CD 163

CD163 is a transmembrane protein mediating the endocytosis of haptoglobin-haemoglobin complexes. It is expressed on chromosome 12p13.3 and is a member of the cysteine-rich scavenger receptor superfamily. It is highly expressed by tissue macrophages and to a lesser extent by circulating monocytes. In a soluble form in plasma, it has an anti-inflammatory function. Expression is upregulated in inflamed tissues under the regulation of glucocorticoids, IL-10 and other modulators.

Immunohistochemical expression

CD163 shows a greater specificity for both non-neoplastic cells and tumours of monocyte/macrophage lineage than does CD68¹.

On flow cytometry, expression of CD163 in AML is largely restricted to FAB type M5 (16 of 19 cases) and to a lesser extent M4 (3 of 12 cases), other subtypes being negative (41 of 47 cases) or showing staining of less than 10% of cells (6 of 47 cases)¹⁷.

		CD163	CD68
	Haematolymphoid diseases
	AML FAB M5	2/61	11/11 (FAB M4 or M5)2
	AML other than FAB M5	0/161	2/18 FAB other than M4 or M5)2
	Mast cell leukaemia	0/11
	Lymphomas	0/70 (11 Angioimmunoblastic T cell, 1 Burkitt's, 2 CLL/SLL, 12 DLBCL, 27 follicular lymphomas, 2 lymphoplasmacytic, 6 marginal zone, 1 myeloma, 3 peripheral T cell, 1 precursor T cell, 2 PTLD)1	16% of 4215,11
	Follicular dendritic cell tumour	0/41	6/133
	Haemophagocytic lymphohistiocytosis	4/41
	Histiocytic sarcoma	3/41	26/263,4,5, 14/1416
	Langerhans cell histiocytosis	3/51	14/173
	Littoral cell angioma	6/61	6/66
	Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfmann disease)	5/61	20/2015
	Mesenchymal neoplasms
	Benign fibrous histiocytoma	6/91	4/45
	Atypical fibrous histiocytoma	9/161
	Epithelioid histiocytoma	1/11
	Giant cell tumour (tenosynovial)	7/8 (positivity in the epithelioid cell, negativity in osteoclast-like giant cells)1, 5/5 (strong positivity in the small histiocytic cells, variable reactivity in plump mononuclear cells and negativity in osteoclast-like giant cells)8	4/48
	Atypical fibroxanthoma	1/31	21/377
	DFSP	1/4 (in the positive case, staining was limited to less than 10% of tumour cells)1	1/15
	Juvenile xanthogranuloma	1/11
	Atypical lipomatous tumour	2/24 (in the positive cases, staining was limited to less than 10% of tumour cells)1
	Leiomyosarcoma	1/33 (in the positive case, staining was limited to less than 10% of tumour cells)1
	MFH	2/53 (in the positive cases, staining was limited to less than 10% of tumour cells)1	42/715,13,14
	SFT	1/9 (in the positive case, staining was limited to less than 10% of tumour cells)1
	Alveolar soft part sarcoma	0/21
	Angiosarcoma	0/71	2/46
	Carcinosarcoma	0/71
	Myxoid chondrosarcoma	0/21
	Clear cell sarcoma	0/21
	Dermoid cyst	0/11
	DSRCT	0/31
	Elastofibroma	0/11
	Endometrial stromal sarcoma	0/61
	Epithelioid sarcoma	0/11
	Ewing's sarcoma	0/21
	Fibromatosis	0/141
	Fibromyxoid sarcoma	0/11
	Fibrosarcoma	0/31
	Ganglioneuroma	0/11
	GIST	0/381
	Glomus tumour	0/41
	Granular cell tumour	0/21	20/215,9,10
	Haemangioendothelioma	0/31
	Haemangioma	0/31	5/106
	Haemangiopericytoma	0/11
	Hibernoma	0/11
	Inflammatory pseudotumour	0/21
	Kaposi's sarcoma	0/21
	Leiomyoma	0/91
	Lipoblastomatosis	0/41
	Lymphangioma	0/11
	MPNST	0/151
	Myofibrosarcoma	0/21
	Myxoma	0/11
	Myxosarcoma	0/11
	Neurofibroma	0/21	18/185,9
	Nodular fasciitis	0/21
	Osteosarcoma	0/71
	Rhabdomyosarcoma	0/111
	Sarcoma, NOS	0/71
	Schwannoma	0/31	21/265,9
	Synovial sarcoma	0/141
	Non-haematolymphoid, non-mesenchymal tumours
	Adrenal	0/8 (3 adenomas, 1 neuroblastoma, 4 phaeochromocytomas)1
Bladder	0/22 (21 transitional cell carcinomas, 1 phaeochromocytoma)1
Breast	0/14 (8 adenomas/papillomas, 6 ductal carcinomas)1
Cervix	0/8 (8 carcinomas)1
Colon	0/95 (87 adenocarcinomas, 4 adenomas, 2 carcinoids, 2 squamous cell carcinomas)1
ENT	0/30 (29 squamous cell carcinomas, 1 low grade tumour)1
Gallbladder	0/1 (1 cholangiocarcinoma)1
Kidney	0/44 (34 renal cell carcinomas, 5 transitional cell carcinomas, 3 Wilm's tumours, 1 nephroma, 1 oncocytoma)1
Liver	0/18 (14 hepatocellular carcinomas, 2 carcinoids, 1 cholangiocarcinoma, 1 hepatoblastoma)1
Lung	0/54 (52 carcinomas, 2 neuroendocrine tumours)1
Ovary	0/46 (28 serous, 10 adenocarcinomas, 6 clear cell, 1 mucinous, 1 seminoma)1
Malignant melanoma	0/221	31/565,12
Oesophagus	0/16 (8 squamous, 7 adenocarcinomas)1
Pancreas	0/12 (9 adenocarcinomas, 1 adenoma, 1 islet cell tumour, 1 anaplastic)1
Pleura	0/4 (mesotheliomas)1
Prostate	0/34 (34 carcinomas)1
Skin,BCC	0/11
Stomach	0/26 (26 adenocarcinomas)1
Testis	0/12 (11 seminomas, 1 malignant mixed tumour)1
Thymus	0/1 (thymoma)1
Thyroid	0/17 (16 papillary, 1 follicular)1
Uterus	0/31 (26 endometrioid, 4 clear cell, 1 mixed Mullerian tumour)1
Vulva	0/2 (1 squamous cell carcinoma, 1 Paget's disease)1

Diagnostic utility

Identification of entities of monocyte/macrophage differentiation.

• Differentiation of synovial macrophages (positive) from synovial fibroblasts (negative): both cell types are positive for CD68.

• Splenic littoral cell angioma (positive) from reactive splenic proliferations (negative)¹.

References

¹ Nguyen TT, Schwartz EJ, West RB, et al. Expression of CD163 (hemoglobin scavenger receptor) in normal tissues, lymphomas, carcinomas, and sarcomas is largely restricted to the monocyte/macrophage lineage. Am J Surg Pathol 2005; 29:617-24

² Davey FR, Erber WN, Gatter KC, et al. The use of monoclonal antibody Y1/82A in the identification of acute myeloblastic and monocytic leukemias. Am J Clin Pathol 1988; 89:76-80

³ Pileri SA, Grogan TM, Harris NL, et al. Tumours of histiocytes and accessory dendritic cells: an immunohistochemical approach to classification from the International Lymphoma Study Group based on 61 cases. Histopathology 2002; 41:1-29

⁴ Hanson CA, Jaszcz W, Kersey JH, et al. True histiocytic lymphoma: histopathologic, immunophenotypic and genotypic analysis. Br J Haematol 1989; 73:187-98

⁵ Gloghini A, Volpe R, Canzonieri V, et al. Immunohistochemical characterization of Ki-M6 monoclonal antibody in Bouin-fixed, paraffin-embedded sections of normal and neoplastic human tissues. Virchows Arch A Pathol Anat Histopathol 1991; 418:355-60

⁶ Arber DA, Strickler JG, Chen YY, et al. Splenic vascular tumors: a histologic, immunophenotypic, and virologic study. Am J Surg Pathol 1997; 21:827-35

⁷ Longacre TA, Smoller BR,Rouse RV. Atypical fibroxanthoma. Multiple immunohistologic profiles. Am J Surg Pathol 1993; 17:1199-209

⁸ Furlong MA, Motamedi K, Laskin WB, et al. Synovial-type giant cell tumors of the vertebral column: a clinicopathologic study of 15 cases, with a review of the literature and discussion of the differential diagnosis. Hum Pathol 2003; 34:670-9

⁹ Tos AP, Doglioni C, Laurino L, et al. KP1 (CD68) expression in benign neural tumours. Further evidence of its low specificity as a histiocytic/myeloid marker. Histopathology 1993; 23:185-7

¹⁰ Tsang WY,Chan JK. KP1 (CD68) staining of granular cell neoplasms: is KP1 a marker for lysosomes rather than the histiocytic lineage? Histopathology 1992; 21:84-6

¹¹ Carbone A, Gloghini A, Volpe R, et al. KP1 (CD68)-positive large cell lymphomas: a histopathologic and immunophenotypic characterization of 12 cases. Hum Pathol 1993; 24:886-96

¹² Facchetti F, Bertalot G,Grigolato. PG KP1 (CD 68) staining of malignant melanomas. Histopathology 1991; 19:141-5

¹³ Binder SW, Said JW, Shintaku IP, et al. A histiocyte-specific marker in the diagnosis of malignant fibrous histiocytoma. Use of monoclonal antibody KP-1 (CD68). Am J Clin Pathol 1992; 97:759-63

¹⁴ Smith ME, Costa MJ,Weiss SW. Evaluation of CD68 and other histiocytic antigens in angiomatoid malignant fibrous histiocytoma. Am J Surg Pathol 1991; 15:757-63

¹⁵ Eisen RN, Buckley PJ,Rosai J. Immunophenotypic characterization of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). Semin Diagn Pathol 1990; 7:74-82

¹⁶ Hornick, J. L., E. S. Jaffe, et al. (2004). "Extranodal histiocytic sarcoma: clinicopathologic analysis of 14 cases of a rare epithelioid malignancy." Am J Surg Pathol 28(9): 1133-44.

¹⁷ Walter RB, Bachli EB, Schaer DJ, et al. Expression of the hemoglobin scavenger receptor (CD163/HbSR) as immunophenotypic marker of monocytic lineage in acute myeloid leukemia. Blood 2003; 101:3755-6

This page last revised 30.6.2005.

©SMUHT/PW Bishop