Tumoral calcinosis is a rare ectopic calcification syndrome characterized by irregular soft tissue masses originally described as being found mainly in large joints. We report 3 cases of tumoral calcinosis that occurred in unusual locations, the metacarpophalageal and proximal interphalangeal joints of the hand. The patients were women who ranged in age from 26 to 44; all presented with complaints of painful swelling of the joints. Laboratory tests demonstrated normal serum phosphate and calcium levels. Radiologic examination disclosed para-articular calcified masses. On surgical excision, the deep-seated calcified masses were attached to collateral ligaments of the joints. Milky and chalklike fluid was released during surgery. The masses measured 1.5, 0.9, and 0.8 cm in length and had irregular surfaces. Microscopically, the masses had fibrous capsule and the inner small cystic spaces that contained granular, calcified material. These cysts contained proliferating capillaries, mononuclear lymph plasma cells, and giant cells. No recurrences were found in any of the patients during the follow-up periods.
Tumoral calcinosis is an uncommon disorder characterized by the presence of calcified, para-articular masses. Tumoral calcinosis was originally termed endotheliome calcifie in 1899 by Duret,1 and later as lipocalcinogranulomatosis in 1935 by Teutschlaender.2 The term tumoral calcinosis was proposed by Inclan et al3 in 1945 and was accepted worldwide. Unlike similar calcifications associated with chronic renal failure, malignancy, hypervitaminosis D, and milk-alkali syndrome, tumoral calcinosis shows no demonstrable abnormalities in calcium metabolism.
Tumoral calcinosis has been found in patients in Africa but rarely reported in other countries.4 More than 250 cases have been reported.5 Tumoral calcinosis usually presents as a painless solitary swelling or multiple painless swellings of large joints, particularly the extensor aspects of the hips, elbows, shoulders, and knees.4 Little is known about tumoral calcinosis in small joints, and only rare cases have been reported as occurring in the hand.6,7 We report 3 cases of tumoral calcinosis occurring in the small joints of the hand. All 3 cases had associated painful swelling, making the location and the symptoms unusual.
REPORT OF CASES
A 26-year-old woman visited the Department of Orthopedic Surgery, Inje University Ilsan Paik Hospital, complaining of pain in the left palm that had persisted for 4 months and did not subside with analgesic treatment. There was no history of trauma or disease. Serum phosphate and calcium levels were within normal range. On radiologic examination, extraosseous calcification was seen on the radial aspect of the head of the fourth metacarpal (Figure 1, A and B). Surgical exploration revealed a calcified mass attached to the fourth radial collateral ligament. Milky white fluid was released during the excision. The extracted mass measured 1.5 × 0.9 × 0.3 cm.
A 44-year-old woman developed pain at the dorsum of the right hand 4 weeks before presentation, which was aggravated 1 week before admission. She had no history of previous trauma. Serum levels of phosphate and calcium were within normal range. Radiologic examination disclosed a small calcified mass at the head of the third metacarpal. Surgical exploration revealed a mass at the radial collateral ligament of the third metacarpophalangeal joint. The extracted mass measured 0.9 × 0.6 × 0.3 cm.
A 29-year-old woman complained of painful swelling, which had persisted for 1 year, of the ring finger of her right hand. The symptom was not relieved with medical treatment. Laboratory examination, including serum phosphate and calcium levels, was normal. Radiologic evaluation revealed a calcified nodule at the fourth proximal interphalangeal joint. The mass was surgically removed; it measured 0.8 × 0.7 × 0.4 cm.
The masses from the three patients were similar in gross appearance. They consisted of whitish, friable fragments with irregular contours. Cross sections revealed a granular cut surface and released materials similar in texture to toothpaste or chalk.
Microscopic examination revealed both active granulomatous lesions and acellular, quiescent fibrotic tissues. In case 1, cystic cavities were present within collagenous stroma (Figure 2, A and B). The cavities occupied more than two thirds of the mass and were filled with granular, calcified materials and surrounded by granulomatous layers (Figure 2, C). Typical psammoma-like bodies were noted in cases 1 and 2. The cystic walls consisted of calcium globules, foamy histiocytes, multinucleated giant cells, and some lymphocytes and neutrophils. Unlike case 1, the formation of cystic cavities did not occur in cases 2 and 3. Instead, characteristic fibrohistiocytic nodules were easily found in hyalinized stroma (Figure 3). Mitotic figures are rare. No hemosiderin-containing macrophages were noted with iron staining. The Ki-67 proliferation index was 1 to 2 per 10 high-power fields. A summary of the microscopic findings is listed in the Table.
Tumoral calcinosis is a distinct clinicopathologic entity that is characterized by tumorlike periarticular deposits of calcium. It is usually found in the large joints of the hip, shoulder, and elbow. Since Duret1 first described this disease in 1899 in a 17-year-old girl and then in her younger brother, more than 250 cases have been reported.5 However, cases of idiopathic tumoral calcinosis affecting the hand are rare. Fewer than 10 cases have been reported in the literature.4,6,7
It has been suggested that tumoral calcinosis should be divided into 3 subtypes on a pathogenetic basis: (1) primary normophosphatemic tumoral calcinosis—in patients with normal serum phosphate and serum calcium levels and no evidence of disorders previously associated with soft tissue calcification; (2) primary hyperphosphatemic tumoral calcinosis—in patients with an elevated serum phosphate level, a normal serum calcium level, and no evidence of disorders previously associated with soft tissue calcification; and (3) secondary tumoral calcinosis—in patients with a concurrent disease capable of causing multiple soft tissue calcification and familial occurrence.8 The present cases have normal serum phosphate and serum calcium levels, solitary calcification, and no evidence of previous soft tissue calcification. These features indicate that our cases could be classified as primary normophosphatemic tumoral calcinosis.
Some cases of familial tumoral calcinosis have shown associated molecular abnormality. Recently, fibroblast growth factor-23 was markedly elevated in patients with the recessive form of familial tumoral calcinosis.9 However, primary normophosphatemic forms occur without a clearly identifiable or predisposing cause. A localized soft tissue alteration is suggested as a pathogenetic role because patients with primary normophosphatemic tumoral calcinosis usually have a single calcification and no abnormal findings of mineral homeostasis. An aberrant tissue response to local trauma may be a cause of this type of tumoral calcinosis.8 Pakasa and Kalengayi4 have suggested a hemorrhage-related histogenesis because of the strong association of tumoral calcinosis with stromal hemosiderin deposition. Trauma has been rarely reported by patients with tumoral calcinosis.10 Minor repeated trauma and tissue injury seem to play a role in the calcifying process; it probably serves as a trigger mechanism that leads to a chain of events, beginning with hemorrhage, fat necrosis, fibrosis, and collagenization, and ending with collagenolysis and ultimately massive calcification.5 It was proposed that the pressure of sleeping on the hard ground may explain the principal sites of calcification in African blacks.11
Slavin et al12 proposed dividing tumoral calcinosis into 3 stages based on the severity of calcification, granulomatous tissue, and fibrosis. Stage 1 (active lesions) is declared on the basis of cystic cavities with a multilayered granulomatous border having foreign body, multinucleated giant cells, and histiocytes. The cavities are filled with granular, calcified material and edema fluid. Stage 2 (intermediate lesions) contains a complex mixture of less prominent granulomatous tissue and acellular, quiescent fibrotic tissue. The calcium deposits tend to be more prominent. Stage 3 (inactive lesions) is characterized by hyaline, acellular fibrotic tissue that is filled with dense basophilic calcification. Ossesous metaplasia is occasionally found. According to this classification, all of our cases belong to stage 2 (intermediate lesions).
Tumoral calcinosis should be differentiated from secondary calcinosis, calcinosis universalsis, calcinosis circumscripta, soft tissue chondroma, pseudogout, and calcareous tendinitis based on its clinical or pathologic characteristics. Secondary tumoral calcinosis is characterized by familial occurrence, multiple calcifications (including kidney, lungs, heart, and stomach), no history of antecedent trauma, and the presence of underlying disorders such as chronic renal failure, secondary hyperparathyroidism, hypervitaminosis D, milk-alkali syndrome, and metastatic bone tumor. It is suggested that calcifications in patients with these maladies arise as a consequence of effects of the underlying disease process on mineral homeostasis. Secondary tumoral calcinosis can be differentiated from primary tumoral calcinosis with careful patient history and laboratory evaluation.
Calcinosis universalis and calcinosis circumscripta are defined by calcification in the skin and subcutis, and normal serum calcium and phosphorus levels. Calcinosis universalis develops multiple nodules or plaques and is associated with manifestations of scleroderma or dermatomyositis. Calcinosis circumscripta most commonly involves the hand and wrist of middle-aged women. It is associated in a large percentage of cases with Raynaud disease or scleroderma, sclerodactyly, or polymyositis. Clinical and laboratory evaluation for systemic or localized connective disease can discriminate these lesions from primary tumoral calcinosis. None of our cases showed any symptoms or signs related to connective tissue diseases.
Soft tissue chondromas occur commonly in the hands, especially in the fingers of middle-aged adults. Most are solitary and may adhere to tendons, tendon sheaths, or joint capsules. Heavily calcified chondromas may reveal granular areas with giant cell reaction resembling tumoral calcinosis. However, soft tissue chondroma can be easily delineated from tumoral calcinosis by well-defined lobules of aggregates of chondrocytes.
Tophaceous pseudogout (tumoral calcium pyrophosphate dihydrate deposition disease) is another entity causing massive calcified deposits in the periarticular tissue of the hand. Unlike tumoral calcinosis, tophaceous pseudogout mainly affects the elderly (average age, 60 years) and has a crystalline appearance when seen by polarizing microscope.
Calcareous tendinitis (calcific tendinitis) is a periarticular inflammatory disease with juxta-articular deposits of calcium hydroxyapatite. Rare cases of calcareous tendinitis have been described in the fingers.13 The pathologic findings of this entity include calcific material formed into psammoma-like bodies, together with exudates, including many neutrophils.14 These histologic findings are similar to those of tumoral calcinosis. However, characteristic findings of tumoral calcinosis (fibrohistiocytic nodules, hyaline stroma, and cavity formation) are less well known in calcareous tendinitis. Also, the inflammtory symptoms of calcareous tendinitis resolve spontaneously without treatment after a few days or a few weeks. Radiologic findings also disappear in 10 to 90 days.13 In contrast, symptoms of tumoral calcinosis persist with conservative treatment, as witnessed in our cases. Complete and meticulous surgical removal of the lesion and capsule offers a cure without local recurrence.6,7
In summary, this report describes 3 cases of tumoral calcinosis that developed in small joints of the hand. Generally, lesions have been found in large joints of the hip, shoulder, and elbow. Involvement of small joints of the hand seems to be rare.6,7 Our cases involved the hands and the sizes of the masses ranged from 0.8 to 1.5 cm in diameter. We conclude that tumoral calcinosis should be considered in the differential diagnosis of a painful mass that develops in the small joints of the hand.
This work was supported by a grant from Inje University, 2005.
The authors have no relevant financial interest in the products or companies described in this article.