Primary Gastrointestinal T/NK Cell Lymphoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patient Selection and Histological Review
2.2. Statistical Analysis
3. Results
3.1. Clinicopathologic Characteristics of Primary Gastrointestinal T/NK Cell Lymphoma
3.2. Comparison of Clinical Features of Primary Gastrointestinal T/NK Cell Lymphoma Subtypes
3.3. Morphologic and Immunophenotypic Features of Primary Gastrointestinal T/NK Cell Lymphoma Subtypes
3.4. Survival Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
ALCL: ALK- | anaplastic large cell lymphoma, ALK-negative |
ALCL, ALK+ | anaplastic large cell lymphoma, ALK-positive |
B2M | beta-2 microglobulin |
CR | complete remission |
CT | computed tomography |
EBER | Epstein-Barr virus-encoded RNA |
EBV | Epstein-Barr virus |
ECOG | Eastern Cooperative Oncology Group |
ENKTL | extranodal NK/T-cell lymphoma, nasal type |
FISH | fluorescence in situ hybridization |
GI-TNKL | primary gastrointestinal T/NK cell lymphoma |
HR | hazard ratio |
IHC | immunohistochemical staining |
IPI | international prognostic index |
ITCL, NOS | intestinal T-cell lymphoma, NOS |
LDH | lactate dehydrogenase |
MALT | mucosa-associated lymphoid tissue |
MEITL | monomorphic epitheliotropic intestinal T-cell lymphoma |
OS | overall survival |
PD | progressive disease |
PFS | progression-free survival |
PR | partial response |
SD | stable disease |
TCR | T-cell receptor |
WHO | World Health Organization |
References
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Characteristics | n (%) |
---|---|
Median age (range) | 58 years (34–84) |
Male/Female (M:F ratio) | 22/16 (1.4:1) |
Subtypes of lymphoma | |
ENKTL | 13 (34.2) |
MEITL | 12 (31.6) |
ITCL, NOS | 7 (18.4) |
ALCL, ALK- | 5 (13.2) |
ALCL, ALK+ | 1 (2.6) |
Location | |
Esophagus | 1 (2.6) |
Stomach | 9 (23.7) |
Small intestine | 27 (71.1) |
Duodenum | 4 (10.5) |
Jejunum | 15 (39.5) |
Ileum | 8 (21.1) |
Ileocecum | 5 (13.2) |
Large intestine | 13 (34.2) |
Ascending/transverse | 6 (15.8) |
Descending/sigmoid | 6 (15.8) |
Rectum | 1 (2.6) |
Multiple site involvement | 12 (31.6) |
Initial presentation | |
Abdominal pain and discomfort | 20 (52.6) |
Weight loss and poor oral intake | 8 (21.1) |
Diarrhea | 7 (18.4) |
GI bleeding | 5 (13.2) |
Vomiting | 3 (7.9) |
No symptom | 2 (5.3) |
GI complication | 24 (63.2) |
Perforation | 15 (39.5) |
Hemorrhage | 4 (10.5) |
Fistula formation | 3 (7.9) |
Obstruction | 2 (5.3) |
No initial GI complication | 14 (36.8) |
Lugano stage | |
I | 8 (21) |
II | 12 (31.6) |
IV | 18 (47.4) |
ECOG performance status ≥ 2 | 3/34 (7.9) |
IPI score ≥ 3 | 12 (31.6) |
Anemia | 21 (55.3) |
Lymphopenia | 21 (55.3) |
Thrombocytopenia | 2 (5.3) |
Diagnostic procedure | |
Endoscopic biopsy | 19 (50) |
Surgery | 19 (50) |
First treatment | |
Surgery with adjuvant therapy | 15 (39.5) |
Non-surgical therapy | 14 (36.8) |
Surgery | 4 (10.5) |
Unknown | 5 (13.2) |
First line non-surgical treatment | 29 |
CTx alone | 24 (82.8) |
CTx + autoPBSCT | 3 (10.3) |
CTx + RTx + autoPBSCT | 1 (3.5) |
RTx + CTx | 1 (3.4) |
Variable | Total | ENKTL | MEITL | ITCL, NOS | ALCL, ALK- | ALCL, ALK+ | p Value | |
---|---|---|---|---|---|---|---|---|
n = 38 (100%) | n = 13 (34.2%) | n = 12 (31.6%) | n = 7 (18.4%) | n = 5 (13.2%) | n = 1 (2.6%) | |||
Age > 60 | 13 (34.2) | 5 (38.5) | 2 (16.7) | 4 (57.1) | 2 (40) | 0 (0) | 0.882 | |
Mean age | 58.3 | 58.9 | 55.5 | 62 | 63 | 34 | 0.297 | |
Sex | Male | 22 (57.9) | 9 (69.2) | 6 (50) | 3 (42.9) | 3 (60) | 1 (100) | 0.777 |
Female | 16 (42.1) | 4 (30.8) | 6 (50) | 4 (57.1) | 2 (40) | 0 (0) | ||
Main-location | Esophagus | 1 (2.6) | 0 (0) | 0 (0) | 0 (0) | 1 (20) | 0 (0) | 0.002 |
Stomach | 9 (23.7) | 2 (15.4) | 1 (8.3) | 2 (28.6) | 3 (60) | 1 (100) | ||
SI | 17 (44.7) | 5 (38.5) | 9 (75) | 3 (42.9) | 1 (20) | 0 (0) | ||
IC | 7 (18.4) | 2 (15.4) | 0 (0) | 2 (28.6) | 0 (0) | 0 (0) | ||
LI | 4 (10.5) | 4 (30.8) | 2 (16.7) | 0 (0) | 0 (0) | 0 (0) | ||
Esophageal/gastric involvement | 10 (26.3) | 2 (15.4) | 1 (8.3) | 2 (28.6) | 4 (80) | 1 (100) | 0.003 | |
Multiple site involvement | 13 (34.2) | 4 (30.8) | 5 (41.7) | 3 (42.9) | 1 (20) | 0 (0) | 0.767 | |
GI complication | 24 (63.2) | 10 (76.9) | 8 (66.7) | 4 (57.1) | 2 (40) | 0 (0) | 0.074 | |
GI perforation | 15 (39.5) | 8 (61.5) | 5 (41.7) | 1 (14.3) | 1 (20) | 0 (0) | 0.026 | |
Lugano stage | I/II | 20 (52.6) | 5 (38.5) | 6 (50) | 4 (57.1) | 4 (80) | 1 (100) | 0.085 |
IV | 18 (47.4) | 8 (61.5) | 6 (50) | 3 (42.9) | 1 (20) | 0 (0) | ||
Elevated serum LDH level | 17/36 (42.7) | 5/11 (45.5) | 5 (45.5) | 4 (57.1) | 2 (40) | 1 (100) | 0.663 | |
Elevated serum B2M level | 22/30 (73.3) | 7/8 (87.5) | 7/11 (63.6) | 4/6 (66.7) | 3/4 (75) | 1 (100) | 0.857 | |
IPI score ≥ 3 | 12 (31.6) | 5 (38.5) | 4 (33.3) | 2 (28.6) | 1 (20) | 0 (0) | 0.365 | |
Initial treatment | OP ± CTx/RTx | 23 (62.2) | 10 (83.3) | 8 (66.7) | 4 (57.1) | 1 (20) | 0 (0) | 0.009 |
CTx/RTx | 14 (37.8) | 2 (16.7) | 4 (33.3) | 3 (42.9) | 4 (80) | 1 (100) | ||
CTx response | CR | 15/28 (53.6) | 5/8 (62.5) | 5/10 (50) | 3/6 (50) | 1/3 (33.3) | 1 (100) | 0.486 |
PR | 6/28 (21.4) | 0/8 (0) | 3/10 (30) | 1/6 (16.7) | 2/3 (66.7) | 0 (0) | ||
SD | 1/28 (3.6) | 0/8 (0) | 0/10 (0) | 1/6 (16.7) | 0/3 (0) | 0 (0) | ||
PD | 5/28 (21.4) | 3/8 (37.5) | 2/10 (20) | 1/6 (16.7) | 0/3 (0) | 0 (0) | ||
Recurrence/progression | 32 (84.2) | 9 (69.2) | 12 (100) | 6 (85.7) | 5 (100) | 0 (0) | 0.116 | |
Median OS (months) | 9.6 | 5.1 | 11.2 | 16.6 | 9.6 | - | 0.829 | |
Median PFS (months) | 5.1 | 3.8 | 5.8 | 7.7 | 2.8 | - | 0.844 |
Variable | Total | ENKTL | MEITL | ITCL, NOS | ALCL, ALK- | ALCL, ALK+ |
---|---|---|---|---|---|---|
n = 38 | n = 13 | n = 12 | n = 7 | n = 5 | n = 1 | |
Endoscopy | ||||||
Mass | 10/21 (47.6) | 2/6 (33.3) | 2/5 (40) | 2/5 (40) | 3/4 (75) | 1 (100) |
Deep ulcer | 5/21 (23.8) | 3/6 (50) | 0/5 (0) | 1/5 (20) | 1/4 (25) | 0 (0) |
Superficial ulcer | 5/21 (23.8) | 1/6 (16.7) | 2/5 (40) | 2/5 (40) | 0/4 (0) | 0 (0) |
Normal | 1/21 (4.8) | 0/6 (0) | 1/5 (20) | 0/5 (0) | 0/4 (0) | 0 (0) |
Depth of invasion | ||||||
Mucosa/submucosa | 0/19 (0) | 0/7 (0) | 0/8 (0) | 0/3 (0) | 0/1 (0) | - |
Muscularis propria | 2/19 (10.5) | 0/7 (0) | 1/8 (12.5) | 0/3 (0) | 1/1 (100) | - |
Subserosa/serosa | 17/19 (89.5) | 7/7 (100) | 7/8 (87.5) | 3/3 (100) | 0/1 (0) | - |
Regional lymph node involvement | 24 (63.2) | 10 (76.9) | 6 (50) | 5 (71.4) | 2 (40) | 1 (100) |
Cell size | ||||||
Small to medium | 3 (7.9) | 1 (7.7) | 2 (16.7) | 0 (0) | 0 (0) | 0 (0) |
Medium to large | 26 (68.4) | 10 (76.9) | 10 (83.3) | 5 (71.4) | 2 (40) | 0 (0) |
Large pleomorphic | 9 (23.7) | 2 (15.4) | 0 (0) | 2 (28.6) | 3 (60) | 1 (100) |
Cell shape | ||||||
Heterogeneous | 24/36 (66.7) | 13 (100) | 0 (0) | 5 (71.4) | 5 (100) | 1 (100) |
Monomorphic | 12/36 (33.3) | 0 (0) | 12 (100) | 2 (28.6) | 0 (0) | 0 (0) |
Angiocentricity | 6/36 (16.7) | 6 (46.2) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
Epitheliotropism | 12/36 (33.3) | 0 (0) | 12 (100) | 0 (0) | 0 (0) | 0 (0) |
CD3 | 37 (97.4) | 13 (100) | 12 (100) | 7 (100) | 4 (80) | 1 (100) |
CD4 | 9/25 (36) | 2/8 (25) | 1/9 (11.1) | 4/5 (80) | 2/3 (66.7) | - |
CD8 | 15/26 (57.7) | 3/9 (33.3) | 8/11 (72.7) | 4/5 (80) | 0/2 (0) | - |
CD10 | 1/15 (6.7) | 0/6 (0) | 0/5 (0) | 0/1 (0) | 1/2 (50) | 0 (0) |
CD30 | 12/33 (36.4) | 4/11 (36.4) | 1/8 (12.5) | 1/5 (20) | 5 (100) | 1 (100) |
CD56 | 21/36 (58.3) | 9 (69.2) | 11 (91.7) | 1 (14.3) | 0/4 (0) | - |
CD103 | 6/19 (31.6) | 0/5 (0) | 6/10 (60) | 0/2 (0) | 0/2 (0) | - |
Granzyme B | 28/33 (50.9) | 10/10 (100) | 9/11 (81.8) | 5/6 (83.3) | 3/5 (6)) | 1 (100) |
TIA-1 | 13/18 (72.2) | 7/7 (100) | 4/6 (66.7) | 0/2 (0) | 2/3 (66.7) | - |
PD-1 | 1/15 (6.7) | 0/6 (0) | 0/5 (0) | 0/2 (0) | 1/2 (50) | - |
ALK | 1/16 (6.25) | 0/7 (0) | 0/5 (0) | 0/2 (0) | 0 (0) | 1 (100) |
Ki-67 L.I. (%, average) | 70.6 | 70 | 83.3 | 41.7 | 75 | 100 |
EBER ISH | 9/26 (34.6) | 8/8 (100) | 0/9 (0) | 0/6 (0) | 0/3 (0) | - |
TCR gene rearrange-ment a | 8/11 (72.7) | 2/5 (40) | 5/5 (100) | 1/1 (100) | - | - |
TCRG | 5/11 | 1/5 | 3/5 | 1/1 | - | - |
TCRB | 4/11 | 1/5 | 3/5 | 0/1 | - | - |
TCRD | 1/11 | 0/5 | 1/5 | 0/1 | - | - |
Overall Survival | Progression Free Survival | |||||||
---|---|---|---|---|---|---|---|---|
Variables | Univariate | Multivariate | Univariate | Multivariate | ||||
p Value | HR (95% CI) | p Value | HR (95% CI) | p Value | HR (95% CI) | p Value | HR (95% CI) | |
>60 years | 0.066 | 2.369 (0.953–4.350) | - | - | 0.050 | 2.079 (1.001–4.318) | - | - |
Male | 0.728 | 1.141 (0.542–2.403) | - | - | 0.424 | 1.335 (0.657–2.711) | - | - |
Subtypes | ||||||||
ENKTL | 0.831 | 1 (reference) | - | - | 0.846 | 1 (reference) | - | - |
MEITL | 0.453 | 1.429 (0.563–3.626) | - | - | 0.426 | 1.430 (0.593–3.450) | - | - |
ITCL, NOS | 0.960 | 1.009 (0.312–3.019) | - | - | 0.762 | 1.175 (0.414–3.340) | - | - |
ALCL, ALK- | 0.602 | 1.397 (0.439–4.135) | - | - | 0.488 | 1.480 (0.489–4.477) | - | - |
Location | ||||||||
Esophagus | 0.171 | 1 (reference) | 0.383 | 1 (reference) | ||||
Stomach | 0.563 | 1.856 (0.228–15.082) | - | - | 0.496 | 0.477 (0.057–4.025) | - | - |
Small intestine | 0.504 | 2.012 (0.259–15.606) | - | - | 0.434 | 0.437 (0.055–3.470) | - | - |
Ileocecum | 0.631 | 0.554 (0.050–6.174) | - | - | 0.125 | 0.145 (0.012–1.707) | - | - |
Large intestine | 0.601 | 0.544 (0.055–5.326) | - | - | 0.212 | 0.242 (0.026–2.249) | - | - |
Multiple site | 0.990 | 1.005 (0.453–2.228) | - | - | 0.930 | 1.034 (0.493–2.170) | - | - |
UGI involvement | 0.404 | 0.715 (0.324–1.574) | - | - | 0.282 | 0.651 (0.297–1.424) | - | - |
GI complication | 0.348 | 1.448 (0.668–3.139) | - | - | 0.112 | 1.854 (0.865–3.971) | - | - |
GI perforation | 0.219 | 1.598 (0.757–3.376) | - | - | 0.305 | 1.449 (0.713–2.945) | - | - |
Tx with surgery | 0.798 | 0.906 (0.425–1.930) | - | - | 0.782 | 1.105 (0.545–2.242) | - | - |
Lugano stage IV | 0.051 | 2.214 (0.996–4.533) | - | - | 0.041 | 2.119 (1.031–4.354) | 0.299 | 0.461 (0.107–1.989) |
IPI ≥ 3 | <0.001 | 4.922 (2.022–11.979) | 0.485 | 1.570 (0.442–5.581) | 0.001 | 4.209 (1.846–9.597) | 0.391 | 1.686 (0.511–5.556) |
Elevated LDH | 0.038 | 2.248 (1.045–4.835) | 0.015 | 5.045 (1.365–18.654) | 0.019 | 2.446 (1.155–5.718) | 0.076 | 2.903 (0.894–9.424) |
Elevated B2M | 0.023 | 3.685 (1.194–11.368) | 0.429 | 1.835 (0.407–8.273) | 0.037 | 2.940 (1.066–8.108) | 0.827 | 1.160 (0.308–4.369) |
Initial Tx response | ||||||||
CR | 0.001 | 1 (reference) | 0.003 | 1 (reference) | <0.001 | 1 (reference) | 0.005 | 1 (reference) |
PR | 0.012 | 5.064 (1.418–18.079) | 0.058 | 6.374 (0.940–43.236) | 0.001 | 10.720 (2.56–44.84) | 0.043 | 5.911 (1.061–32.928) |
SD | 0.385 | 2.611 (0.299–22.781) | 0.429 | 2.662(0.235–30.093) | 0.002 | 61.45 (4.58–824.33) | 0.006 | 45.692 (3.12–790.67) |
PD | <0.001 | 24.554 (5.353–112.62) | <0.001 | 63.369 (6.60–608.41) | <0.001 | 24.22 (5.31–110.43) | 0.001 | 16.976 (3.14-91.65) |
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Kim, E.K.; Jang, M.; Yang, W.I.; Yoon, S.O. Primary Gastrointestinal T/NK Cell Lymphoma. Cancers 2021, 13, 2679. https://doi.org/10.3390/cancers13112679
Kim EK, Jang M, Yang WI, Yoon SO. Primary Gastrointestinal T/NK Cell Lymphoma. Cancers. 2021; 13(11):2679. https://doi.org/10.3390/cancers13112679
Chicago/Turabian StyleKim, Eun Kyung, Mi Jang, Woo Ick Yang, and Sun Och Yoon. 2021. "Primary Gastrointestinal T/NK Cell Lymphoma" Cancers 13, no. 11: 2679. https://doi.org/10.3390/cancers13112679