Jeffrey S. Silverman HT,HTL,QIHC (ASCP)

E-Mail Address:peptolab@hamptons.com


I am currently studying the role of interactions between two subsets of microvascular dendritic cells- fibroblasts that express the human progenitor antigen CD34 and histiocytes that express coagulation factor XIIIa. Dendritic cells normally indigenous to the collagenous connective tissue have been characterized by molecular methods of immunohistochemistry. In most normal collagenous connective tissue, one can demonstrate two major subsets of dendritic mesenchymal cells. The more numerous are undifferentiated dendritic fibroblasts that express the human progenitor cell antigen CD34. These cells are concentrated in the adventitia of vessels and adnexa and are scattered also throughout the interstitium, including among normal adipocytes both in somatic and visceral connective tissue. These putative fibroblastic "reserve cells" are accompanied by fewer scattered dendritic histiocytes that express the transglutaminase coagulation factor XIIIa. These two cells both appear early during embryogenesis and together in the adult represent cellular components of the microvascular unit by which the organism effects tissue repair and remodeling. Moreover, proliferating microvascular CD34+ fibroblasts and FXIIIa+ histiocytes together constitute the principle cellular components of a diverse family of fibrovascular and fibrohistiocytic connective tissue tumors. Thus, these two normal indigenous stromal cells togegther provide an attractive unifying theory for the nosology and biologic interrelationships for a broad category of mesenchymal tumors arising from the collagenous microvascular unit. While soft tissue tumors are relatively rare, the ubiquity of these two "fibrohistiocytic" stromal cells in most visceral and somatic mesenchyme also makes them attractive targets for research into stromal involvement in invasion, metastasis, and angiogenesis in epithelial malignancies. I am interested in hearing from pathologists who encounter unusual fibrohistiocytic, myofibroblastic, myxoid, or vascular neoplasms who find this theory interesting and who would like to obtain a free immunophenotyping or enter into a collaboration with me in this regard. Some selected references involving my work appear below:
Tamsen A, Silverman JS. 1995. GIST: Letter to the editor. Am J Surg Pathol 19:1444-1445.

Caracuel E, Silverman JS. 1995. Myxoid malignant fibrous histiocytoma: Immunohistochemical study of a case showing bimodal cellular populations of factor XIIIa+ dendrophages and CD34+ fibroblasts. Patologia (Spain) 28:271-276.

Silverman JS, Knapik M. 1996 Fibroma of tendon sheath and tendosynovial giant cell tumors are rich in factor XIIIa dendrophages. J Histotechnology 19: 45-52.

Silverman JS, Knapik M. 1996. Correspondence re: Tendon sheath fibroma and giant cell tumor. Letter to the editor. Mod Pathol 9:82-84.

Silverman JS, Knapik M. 1996. Tendon sheath giant cell tumors. Letter. Hum Pathol 27:429-430.

Berrutti L, Silverman JS. 1996. Cardiac myxoma is rich in FXIIIa+ dendrophages. Immunohistochemical study of four cases. Histopathology 28:529-535.

Silverman JS. 1996. CD34 and factor XIIIa-positive dendritc cell subsets in fibrohistiocytic and other soft tissue tumors: A molecular model for neoplastic fibrovascular mesenchyme. Cell Vision 3:251 (Abstract of platform presentation at the Fourth International Conference and Workshop on Molecular Morphology June 3-6, 1996, Montreal, Canada).

Silverman JS, Tamsen A. 1996. Demonstration of CD34 and factor XIIIa+ dendritic cell subsets in intramuscular myxoma and comparison with umbilical cord Wharton's jelly. A molecular model for myxoid differentiation. Cell Vision 3:252 (Abstract of poster presented at the Fourth International Conference and Workshop on Molecular Morphology June 3-6, 1996, Montreal, Canada).

Silverman JS, Tamsen A. 1996. Mammary fibroadenomas and some phyllodes tumors are composed of CD34+ fibroblasts and FXIIIa+ dendrophages. Histopathology 29:411-419.

Silverman JS, Tamsen A. 1996. Hemangiopericytoma is an angioblastic fibrohistiocytic tumor composed of CD34- positive and factor XIIIa- positive dendritic cell subsets. Cell Vision 3:375-381.

Silverman JS, Tamsen A. Early ontogeny of factor XIIIa+ dendritic cells in developing human long bone marrow. Blood 88:4072-4078 (illustrated letter with response).

Silverman JS, Brustein SM. 1996. Myxoid dermatofibrohistiocytoma. An indolent post-traumatic tumor composed of CD34+ epithelioid and dendritic cells and factor XIIIa+ dendrophages. J Cutan Pathol 23:551-557.

Silverman JS, Berrutti L. 1996. Letter to the editor. Cardiac myxoma immunohistochemistry: Value of CD34,CD31, and factor XIIIa staining. Diag Cytopathol 15:455-456

Silverman JS, Dana MM. 1997. Pleomorphic hyalinizing angiectatic tumor of soft parts: Immunohistochemical case study shows cellular composition by CD34+ fibroblasts and factor XIIIa+ dendrophages. J Cutan Pathol 24:377-383.

Silverman JS, Lomvardias S. 1997. An unusual soft tissue tumor with features of angiomatoid malignant fibrous histiocytoma composed of bimodal CD34 and factor XIIIa positive dendritic cell subsets. Pathol Res Pract 193: 51-58.

Silverman JS, Albukerk J. 1997. Correspondence. Reticuloendothelial hemangioendothelioma. Histopathology 30:393-394. (illustrated letter)

Silverman JS, Tamsen A. 1997. Correspondence re: Hamele-Bena D, Cranor ML, Sciotto C, Erlandson R, Rosen PP. Uncommon presentation of mammary myofibroblastoma. Mod Pathol 10:270-272.

Silverman JS, Tamsen A. 1997. Fibrohistiocytic differentiation in subcutaneous fatty tumors: Study of spindle cell, pleomorphic, myxoid, and atypical lipoma and dedifferentiated liposarcoma cases composed in part of CD34+ fibroblasts and FXIIIa+ histiocytes. J Cutan Pathol 24: 484-493.

Silverman JS, Albukerk J, Tamsen A. 1997. Comparison of angiomyofibroblastoma and aggressive angiomyxoma in both sexes: Four cases composed of bimodal CD34 and Factor XIIIa positive dendritic cell subsets. Pathol Res Pract 193: 673-682

Silverman JS, Chumas J. 1997. Adenomatoid tumors of the female genital tract. Immunohistochemical study of CD34 and Factor XIIIa in 8 cases. J Histotechnol 21:59-64.

Silverman JS, Tamsen A. 1998. Whence cometh neointimal myofibroblasts? Circulation 97(1): 116.

Silverman JS, Tamsen A. 1998. Giant cell angiofibroma: A cutaneous case with focal dermatofibrosarcoma protuberans showing bimodal CD34+ fibroblastic and FXIIIa+ histiocytic spindle cell proliferation. J Cutan Pathol 25:265-270.

Silverman JS, Tamsen A. 1998. Interactive CD34+ fibroblasts and factor XIIIa -positive histiocytes in cutaneous mesenchymal tumors. Am J Dermatopathol 20:317-320. See also replies fro Dr. Morgan and Zelger.

Silverman JS, Tamsen A. 1998. High grade malignant fibrous histiocytomas have bimodal cycling populations of factor XIIIa+ dendrophages and dedifferentiated mesenchymal cells possibly derived from CD34+ fibroblasts. Cell Vision 5: 73-76 illust abst

Silverman JS, Tamsen A. 1998. Observations on the role of factor XIIIa+ dendritic mammary stromal cells in myofibroblastic stromal remodeling and angiogenesis in mammary carcinoma. Cell Vision 5: 77-79 illust abst

Silverman JS, Hamilton J, Tamsen A. 1998. Mammary myofibroblastoma. Case report and immunohistochemical comparison with stromal hyperplasias showing bimodal CD34+ and factor XIIIa+ fibrohistiocytic immunophenotype. J Histotechnol (in press Dec. 1998)

Silverman JS, Tamsen A. 1998. CD34 and Factor XIIIa- positive microvascular dendritic cells and the family of fibrohistiocytic mesenchymal tumors. Am J Dermatopathol 20:533-536.

Silverman JS, Tamsen. 1998. Comparison of angiomyofibroblastoma and aggressive angiomyxoma in both sexes: Four cases composed of bimodal CD34 and factor XIIIa positive dendritic cell subsets- Reply to M Zamecnik’s and M. Michal’s letter. Pathol Res Pract 194:737-738.

Silverman JS, Hamilton J, Tamsen A. 1999. Letter to the editor (Mammary myofibroblastoma). Hum Pathol 30:359-360.

My Links

Protein Reviews on the Web
Excellent resource for learning about CD antigens. Check out http://www.ncbi.nlm.nih.gov/PROW/forum/cd34.htm This is my posting of theories and speculation regarding the role of CD34 in fibroblast differentiation and stromal remodeling.

CATALOG OF ELECTRONIC JOURNALS OF PATHOLOGY AND

Self explanatory, many other links

Last Updated on 6/19/99 by Jeffrey S. Silverman HT,HTL,QIHC (ASCP).