Because CD21 has been considered one of the most reliable FDC markers [11
], pathologists have routinely used CD21 immunohistochemical stain on paraffin-embedded tissue sections to highlight the atrophic, expanded, or disrupted FDC meshworks in benign and neoplastic conditions, such as CDs, PTCGs, FLs, NLPHLs, and AITLs. In our study, however, we found that CD21 immunostaining occasionally failed to stain FDCs. Therefore, when searching for FDC differentiation in a diagnostic work-up, it is prudent to use more than one FDC markers.
We confirmed that podoplanin, as detected by the D2-40 monoclonal antibody, is expressed in FDCs. In fact, D2-40 detected FDCs more often than CD21 in almost all the reactive conditions. The biological function of podoplanin is poorly understood. In vitro studies indicated that podoplanin is involved in mediating cell motility by promoting rearrangement of the actin cytoskeleton [13
]. Further studies are needed to determine whether podoplanin has a similar function in FDCs. Strong podoplanin expression has been detected in myoepithelial cells of the breast and salivary glands, as well as in myofibroblasts of the prostate [8
]. Therefore, positive staining of FDCs by D2-40 may help support the hypothesis that FDCs are derived from stromal myofibroblasts.
FDC sarcomas are rare neoplasms that were first reported by Monda and their associates in 1986 [14
]. They have been increasingly recognized to occur at a variety of anatomic sites. The morphology of our cases reported here was typical for FDC sarcoma. Two cases were located in lymph nodes, one in extranodal soft tissue, and one with multi-focal involvement in lymph node, liver and spleen. The hepatic and splenic involvement in case 2 could represent metastases from the lymph node. Because of the histologic overlap, either a panel of immunohistochemical stains and/or electron microscopy has been required to distinguish FDC sarcoma from other low-grade, spindle cell neoplasms. Most FDC sarcoma/tumor cases are positive for one or more FDC-associated antigens, such as CD21, CD23, or CD35 [11
]. However, many cases showed only focal and/or weak staining for these markers [17
CD21 has been considered the most reliable FDC marker for diagnosing FDC sarcoma [11
]. In our study, however, only 2 of the 4 FDC sarcomas expressed CD21, and in both cases, the staining was focal. Clusterin, a relatively new FDC marker, has shown excellent sensitivity for FDC sarcomas [19
]. One immunohistochemical study reported that 12/12 FDC sarcomas/tumors expressed clusterin [19
]. In our study, 3/4 FDC sarcomas expressed clusterin. D2-40 was also positive in 3/4 FDC sarcomas. In our limited experience in diagnosing FDC sarcomas, D2-40 appears to be more sensitive than CD21 or CD23, and at least as sensitive as clusterin. Since only one out of four FDC sarcomas was tested for CD35, we cannot compare the sensitivity of these antibodies.
Although D2-40 appears to be highly sensitive for the diagnosis of FDC sarcoma, it is well known that D2-40 also stains several other types of spindle cell sarcomas, such as angiosarcoma and Kaposi's sarcoma [21
]. However, the unique morphology of these tumors should readily separate them from FDC sarcoma/tumor.
To our knowledge, we are the first to demonstrate that D2-40 could be useful in confirming the diagnosis of FDC sarcoma. Further studies with more cases are needed to confirm our findings. In addition, we have also shown that D2-40 is superior or equal to CD21 for evaluating atrophic, expanded, or disrupted reactive FDC meshworks in a variety of lymphocytic disorders, such as FL, PTGC, CD, and NLPHL. In conclusion, D2-40 is a new marker that appears to be both sensitive and specific for reactive and neoplastic FDCs.