Tenosynovitis with psammomatous calcification is an extremely rare clinicopathological condition. Since it was first described by Gravanis and Gaffney in 1983(1), only a few additional cases have been examined in the English language literature (2-5). This variant of calcifying tenosynovitis or calcific tendonitis is characterized histopathologically by the presence of numerous psammomatous calcifications surrounded by a granulomatous reaction comprising a mixture of histiocytes and fibroblasts (2-5). Recently, Michal et al (6) investigated a large case series of this disease, and confirmed that the disease exhibited a tendency to affect the fingers or toes of young to middle-aged women, and appeared to be associated with trauma and/or repetitive activity. They concluded that tenosynovitis with psammomatous calcification is a distinctive trauma-associated subtype of idiopathic calcifying tenosynovitis.

However, the pathogenesis of tenosynovitis with psammomatous calcification remains unclear. Although an association of this disease with repetitive tendinous injury has been described previously (2,6), other studies have described cases without a history of trauma (3,4). Bone morphogenetic protein (BMP)-1, also known as procollagen C-peptidase, is a multifunctional protein regulating of hard tissue mineralization (7). BMP-1 expression has been suggested to be associated with ectopic ossification (8) and psammoma formation in papillary thyroid cancer (9). The present study described a case report of tenosynovitis with psammomatous calcification that occurred in the wrist of an elderly female, and the immunohistochemical analysis of the mechanism of psammomatous calcification formation, particularly association with BMP-1 expression.

A 66-year-old Japanese female presented with pain in the right wrist. She had a history of De Quervain's disease and infliximab use for ulcerative colitis, but no history of trauma to the wrist. Radiographic imaging demonstrated a calcified lesion in the palmar side of the right wrist, around the lunar and capitate bones. The lesion was surgically resected following a clinical diagnosis of ectopic bone formation.

Samples were fixed in 10% formalin at room temperature for 24 h and paraffin-embedded specimens (60˚C, 4 h) of the resected lesion were processed for routine histological examination and immunohistochemical analyses. Immunohistochemical analyses were performed using autostainers (XT System Benchmark; OptiView DAB Universal Kit, Roche Diagnostics) and Autostainer link 48 (Envision FLEX; cat. no. K8000; Dako; Agilent Technologies). The primary antibodies used were a mouse monoclonal antibody against α-smooth muscle actin (α-SMA; clone name, 1A4; 20 min at room temperature; Dako; Agilent Technologies), a rabbit polyclonal antibody against BMP-1 (cat. no. ab205394; 32 min at room temperature; Abcam) and a mouse monoclonal antibody against CD163 (clone name, 10D6; 32 min at room temperature; Leica Microsystems, Ltd). Light microscopic examination of 3-µm H&E-stained (hematoxylin, 3 min and eosin, 5 min at room temperature) sections (magnification, x12.5, x100 and x400) revealed a well-circumscribed lesion with a central cystic cavitation (Fig. 1A), and the notable feature of numerous psammomatous calcifications (Fig. 1B). These calcifications were surrounded by histiocytes, and a few multinucleated giant cells and fibroblastic spindle cells (Fig. 1C). Neither foamy cells nor siderophages were observed within the lesion.

Light microscopic analyses of immunohistochemistry (magnification, x400) revealed that these histiocytes were positive for CD163 (Fig. 1D). A small number of α-SMA-positive spindle cells were also detected, and the histiocytes and spindle cells surrounding the psammomatous calcification expressed BMP-1 (Fig. 1E). Based on these features, a final diagnosis of tenosynovitis with psammomatous calcification was made.

In the present report, a case of tenosynovitis with psammomatous calcification was described. In addition, to the best of our knowledge, this was the first time immunohistochemical analysis was used to identify the potential mechanism of psammoma formation. Table I summarizes the clinicopathological features of the case in the present study, and those of previously described cases. As demonstrated, this disease affects patients with a median age of 44 years (14-83 years), with a female predominance (male:female ratio, 4:30), particularly in young to middle-aged women. Of the patients examined previously and in the presents study, 12 of 25 had a history of trauma or repetitive activity. The majority of cases occurred in the hand, in particular in the finger, or the foot, and the most common complaint was a painful mass. A previous study involving the largest case series revealed these aforementioned clinicopathological features of tenosynovitis with psammomatous calcification (6), which is believed to be a distinct clinicopathological condition involving an unusual reactive or degenerative process in the chronically traumatized tendon and peritendinous tissue (2,6). However, the underlying molecular mechanism of development of this disease remains unclear.

BMP-1, also known as procollagen C-peptidase may convert a variety of precursor proteins, including procollagen and dentin matrix protein, into active forms, resulting in their involvement in cell adhesion and the regulation of hard tissue mineralization (7). Therefore, the present study focused on the association between psammomatous calcification of this lesion and BMP-1 expression. From the data in the present study, the expression of BMP-1 in histiocytes and spindle cells surrounding the psammomatous calcification was clearly observed. This suggests that the expression of BMP-1 may be associated with the development of psammomatous calcification.

In conclusion, the present study described a typical case of tenosynovitis with psammomatous calcification and reviewed its clinicopathological characteristics. The results suggested that the expression of BMP-1 in the histiocytes and spindle cells surrounding the psammomatous calcification may be associated with development of this condition.