CD34

Synonyms: myeloid progenitor cell antigen

by Assia Bassarova

Background

CD34 is a 115-kDa transmembrane sialomucin encoded on a gene located on chromosome 1q32.1 The protein is a heavy glycosylated cell surface type I transmembrane protein expressed by human haematopoietic progenitor cells (HPC). It is expressed in activated bone marrow progenitor cells, which give rise to the hematopoietic and angioblastic lineages. While CD34 expression is lost during differentiation in the hematopoietic lineage, it is maintained in the angioblastic one. In addition, evidence exists supporting the idea that a subset of CD34-positive stromal cells derived from bone marrow and muscle represents a type of mesenchymal stem cell. The function of the CD34 molecule has recently been proposed, and mounting evidence indicates that it is related to cell adhesion. The lq32 region to which the CD34 gene is mapped is occupied with genes encoding several adhesion the CD34 molecule is involved in regulation of adhesion and compartmentalisation of HPC in bone marrow. The CD34 molecule may also be related to transmembrane signalling.

Staining in normal tissues

CD34 protein (using mAb QBEND10) is detected in only 1-3 % bone marrow precursor cells including hematogones, where it might act as a ligand for lectins in the cells of the bone marrow stroma. CD34 disappears from all haematological cell lines during maturation. Megakaryocytes are variably positive for CD34. CD34 molecules expressed on high endothelial venules function as a ligand for L-selectin on leukocytes. CD34 molecule expressed on high endothelial venules, is involved in the  regulation of cell-to-cell interaction, affecting leukocyte adhesion and transendothelial migration.
CD34 is expressed on the luminal surface and membrane processes interdigitating between endothelial cells, but is absent from large veins and arteries. CD34 is also absent from sinuses in the placenta and spleen. Lymphatics are generally weakly stained. CD34 is furthermore expressed in fibroblast-like dendritic cells in, e.g., portal tracts of the liver, Peyer’s patches, and in healing wounds. In smooth muscle cells, a variable CD34 staining is found.

Staining in tumors

  • CD34 is detected in myeloid blasts in myelodysplastic syndrome and acute myeloid leukaemia, as well as lymphoblasts in most cases of B-acute lymphoblastic leukaemia. Mature B- and T-cell lymphomas and leukaemias are CD34 negative.
  • The majority of vascular tumours, including epitheloid hemangioendothelioma, angiosarcoma and Kaposi sarcoma are CD34 positive.
  • However, only about 30% of the lymphangiomas are CD34 positive.
  • There is a growing number of CD34-reactive cutaneous tumors reported. They include benign and malignant neoplasms as well as reactive and hamartomatous lesions of diverse lineages of differentiation, including fibroblastic, myofibroblastic, fibrohistiocytic, vascular, neural, adipocytic, smooth muscle, hematopoietic, melanocytic and epithelial tumors. CD34 reactivity is usually observed in spindle cells, but expression in epithelioid and pleomorphic cells can be found in some entities.
  • CD34 positivity is seen in most cases of dermatofibrosarcoma protuberans and related giant cell fibroblastoma, myxoinflammatory fibroblastic sarcoma, solitary fibrous tumor, lipofibromatosis, nuchal type and sclerosing fibroma, superficial angiomyxoma and superficial acral fibromyxomas, spindle cell lipoma and pleomorphic liposarcoma, peripheral nerve sheath tumors, neurofibroma and palisaded encapsulated neuroma, fibrofolliculomas and trichodiscomas, tumors completely or partially differentiatedtoward the external root sheath of the hair follicle, such as trichilemmoma.
  • Gastrointestinal stromal tumor shows strong positivity in about 80% of the cases, (which are also CD117 positive), and a varying proportion of meningioma. Schwannoma is CD34 positive mainly in Antoni B areas.
  • About 50% of epitheloid sarcomas show strong focal or generalized staining for this antigen. Some synovial sarcomas may show focal staining.

Staining pattern

A strong and distinct, predominantly membranous staining reaction of virtually all endothelial cells and myeloid blasts.

Control tissue

Liver and appendix are recommended tissue controls for CD34.
In liver a moderate to strong predominately membranous staining reaction of endothelial cells in the portal vessels must be seen. The periportal sinusoidal endothelial cells are “low expressors” and must be weakly positive as well. The liver cells are completely negative.
In the appendix all endothelial cells and, in particular endothelial cells lining the small vessels in lamina propria, Cajal cells in muscularis propria and stromal fibroblast-like cells must reveal strong and distinct, predominantly membranous staining. The epithelial and smooth muscle cells have to be completely negative.

Application

  • In hematopathology CD34 is part of the panel for classification of myeloid and lymphoid neoplasms.
  • CD34 is also important marker in dermatopathology, especially in cutaneous soft tissue tumors. It has high diagnostic significance in the differential diagnosis of dermatofibrosarcoma protuberans and some difficult cases of cellular dermatofibroma. It is also useful confirming vascular origin of some spindle cell neoplasms.
  • CD34 is also used in the panel for identification of gastrointestinal stromal tumour
  • Alone or together with CD31 may be used for evaluation of micro-vessel density in tumors, as well as confirming tumor emboli in vasculature.

Selected references

  1. Sutherland DR, Keating A. The CD34 antigen: structure, biology, and potential clinical applications. J Hematother. 1992 Summer;1(2):115-29. doi: 10.1089/scd.1.1992.1.115. PMID: 1285404.
  2. Steen R, Egeland T. CD34 molecule epitope distribution on cells of haematopoietic origin. Leuk Lymphoma. 1998 Jun;30(1-2):23-30. doi: 10.3109/10428199809050926. PMID: 9669673.
  3. Gangenahalli GU, Singh VK, Verma YK, et al. Hematopoietic stem cell antigen CD34: role in adhesion or homing. Stem Cells Dev. 2006 Jun;15(3):305-13. doi: 10.1089/scd.2006.15.305. PMID: 16846369.
  4. Hughes MR, Canals Hernaez D, et al. A sticky wicket: Defining molecular functions for CD34 in hematopoietic cells. Exp Hematol. 2020 Jun;86:1-14. doi: 10.1016/j.exphem.2020.05.004. Epub 2020 May 16. PMID: 32422232.
  5. Tardío JC. CD34-reactive tumors of the skin. An updated review of an ever-growing list of lesions. J Cutan Pathol. 2009 Jan;36(1):89-102. doi: 10.1111/j.1600-0560.2008.01212.x. PMID: 19125742.