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
|
2/18FAB 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