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Tumoral calcinosis presenting as adhesive capsulitiscase report and literature review.

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Tumoral calcinosis (TC) is an uncommon disorder characterized by large calcific soft tissue deposits,
usually adjacent to large joints. In the past, the etiology
was unclear, but recently, TC has been considered to be
an inherited metabolic disorder, characterized by elevated serum phosphorus and 1,25-dihydroxyvitamin D
levels, normocalcemia, and calcific deposits. However,
these features have been shown to vary widely, with
formes frustes of TC now being recognized. We report
an unusual case of TC, which presented as an adhesive
capsulitis, in an elderly North American black woman.
The patient’s nationality, late age of presentation, aad
multiple sites of involvement are uncommon features of
TC. The clinicopathologic features and possible etiologies of this rare condition are briefly reviewed.
Case report. The patient, a 76-year-old North
American black woman, presented with a 3-month
history of left shoulder and arm pain of insidious
onset. No previous shoulder or neck trauma was
reported. The pain involved the entire shoulder and
upper arm circumference, was constant, and caused
increased restriction of all shoulder movement to the
point that the patient required assistance in dressing
and bathing. Nonsteroidal antiinflammatory drug therapy, prescribed by a family physician who had diagFrom the Division of Rheumatology and Immunology,
Department of Medicine, Medical University of South Carolina,
Alan D. Croock, MBBCh, FCP(SA); Richard M. Silver,
Address reprint requests to Alan D. Croock, MD, Medical
University of South Carolina, Division of Rheumatology, 171
Ashley Avenue, Charleston, SC 29425.
Submitted for publication August 1 1 , 1986; accepted September 15, 1986.
Arthritis and Rheumatism, Vol. 30, No. 4 (April 1987)
nosed severe bursitis, was unsuccessful. There were
no symptoms of cervical spondylosis, brachial plexus
abnormalities, or cardiothoracic, pulmonary, endocrine, or autoimmune disease. Of note, there was no
history of excessive milk or vitamin D intake or of
recent or past renal disease. The patient also reported
vague pain in the left hip and thigh regions, of 2
months duration, unrelated to trauma. There had been
no previous symptoms suggestive of an inflammatory
polyarthropathy. Family history was noncontributory .
Physical examination revealed an obese, afebrile,edentulous female with a blood pressure of
160/80 mm Hg, normal pulses, and no evidence of
systemic disease. Of note, there was no lymphadenopathy, intrathoracic disease, abdominal visceromegaly ,
generalized myopathy, or neuropathy.
Examination of the left shoulder revealed features of an adhesive capsulitis, with minimal mobility
in all ranges of motion tested. Deep palpation around
the left shoulder and left thigh, circumferentially,
elicited tenderness. There were no abnormalities of
the other joints of the arms, nor was there evidence of
bicipital tendinitis or carpal tunnel syndrome. Mobility
of both hip joints was normal, and straight-leg raising
was not limited. The trochanteric bursae were not
tender. The provisional clinical diagnosis was adhesive capsulitis of the left shoulder and nonspecific left
thigh pain.
Laboratory investigations revealed a normal
hemoglobin level (13.7 g d d l ) , white blood cell count
(5,000/mm3), and platelet count (216,000/mm3). The
Westergren erythrocyte sedimentation rate was normal (35 mdhour). Calcium and inorganic phosphorus
levels were normal (9.4 mg/dl and 3.8 mg/dl, respectively), thereby excluding overt parathyroid disease
and milk-alkali syndrome. Serum alkaline phosphatase
was elevated (231 unitsfliter; normal 30-1 15). Alkaline
phosphatase isoenzyme studies revealed a moderately
elevated bone fraction. Levels of serum 5’-nucleotidase, uric acid, urea nitrogen, creatinine, albumin,
bilirubin, serum glutamic oxaloacetic transaminase,
serum glutamic pyruvic transaminase, T3, T4, and
thyroid-stimulating hormone were all normal. Rheumatoid factor and antinuclear antibody were absent.
The serum 25-hydroxyvitamin D level was 5 ng/ml
(normal 6-11 in young adult blacks), and the serum
1,25- dihydroxyvitamin D level was 49 pg/ml (normal
3040 in young adult blacks). The serum immunoreactive parathyroid hormone (PTH) level was 89 pg/ml
(normal <90, mid-molecule radioimmunoassay).
Radiographs of the shoulders and hips revealed
lobulated, circumferential, soft tissue calcification
around the left shoulder, proximal ends of both femoral shafts, and subtrochanteric regions (Figures lA, B,
and C). The shoulder and hip joints per se were
nomial. These soft tissue radiologic findings were
considered to be typical of tumoral calcinosis, particularly in the absence of renal or systemic disease. The
patient refused to undergo surgical exploration or any
biopsy procedure. Physical therapy, including local
heat and ultrasound, and oral nonsteroidal agents
produced minimal improvement of her symptoms.
Discussion. Tumoral calcinosis (TC) is a distinct
entity in which deposits of calcified material are
formed. They are typically large and lobulated in
appearance, and occur adjacent to large joints. Although previously considered to be a rare condition,
TC has been reported with increasing frequency in the
black populations of southern, central, and eastern
Africa. It is rare in Europe and North America (1).
The earliest report of a TC-type condition was
by Giard, who, in 1898,described 2 affected members
in 1 family (2). By 1965,only 23 additional cases had
been reported in the literature. In 1966, Palmer (2)
reported 50 new cases of TC; the majority of these
were seen at 1 hospital in the southern African nation
of Rhodesia, now Zimbabwe. Numerous case reports
have followed. In 1982, McKee et a1 reported on 56
Malawi subjects who presented with TC during a
10-year period (1970-1979) (1).
The term tumoral calcinosis was first used by
Inclan in 1943 (3). The disease has also been called
tumoral lipocalcinosis and lipocalcinogranulomatosis
(1). In New Guinea, it is known as “hip-stone’’ (4). In
addition to the cases reported in Malawi and southern
Africa (1,2), the condition has been seen in Sudan,
Kenya, Uganda, Nigeria, New Guinea, Europe, India,
and Iran (4-9). The majority of the patients are black,
but there are occasional occurrences in Arabs, Indians, and whites (1). It affects a wide age spectrum, but
particularly people under 30. In the review of 56
patients by McKee and coworkers, 41% were under 21
years old, and the fema1e:male ratio was 2:l (1).
Palmer found a similar age distribution (6-25 years),
but a male predominance (2). Veress et a1 found a
ma1e:female ratio of 2:1 among Sudanese patients (5).
The lesions may be observed incidentally on
radiography, but they do not cause clinical symptoms
until they reach a significant size; the disease generally
presents as an isolated large swelling in close proximity to a joint. There is usually minimal or no impairment of joint mobility, although our patient had a
typical frozen shoulder on presentation. The predominantly involved areas are the hip, elbow, and scapula.
The condition is often misdiagnosed as a tumor, calcified bursa, tuberculosis, cyst, metastatic calcification, or onchdcerciasis. There is a typical radiographic
appearance, which consists of dense, lobulated calcific
nodules, often massive, in the soft tissues adjacent to
one of the joints mentioned above. The joint itself and
the bones appear normal.
The lesions usually involve the soft tissues or
skeletal muscle, but occasionally may be much more
superficial, presenting as skin “tumors.” In 17 of the
56 cases reported by McKee et al, the reticular dermis
was predominantly involved (1). Macroscopically, the
lesions consist of multiple cysts surrounded by dense,
fibrous tissue. When sectioned, they are seen to contain either a white granular fluid, likened to procainepenicillin (6), or a more densely calcified material.
Histologically, the lesions can be divided into early
and late stages. The former consists of collagen
necrobiosis which results in cyst formation and a
foreign body granulomatous response. After further
collagen degradation, calcification occurs, first of a
granular type, then followed by dense deposits which,
rarely, may undergo metaplasia (1).
The etiology of TC is still unknown. Early
hypotheses included calcifying endothelioma, calcified
bursa, aberrant synovial tissue, and a clinical form of
“calciphylaxis” (5). Other theories have been presented in the more recent literature. One is that TC is
a form of dystrophic calcification related to mechanical trauma or injury. The main evidence in favor of this
thesis is the distribution of lesions characterized by
deposits related to pressure areas, with possible focal
ischemia resulting in collagen damage (1,5). A low-
Figure 1. Radiographs of the patient’s left shoulder (A) and both upper thighs (B and C), illustrating dense, lobulated, calcific soft tissue
deposits typical of tumoral calcinosis.
grade vasculitis has been documented in some cases
(5). Foreign body reaction is also considered to be a
possible etiology, since most patients have single-site
Another hypothesis relates TC to an abnormality of calcium and phosphorus metabolism, particularly in the setting of renal failure (10,ll). TC has been
reported in 2 patients who were receiving 1-ahydroxycholecalciferol therapy, and the authors of the
report suggested that vitamin D therapy in patients
with renal failure stimulates the progression of metastatic calcification to tumoral calcinosis (12). Results
of studies of calcium and phosphorus levels in patients
with TC have varied. Some authors have found elevated serum phosphorus levels, while others have
found normal values (1). In view of the former findings, a possible recessive inborn error of phosphorus
metabolism has been suggested. Some patients have
shown clinical and radiologic improvement on treatment with phosphorus deprivation and phosphorusbinding antacids (13). Such therapy was not considered for our patient, who had normal values of serum
calcium, phosphorus, and FTH.
Lyles et a1 (14), in a study of 14 of 27 subjects in
a kindred, concluded that TC is an autosomal dominant disorder with variable clinical expression. They
found a dental lesion in 3 members of the kindred. This
previously unreported lesion, consisting of short bulbous roots, pulp stones, and radicular dentin deposited
in swirls, is apparently specific to TC. Lyles et a1 also
noted that serum 1,254ihydroxyvitamin D levels were
elevated in all affected subjects, even those with no
other clinical markers of the disorder (14). No firstdegree relatives of our patient were available for
Under normal circumstances, PTH is a major
regulator of serum 1,254ihydroxyvitamin D. Serum
levels are elevated in primary hyperparathyroidism. In
addition, hypophosphatemia stimulates increased production of 1,254ihydroxyvitamin D. Lyles et a1 reported on 11 affected patients from 2 kindreds, who
were all found to have elevated 1,254ihydroxyvitamin D levels and normocalcemia (15). PTH levels were
found to vary inversely with the serum phosphorus (P)
concentrations, as well as with the renal TmP/GFR
ratios (TmP = tubular maximum for P; GFR =
glomerular filtration rate). The authors concluded that
the serum PTH may continuously regulate the serum
phosphorus concentration, and that depression of the
latter by PTH may protect affected subjects from
developing the calcific tumors characteristically asso-
ciated with TC. However, the finding of a normal
serum PTH value and normophosphatemia in our
patient, who had multiple tumor deposits, is not consistent with this theory. The serum 1,254ihydroxyvitamin D level was 49 pglml in our patient. This may
represent an elevated value in an elderly black subject. Low serum 1,25-hydroxyvitamin D levels are
characteristic of blacks and are attributed to impaired
dermal production of previtamin D3, because of skin
pigment (16).
It is of interest that the vast majority of cases
reported from Africa had singly localized deposits of
TC. This would negate the theory that a generalized
biochemical disorder is etiologically related. In McKee and colleagues’ series (l), only 2 patients had
multiple lesions; 1 of these patients had a recurrent
lesion. The duration was known in 14 cases; it ranged
from 6-24 months. The lesions were located in the area
of the hip (69% of all patients), elbow (9%), scapula
(9%), sacrum (6%), ankle (3%), and scalp (1%). Our
patient was atypical in that she had 3 sites of involvement: 1 shoulder and both hips. Her case was also
unusual with respect to the late age of presentation.
The majority of patients present with the disease in the
second or third decade of life. The significance of the
finding of a moderately elevated level of serum alkaline phosphatase of bone origin in our patient is
Surgery is the only recognized treatment for
TC. Recurrences may occur, however, since complete
excision is often difficult. In fact, a saw has frequently
been required by pathologists to cut through tissue
specimens (1) ! Spontaneous regression of a tumor
mass has not been known to occur. Hyperphosphatemic patients may be treated with phosphorus
deprivation and phosphorus-binding antacids (13).
In summary, we have reported an unusual case
of tumoral calcinosis in an elderly North American
black woman. The patient’s nationality, late age of
presentation, and multiple-site involvement are particularly noteworthy.
Acknowledgments. We express our gratitude to Dr.
Norman H. Bell and associates (Veterans Administration
Medical Center, Charleston and Departments of Medicine
and Rheumatology , Medical University of South Carolina)
for performing the vitamin D assays, Dr. Betty Roof (Division of Endocrinology, Medical University of South Carolina) for performing the parathyroid hormone assay, and Dr.
E. Carwile LeRoy (Division of Rheumatology and Immunology, Medical University of South Carolina) for reviewing the
manuscript. We also thank Judy Anderson for typing the
1. McKee PH, Liomba NG, Hutt MSR: Tumoral calcinosis: a pathological study of fifty-six cases. Br J Dermatol 107:669-674, 1982
2. Palmer PES: Tumoural calcinosis. Br J Radio1 39518525, 1966
3. Inclan A: Tumoral calcinosis. JAMA 121:490-495, 1943
4. Berg D: Tumoral calcinosis. Br J Surg 59570-571, 1972
5. Veress B, Malik MOA, El Hassan AM: Tumoral
lipocalcinosis: a clinicopathological study of 20 cases. J
Pathol 119:113-118, 1976
6. McClatchie S, Bremner AD: Tumoral calcinosis, an
unrecognized disease. Br Med J 1:153-155, 1969
7. Owor R: Tumoral calcinosis in Uganda. Trop Geogr
Med 24:39-43, 1972
8. Reddy CRRM, Rao BS: Tumoral calcinosis. J Indian
Med Assoc 43:336-337, 1964
9. Wilson AL, Chatter EH: Tumoral calcinosis: an obscure
disease. J Irish Med Assoc 69:6143, 1976
10. Barton DL, Reeves RJ: Tumoral calcinosis: report of 3
cases and review of the literature. AJR 86:351-358, 1961
11. Levin RT, Genovesse PD: Report of a case of longstand-
ing renal insufficiency with extensive metastatic calcification (renal osteitis fibrosa cystica). AJR 64:423429,
12. Walker GS, Davison AM, Peacock M, McLachlan MSF:
Tumoral calcinosis: a manifestation of extreme metastatic calcification occumng with l-a-hydroxycholecalciferol therapy. Postgrad Med J 53570-573, 1977
13. Mozzaferrian G, LaEerty FW, Pearson OH: Treatment
of tumoral calcinosis with phosphorus deprivation. Ann
Intern Med 77:741-745, 1972
14. Lyles KW, Burkes EJ, Ellis GJ, Lucas KJ, Dolan EA,
Drezner MK: Genetic transmission of tumoral calcinosis: autosornal dominant with variable clinical expressivity. J Clin Endocrinol Metab 60:1093-1096, 1985
15. Lyles KW, Halsey DL, Friedman NE, Drezner MK,
Lobaugh B: Modulation of serum phosphorus levels and
expression of calcific tumors (abstract). Seventh Annual
ScientificMeeting of the American Society for Bone and
Mineral Research, Washington, DC, June 15-18, 1985
16. Bell NH, Greene A, Epstein S, Oexmann MJ, Shaw S,
Shary J: Evidence for alteration of the vitamin Dendocrine system in blacks. J Clin Invest 76:470473,
In the article entitled "Sulfasalazine in Rheumatoid Arthritis: A Double-Blind, Placebo-Controlled Trial" by
Pinals et al in the December 1986 issue of Arthritis and Rheumatism, four words were inadvertently omitted
from the third line of the second column on page 1428. The line should read, ". . . involvement of previously
inactive joints in a number fewer than 10% of initially active joints."
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report, literatury, tumoral, adhesive, presenting, capsulitiscase, calcinosis, review
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