Bone Marrow Fibrin-Ring Granuloma: Review of 24 Cases

Hee-Jung Chung; Hyun-sook Chi; Young-Uk Cho; Seongsoo Jang; Chan-Jeoung Park

doi:10.3343/kjlm.2007.27.3.182

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Chung, Chi, Cho, Jang, and Park: Bone Marrow Fibrin-Ring Granuloma: Review of 24 Cases

Original Article

Korean J Leg Med 2007;27(3):182-187.

Published online: 10 February 2007

DOI: https://doi.org/10.3343/kjlm.2007.27.3.182

Bone Marrow Fibrin-Ring Granuloma: Review of 24 Cases

Hee-Jung Chung, M.D., Hyun-sook Chi, M.D., Young-Uk Cho, M.D., Seongsoo Jang, M.D., Chan-Jeoung Park, M.D.

Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea

Received 26 February 2007 Revised 26 April 2007 Accepted 23 May 2007

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Fibrin-ring granuloma (FRG), which can be found in bone marrow or the liver, is a subtype of epithelioid granuloma characterized by a central fat vacuole and annular peripheral fibrinoid materials. FRG has been proven to be associated with many etiologies such as several infectious organisms (Coxiella burnett; Epstein-Barr Virus, EBV; cytomegalovirus, CMV; and hepatitis A virus), allopurinol induced hepatitis, Hodgkin's lymphoma, and peripheral T-cell lymphoma.

Methods

We retrospectively reviewed 24 patients diagnosed with FRG by bone marrow biopsy at a single institute between 1995 and 2004. We reviewed clinical symptoms and laboratory findings of the patients, classified them by etiology, and compared prognosis of each group.

Results

The most common cause of FRG was acute or chronic EBV infection. Chronic or acute EBV infection was associated with 41.4% of patients (10/24). Of the remaining patients, 33.3% (8/24) were leukemia or lymphoma patients after chemotherapy, 4.2% (1/24) was a patient with hepatic failure, and 20.8% (5/24) were diagnosed as fever of unknown origin. The most common symptom and clinical finding were fever and cytopenia. EBV-associated group comprised chronic active EBV infection, EBV-associated hemophagocytic histiocytosis, acute EBV infection, EBV-associated lymphoproliferative disease, and Langerhans' cell histiocytosis. The EBV-associated group showed a lower survival probability compared with the non-EBV group (P<0.05).

Conclusions

Patients with bone marrow fibrin ring granuloma accompanied by fever require an active workup to find out the cause of infectious agents including EBV infection particularly due to their poor prognosis.

Keywords: Epstein-Barr virus (EBV), Bone marrow, Fibrin-ring granuloma

References

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Fig. 1.

(A) Multiple fibrin-ring granulomas in UPN 5 (BM clot section, Hematoxylin-Eosin stain, ×400). EBV PCR with BM sample revealed positive. (B) Fibrin-ring granulomas in UPN 10. Serial result of real-time EBV quantitative PCR presented 15,720 copies/mL at the diagnosis of FRG and decreased to 2,490 copies/mL after 10 days (BM biopsy specimen, Hematoxylin-Eosin stain, ×400). (C) Masson's trichrome stain of fibrin-ring granulomas in UPN 10 (BM biopsy specimen, trichrome stain, ×400).

Fig. 2.

Kaplan-Meier survival curves of patients. EBV positive group shows a significantly low survival rate. The median survival of EBV positive group is 1.4 months (mean=2.0 months) and that of negative group is 11.8 months (mean=50.7 months).

Abbreviation: UPN, unique patient number.

Table 1.

Clinical and laboratory data of patients

Group	UPN	Age/Sex	Diagnosis	Clinical feature				Laboratory data						Outcome
Group	UPN	Age/Sex	Diagnosis	Fever	Hepatomegaly	Splenomegaly	LAP	WBC (/μL)	Hb (g/dL)	PLT (× 10³/μL	AST (IU/L)	ALT (IU/L)	LDH (IU/L)	Outcome
1	5	37/M	CAEBV	+	+	−	−	3,700	9.9	179	73	140	NT	Dead
	7	41/M	CAEBV	+	+	+	−	4,200	16.5	121	127	250	NT	Dead
	3	46/M	CAEBV	+	+	+	−	16,300	9.9	246	38	19	16,170	Dead
	4	62/M	CAEBV	+	+	−	−	10,400	9.8	129	46	16	738	Dead
	2	3/M	EBV-HLH	+	+	+	−	2,400	9.9	186	231	222	NT	Dead
	1	34/M	EBV-HLH	+	+	+	+	1,000	7.6	21	508	149	3,136	Dead
	8	50/M	Acute EBV	+	−	−	+	5,800	12.1	184	314	226	4.659	Alive
	6	8/F	LCH	+	+	+	−	5,600	12.1	124	113	85	NT	Alive
	9	36/M	EBV associated LPD	+	−	+	+	18,600	5.6	326	142	200	1,563	Dead
	10	35/M	T-cell lymphoma on skin, EBV ISH+	−	+	+	+	2,100	10.2	95	174	166	346	Dead
2	11	40/M	T-cell lymphoma	−	−	−	+	7,000	10.0	458	39	47	847	Alive
	15	50/M	T-cell lymphoma	+	−	−	+	1,800	12.1	153	74	48	1.458	Dead
	12	55/M	T-cell lymphoma	+	−	−	+	600	7.6	14	274	117	2.926	Alive
	18	60/M	T-cell lymphoma	+	+	+	+	19,100	9.8	230	28	35	534	Alive
	14	69/M	Hodgkin's lymphoma	+	+	+	+	3,300	10.5	66	68	48	1.941	Alive
	16	52/F	AML M1	−	−	−	−	9,800	10.9	468	54	171	332	Alive
	13	46/M	AML M2	+	−	+	−	5,400	8.3	10	39	105	605	Alive
	17	53/F	ALL L2	−	−	−	−	1,000	8.7	43	15	33	448	Dead
3	19	33/F	Hepatic failure	+	+	+	+	1,800	13.5	179	162	131	2,134	Dead
4	23	36/M	FUO	+	−	−	−	7,500	11.5	210	29	51	898	Alive
	20	38/M	FUO	+	+	−	−	6,000	12.1	248	70	45	NT	Dead
	22	59/M	FUO	+	−	−	−	16,100	13.2	534	31	44	294	Alive
	21	67/M	FUO	+	−	−	−	6,000	11.4	130	38	30	NT	Alive
	24	76/M	FUO	+	−	−	−	21,000	12.3	309	19	19	713	Alive

Abbreviations: UPN, unique patient number; LAP, lymphadenopathry; NT, not tested; CAEBV, chronic active EBV infection; EBV-HLH, EBV associated hemophagocytic lymphohistiocytosis; LCH, Langerhans' cell histiocytosis; LPD, Lymphoproliferative disease; ISH, in situ hybridization; FUO, fever of unknown origin.

Table 2.

Four groups of patients with fibrin-granuloma according to their etiology

Group	N of patient (n)	% of patient
I Acute or Chronic EBV infection	10	41.7
II Leukemia or lymphoma after chemotherapy	8	33.3
III Hepatic failure	1	4.2
IV FUO	5	20.8
Total	24	100.0

Abbreviations: See Table 1.

Table 3.

Review of the literature: bone marrow fibrin-ring granuloma

Diagnosis	N of patient	Specimen	Author	Year
Hodgkin's lymphoma	1	BM	Delsol et al.[18]	1980
Acute EBV infection	1	BM	Voigt et al.[4]	1983
Acute EBV infection	1	BM	Blanco P et al.[1]	2003
EBV-HLH	1	BM and liver	Kang et al.[16]	1995
After drug therapy of Lyme disease	1	BM	Kvasnicka HM et al.[2]	2002
Peripheral T-cell lymphoma	1	BM	Raya Sanchez JM et al.[7]	2001
Q-fever	1	BM	Rexroth G et al.[19]	2000
CMV infection	2	BM	Young JF et al.[5]	1993
Q-fever	4	BM	Srigley JR et al.[20]	1985

Abbreviations: See Table 1.

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