506:(EBV+DLBCL) at a site in the brain near the original hematoma; this case suggests that FA-DLBCL may transform into the far more malignant Epstein-Barr virus-associated lymphoproliferative disease, EBV+ DLBCL. The limited number of FA-DLBCL cases reported as of 2019 does not definitively show which of their treatment(s) is superior. However, the findings do suggest that cases amenable to complete surgical removal are cured by surgery alone and should be considered as an Epstein-Barr positive lymphoproliferative disease while disease in the heart, vasculature, or hematoma may be associated with serious complications and require chemotherapy.
193:, has deposited. It is almost always discovered as an incidental finding in specimens taken from these sites when they are examined for reasons not directly related to the FA-DLBCL infiltrates. As reviewed in a publication of 2019, the disorder has been diagnoses in 47 individuals who are predominantly elderly males; it is almost uniformly amenable to various treatments and takes a benign course. However, the disease, when occurring within vascular or cardiac sites, does have a risk of being complicated by the development of
498:; or a combination of these modalities. Regardless of treatment type, 30 of the 36 cases of FA-DBCL for which there is follow-up results had a benign course with no disease recurrence over 1 to 130 months. All cases arising in pseudocysts had favorable results. Local recurrences of the disease in non-pseudocyst sites did occur but responded to further treatment. Three individuals with disease located in thrombi had serious
358:. Since the EBV-infected cells are subject to immune attack when they leave these sites, FA-DLBCL remains, it is thought, an otherwise non-invasive, non-metastasizing, site-limited disease. Unlike most other forms of DLBCL, including DLBCL-CI, the neoplastic cells in FA-DLBCL have relatively few gene abnormalities, or abnormal expressions of genes such as
329:(i.e. a tube placed within a blood vessel to keep it open). Most cases have involved atrial myxomas (~31%), pseudocysts (~28%), prosthetic devices (23%), and chronic hematoma (18%). Symptoms of the disease are attributable to the pre-existing condition, not the FA-DLBCL that has developed in the immune-sequestered site.
448:
foreign bodies, hematomas, thrombi formed in large arteries, and myxomas. Also unlike DLBCL-CI, the lesions in FA-DLBCL do not form masses and, in almost all cases, do not extend beyond their site of origin; typically, FA-DLBCL lesions are small infiltrates composed of sheets, ribbons, or clusters of
443:
FA-DLBCL-CI and (FA-DLBCL) are B-cell lymphomas. Both diseases appear driven by EBV-infected (latency stage III), large, activated B-cells and develop in spaces known or thought to be sequestered from the immune system. Unlike DLBCL-CI, FA-DLBCL is discovered as an incidental infiltrate that develops
453:
and usually have few or no other types of inflammatory cells. The disease often appears to be a non-malignant proliferation of EBV+ large B cells that are unable to survive outside of the sequestered sites: DLBCL-CI is an aggressive lymphoma with a five-year overall survival rate of 20–35% while
664:
Boyer DF, McKelvie PA, de Leval L, Edlefsen KL, Ko YH, Aberman ZA, Kovach AE, Masih A, Nishino HT, Weiss LM, Meeker AK, Nardi V, Palisoc M, Shao L, Pittaluga S, Ferry JA, Harris NL, Sohani AR (March 2017). "Fibrin-associated EBV-positive Large B-Cell
Lymphoma: An Indolent Neoplasm With Features
337:
Current studies suggest that EBV transforms the B-cells which it infects into rapidly proliferating cells that in the case of FA-DLBCL are able to avoid attack by the immune system because they are in sites devoid of small blood vessels, overloaded with fibrin
431:). The lesions show relatively little or no evidence of chronic inflammation except for some cases arising in pseudocysts or chronic hematomas which may show lymphoplasmacytic cells (i.e. cells with combined morphologic features of lymphocytes and
390:
examination of tissues obtained at surgery conducted for reasons not related to FA-DLBCL. Microscopically, these tissues are composed of small foci of infiltrates composed of large lymphoid cells embedded in a background of fibrin or debris.
923:
King RL, Goodlad JR, Calaminici M, Dotlic S, Montes-Moreno S, Oschlies I, Ponzoni M, Traverse-Glehen A, Ott G, Ferry JA (December 2019). "Lymphomas arising in immune-privileged sites: insights into biology, diagnosis, and pathogenesis".
127:. However, FA-DLBCL differs from DLBCL-CI in many other ways, including, most importantly, its comparatively benign nature. Some researchers have suggested that this disease should be regarded as a non-malignant or pre-malignant
427:. Typically, these cells evidence a high rate of proliferation and are activated rather than non-activated B-cells (i.e. germinal center B-cells or unclassifiable B-cells) as identified by immunohistochemical analyses (see
967:
Boroumand N, Ly TL, Sonstein J, Medeiros LJ (July 2012). "Microscopic diffuse large B-cell lymphoma (DLBCL) occurring in pseudocysts: do these tumors belong to the category of DLBCL associated with chronic inflammation?".
122:
provisionally classified FA-DLBCL as a DLBCL-CI. Similar to DLBCL-CI, FA-DLBCL involves the proliferation of EBV-infected large B-cells in restricted anatomical spaces that afford protection from an individual's
103:
424:
420:
135:
217:
Individuals with FA-DLBCL are typically males (~70% of cases) aged 25–96 years (~75% of cases are >50 years old). They present with abnormalities associated with a long-standing (1–20 years):
503:
118:. In this protected environment, the B-cells proliferate excessively, acquire malignant gene changes, form tumor masses, and often spread outside of the protected environment. In 2016, the
435:) surrounding the neoplastic B cell infiltrates. The lesions also show no evidence of tumor mass formation at the site of disease and do not extend beyond their sites of origin.
102:, proliferates excessively, invades multiple tissues, and often causes life-threatening tissue damage. DLBCL have various forms as exemplified by one of its subtypes,
166:
of the virus. Some weeks, months, years, or decades thereafter, a very small fraction of these carriers develop any one of various EBV-associated benign or
711:
Korkolopoulou P, Vassilakopoulos T, Milionis V, Ioannou M (July 2016). "Recent
Advances in Aggressive Large B-cell Lymphomas: A Comprehensive Review".
530:
Grimm KE, O'Malley DP (2019). "Aggressive B cell lymphomas in the 2017 revised WHO classification of tumors of hematopoietic and lymphoid tissues".
170:
diseases. In FA-DLBCL as well as DLBCL-CI, EBV infects B-cells to promote their proliferation and thereby the development of either disease.
378:, is overexpressed in the neoplastic B-cells of FA-DLBCL and may contribute further to the ability of these cells to avoid immune attack.
350:, a specialized type of lymphocyte that can kill EBV-infected cells. These immune privileged sites are typically located in certain
819:
Zanelli M, Zizzo M, Montanaro M, Gomes V, Martino G, De Marco L, Fraternali
Orcioni G, Martelli MP, Ascani S (September 2019).
502:; two of them died from this complication. One individual who had a FA-DLBCL removed from a subdural hematoma developed an
1022:
428:
128:
87:
873:
Sukswai N, Lyapichev K, Khoury JD, Medeiros LJ (November 2019). "Diffuse large B-cell lymphoma variants: an update".
821:"Fibrin-associated large B-cell lymphoma: first case report within a cerebral artery aneurysm and literature review"
395:
analyses reveals that the large neoplastic cells are B-cells by their expression of B-cell marker proteins (e.g.
119:
757:
Rezk SA, Zhao X, Weiss LM (June 2018). "Epstein—Barr virus-associated lymphoid proliferations, a 2018 update".
151:
375:
318:
178:
142:(EBV) proliferate excessively in one or more tissues. EBV infects ~95% of the world's population to cause
147:
392:
173:
FA-DLBCL most commonly develops within immunologically sequestered sites such as body cavities (e.g.
163:
111:
449:
proliferating large B cells within avascular tissues that are often coated with or contain abundant
475:
467:
598:"EBV-Positive Lymphoproliferations of B- T- and NK-Cell Derivation in Non-Immunocompromised Hosts"
993:
949:
898:
782:
736:
690:
555:
314:
139:
1017:
985:
941:
890:
852:
774:
728:
682:
629:
547:
347:
322:
240:
229:
43:
27:
977:
933:
882:
842:
832:
766:
720:
674:
619:
609:
539:
471:
343:
272:
268:
303:
252:
202:
186:
847:
820:
624:
597:
233:
221:
543:
444:
in or around sites that are not involved in chronic inflammation such as pseudocysts,
1011:
953:
902:
740:
299:
159:
124:
115:
997:
786:
559:
694:
665:
Distinct From
Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation".
495:
487:
463:
419:) and are infected with the EBV by their expression of this virus's proteins, e.g.
387:
355:
225:
143:
770:
271:(i.e. fluid accumulation within the potential space between the two layers of the
981:
886:
724:
678:
432:
351:
295:
937:
837:
483:
291:
283:
248:
190:
174:
107:
95:
32:
614:
491:
167:
91:
56:
48:
989:
945:
894:
856:
778:
732:
686:
633:
551:
499:
276:
256:
244:
198:
194:
36:
479:
339:
206:
450:
182:
99:
342:
and/or debris resulting from the death of cells, and therefore lack
445:
408:
371:
326:
260:
155:
104:
diffuse large B-cell lymphoma associated with chronic inflammation
416:
412:
404:
400:
396:
370:
which are implicated in the development of malignancy. However,
287:
138:(EBV+ LPD), i.e. disease in which lymphocytes infected with the
366:
360:
504:
Epstein-Barr virus-associated diffuse large B-cell lymphoma
596:
Dojcinov SD, Fend F, Quintanilla-Martinez L (March 2018).
162:
phase in which the infected individual becomes a lifetime
136:
Epstein–Barr virus-associated lymphoproliferative disease
73:
65:
55:
42:
26:
21:
454:FA-DLBCL, usually has a highly favorable outcome.
462:Cases of FA-DLBCL have been treated by surgery;
591:
589:
84:Fibrin-associated diffuse large B-cell lymphoma
22:Fibrin-associated diffuse large B-cell lymphoma
918:
916:
914:
912:
868:
866:
814:
812:
810:
808:
806:
804:
802:
800:
798:
796:
752:
750:
706:
704:
659:
657:
655:
653:
651:
649:
647:
645:
643:
587:
585:
583:
581:
579:
577:
575:
573:
571:
569:
525:
523:
521:
519:
8:
86:(FA-DLBCL) is an extremely rare form of the
970:The American Journal of Surgical Pathology
667:The American Journal of Surgical Pathology
386:FA-DLBCL is an incidental finding made by
18:
846:
836:
623:
613:
298:) or cyst of the kidneys, spleen, ovary,
515:
106:(DLBCL-CI). DLBCL-CI is an aggressive
77:rare, none due directly to the disease
7:
185:, a breakdown product of the blood
131:rather than a malignant DLBCL-CI.
14:
544:10.1016/j.anndiagpath.2018.09.014
376:adaptive arm of the immune system
372:programmed death-ligand 1 (PD-L1)
247:between the inner layer of the
713:Advances in Anatomic Pathology
602:Pathogens (Basel, Switzerland)
532:Annals of Diagnostic Pathology
94:in which a particular type of
88:diffuse large B-cell lymphomas
1:
771:10.1016/j.humpath.2018.05.020
374:, which acts to suppress the
317:of a foreign body such as an
114:that are walled off from the
982:10.1097/PAS.0b013e3182515fb5
887:10.1016/j.pathol.2019.08.013
725:10.1097/PAP.0000000000000117
679:10.1097/PAS.0000000000000775
500:thromboembolic complications
129:lymphoproliferative disorder
197:due to the dislodgement of
177:) and foreign bodies (e.g.
1039:
938:10.1007/s00428-019-02698-3
110:that develops in sites of
838:10.1186/s12885-019-6123-1
120:World Health Organization
615:10.3390/pathogens7010028
201:that travel through the
152:infectious mononucleosis
310:intravascular thrombi;
306:, or other tissue; and
179:artificial heart valves
439:Differential diagnosis
319:artificial heart valve
304:retroperitoneal space
148:non-specific symptoms
1023:Non-Hodgkin lymphoma
393:Immunohistochemistry
164:asymptomatic carrier
112:chronic inflammation
476:hydroxydaunorubicin
245:collection of blood
90:(DLBCL). DLBCL are
490:) or R-CHOP (i.e.
344:inflammatory cells
140:Epstein-Barr virus
51:of involved tissue
466:regimens such as
429:activated B-cells
348:cytotoxic T-cells
323:joint replacement
296:endothelial cells
241:subdural hematoma
230:connective tissue
81:
80:
61:good to excellent
44:Diagnostic method
16:Medical condition
1030:
1002:
1001:
964:
958:
957:
920:
907:
906:
870:
861:
860:
850:
840:
816:
791:
790:
754:
745:
744:
708:
699:
698:
661:
638:
637:
627:
617:
593:
564:
563:
527:
472:cyclophosphamide
259:surrounding the
19:
1038:
1037:
1033:
1032:
1031:
1029:
1028:
1027:
1008:
1007:
1006:
1005:
966:
965:
961:
926:Virchows Archiv
922:
921:
910:
872:
871:
864:
818:
817:
794:
759:Human Pathology
756:
755:
748:
710:
709:
702:
663:
662:
641:
595:
594:
567:
529:
528:
517:
512:
460:
441:
384:
335:
253:arachnoid mater
232:in the heart's
215:
205:to cause, e.g.
203:vascular system
187:clotting factor
134:FA-DLBCL is an
17:
12:
11:
5:
1036:
1034:
1026:
1025:
1020:
1010:
1009:
1004:
1003:
976:(7): 1074–80.
959:
932:(5): 647–665.
908:
862:
792:
746:
700:
673:(3): 299–312.
639:
565:
514:
513:
511:
508:
459:
456:
440:
437:
383:
380:
356:foreign bodies
334:
331:
273:cavum vaginale
222:cardiac myxoma
214:
211:
158:then enters a
79:
78:
75:
71:
70:
69:extremely rare
67:
63:
62:
59:
53:
52:
46:
40:
39:
30:
24:
23:
15:
13:
10:
9:
6:
4:
3:
2:
1035:
1024:
1021:
1019:
1016:
1015:
1013:
999:
995:
991:
987:
983:
979:
975:
971:
963:
960:
955:
951:
947:
943:
939:
935:
931:
927:
919:
917:
915:
913:
909:
904:
900:
896:
892:
888:
884:
880:
876:
869:
867:
863:
858:
854:
849:
844:
839:
834:
830:
826:
822:
815:
813:
811:
809:
807:
805:
803:
801:
799:
797:
793:
788:
784:
780:
776:
772:
768:
764:
760:
753:
751:
747:
742:
738:
734:
730:
726:
722:
719:(4): 202–43.
718:
714:
707:
705:
701:
696:
692:
688:
684:
680:
676:
672:
668:
660:
658:
656:
654:
652:
650:
648:
646:
644:
640:
635:
631:
626:
621:
616:
611:
607:
603:
599:
592:
590:
588:
586:
584:
582:
580:
578:
576:
574:
572:
570:
566:
561:
557:
553:
549:
545:
541:
537:
533:
526:
524:
522:
520:
516:
509:
507:
505:
501:
497:
493:
489:
485:
481:
477:
473:
469:
465:
457:
455:
452:
447:
438:
436:
434:
430:
426:
422:
418:
414:
410:
406:
402:
398:
394:
389:
381:
379:
377:
373:
369:
368:
363:
362:
357:
353:
352:body cavities
349:
345:
341:
332:
330:
328:
324:
320:
316:
313:
309:
305:
301:
300:adrenal gland
297:
293:
289:
285:
282:
278:
274:
270:
266:
262:
258:
254:
250:
246:
242:
239:
235:
231:
228:of primitive
227:
223:
220:
212:
210:
208:
204:
200:
196:
192:
188:
184:
180:
176:
171:
169:
165:
161:
157:
153:
149:
145:
141:
137:
132:
130:
126:
125:immune system
121:
117:
116:immune system
113:
109:
105:
101:
97:
93:
89:
85:
76:
72:
68:
64:
60:
58:
54:
50:
47:
45:
41:
38:
34:
31:
29:
25:
20:
973:
969:
962:
929:
925:
881:(1): 53–67.
878:
874:
828:
824:
762:
758:
716:
712:
670:
666:
605:
601:
535:
531:
496:radiotherapy
494:plus CHOP);
488:prednisolone
464:chemotherapy
461:
442:
433:plasma cells
388:histological
385:
365:
359:
336:
333:Pathogenesis
311:
307:
280:
264:
237:
226:myxoid tumor
218:
216:
213:Presentation
172:
133:
83:
82:
325:, or metal
290:that lacks
267:testicular
199:blood clots
175:pseudocysts
144:no symptoms
1012:Categories
831:(1): 916.
825:BMC Cancer
510:References
484:prednisone
346:including
292:epithelial
284:pseudocyst
249:dura mater
191:fibrinogen
108:malignancy
96:lymphocyte
33:Hematology
954:209429124
903:208142227
875:Pathology
765:: 18–41.
741:205915174
608:(1): 28.
492:rituximab
458:Treatment
382:Diagnosis
269:hyrocoele
195:embolisms
168:malignant
92:lymphomas
66:Frequency
57:Prognosis
49:Histology
28:Specialty
1018:Lymphoma
998:31478084
990:22472958
946:31863183
895:31735345
857:31519155
787:47010934
779:29885408
733:27271843
687:28195879
634:29518976
560:53196244
552:30380402
538:: 6–10.
315:implants
286:(i.e. a
277:testicle
257:meninges
251:and the
243:(i.e. a
224:(i.e. a
181:) where
146:, minor
37:oncology
848:6743119
695:3521190
625:5874754
480:oncovin
340:thrombi
275:, of a
255:of the
207:strokes
160:latency
996:
988:
952:
944:
901:
893:
855:
845:
785:
777:
739:
731:
693:
685:
632:
622:
558:
550:
482:, and
470:(i.e.
451:fibrin
415:, and
354:or on
234:atrium
183:fibrin
154:. The
100:B-cell
98:, the
74:Deaths
994:S2CID
950:S2CID
899:S2CID
783:S2CID
737:S2CID
691:S2CID
556:S2CID
446:cysts
421:EBNA2
409:CD79a
327:stent
261:brain
156:virus
150:, or
986:PMID
942:PMID
891:PMID
853:PMID
775:PMID
729:PMID
683:PMID
630:PMID
548:PMID
468:CHOP
425:LMP1
423:and
417:MUM1
413:PAX5
405:CD45
401:CD30
397:CD20
364:and
288:cyst
978:doi
934:doi
930:476
883:doi
843:PMC
833:doi
767:doi
721:doi
675:doi
620:PMC
610:doi
540:doi
486:or
367:p53
361:MYC
294:or
279:);
236:);
1014::
992:.
984:.
974:36
972:.
948:.
940:.
928:.
911:^
897:.
889:.
879:52
877:.
865:^
851:.
841:.
829:19
827:.
823:.
795:^
781:.
773:.
763:79
761:.
749:^
735:.
727:.
717:23
715:.
703:^
689:.
681:.
671:41
669:.
642:^
628:.
618:.
604:.
600:.
568:^
554:.
546:.
536:38
534:.
518:^
478:,
474:,
411:,
407:,
403:,
399:,
321:,
312:f)
308:e)
302:,
281:d)
265:c)
263:;
238:b)
219:a)
209:.
189:,
35:,
1000:.
980::
956:.
936::
905:.
885::
859:.
835::
789:.
769::
743:.
723::
697:.
677::
636:.
612::
606:7
562:.
542::
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.