Perineuriomas are rare benign soft tissue
tumors having an immunophenotype paralleling the normal perineurial cell [
S-100 protein negative and
epithelial membrane antigen (EMA) positive]. Because EMA expression in
perineuriomas may be focal and/or faint, there is continued interest in the development of new markers of perineurial differentiation. Perineurial cells differ from almost all other mesenchymal cell types by virtue of their formation of tight junctions. In the course of evaluating a group of novel tight junction-associated
proteins, we noted high levels of expression of
claudin-1 by normal perineurial cells and have systematically extended these observations to
perineuriomas. Twelve EMA-positive/S-100-negative
perineuriomas were retrieved from our consultation archives and compared with 39
tumors in the differential diagnosis of
perineurioma (seven
dermatofibrosarcoma protuberans, eight low-grade fibromyxoid
sarcomas, three
desmoplastic fibroblastomas, seven
fibromatoses, nine
neurofibromas, and five
schwannomas). All cases were immunostained for
claudin-1 using standard
avidin-
biotin technique. Cases were scored as 3+ (>50% positive cells), 2+ (25-50% positive cells), and 1+ (5-24% positive cells). In all cases positive internal controls in the form of epithelium, normal perineurium, or endothelial cells were present. Positive staining for
claudin-1 was visualized in a distinctly particulate pattern along the cell membrane. Cytoplasmic staining was infrequent and was not scored as positive.
Claudin-1 expression was present in 11 of 12 (92%)
perineuriomas studied (seven at 3+, three at 2+, and one at 1+). In all but two cases, the degree of
claudin expression was equal to or greater than the corresponding EMA immunostain.
Claudin-1 expression was not noted in any cases of
dermatofibrosarcoma protuberans, low-grade fibromyxoid
sarcoma,
desmoplastic fibroblastoma, or
fibromatosis. Six of nine cases of
neurofibroma contained a significant number of claudin-1-positive cells that were thought to be perineurial in origin, based on the staining of long, delicate cytoplasmic processes. One of four
schwannomas contained a subpopulation of perivascular, dendritic, claudin-1-positive cells of presumed perineurial lineage. This is the first study to document expression of
claudin-1 in perineurial cells and suggests a role for
claudin-1 immunohistochemistry in the diagnosis of
perineuriomas. Although
claudin-1 should not replace EMA in the diagnosis of
perineurioma, we think that it may play a valuable adjunctive role in difficult cases. In particular,
claudin-1 is often a more robust marker than EMA in a given
perineurioma.
Claudin-1 is not expressed within the lesional cells of the mesenchymal
tumors that enter into the differential diagnosis of
perineurioma.