We present here the case of a haemodialysis patient with tumoral calcinosis caused by low bone turnover. Tumoral calcinosis in one site was surgically resected and tumoral calcinosis in another site regressed spontaneously after treatment modification. The surgically resected specimen revealed recruitment of multi-nucleated giant cells positive for CD68 and calcitonin receptor, indicative of osteoclast-like features.
Previous histopathological studies of resected tissues of tumoral calcinosis have already reported the presence of multi-nucleated giant cells and inflammatory cells surrounding the calcified region [
5], and several groups have provided some explanation for the regression of ectopic calcification [
6–8]. Veress
et al. [
7] histopathologically evaluated 20 patients with tumoral calcinosis, and proposed the involvement of the multi-nucleated giant cells in the regression process. Using a rat model, Bas
et al. [
8] found infiltrating CD68-positive mononuclear cells in the walls of calcified artery and reported the reversibility of arterial medial calcification. Although these two reports indicated the association of CD68-positive cells with regression of ectopic calcifications, they did not fully describe all the features of the giant cells.
In our patient, the multi-nucleated giant cells and mononuclear cells around the calcified masses were positive for CD68, TRACP and calcitonin receptor. Thus, these multi-nucleated giant cells are phenotypically similar to osteoclasts since CD68 is a marker of macrophage differentiation and TRACP and calcitonin receptor are markers of osteoclasts. We also found these giant cells positive for RANK, which is essential for osteoclast maturation in the bone into activated osteoclasts that can interact with RANK-ligand [
9]. Thus, we hypothesized that the mononuclear cells of macrophage lineage are recruited to tumoral calcinosis and eventually become multi-nucleated giant cells with osteoclast-like phenotype by fusion, where they participate in resorption of the calcified material similar to the resorption of bone by osteoclasts.
Regarding the regression process in tumoral calcinosis, we speculate that such process depends on the relative balance between passive accumulation and active resorption of Ca–P products. It is likely that the osteoclast-like multi-nucleated giant cells are involved in removal of calcified material during the active resorption process. This hypothesis is proven by the clinical results that appropriate medical and surgical treatment can occasionally lead to spontaneous regression of tumoral calcinosis [
2–4]. In the present case, before changing treatment, passive accumulation was dominant over active resorption. After changing treatment, the bone turnover improved, and active resorption process became relatively dominant. Finally, regression of tumoral calcinosis around the ‘left knee’ was evident radiologically.
The present report has a few limitations. First, the specimen examined was from the ‘left femur head’ and not from the ‘left knee’ where spontaneous regression was noted. Second, whereas recruitment of giant cells was demonstrated, no evidence of activation and phagocytosis by giant cells was presented.
In summary, we described here the case of a haemodialysis patient with tumoral calcinosis whose surgically resected specimen revealed recruitment of multi-nucleated giant cells with osteoclast-like features. We conclude that these cells were involved in the active resorption process of tumoral calcinosis.
Conflict of interest statement. None declared.
