CD34

CD34 is a 110 kDa transmembrane glycoprotein encoded by a gene at 1q32. Its function is unknown. 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 ALL, granulocytic sarcoma

• 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:

	CD34	SMA
normal breast	positive	negative
fibroadenoma	positive	positive
apocrine cysts	positive	negative
usual type epithelial hyperplasia	positive	negative
DCIS	variable, more often negative around high grade DCIS	positive
infiltrating ductal carcinoma	negative	positive
radial scar	negative	positive

• 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

¹Khalifa, 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.

²Nakayama 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.

³Bates 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.

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

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

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

⁷T 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.

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

⁹Westra, 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.

¹⁰Abrahams 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.

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

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

This page last revised 21.12.2001.

©SMUHT/PW Bishop