Clusterin, a Follicular Dendritic Cell-Associated Apolipoprotein, Is Expressed in Normal Synoviocytes and in Tenosynovial Giant Cell Tumors of Localized and Diffuse Types: Diagnostic and Histogenetic Implications
JM Boland, AL Folpe, JL Hornick, KL Grogg. Mayo Clinic, Rochester, MN; Brigham and Women's Hospital, Boston, MA
Background: Tenosynovial giant cell tumors (TGCT) comprise a family of lesions arising from synovium of joints, bursae or tendon sheath. TGCT are classified into localized (LTGCT) and diffuse (DTGCT) types, based on growth pattern and clinical behavior. TGCT were once thought to be reactive lesions, based on the heterogeneous histology including mononuclear cells, multinucleated giant cells, foam cells, and inflammatory cells. However, recent studies have shown recurrent clonal genetic abnormalities, confirming their neoplastic nature. The mononuclear component includes two cell types: small histiocytoid cells and large mononuclear cells (LMC) with abundant cytoplasm. The LMCs are positive for desmin in about 50% of cases, which highlights dendritic processes. The exact function and histogenesis of these cells has been unclear. The current study seeks to further characterize the phenotype of the cells comprising TGCT, and investigates the diagnostic utility of the marker clusterin, a recently identified follicular dendritic cell (FDC) associated glycoprotein that has diverse functions as a chaperone, lipoprotein transport, and cytoprotective protein.
Design: Immunostaining for clusterin was performed on 11 cases of LTGCT and 29 cases of DTGCT (23 intraarticular, 6 extraarticular). Most were also stained for desmin, the histiocyte marker CD163, and FDC markers CD21 and CD35.
Results: Clusterin staining was diffuse and strong in the LMCs in all cases. Desmin positivity was identified in 24/34 cases (71%), but was seen in only a subset of the LMCs (<5% to 80%), with 19/24 cases (79%) showing positivity in 10% or less of the LMCs. The LMCs were negative for CD163, CD21 and CD35. The smaller histiocytoid cells were positive for CD163, and negative for clusterin, CD21 and CD35. When present, adjacent non-neoplastic synovium was positive for clusterin and very focally positive for desmin.
Conclusions: Clusterin is a highly sensitive marker for TGCT, which has diagnostic utility in challenging cases, such as small biopsies, extraarticular DTGCT and cases with unusual histology. The observed staining patterns provide evidence linking the LMCs with normal synovial lining cells, and confirm that the LMCs are not of histiocytic derivation. Interestingly, clusterin expression and dendritic morphology are features shared by synovial lining cells and FDCs.
Category: Bone & Soft Tissue
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 13, Monday Morning