γ-Synuclein Is a Promising New Marker for Staining Reactive Follicular Dendritic Cells, Follicular Dendritic Cell Sarcoma, Kaposi Sarcoma, and Benign and Malignant Vascular Tumors

Abstract

Synucleins are small soluble proteins found in normal brain that facilitate rapid release of neurotransmitters. α-synuclein is a major component of the Lewy body of neurodegenerative diseases and γ-synuclein is a marker of aggressive carcinomas. As the role of γ-synuclein has not yet been investigated in the lymphoid system, we immunohistochemically stained normal lymphoid organs, lymph nodes with reactive lymphoid hyperplasia, and malignant lymphomas. The anti-γ-synuclein antibody strongly stained the follicular dendritic cell (FDC) meshworks and vascular and lymphatic endothelial cells in reactive lymphoid tissues, in B-cell lymphomas with a nodular pattern, and in angioimmunoblastic T-cell lymphomas. There were no γ-synuclein-positive FDC meshworks in B-cell or T-cell lymphomas with a diffuse pattern. This is in contrast to CD21, which only stained the arms of the FDCs; γ-synuclein highlighted both the long slender cellular processes and the cell body, thereby clearly demonstrating the number of individual FDCs. In addition, γ-synuclein was strongly expressed by the neoplastic counterpart of reactive FDCs (FDC sarcoma) and by the neoplastic counterparts of normal lymphatic and vascular endothelial cells (Kaposi sarcoma, hemangioma, and angiosarcoma). Only a few spindle cell neoplasms (SSNs) derived from smooth muscle, peripheral nerve, or gastrointestinal stroma expressed γ-synuclein; however, γ-synuclein was not expressed by 11 other types of SSNs tested. These results suggest that γ-synuclein is a promising new adjunct marker for identifying reactive FDCs and for diagnosing FDC sarcoma and benign and malignant vascular tumors.

Follicular Dendritic Cell Sarcoma

“…24 c-Synuclein is a relatively recent marker shown to strongly stain follicular dendritic cell meshwork and may also be considered helpful in identifying FDCS. 25 Additionally, the tumor is usually positive for vimentin, fascin, desmoplakin, EGFR, and human leukocyte antigen-DR. It is variably positive for epithelial membrane antigen, S100, and CD68, which can present diagnostic pitfalls.…”

Frequent expression of follicular dendritic cell markers in Hodgkin lymphoma and anaplastic large cell lymphoma

“…Because γ-synuclein is a newly introduced FDC marker, there are no data regarding γ-synuclein expression in lymphoid cells 16. We observed γ-synuclein in a limited number of HRSs, and far fewer ALCL cells with low intensity in both types.…”

“…Unlike classic FDC markers, such as CD21, CD23 and CD35, which react to only FDCs and a minor subset of B-lymphocyte, these new markers are reactive to FDCs, stromal cells, such as endothelial cells and fibroblasts, and some other benign and neoplastic lymphocytes. However, the original reactivity or protein function of these markers was not targeted to FDCs; (1) GLI-3 is a transcriptional factor of the hedgehog signalling pathway;15 (2) fascin is a globular actin-bundling protein;7 (3) TUBB3 is considered a neurone-specific cytoskeletal marker;18 (4) γ-synuclein is found in the nervous system and retina;16 and (5) clusterin is associated with the regulation of the stress response and apoptosis 19 20. The incidental findings of positivity on FDCs, HRSs and ALCL cells are quite interesting and practically useful.…”

Primary follicular dendritic cell sarcoma of the urinary bladder: the first case report and potential diagnostic pitfalls

“…Although approximately 60% of FDCS cases arise in lymph nodes, they can also occur in extranodal sites, such as the liver, lung, tonsil, spleen, soft tissue, digestive tract, retroperitoneum, nasopharynx, oral cavity, or breast [3, 4, 7–13]. However, the urinary bladder is a very unusual site for FDCS and, to the best of our knowledge, no case of primary bladder FDCS has previously been reported.…”