Clinicopathological findings, prognosis, and Epstein–Barr virus infection in rheumatoid arthritis patients with other iatrogenic immunodeficiency-associated T- and NK-cell lymphoproliferative disorders
Abstract Background Other iatrogenic immunodeficiency-associated (OIIA) T- and natural killer (NK)-cell lymphoproliferative disorders (TNK-LPDs) are rare in patients with rheumatoid arthritis (RA). Methods We investigated the clinicopathological characteristics, Epstein–Barr virus (EBV) infection, g...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-12-01
|
| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-022-10358-0 |
| _version_ | 1797977406579933184 |
|---|---|
| author | Shoichi Kimura Yumi Oshiro Hiromi Iwasaki Masanori Kadowaki Masao Ogata Tsutomu Daa Toshifumi Sakata Shigeto Kawauchi Ziyao Wang Yasushi Takamatsu Morishige Takeshita |
| author_facet | Shoichi Kimura Yumi Oshiro Hiromi Iwasaki Masanori Kadowaki Masao Ogata Tsutomu Daa Toshifumi Sakata Shigeto Kawauchi Ziyao Wang Yasushi Takamatsu Morishige Takeshita |
| author_sort | Shoichi Kimura |
| collection | DOAJ |
| description | Abstract Background Other iatrogenic immunodeficiency-associated (OIIA) T- and natural killer (NK)-cell lymphoproliferative disorders (TNK-LPDs) are rare in patients with rheumatoid arthritis (RA). Methods We investigated the clinicopathological characteristics, Epstein–Barr virus (EBV) infection, genetic findings, therapeutic response, and prognostic factors in 21 RA patients with OIIA TNK-LPDs and compared these with those of 39 with OIIA B-cell LPDs (B-LPDs) and 22 with non-OIIA B-LPDs. Results Immunohistologically, 11 patients (52%) showed CD4+ T-LPDs, and 7 had a T follicular helper (TFH) phenotype. The other nine patients (43%) showed CD8+ T-LPDs, and the remaining one (5%) had features of CD3+ CD4− CD8− nasal type TNK-cell lymphoma. CD30+, p53+, and CMYC+ atypical lymphocytes were identified in seven (33%), eight (38%), and five (24%) patients, respectively. In situ hybridisation detected EBV-encoded RNA (EBER) + large atypical lymphocytes in five patients (24%). Nine of 17 patients (53%) showed clonal peaks of TCRγ by polymerase chain reaction. Withdrawal of MTX and biologic drugs was effective in 12 patients (57%), and 8 (38%) received chemotherapies. Two patients with TFH+ or EBV+ CD4+ CD30+ large cell peripheral T-cell lymphoma, one with CD8+ systemic anaplastic large cell lymphoma, and two with systemic EBV+ CD8+ T-cell lymphoma of childhood showed a lethal progressive clinical course within 13 months. Moreover, > 500 U/L LDH, large atypical lymphocytes, expression of CD30, p53, and CMYC, and EBER+ atypical lymphocytes were significantly poor prognostic factors for overall survival (p < 0.05). Median interval from RA onset to OIIA TNK-LPDs was 72 months, which was shorter than 166 months in OIIA B-LPDs (p = 0.003). EBV+ atypical and reactive lymphocytes were frequently found in 15 patients with OIIA TNK-LPDs (71%), in 27 with OIIA B-LPDs (69%), and only in 3 with non-OIIA B-LPDs (14%). Conclusions OIIA TNK-LPDs occurred in early phase of RA, compared with OIIA B-LPDs, and occasionally showed a lethal progressive clinical course. Detection of OIIA TNK-LPD patients with poor prognostic factors is necessary. EBV infection in immunosuppressed patients due to persistent RA, MTX, and biologic drugs may play a role in forming the tumour microenvironment and lymphomagenesis of TNK-LPDs. |
| first_indexed | 2024-04-11T05:06:24Z |
| format | Article |
| id | doaj.art-67fc5f989e3c4e2ab24787d047071356 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-11T05:06:24Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-67fc5f989e3c4e2ab24787d0470713562022-12-25T12:19:34ZengBMCBMC Cancer1471-24072022-12-0122111410.1186/s12885-022-10358-0Clinicopathological findings, prognosis, and Epstein–Barr virus infection in rheumatoid arthritis patients with other iatrogenic immunodeficiency-associated T- and NK-cell lymphoproliferative disordersShoichi Kimura0Yumi Oshiro1Hiromi Iwasaki2Masanori Kadowaki3Masao Ogata4Tsutomu Daa5Toshifumi Sakata6Shigeto Kawauchi7Ziyao Wang8Yasushi Takamatsu9Morishige Takeshita10Graduate School of Medical Sciences, Division of Pathomorphology, Fukuoka UniversityDepartment of Pathology, Matsuyama Red Cross HospitalDepartment of Haematology, Clinical Research Centre, National Hospital Organization Kyushu Medical CentreDepartment of Haematology, Clinical Research Centre, National Hospital Organization Kyushu Medical CentreDepartment of Hematology, Faculty of Medicine, Oita UniversityDepartment of Pathology, Faculty of Medicine, Oita UniversityDepartment of Otolaryngology, Faculty of Medicine, and Fukuoka UniversityDepartment of Pathology, Clinical Research Centre, National Hospital Organization Kyushu Medical CentreGraduate School of Medical Sciences, Division of Pathomorphology, Fukuoka UniversityDepartment of Internal Medicine, Division of Medical Oncology, Hematology and Infectious Disease, Faculty of Medicine, Fukuoka UniversityGraduate School of Medical Sciences, Division of Pathomorphology, Fukuoka UniversityAbstract Background Other iatrogenic immunodeficiency-associated (OIIA) T- and natural killer (NK)-cell lymphoproliferative disorders (TNK-LPDs) are rare in patients with rheumatoid arthritis (RA). Methods We investigated the clinicopathological characteristics, Epstein–Barr virus (EBV) infection, genetic findings, therapeutic response, and prognostic factors in 21 RA patients with OIIA TNK-LPDs and compared these with those of 39 with OIIA B-cell LPDs (B-LPDs) and 22 with non-OIIA B-LPDs. Results Immunohistologically, 11 patients (52%) showed CD4+ T-LPDs, and 7 had a T follicular helper (TFH) phenotype. The other nine patients (43%) showed CD8+ T-LPDs, and the remaining one (5%) had features of CD3+ CD4− CD8− nasal type TNK-cell lymphoma. CD30+, p53+, and CMYC+ atypical lymphocytes were identified in seven (33%), eight (38%), and five (24%) patients, respectively. In situ hybridisation detected EBV-encoded RNA (EBER) + large atypical lymphocytes in five patients (24%). Nine of 17 patients (53%) showed clonal peaks of TCRγ by polymerase chain reaction. Withdrawal of MTX and biologic drugs was effective in 12 patients (57%), and 8 (38%) received chemotherapies. Two patients with TFH+ or EBV+ CD4+ CD30+ large cell peripheral T-cell lymphoma, one with CD8+ systemic anaplastic large cell lymphoma, and two with systemic EBV+ CD8+ T-cell lymphoma of childhood showed a lethal progressive clinical course within 13 months. Moreover, > 500 U/L LDH, large atypical lymphocytes, expression of CD30, p53, and CMYC, and EBER+ atypical lymphocytes were significantly poor prognostic factors for overall survival (p < 0.05). Median interval from RA onset to OIIA TNK-LPDs was 72 months, which was shorter than 166 months in OIIA B-LPDs (p = 0.003). EBV+ atypical and reactive lymphocytes were frequently found in 15 patients with OIIA TNK-LPDs (71%), in 27 with OIIA B-LPDs (69%), and only in 3 with non-OIIA B-LPDs (14%). Conclusions OIIA TNK-LPDs occurred in early phase of RA, compared with OIIA B-LPDs, and occasionally showed a lethal progressive clinical course. Detection of OIIA TNK-LPD patients with poor prognostic factors is necessary. EBV infection in immunosuppressed patients due to persistent RA, MTX, and biologic drugs may play a role in forming the tumour microenvironment and lymphomagenesis of TNK-LPDs.https://doi.org/10.1186/s12885-022-10358-0Rheumatoid arthritisIatrogenic immunodeficiencyMethotrexateT cells, NK cells, lymphoproliferative disordersEpstein–Barr virus |
| spellingShingle | Shoichi Kimura Yumi Oshiro Hiromi Iwasaki Masanori Kadowaki Masao Ogata Tsutomu Daa Toshifumi Sakata Shigeto Kawauchi Ziyao Wang Yasushi Takamatsu Morishige Takeshita Clinicopathological findings, prognosis, and Epstein–Barr virus infection in rheumatoid arthritis patients with other iatrogenic immunodeficiency-associated T- and NK-cell lymphoproliferative disorders BMC Cancer Rheumatoid arthritis Iatrogenic immunodeficiency Methotrexate T cells, NK cells, lymphoproliferative disorders Epstein–Barr virus |
| title | Clinicopathological findings, prognosis, and Epstein–Barr virus infection in rheumatoid arthritis patients with other iatrogenic immunodeficiency-associated T- and NK-cell lymphoproliferative disorders |
| title_full | Clinicopathological findings, prognosis, and Epstein–Barr virus infection in rheumatoid arthritis patients with other iatrogenic immunodeficiency-associated T- and NK-cell lymphoproliferative disorders |
| title_fullStr | Clinicopathological findings, prognosis, and Epstein–Barr virus infection in rheumatoid arthritis patients with other iatrogenic immunodeficiency-associated T- and NK-cell lymphoproliferative disorders |
| title_full_unstemmed | Clinicopathological findings, prognosis, and Epstein–Barr virus infection in rheumatoid arthritis patients with other iatrogenic immunodeficiency-associated T- and NK-cell lymphoproliferative disorders |
| title_short | Clinicopathological findings, prognosis, and Epstein–Barr virus infection in rheumatoid arthritis patients with other iatrogenic immunodeficiency-associated T- and NK-cell lymphoproliferative disorders |
| title_sort | clinicopathological findings prognosis and epstein barr virus infection in rheumatoid arthritis patients with other iatrogenic immunodeficiency associated t and nk cell lymphoproliferative disorders |
| topic | Rheumatoid arthritis Iatrogenic immunodeficiency Methotrexate T cells, NK cells, lymphoproliferative disorders Epstein–Barr virus |
| url | https://doi.org/10.1186/s12885-022-10358-0 |
| work_keys_str_mv | AT shoichikimura clinicopathologicalfindingsprognosisandepsteinbarrvirusinfectioninrheumatoidarthritispatientswithotheriatrogenicimmunodeficiencyassociatedtandnkcelllymphoproliferativedisorders AT yumioshiro clinicopathologicalfindingsprognosisandepsteinbarrvirusinfectioninrheumatoidarthritispatientswithotheriatrogenicimmunodeficiencyassociatedtandnkcelllymphoproliferativedisorders AT hiromiiwasaki clinicopathologicalfindingsprognosisandepsteinbarrvirusinfectioninrheumatoidarthritispatientswithotheriatrogenicimmunodeficiencyassociatedtandnkcelllymphoproliferativedisorders AT masanorikadowaki clinicopathologicalfindingsprognosisandepsteinbarrvirusinfectioninrheumatoidarthritispatientswithotheriatrogenicimmunodeficiencyassociatedtandnkcelllymphoproliferativedisorders AT masaoogata clinicopathologicalfindingsprognosisandepsteinbarrvirusinfectioninrheumatoidarthritispatientswithotheriatrogenicimmunodeficiencyassociatedtandnkcelllymphoproliferativedisorders AT tsutomudaa clinicopathologicalfindingsprognosisandepsteinbarrvirusinfectioninrheumatoidarthritispatientswithotheriatrogenicimmunodeficiencyassociatedtandnkcelllymphoproliferativedisorders AT toshifumisakata clinicopathologicalfindingsprognosisandepsteinbarrvirusinfectioninrheumatoidarthritispatientswithotheriatrogenicimmunodeficiencyassociatedtandnkcelllymphoproliferativedisorders AT shigetokawauchi clinicopathologicalfindingsprognosisandepsteinbarrvirusinfectioninrheumatoidarthritispatientswithotheriatrogenicimmunodeficiencyassociatedtandnkcelllymphoproliferativedisorders AT ziyaowang clinicopathologicalfindingsprognosisandepsteinbarrvirusinfectioninrheumatoidarthritispatientswithotheriatrogenicimmunodeficiencyassociatedtandnkcelllymphoproliferativedisorders AT yasushitakamatsu clinicopathologicalfindingsprognosisandepsteinbarrvirusinfectioninrheumatoidarthritispatientswithotheriatrogenicimmunodeficiencyassociatedtandnkcelllymphoproliferativedisorders AT morishigetakeshita clinicopathologicalfindingsprognosisandepsteinbarrvirusinfectioninrheumatoidarthritispatientswithotheriatrogenicimmunodeficiencyassociatedtandnkcelllymphoproliferativedisorders |