550:, to the CHOP regimen appears to have improved these results: in one study, patients receiving the R-CHOP regimen had a three-year overall survival rate of 75%. Since treatment of the variant form of nodular lymphocyte predominant Hodgkin lymphoma using different and less aggressive drug regimens achieves better results than the regimens used to treat THRLBCL, it is clinically important to distinguish the two diseases.
135:(i.e. microscopic appearances), genetic abnormalities, and apparent etiologies. Indeed, NLPHL can, in rare cases, progress into THRLBCL. Comapared to THRLBCL, however, these variant NLPHL cases are less aggressive, are more responsive to treatment, and have a better prognosis. Thus, THRLBCL and NLPHL may be biologically related diseases that represent opposite ends of a severity spectrum.
144:
the male to female ratio was 4:1. Patients typically present with enlarged lymph nodes in the neck, arm pit, and groin areas but on further examination are found to have involvement of their spleen (31% of cases), liver (52% of cases), bone marrow (27% of cases) and lung/or (13%) as determined by finding enlarged spleens and/or livers on physical examination or
301:
that alter the expression of key genes in B-cells to result in the increasingly malignant behavior of these cells. However, the underlying causes for these gene changes as well as the identity of the genes whose changes contribute to the malignant behavior of the neoplastic B-cells in THRLBC have yet
276:
which codes for c-Rel, a protein that controls the maturation of B-cells and is implicated in the development of many cancers including lymphomas; as well as losses o the short armes of chromosomes 1 and 9 and 19.2 and 11.2 sites, respectively. These studies allow the possibility that THRLBC, similar
143:
T-cell/histiocyte-rich large B-cell lymphoma most commonly afflicts middle-aged (i.e. 49–57 years old) individuals but has been diagnosed in persons aged 4 to 92 years. The disease has a male predominance ranging between 1.7:1 to 3:1 in different studies. In a review of 36 reported pediatric cases,
123:
in the neck, arm pit, or groin. However, most cases are at an advanced stage at diagnoses: further examinations frequently reveal that the disease has spread to multiple internal organs and tissues. The course of the disease is usually characterized as being poorly responsive to treatment: the
446:
While the histological features of THRLBCL are distinctly different that those found in other DLBCL subtypes, they can closely resemble, and be mistaken for, those found in the variant form of nodular lymphocyte predominant
Hodgkin lymphoma. Some important histological features that favor the
317:
The diagnosis of THRLBCL, particularly as it pertains to differentiating it from DLBCL and other lymphomas, depends on examining involved tissues obtained by biopsy or operation for their
1199:
Meyer SN, Scuoppo C, Vlasevska S, Bal E, Holmes AB, Holloman M, Garcia-Ibanez L, Nataraj S, Duval R, Vantrimpont T, Basso K, Brooks N, Dalla-Favera R, Pasqualucci L (September 2019).
752:
Hartmann S, Eichenauer DA (January 2020). "Nodular lymphocyte predominant
Hodgkin lymphoma: pathology, clinical course and relation to T-cell/histiocyte rich large B-cell lymphoma".
321:, i.e. microscopic anatomy. The tissues involved in THRLBCL commonly show an effacement of their normal architecture by a diffusely growing infiltrate of non-malignant
1031:
Papoudou-Bai A, Hatzimichael E, Barbouti A, Kanavaros P (August 2017). "Expression patterns of the activator protein-1 (AP-1) family members in lymphoid neoplasms".
486:
454:
CD163-expressing histiocytes (cases of THRLBCL in which histiocytes are absent appear to take a less aggressive course than cases in which these cells are present);
128:
1342:
Schuhmacher B, Bein J, Rausch T, Benes V, Tousseyn T, Vornanen M, Ponzoni M, Thurner L, Gascoyne R, Steidl C, Küppers R, Hansmann ML, Hartmann S (February 2019).
795:
Grimm KE, O'Malley DP (February 2019). "Aggressive B cell lymphomas in the 2017 revised WHO classification of tumors of hematopoietic and lymphoid tissues".
204:
Due to its rarity, the causes of THRLBCL have not been well studied and consequently remained unclear. The malignant B-cells in the disease commonly have
1201:"Unique and Shared Epigenetic Programs of the CREBBP and EP300 Acetyltransferases in Germinal Center B Cells Reveal Targetable Dependencies in Lymphoma"
698:
Korkolopoulou P, Vassilakopoulos T, Milionis V, Ioannou M (July 2016). "Recent
Advances in Aggressive Large B-cell Lymphomas: A Comprehensive Review".
124:
disease's survival rates in past studies have been only ~46%. However, recent studies suggest that novel treatments can improve these survival rates.
241:
which codes for serine/threonine-protein kinase, a protein that regulates several signaling pathways that control cell proliferation and survival;
1164:
Beaurivage C, Champagne A, Tobelaim WS, Pomerleau V, Menendez A, Saucier C (June 2016). "SOCS1 in cancer: An oncogene and a tumor suppressor".
309:. Studies suggest that the latter cells help to create a microenvironment that is tolerant or promotes tumor growth and spread to other sites.
290:
131:(NLPHL). That is, some cases of variant NLPHL, which is a relatively indolent malignancy, share with THRLBCL similar disease presentations,
115:
THRLBCL commonly afflicts middle-aged individuals but has been diagnosed in rare pediatric cases. The disease usually presents with
217:
which codes for JunB, a protein that regulates cell growth and survival and is highly expressed in other lymphocyte malignancies;
572:"Hypercalcemia in T-Cell/Histiocyte-Rich Large B-Cell Lymphoma: An Unusual Presentation of a Rare Disease and Literature Review"
364:. These infiltrates often resemble these seen in inflammation. The malignant B-cells in THRLBCL are definitively identified by
1402:
507:
278:
97:
333:(i.e. malignant) B-cells. The malignant B-cells represent <10% of the cells in these lesions and bear resemblances to
267:
The neoplastic cells in this disease also show gains on the short arm of chromosome 2 at position 16.1 which affect the
1125:"SGK1 protein expression is a prognostic factor of lung adenocarcinoma that regulates cell proliferation and survival"
634:
Sukswai N, Lyapichev K, Khoury JD, Medeiros LJ (November 2019). "Diffuse large B-cell lymphoma variants: an update".
458:
457:
a diffuse rather than nodular cell infiltration pattern with any nodular infiltrates present in THRLBCL containing
1004:
Barut F, Kandemir NO, Gun BD, Ozdamar SO (July 2016). "T-cell/histiocyte-rich large B-cell lymphoma of stomach".
298:
260:
535:
434:
cell surface proteins. Before making a diagnosis of THRLBCL in a pediatric population, congenital and acquired
342:
229:) which codes for dual specificity protein phosphatase 2, a protein that regulates several components of the
1344:"JUNB, DUSP2, SGK1, SOCS1 and CREBBP are frequently mutated in T-cell/histiocyte-rich large B-cell lymphoma"
156:. Rare cases of the disease have presented with involvement of the skin (termed primary cutaneous THRLBCL),
153:
165:
81:
54:
349:, including in particular Hodgkin disease's nodular variant. The non-malignant T-cells generally have a
259:, a gene that is commonly mutated in other DLBCL subtypes as well as other lymphomas and codes for the
104:
worldwide. THRLBCL is distinguished from the other DLBCL subtypes by the predominance of non-malignant
353:
149:
101:
953:
Zheng SM, Zhou DJ, Chen YH, Jiang R, Wang YX, Zhang Y, Xue HL, Wang HQ, Mou D, Zeng WZ (June 2017).
438:, which can cause aberrant immune responses with a histology similar to THRLBCL, must be ruled-out.
281:
as well as a wide array of other cancers results at least in part from the step-wise development of
570:
Conte GA, Harmon JS, Le ML, Sun X, Schuler JW, Levitt MJ, Chinnici AA, Hossain MA (December 2019).
511:
490:
350:
1056:
843:"T-cell/histiocyte-rich large B-cell lymphoma in a child: A case report and review of literature"
820:
777:
723:
659:
519:
305:
The neoplastic B-cells in THRLBCL infiltrations are dominated by high numbers of histiocytes and
294:
1397:
1373:
1324:
1283:
1232:
1181:
1146:
1105:
1048:
1013:
986:
928:
874:
812:
769:
715:
651:
601:
365:
37:
1303:"Diffuse large B-cell lymphoma: 2019 update on diagnosis, risk stratification, and treatment"
1363:
1355:
1314:
1273:
1263:
1222:
1212:
1173:
1136:
1095:
1087:
1040:
976:
966:
955:"Pancreatic T/histiocyte-rich large B-cell lymphoma: A case report and review of literature"
918:
910:
864:
854:
804:
761:
707:
643:
591:
583:
515:
435:
415:
411:
230:
226:
77:
346:
145:
116:
93:
899:"T-Cell/Histiocyte-Rich Large B-Cell Lymphoma: Report of the First Case in the Mandible"
897:
Silva RNF, Mendonça EF, Batista AC, Alencar RCG, Mesquita RA, Costa NL (December 2019).
1368:
1343:
1278:
1251:
1227:
1200:
1141:
1124:
1100:
1075:
981:
954:
923:
898:
869:
842:
596:
571:
306:
808:
1391:
781:
727:
663:
543:
539:
423:
273:
157:
824:
1060:
531:
503:
189:
1359:
1217:
765:
711:
647:
542:
of 50% to 64%, and 5-year overall survival rates of 46% to 58%. The addition of
523:
357:
338:
334:
326:
177:
173:
120:
109:
73:
1177:
1044:
914:
527:
361:
360:. And, the histiocytes, which are not always present in these lesions, have a
330:
181:
85:
42:
971:
1268:
1091:
859:
547:
479:
318:
286:
253:
and tumor suppressor which codes for suppressor of cytokine signaling 1; and
132:
1377:
1328:
1287:
1236:
1185:
1150:
1109:
1052:
1017:
990:
932:
878:
816:
773:
719:
655:
605:
100:(DLBCL). DLBCL are a large group of lymphomas that account for ~25% of all
388:). These cells may also express other identifying marker proteins such as
127:
Many studies have found that THRLBCL can overlap with the variant form of
250:
205:
169:
89:
46:
193:
1319:
1302:
587:
426:
cell surface proteins. And, the histiocytes in these lesions express
356:
as indicated by their larger than normal size and irregularly shaped
322:
256:
161:
105:
69:
431:
399:
381:
245:
221:
185:
472:
464:
427:
407:
403:
389:
385:
377:
373:
369:
297:(i.e. increases in the number of copies of specific genes), and
282:
237:
213:
59:
Variant form of nodular lymphocyte predominant
Hodgkin lymphoma
468:
419:
394:
269:
112:
over malignant B-cells in its tumors and tissue infiltrates.
1129:
International
Journal of Clinical and Experimental Pathology
447:
diagnosis of THRLBCL over NLPHL include the presence of:
502:
Patients diagnosed with THRLBCL have been treated with
180:. Many patients will also complain of having systemic
510:. These earlier used chemotherapy regimens (e.g. the
1250:
Kober-Hasslacher M, Schmidt-Supprian M (July 2019).
88:that, for example, bind to and neutralize invasive
53:
36:
26:
21:
1252:"The Unsolved Puzzle of c-Rel in B Cell Lymphoma"
1076:"Regulatory Roles of MAPK Phosphatases in Cancer"
410:. The T cells in these lesions are predominantly
514:regimen consisting of three chemotherapy drugs (
1006:The Journal of the Pakistan Medical Association
693:
129:nodular lymphocyte predominant Hodgkin lymphoma
96:, THRLBCL is a rarely occurring subtype of the
948:
946:
944:
942:
892:
890:
888:
841:Wei C, Wei C, Alhalabi O, Chen L (June 2018).
836:
834:
747:
745:
743:
741:
739:
737:
691:
689:
687:
685:
683:
681:
679:
677:
675:
673:
629:
627:
625:
623:
621:
619:
617:
615:
565:
563:
485:few or no small lymphocytes, variant Hodgkin
406:(30% of cases), and, in a minority of cases,
8:
66:T-cell/histiocyte-rich large B-cell lymphoma
22:T-cell/histiocyte-rich large B-cell lymphoma
18:
1367:
1318:
1277:
1267:
1226:
1216:
1140:
1099:
980:
970:
922:
868:
858:
595:
478:cells strongly expressing the BAT3/BAG6
559:
368:to detect B-cell marker proteins (e.g.
392:(50–90% of cases), the product of the
176:, brain, tongue, uterus, stomach, and
7:
414:as indicated by their expression of
480:ubiquitin domain-containing protein
1033:Clinical and Experimental Medicine
14:
1123:Pan H, Lv W, Li Z, Han W (2019).
959:World Journal of Gastroenterology
809:10.1016/j.anndiagpath.2018.09.014
233:that controls cell proliferation;
152:, and/or THRLBCL infiltrates in
847:World Journal of Clinical Cases
1307:American Journal of Hematology
1074:Low HB, Zhang Y (April 2016).
797:Annals of Diagnostic Pathology
700:Advances in Anatomic Pathology
526:plus a glucocorticoid, either
362:non-epithelial cell appearance
98:diffuse large B-cell lymphomas
76:that normally function in the
1:
225:(a gene suspected of being a
119:, i.e. bulky enlargements of
92:. Among the various forms of
68:(THRLBCL) is a malignancy of
1360:10.3324/haematol.2018.203224
1301:Liu Y, Barta SK (May 2019).
1218:10.1016/j.immuni.2019.08.006
766:10.1016/j.pathol.2019.10.003
712:10.1097/PAP.0000000000000117
648:10.1016/j.pathol.2019.08.013
508:regimens used to treat DLBCL
451:<10% neoplastic B-cells;
1419:
1178:10.1016/j.cyto.2016.01.005
459:follicular dendritic cells
398:gene, c-Myc (most cases),
299:chromosomal translocations
231:ERK/MAPK signaling pathway
208:in several genes such as:
1045:10.1007/s10238-016-0436-z
915:10.1007/s12105-018-0948-9
576:World Journal of Oncology
436:immunodeficiency diseases
277:to the other subtypes of
261:transcription coregulator
972:10.3748/wjg.v23.i24.4467
506:regimens similar to the
422:T-cell co-receptor, and
1269:10.3390/cancers11070941
1092:10.4110/in.2016.16.2.85
903:Head and Neck Pathology
860:10.12998/wjcc.v6.i6.121
536:complete response rates
263:, CREB-binding protein.
540:overall survival rates
538:of 48% to 85%, 3-year
442:Differential diagnosis
166:gastrointestinal tract
148:; abnormal results on
82:adaptive immune system
55:Differential diagnosis
102:non-Hodgkin lymphomas
1403:Non-Hodgkin lymphoma
491:Reed-Sternberg cells
475:-expressing T-cells;
343:Reed–Sternberg cells
154:bone marrow biopsies
150:liver function tests
291:altered expressions
192:, weight loss, and
520:hydroxydoxorubicin
1320:10.1002/ajh.25460
1211:(3): 535–547.e9.
965:(24): 4467–4472.
588:10.14740/wjon1246
412:cytotoxic T cells
366:immunophenotyping
80:component of the
63:
62:
16:Medical condition
1410:
1382:
1381:
1371:
1339:
1333:
1332:
1322:
1298:
1292:
1291:
1281:
1271:
1247:
1241:
1240:
1230:
1220:
1196:
1190:
1189:
1161:
1155:
1154:
1144:
1120:
1114:
1113:
1103:
1071:
1065:
1064:
1028:
1022:
1021:
1001:
995:
994:
984:
974:
950:
937:
936:
926:
894:
883:
882:
872:
862:
838:
829:
828:
792:
786:
785:
749:
732:
731:
695:
668:
667:
631:
610:
609:
599:
567:
516:cyclophosphamide
402:(40% of cases),
285:changes such as
227:tumor suppressor
108:lymphocytes and
94:B-cell lymphomas
78:humoral immunity
19:
1418:
1417:
1413:
1412:
1411:
1409:
1408:
1407:
1388:
1387:
1386:
1385:
1341:
1340:
1336:
1300:
1299:
1295:
1249:
1248:
1244:
1198:
1197:
1193:
1163:
1162:
1158:
1122:
1121:
1117:
1073:
1072:
1068:
1030:
1029:
1025:
1003:
1002:
998:
952:
951:
940:
896:
895:
886:
840:
839:
832:
794:
793:
789:
751:
750:
735:
697:
696:
671:
633:
632:
613:
569:
568:
561:
556:
500:
444:
416:T-cell receptor
347:Hodgkin disease
315:
307:dendritic cells
302:to be defined.
202:
146:medical imaging
141:
117:lymphadenopathy
17:
12:
11:
5:
1416:
1414:
1406:
1405:
1400:
1390:
1389:
1384:
1383:
1354:(2): 330–337.
1334:
1313:(5): 604–616.
1293:
1242:
1191:
1156:
1135:(2): 391–408.
1115:
1080:Immune Network
1066:
1039:(3): 291–304.
1023:
996:
938:
909:(4): 711–717.
884:
853:(6): 121–126.
830:
787:
760:(1): 142–153.
733:
669:
611:
582:(6): 231–236.
558:
557:
555:
552:
499:
496:
495:
494:
483:
476:
462:
455:
452:
443:
440:
314:
311:
295:amplifications
265:
264:
254:
242:
234:
218:
201:
198:
140:
137:
72:. B-cells are
61:
60:
57:
51:
50:
40:
34:
33:
28:
24:
23:
15:
13:
10:
9:
6:
4:
3:
2:
1415:
1404:
1401:
1399:
1396:
1395:
1393:
1379:
1375:
1370:
1365:
1361:
1357:
1353:
1349:
1348:Haematologica
1345:
1338:
1335:
1330:
1326:
1321:
1316:
1312:
1308:
1304:
1297:
1294:
1289:
1285:
1280:
1275:
1270:
1265:
1261:
1257:
1253:
1246:
1243:
1238:
1234:
1229:
1224:
1219:
1214:
1210:
1206:
1202:
1195:
1192:
1187:
1183:
1179:
1175:
1171:
1167:
1160:
1157:
1152:
1148:
1143:
1138:
1134:
1130:
1126:
1119:
1116:
1111:
1107:
1102:
1097:
1093:
1089:
1085:
1081:
1077:
1070:
1067:
1062:
1058:
1054:
1050:
1046:
1042:
1038:
1034:
1027:
1024:
1019:
1015:
1011:
1007:
1000:
997:
992:
988:
983:
978:
973:
968:
964:
960:
956:
949:
947:
945:
943:
939:
934:
930:
925:
920:
916:
912:
908:
904:
900:
893:
891:
889:
885:
880:
876:
871:
866:
861:
856:
852:
848:
844:
837:
835:
831:
826:
822:
818:
814:
810:
806:
802:
798:
791:
788:
783:
779:
775:
771:
767:
763:
759:
755:
748:
746:
744:
742:
740:
738:
734:
729:
725:
721:
717:
713:
709:
706:(4): 202–43.
705:
701:
694:
692:
690:
688:
686:
684:
682:
680:
678:
676:
674:
670:
665:
661:
657:
653:
649:
645:
641:
637:
630:
628:
626:
624:
622:
620:
618:
616:
612:
607:
603:
598:
593:
589:
585:
581:
577:
573:
566:
564:
560:
553:
551:
549:
545:
544:immunotherapy
541:
537:
533:
529:
525:
521:
517:
513:
509:
505:
497:
492:
488:
484:
481:
477:
474:
470:
466:
463:
460:
456:
453:
450:
449:
448:
441:
439:
437:
433:
429:
425:
421:
417:
413:
409:
405:
401:
397:
396:
391:
387:
383:
379:
375:
371:
367:
363:
359:
355:
352:
348:
344:
341:, and/or the
340:
336:
332:
328:
325:lymphocytes,
324:
320:
312:
310:
308:
303:
300:
296:
292:
288:
284:
280:
275:
274:protooncogene
272:
271:
262:
258:
255:
252:
248:
247:
243:
240:
239:
235:
232:
228:
224:
223:
219:
216:
215:
211:
210:
209:
207:
199:
197:
195:
191:
187:
183:
179:
175:
171:
167:
163:
159:
158:thyroid gland
155:
151:
147:
138:
136:
134:
130:
125:
122:
118:
113:
111:
107:
103:
99:
95:
91:
87:
84:by secreting
83:
79:
75:
71:
67:
58:
56:
52:
48:
44:
41:
39:
35:
32:
29:
25:
20:
1351:
1347:
1337:
1310:
1306:
1296:
1259:
1255:
1245:
1208:
1204:
1194:
1169:
1165:
1159:
1132:
1128:
1118:
1086:(2): 85–98.
1083:
1079:
1069:
1036:
1032:
1026:
1012:(7): 905–7.
1009:
1005:
999:
962:
958:
906:
902:
850:
846:
800:
796:
790:
757:
753:
703:
699:
642:(1): 53–67.
639:
635:
579:
575:
532:prednisolone
504:chemotherapy
501:
487:i.e. popcorn
445:
393:
339:immunoblasts
316:
304:
268:
266:
244:
236:
220:
212:
203:
200:Pathogenesis
190:night sweats
178:soft tissues
172:, jaw bone,
142:
139:Presentation
126:
114:
65:
64:
30:
358:cell nuclei
335:centroblast
327:histiocytes
174:nasopharynx
133:histologies
121:lymph nodes
110:histiocytes
74:lymphocytes
27:Other names
1392:Categories
1262:(7): 941.
554:References
534:) achieve
528:prednisone
354:morphology
331:neoplastic
249:, a known
182:B symptoms
86:antibodies
43:Hematology
1172:: 87–94.
782:208537001
754:Pathology
728:205915174
664:208142227
636:Pathology
548:rituximab
498:Treatment
384:, and/or
345:found in
319:histology
313:Diagnosis
287:mutations
206:mutations
90:pathogens
38:Specialty
1398:Lymphoma
1378:30213827
1329:30859597
1288:31277480
1237:31519498
1205:Immunity
1186:26811119
1166:Cytokine
1151:31933845
1110:27162525
1053:27600282
1018:27427148
991:28706431
933:30019325
879:29988902
825:53196244
817:30380402
803:: 6–10.
774:31785822
720:27271843
656:31735345
606:31921379
524:oncovin)
351:reactive
251:oncogene
184:such as
170:pancreas
47:Oncology
1369:6355500
1279:6678315
1256:Cancers
1228:7362711
1142:6945076
1101:4853501
1061:4778071
982:5487512
924:6854205
870:6033745
597:6940034
471:-, and
194:malaise
70:B cells
31:THRLBCL
1376:
1366:
1327:
1286:
1276:
1235:
1225:
1184:
1149:
1139:
1108:
1098:
1059:
1051:
1016:
989:
979:
931:
921:
877:
867:
823:
815:
780:
772:
726:
718:
662:
654:
604:
594:
546:drug,
522:, and
329:, and
323:T-cell
257:CREBBP
162:thymus
106:T-cell
1057:S2CID
821:S2CID
778:S2CID
724:S2CID
660:S2CID
482:; and
432:CD163
400:Bcl-2
390:Bcl-6
382:CD79a
279:DLBDL
246:SOCS1
222:DUSP2
186:fever
1374:PMID
1325:PMID
1284:PMID
1233:PMID
1182:PMID
1147:PMID
1106:PMID
1049:PMID
1014:PMID
987:PMID
929:PMID
875:PMID
813:PMID
770:PMID
716:PMID
652:PMID
602:PMID
512:CHOP
489:and
473:CD57
465:PD-1
430:and
428:CD68
408:CD10
404:MUC1
386:PAX5
378:CD22
374:CD20
370:CD19
283:gene
238:SGK1
214:JUNB
1364:PMC
1356:doi
1352:104
1315:doi
1274:PMC
1264:doi
1223:PMC
1213:doi
1174:doi
1137:PMC
1096:PMC
1088:doi
1041:doi
977:PMC
967:doi
919:PMC
911:doi
865:PMC
855:doi
805:doi
762:doi
708:doi
644:doi
592:PMC
584:doi
530:or
469:CD4
467:-,
424:CD5
420:CD8
395:MYC
270:REL
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