 13192
To appear in:
Journal of the Neurological Sciences
Received date: Revised date: Accepted date:
11 January 2014 29 April 2014 6 May 2014
Please cite this article as: Liao Bing, Kamiya-Matsuoka Carlos, Gong Yun, Chen Merry, Wolf Brian A., Fowler Nathan H., Primary Natural Killer/T-cell Lymphoma Presenting as Leptomeningeal Disease, Journal of the Neurological Sciences (2014), doi: 10.1016/j.jns.2014.05.015
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Primary Natural Killer/T-cell Lymphoma Presenting as Leptomeningeal Disease Bing Liao*, M.D., M.Sc. (1,2), Carlos Kamiya-Matsuoka*, M.D. (1), Yun Gong, M.D. (3), Merry
RI P
T
Chen, M.D. (1), Brian A. Wolf, M.D. (5) Nathan H. Fowler, M.D. (4)
1, Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center
SC
(BL, CK-M, MC)
NU
Mailing Address: 1400 Holcombe Boulevard, Room FC7.3000, Unit 431, Houston, Texas 77030
MA
2, Department of Neurology, The University of Texas Medical Branch (BL)
ED
Mailing Address: 301 University Boulevard, Room JSA 9.128, Galveston, Texas 77555
PT
3, Department of Pathology, The University of Texas MD Anderson Cancer Center (YG)
CE
Mailing Address: 1515 Holcombe Boulevard, Office G3.3775, Houston, Texas 77030
Center (NHF)
AC
4, Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer
Mailing Address: 1515 Holcombe Boulevard, R6.1617, Houston, Texas 77030
5, Department of Neurology, Baylor College of Medicine (BAW) Mailing Address: 6501 Fannin Street, NB320, Houston, Texas 77030
*These authors contributed equally to this study
1
ACCEPTED MANUSCRIPT Correspondence to: Dr. Bing Liao
T
Phone: 1-409-772-8058 (O)
RI P
Email: [email protected]
NU
SC
Running Title: Leptomeningeal Natural Killer/T-cell Lymphoma
Disclosure/Conflict of Interest
AC
CE
PT
ED
MA
The authors report no disclosure. This study does not involve use of any grant funds.
2
ACCEPTED MANUSCRIPT KEYWORDS CNS lymphoma
T
Leptomeningeal disease
RI P
Natural Killer/T-cell lymphoma
AC
CE
PT
ED
MA
NU
SC
Epstein-Barr virus
3
ACCEPTED MANUSCRIPT ABSTRACT
T
INTRODUCTION: Primary central nervous system natural killer/T-cell lymphoma (primary-
RI P
CNS-NK/TCL) is a rare non-Hodgkin’s lymphoma. To our knowledge, only five patients have been described previously, all of whom were male, with brain parenchymal involvement and
SC
previous Epstein-Barr virus infection, it has never been reported to present as leptomeningeal
NU
disease as our case. Our objective is to report a rare case of primary-CNS-NK/TCL presenting as
MA
leptomeningeal disease and to share our diagnostic/therapeutic approach to this rare disease.
METHODS: We report a rare case of primary-CNS-NK/TCL presenting as leptomeningeal
ED
disease. The patient was diagnosed and treated at The University of Texas MD Anderson Cancer
PT
Center.
CE
RESULTS: The patient presented with multiple cranial neuropathies and gait ataxia. Brain and
AC
spinal cord magnetic resonance imaging demonstrated leptomeningeal enhancement of the cerebellar folia/vermis, spinal cord dura, and both temporal lobes as well as adjacent brain parenchymal disease. Cerebrospinal fluid (CSF) revealed atypical lymphoma cells of NK/T-cell lineage by flow cytometric immunophenotyping. Molecular analysis using real-time quantitative polymerase chain reaction did not detect Epstein-Barr virus DNA in the lymphoma cells. Bone marrow biopsy revealed no morphologic, flow cytometric, or immunohistochemical evidence of B-, T- or NK-cell lymphoma. Slit-lamp examination demonstrated no evidence of intraocular lymphoma. Whole-body PET scan showed no evidence of malignancy other than CNS disease. The patient was given systemic chemotherapy with high-dose methotrexate, vincristine, and
4
ACCEPTED MANUSCRIPT procarbazine, along with intrathecal therapy with free cytarabine. The patient showed
T
clinicoradiographic improvement and CSF cytology became negative.
RI P
CONCLUSION: This case highlights an atypical presentation of primary-CNS-NK/TCL with a
AC
CE
PT
ED
MA
NU
SC
potentially successful treatment regimen.
5
ACCEPTED MANUSCRIPT INTRODUCTION Natural killer/T-cell lymphomas (NK/TCLs) are a group of rare non-Hodgkin’s lymphomas from
T
post-thymic T-cells. The World Health Organization classifies NK/T-cell tumors into three types:
RI P
extranodal NK/TCLs (nasal and non-nasal), NK-cell leukemias, and blastic NK/TCL.1,2 NK/TCL is an aggressive entity that almost always shows an extranodal presentation and most frequently
SC
affects Asian and South American populations. In 2009, the International Peripheral T-cell
NU
Lymphoma Project reviewed 1,314 cases and reported a four-fold higher relative frequency of extranodal NK/TCL among cases of lymphoma in Asian countries than in Western countries
MA
(22% vs 5%).3 Extranodal NK/TCL is characterized by vascular damage and destruction, prominent necrosis, a cytotoxic phenotype, and association with Epstein-Barr virus (EBV)4 that
ED
may be directly involved in lymphomagenesis. The sites most commonly involved are the upper
PT
aerodigestive tract (80%), and extra-nasal sites such as skin, soft tissue, gastrointestinal tract, and testis make up to 10% of the cases. Bone marrow and central nervous system (CNS) involvement
AC
CE
at presentation are rare,
