CD34

CD34 is a 110 kDa transmembrane sialomucin glycoprotein encoded by a gene at 1q32. Its function is unknown. The exact composition of the carbohydrate moieties contained in its extended N-terminal region is important in determining its interactions with a variety of different ligands: for the CD34 present on high endothelial venules (HEV) to serve as a ligand for L-selectin, the O-linked glycans of HEV CD34 are modified in a specific manner with a variety of sialyl- and sulfo-transferases13. CD 34 is subject to phoshorylation by a variety of kinases including Protein kinase C and tyrosine kinases13.

It is a useful haemopoietic stem cell marker. Antibodies are effective on paraffin-embedded tissue (QBEND10, MY10)12.

Immunohistochemical expression

• normal endothelial cells

• cells of the splenic marginal zone

• dendritic interstitial cells around vessels, nerves, muscle bundles, skin adnexa and the perilobular stroma of the breast7. There is loss of CD34-positivity from stromal cells in association with desmoplasia around colorectal carcinomas2.

• spindle and stellate stromal cells in anal fibroepithelial polyps11.

• vascular neoplasms: CD34 is a less specific and sensitive marker for vascular tumours than are CD31 and Ulex europaeus I lectin

  • Kaposi's sarcoma: 40/40 cases4, 8/17 cases5, where there is coexpression with bcl-2

• immature leukaemias: AML and ALL14, granulocytic sarcoma15

• myelodysplasia in transformation

• variably by smooth muscle cells and tumours (9/364, 2/119 leiomyomas, 11/864, 2/119 leiomyosarcomas)

• gastrointestinal stromal tumours6 (GIST); positive in 50-80% of gastric cases and a lesser proportion in the small intestine3 and large intestine. There is coexpression with bcl-2.

• nerve sheath tumours: 45/544, 9/9(variable numbers of cells)9 neurofibromas, 14/484, 8/9(focal)9 schwannomas, 38 neurofibrosarcomas4. In neurofibromas, the CD34+ cells are present in greatest numbers in myxoid areas. In neurilemmomas, staining is most marked in Antoni B areas. Double staining shows the CD34+ cells to be S-100 negative; these cells are thought to be reactive and non-Schwannian.1

• lipoma6/angiolipoma6/atypical lipoma6/spindle cell lipoma: 27/274. In spindle cell lipoma, there is coexpression with bcl-2

• epithelioid sarcoma6

• haemangiopericytoma (10/104, 7/16(generally weak and patchy)9)

• 92-95% of solitary fibrous tumour (SFT)4, where there is coexpression with bcl-2

• dermatofibrosarcoma protuberans: 89% of cases(31/35)4

• angiomyofibroblastomas

• low grade myxofibrosarcoma: 7/10 cases4

• Superficial acral fibromyxoma

• fibroblasts of normal breast tissue and benign lesions, but lost by the fibroblasts around carcinomas of the breast10:

• The spindle cells of fibroadenomas, myofibroblastomas and phyllodes tumours of the breast7.

CD34 positivity is rare in

• benign fibrous histiocytoma: 4% of cases(6/149)4

• malignant fibrous histiocytoma: 5% of cases(2/38)4

• fibrosarcoma: 3 of 20 cases 4

CD34 is NOT expressed by:

• sarcomatoid mesothelioma: 0/134, 0/209 cases

• synovial sarcoma: 0/1044, 0/139 cases

• fibrosarcoma: 0/129

• fibromatosis: 0 of 19 cases4

• spindle cell thymoma: 0/59

A large series of vascular and non-vascular tumours were investigated for CD31 and CD34 immunoreactivity for comparison with FKBP12.

Diagnostic utility.

• Identification of endothelial differentiation. It is sensitive regardless of tumour grade, recognising greater than 85% of angiosarcomas and Kaposi's sarcomas, but lacks specifity8.

• Identification of gastrointestinal stromal tumours, preferably in combination with CD117.

• differentiation of solitary fibrous tumour (usually positive) from sarcomatoid mesothelioma (usually negative)

• differentiation of dermatofibrosarcoma protuberans (usually positive) from benign fibrous histiocytoma (usually negative)

• differentiation of spindle cell carcinoma of the breast (CD34-) from malignant phyllodes tumour (CD34+)7.

References

1 Khalifa, M. A., Montgomery, E. A., Ismiil, N., Azumi, N. What are the CD34+ cells in benign peripheral nerve sheath tumors? Double immunostaining study of CD34 and S-100 protein. Am J Clin Pathol 2000;114:123-126.

2 Nakayama H, Enzan H, Miyazaki E et al. Differential expression of CD34 in normal colorectal tissue, peritumoral inflammatory tissue, and tumour stroma. J Clin Pathol 2000;53:626-9.

3 Bates AW, Feakins RM, Scheimberg I. Congenital gastrointestinal stromal tumour is morphologically indistinguishable from the adult form. but does not express CD117 and carries a favourable prognosis. Histopathology 2000;37:316-322.

4 Ordonez NG. Localized (solitary) fibrous tumor of the pleura. Adv Anat Pathol 2000;7:327-340.

5 BR DeYoung et al. CD31 immunoreactivity in mesenchymal neoplasms of the skin and subcutis. J Cutn Pathol 1995;22:215-222.

6 JF Graadt van Roggen et al. The histopathological differential of diagnosis of gastrointestinal stromal tumours. J Clin Pathol 2001; 54: 96-103.

7 T Moore and AHS Lee. Expression of CD34 and bcl-2 in phyllodes tumours, fibroadenomas and spindle cell lesion of the breast. Histopathology 2001; 38: 62-67.

8 Diagnostic Immunohistochemistry edited by Professor D. J. Dabbs, page 71

9 Westra, W. H., Gerald, W. L., Rosai, J. Solitary fibrous tumor. Consistent CD34 immunoreactivity and occurrence in the orbit. Am J Surg Pathol 1994;18:992-8.

10 Abrahams A, Chaudan H, Philips J, Pringle JH, Walker RA. There is more than one kind of myofibroblast: analysis of CD34 expression in benign, in-situ and invasive breast lesions. Pathological Society July 2002, abstract 123.

11 Sakai, Y., Matsukuma, S. CD34+ stromal cells and hyalinized vascular changes in the anal fibroepithelial polyps. Histopathology 2002;41:230-235.

12 Leong A S-Y, Cooper K and Leong FJ W-M. Manual of diagnostic antibodies for immunohistology. 2nd edition, 2003

13 Lanza F, Healy L,Sutherland DR. Structural and functional features of the CD34 antigen: an update. J Biol Regul Homeost Agents 2001; 15:1-13

14 Soslow RA, Bhargava V,Warnke RA. MIC2, TdT, bcl-2, and CD34 expression in paraffin-embedded high-grade lymphoma/acute lymphoblastic leukemia distinguishes between distinct clinicopathologic entities. Hum Pathol 1997; 28:1158-65

15 Traweek ST, Arber DA, Rappaport H, et al. Extramedullary myeloid cell tumors. An immunohistochemical and morphologic study of 28 cases. Am J Surg Pathol 1993; 17:1011-9

This page last revised 22.10.2006.

©SMUHT/PW Bishop