Tumoral calcinosis

World J. Surg. 13, 803-808, 1989

World Journal of Surgery 9 1989 by the Socirt6 lnternationale de Chirurgie

Tumoral Calcinosis V . L . N . Prasad, M.S., M . N . A . M . S . , K.N. Naresh, M.D., S.R. Govind Krishna, M.B.B.S., N. Ananthakrishnan, M.S., M . N . A . M . S . , F.I.C.S., F . A . C . S . , F . A . C . G . , and A.J. Veliath, M.D. Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry, India

Tumoral calcinosis is an interesting clinical entity. It is not uncommon in certain countries. We report our experience with 22 patients with this condition seen over a 7-year period and review in detail the modalities of clinical presentation, theories of etiogenesis, histological appearances, and treatment modalities.

7 patients investigated. Skiagraphy merely showed a densely calcified soft tissue mass with no characteristic features (Fig. 2).

Pathology Gross. The lesions appeared as circumscribed, bony-hard

Tumoral calcinosis is an interesting entity characteristic in its anatomic location, behavior, radiological features, and histology. Recognized as early as 1899 [1] and later named as such by Inclan [2], little is known about the exact etiology, although several hypotheses have been suggested. We report the clinical and histological details of 22 patients with tumoral calcinosis studied at our institute over a 7-year period with special emphasis on theories of etiogenesis, clinical presentation, and histopathological appearances.

Clinical M a t e r i a l

Twenty-two patients were studied over a 7-year period. There were 5 men and 17 women. The age range extended from 27 to 75 years. Three of the 5 men and 12 of the 17 women were over 50 years of age. The mean age at presentation was 54.6 years for men and 52.6 years for women. The duration of the lesions ranged from 3 months to 20 years (Table 1). The anatomical sites of the lesions are shown in Table 2. Of the hip lesions, 7 were bilateral. The presenting symptom was swelling in all patients (Fig. 1). In 5 of them, it was associated with significant pain. Skin involvement indicated by fixity or ulceration was noted in 5 patients. Three patients had overlying skin ulcers and 1 patient had multiple sinuses discharging chalky material. The major bulk of the swelling was in the subcutaneous plane. In 3 patients, the lesions extended to the deep fascia. There was no history of trauma in any of these patients nor any familial preponderance. There were no biochemical abnormalities of calcium, phosphorus, or alkaline phosphatase in the

Reprint requests: Dr. N. Ananthakrishnan, Associate Professor, Department of Surgery, Jipmer, Pondicherry 605 006, India.

masses varying from 2.5 to 8 cm in diameter (average, 5.3 cm). The cut section, in the majority of cases, was yellow-white and had a honey-combed appearance with multiple cystic spaces containing chalky-white material. Few lesions were predominantly solid and densely calcified.

Microscopy. The lesions were circumscribed with a border of fibrocollagenous tissue and were located in the subcutis and deeper structures. Extension up to the dermis was seen in 5 cases with ulceration of the overlying skin in 3. Fibrocollagenous tissue surrounding the lesions showed extension of fibrous bands into the adjacent muscles. The majority of the lesions were comprised of multiple cystic areas of varying sizes demarcated by bands of fibrocollagenous septae. The cystic spaces contained loose fibrocollagenous tissue and necrotic debris within which were calcified masses having a deeply basophilic granular appearance (Fig. 3). A cellular reaction consisting of histiocytes, foreign body giant cells, and lymphocytes were seen at the interface of the septae and the calcified masses (Fig. 4). Some of the histiocytes and giant cells were found to contain phagocytosed calcified material (Fig. 4). The fibrocollagenous septae separating the cystic spaces showed focal congestion and edema. A few lesions were essentially solid in nature and comprised of densely calcified masses surrounded by thick, hyalinized and acellular fibrous septae with relatively scanty cellular reaction. In 6 instances, metaplastic bone formation was evident adjacent to calcified masses (Fig. 5). One of these showed both osseous and cartilagenous metaplasia. In 3 of them, the interface of the fibrous septae and the bony spicules showed microscopic foci of calcification, osteoclastic type of giant cells, and mononuclear cells resembling osteoblasts (Fig. 6). Van Geison stain was performed to demonstrate collagen and showed pink-stained collagen plaques within the partially calcified septae and a few scattered fibers in the necrotic debris.

804

World J. Surg. Vol. 13, No. 6, Nov./Dec. 1989

Table 1. Duration of lesions.

Table 2. Site of lesion.

Duration

No. of patients

Site of lesion

No. of patients

Less than 3 months 3-6 months 6 months-1 year 1-2 years 2-5 years 5-10 years More than 10 years

3 2 5 4 4 2 2

Hips Elbow Iliac crest Gluteal Leg

14 1 2 4 1

Fig. 1. Clinical photograph showing the characteristic mass near the hip joint,

Fig. 2. Radiograph showing densely calcified mass adjacent to the pelvis.

Discussion

the chest wall, the inferior angle of the scapula, the sacrum, the scalp, and, occasionally, the hands and feet [3, 5, 7]. Patients, by and large, have no biochemical abnormality and present clinically with symptoms ranging from a simple swelling to large masses with chronically discharging sinuses exuding a chalky material [4]. Pain is a rare accompaniment and is usually associated with ulceration and infection [4]. The lesions are confined radiologically to soft tissue spaces and appear as large, irregular, densely-calcified areas adjacent to joints which, themselves, are normal [9]. Calcification is dense and universal [101. Occasionally, fluid levels have been reported in the lesions [11]. The lesions are usually subcutaneous, although intramuscular extension may occur [3, 7]. In the present series, 3 lesions were found to extend deep to fascia.

Tumoral calcinosis has been referred to earlier by several names such as calcified bursa, calcified lipoma, metastatic calcification [3], and hip stone [4]. Believed to be more common in the dark races [5], tumoral calcinosis has also been reported in Arabs, Indians, and Caucasians [6-8]. The lesion is believed to be rare in Europe and North America, but quite common in South, Central, and East Africa and New Guinea [7]. It typically occurs in the periarticular regions, especially around the hip, the greater trochanter, and behind the elbow [3]. Sixty-nine percent of patients reported by M c K e e and associates had lesions around the hip and 9% had lesions related to the elbow [7]. Other sites are the shoulder (around humoral head and acromioclavicular joint),

V.L.N. Prasad et al.: Tumoral Calcinosis

805

Fig. 3. Cystic area of the lesion showing multiple small cysts with loose fibrocollagenous tissue and dark foci of granular calcification ( H & E x 166).

Fig. 4. The interface of the fibrous septae and areas of calcification showing a striking cellular response comprised of foreign body giant cells, histiocytes, and lymphocytes. Many of the histiocytes and giant cells contain phagocytosed calcified material (H & E x 166). Involvement of the reticular dermis is not uncommon [7], leading to skin ulceration and discharging sinuses [4, 7]. A peculiar feature of the lesion is its occurrence in siblings [5, 12, 13]. In fact, one-third of the disease is believed to be familial [5] and occurs predominantly in adolescents [12]. It has, however, never been reported in more than 1 generation of a family [5]. This occurrence in both men and women of the same generation alone is believed to suggest an autosomal recessive pattern of inheritance [5]. Multiple and recurrent lesions are also known [7]. The age of presentation as reported has varied from 6 to 70 years [7], but the lesions are more common in the third and fourth decades of life [3] and in women [3, 7]. Veress and associates have, however, pointed out a male preponderance [14]. In the series reported by McKee and colleagues, 41% of the patients were younger than 21 years of age and 10% were younger than 10 years old [7]. In our series, the disease was found to most frequently involve older patients with 68.4% of

lesions occurring in patients over 50 years of age. Duration varies from a few months to several years [3]. The growth rate is variable. There are reports wherein lesions have attained a size of 7 cm or more in as short a duration as 3-4 months as welt as lesions which have remained unchanged over several years [3].

Etiology The autosomal recessive mode of inheritance suggested earlier [5, 12, 13] has not found support. Several other interesting theories have been propounded. The lesion has, at various times, been considered to be a calcifying endothelioma [7], a calcified bursa [15], or a clinical form of calciphylaxis due to trauma [14, 16]. The view of Thomson and Tanner is that it is only an aberrant calcified synovial tissue, but this cannot be accepted in the absence of synovial membrane elements in the lesions of these patients [12]. Harkness and Peters believed it to be caused by proliferation of primitive mesenchyme cells of the

806

World J. Surg. Vol. 13, No. 6, Nov./Dec. 1989

Fig. 5. Metaplastic bone formation seen replacing the fibrous septae in one of the cases ( H & E x 166).

Fig. 6. The interface of the fibrous septae and bony spicules showing microscopic foci of calcification (arrow) and scattered mononuclear cells resembling osteoblasts (H & E x 166). paratenon secondary to some stimulus [17]. Thomson and Tanner have' also suggested that the lesion may arise due to collagenolysis followed by calcification [12]. According to this report, the foreign body giant cells are merely osteoclasts that have undergone metaplasia [12]. Trauma may act as a localizing factor. It must, however, be pointed out that most patients with this problem do not report an antecedent history of trauma [5]. Vascular disturbances in the form of a vasculitis of unknown etiology and exogenous pigment deposition were believed to be responsible [7]. Lafferty and associates have suggested that the association of an occasional elevation of serum phosphorus with a familial occurrence suggests an inborn error of metabolism of obscure etiology [13]. This theory, however, lacks convincing proof, as the evidence is conflicting. No consistent change in serum calcium and phosphorus levels have been found [7]. Baldursson and colleagues [5] and Slavin and coworkers [10] found an elevation of serum phosphorus in these patients. Others, how-

ever, found an essentially normal biochemistry [14, 17, 18]. Lesions indistinguishable from tumoral calcinosis sometime occur in patients with chronic renal failure [1%21]. Walker and associates feel that it may be due to vitamin D therapy in patients with chronic renal failure leading to metastatic calcification [22]. All patients who had a biochemical work-up in this series had normal parameters. The most popular and current theory gives a convincing explanation of its occurrence in the poorer socioeconomic group and over pressure points. It is believed that repeated pressure due to sleeping on hard ground with resultant trauma leads to fat necrosis followed by dystrophic calcification [3, 4]; however, no evidence of antecedent fat necrosis has been found histologically in or around any of these lesions [23] nor is it clear why some of these lesions continue to grow [4]. Histologically, our observations were similar to those of McKee and colleagues [7], the lesions comprised essentially of cystic and solid areas containing granular or densely-calcified

V.L.N. Prasad et al.: Tumoral Calcinosis

material surrounded by a cellular reaction consisting of lymphocytes, histiocytes, and foreign body giant cells. Other studies have shown a striking collagen necrobiosis [3, 7] and active vasculitis [7] in a few cases. We were able to demonstrate degenerated collagen fibers in the necrotic debris suggesting collagenolysis but vasculitis was not encountered. Metaplastic bone formation has occasionally been encountered [3, 7, 13, 17]. The lesion is, however, quite distinct from myositis ossificans [23]. Metaplastic cartilage has rarely been seen [13]. In 6 of our cases, metaplastic bone formation was seen with one showing both bone and cartilage. I n 3 of them, the interface of the fibrous septae and bony spicules showed osteoclast-like giant cells and mononuclear cells resembling osteoblasts. Our observations support the conclusions of McKee and associates [7]. The early lesions were characterized by collagen breakdown, cyst formation, and a granulomatous reaction. With further breakdown of collagen, calcification occurs, which is initially granular and later occurs as dense deposits. At this stage, some lesions may show metaplastic bone or cartilage. Chemical analysis of the deposited material has shown it to be calcium phosphate or a mixture of calcium phosphate and calcium carbonate [10]. A rapid exchange of calcium between serum and the tumoral masses and an increased intestinal absorption of calcium has also been documented [13]. Treatment is, essentially, surgical excision with clear margins [4]. Recurrences are known to occur with inadequate excision and are more difficult to excise in view of a lack of tissue planes. Radiotherapy [12, 13, 24], cortisone [13], and probenecid [25] have been tried without benefit. Although the lesions are usually indolent, one fatality has been reported due to secondary infection and amyloidosis [12]. R~sum~

L a calcinose tumorale est une entit6 clinique int6ressante; elle n'est pas rare dans certains pays. Nous rapportons ici notre exp6rience de 22 patients pour une p6riode de 7 ans. Nous analysons pr6sentation clinique, pathog6n~se, histologie, et traitement. Resumen

La calcinosis tumoral es una entidad clfnica interesante que no es rara en ciertos paises. En este articulo se reporta nuestra experiencia con 22 pacientes con calcinosis tumoral vistos a trav6s de un perfodo de 7 afios, con especial 6nfasis en los

Invited Commentary William G. Kraybill, M.D. Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, U.S.A. This article is a useful addition to the literature because it presents a large number of patients with extensive clinicopathologic correlation. While the authors state that there were no

807

modos de presentaci6n, las teorias sobre etiopatog6nesis, apariencia histol6gica, y las modalidades terapet~ticas. References

1. Duret, M.H.: Tumours multiples et singularies des bursa sereuses (endotheliomes, peut-etre d'orgine parasitaire). Bull. Soc. Anatomique (Paris) 74:725, 1899 2. Inclan, A.: Tumoral calcinosis, J.A.M.A. 121:490, 1943 3. McClatchie, S., Bremner, A.D.: Tumoral calcinosis--an unrecognised disease. Br. Med. J. 1:153, 1969 4. Berg, D.: Tumoral calcinosis. Br. J. Surg. 59:570, 1972 5. Baldursson, H., Evans, E.B., Dodge, W.F., Jackson, W.T.: Tumoral calcinosis with hyperphosphatemia A report of a family with incidence in 4 siblings. J. Bone Joint Surg. 51A:913, 1969 6. Wilson, A.L., Chatter, E.H.: Tumoral calcinosis--an obscure disease. J. Irish Med. Assoc. 59:61, 1976 7. McKee, P.H., Liomba, N.G., Hutt, M.S.R.: Tumoral calcinosis: A pathological study of fifty six cases. Br. J. Dermatol. 107:669, 1982 8. Moda, S.K., Marya, S.K.S., Maini, P.S.: Tumoral calcinosis: A case report. Indian J. Surg. 50:80, 1988 9. Palmer, P.E.S.: Tumoral calcinosis. Br. J. Radiol. 39:518, 1966 10. Slavin, G., Klenerman, L., Darby, A., Bansal, S.: Tumoral calcinosis in England. Br. Med. J. 1:147, 1973 11. Leistyna, J.A., Hassan, A.H.I.: Interstitial calcinosis. Am. J. Dis. Child. 107:96, 1964 12. Thomson, J.E.M., Tanner, F.H.: Tumoral calcinosis. J. Bone Joint Surg. 31A:132, 1949 13. Lafferty, F.W., Reynolds, E.S., Pearson, O.H.: Tumoral calcinosis: A metabolic disease of unknown etiology. Am. J. Med. 38z105, 1965 14. Veress, B., Malik, M.O.Z., Ell Hassan, A.M.: Tumoral lipocalcinosis: A clinicopathological study of 20 cases. J. Pathol. 119:113, 1976 15. Ghormely, R.K., McCrary~ W.E.: Multiple calcified bursae and calcified cysts in soft tissues. Trans. Western Surg. Assn. 51:292, 1942 16. Selye, H., Goldie, I., Strebel, R.: Calciphylaxis in relation to calcification in periarticular tissues. Clin. Orthop. 28:181, 1963 17. Harkness, J.W., Peters, H.J.: Tumoral calcinosis: A report of six cases. J. Bone Joint Surg. 49A:721, 1967 18. Frame, B., Herrera, L.F., Mitchell, D.C., Fine, G.: Massive osteolysis and tumoral calcinosis. Am. J. Med. 50:408, 1971 19. Barton, D.L., Reeves, R.J.: Tumoral calcinosis: Report of three cases and review of the literature. Am. J. Roentgenol. 86:351, 1961 20. Levin, R.T., Genovesse, P.D.: Report of a case of longstanding renal insufficiency with extensive metabolic calcification (renal osteitis fibrosa cystica). Am. J. Roentgenol. 641423, 1950 21. Vasudev, K.S., Tapp, E., Harris, M.: Tumoral calcinosis in Britain. Br. Med. J. 1:676, 1973 22. Walker, G.S., Davison, A.M., Peacock, M., McLachlan, M.S.F.: Tumoral calcinosis: A manifestation of extreme metastatic calcification occurring with I,-hydroxycholecalciferoltherapy. Postgrad. Med. J. 53:570, 1977 23. Smit, G.G., Schmaman, A.: Tumoral calcinosis. J. Bone Joint Surg. 49B:698, 1967 24. Reddy, C.R.R.M., Rao, B.S.: Tumoral calcinosis. J. Indian Med. Assn. 43:336, 1964 25. McPhaul, J.J., Engel, F.L.: Hetrotrophic calcification hyperphosphatemia and angioid streaks of the retina. Am. J. Med. 31:488, 1961

biochemical abnormalities in these patients, it would have been useful if they had reported the types of biochemical analysis done and the frequency with which the various studies were done. Tumoral calcinosis is a rare but established disorder usually manifested by large soft tissue calcifications adjacent to large joints; however, it has been reported in a number of other anatomic areas including the eyelid, the hand, the head and neck, and the feet. The etiology of this lesion has been controversial; however, there is a growing body of evidence suggesting that it is related in some way to calcium, phospho-