Characterization of the Proliferated Histiocytes in Acute Leukemia by Performing Immunohistochemistry

Hyojin Chae; Hun Hee Park

doi:10.5045/kjh.2009.44.1.8

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Chae and Park: Characterization of the Proliferated Histiocytes in Acute Leukemia by Performing Immunohistochemistry

Original Article

Korean J Hematol 2009;44(1):8-13.

Published online: 20 March 2009

DOI: https://doi.org/10.5045/kjh.2009.44.1.8

Characterization of the Proliferated Histiocytes in Acute Leukemia by Performing Immunohistochemistry

Hyojin Chae, M.D., Hun Hee Park

Department of Laboratory Medicine, The Catholic University of Korea, Seoul, Korea

Correspondence to：Hun Hee Park Department of Laboratory Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea 505, Banpo-dong, Seocho-gu, Seoul 137-701, Korea Tel: ＋82-2-2258-1655, Fax: ＋82-2-2258-1719 E-mail: phh5240@hanmail.net

Received 2 September 2008 Revised 13 March 2009 Accepted 17 March 2009

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

The bone marrow biopsy sections of acute leukemia patients occasionally reveal a proliferation of large mononuclear cells that accompany the leukemic blasts, and this proliferation shows a starry sky pattern. We characterized these large mononuclear cells by performing immunohistochemistry with 12 different antibodies. The clinical characteristics were examined and then we determined their difference from hemophagocytic lymphohistiocytosis (HLH) and malignant histiocytic disorders.

Methods

Of the 200 acute leukemic bone marrow biopsy samples, 11 ALL and 10 AML cases showed large mononuclear cell proliferations. The panel of antibodies used for immunohistochemistry included those against the mononuclear phagocyte system, and immunohistochemistry was performed on the patients' initial specimens and the complete remission specimens. 10 normal specimens, 4 initial CML specimens and their complete hematologic response specimens were included as controls.

Results

The large mononuclear cells showed immunohistochemical results consistent with histiocytes. They were negative for the markers of dendritic cells the histiocytes and cytokines that are involved in the pathogenesis of HLH and vascular proliferation. Histiocyte proliferation was not observed in the complete remission specimens and in the initial and complete hematological response specimens of the CML patients and the normal bone marrow specimens. None of the cases fulfilled the criteria of HLH, and all 5 ALL cases, for which the immunophenotype results were available, showed a B cell phenotype.

Conclusion

We characterized the large mononuclear cell proliferations as reactive histiocyte proliferations and we differentiated these from those of secondary HLH and malignant histiocytic disorders. A proportion of the large mononuclear cells showed negative results for all 12 antibodies and they showed characteristics that were suggestive of small fat cells. The pathophysiology and the prognostic effect of the reactive histiocyte proliferation accompanying acute leukemia require further study.

Keywords: Histiocyte, Immunohistochemistry, Acute leukemia

References

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Fig. 1.

Bone marrow biopsy specimen of acute leukemia showing prominent starry sky pattern (H&E stain, ×400).

Fig. 2.

Histiocytes showing positive staining with anti-CD68 monoclonal antibody (Immunohistochemical stain, ×400).

Fig. 3.

Histiocytes showing positive staining with S-100 monoclonal antibody (Immunohistochemical stain, ×400).

Table 1.

Antibodies used in the immunohistochemical staining

Specificity	Source	Dilution
CD1a	Labvision	1:50
CD14	Labvision	1:20
CD21 CD29	Labvision Labvision	1:10 1:10
CD35	Labvision	1:50
CD68	Labvision	1:40
CD169	Abcam	1:50
S100	Labvision	1:100
VEGF	Labvision	1:50
Lysozyme	Labvision	1:100
IL-1	Santa cruz	1:50
TNF-α	Hycult biotechnology	1:50

Abbreviations: CD, cluster of differentiation; VEGF, vascular endothelial growth factor; LI, interleukin; TNF, tumor necrosis factor.

Table 2.

Clinical characteristics of ALL patients with histiocytosis

Case	Age	Sex	Phenotype	Outcome (survival, mos)
1	7	M	B	Alive (58+)
2	34	M	ND	Alive (78+)
3	17	M	ND	Alive (68+)
4	7	M	ND	Alive (67+)
5	4	F	ND	Alive (63+)
6	49	F	ND	Alive (61+)
7	4	M	B	Alive (57+)
8	16	M	B	Dead (9)
9	3	M	B	Dead (38)
10	6	M	ND	Alive (44+)
11	27	F	B	Dead (4)

Abbreviation: ND, lineage not-determined.

Table 3.

Clinical characteristics of AML patients with histiocytosis

Case	Age	Sex	Phenotype	Outcome (survival, mos)
1	18	F	M2	Alive (58+)
2	29	M	M2	Alive (58+)
3	38	M	M3	Alive (71+)
4	54	F	M3	Alive (34+)
5	38	F	M4	Dead (5)
6	39	M	M1	Alive (64+)
7	24	M	M2	Dead (12)
8	49	F	M3	Alive (63+)
9	21	M	M3	Alive (61+)
10	33	F	M2	Dead (32)

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