ARTICLE
Tumoral calcinosis (TC) presents as multiple calcified masses in soft
tissues. The condition has been reported in three clinical settings [1].
First, in about one third of the cases it develops within the first two
decades of life as a component of a heritable metabolic disease associated
with hyperphosphatemia and elevated serum 1,25-dihydroxyvitamin D levels
[2]. Second, it is observed in patients of varying ages without hyperphosphatemia
[3]. Third, it is seen in patients undergoing dialysis for renal failure
[4]. Tumoral calcinosis is commonly seen in South, Central, and East Africa
and New Guinea but is rare in Japan, Europe and North America [3]. In
this case report, we describe a Japanese female patient with TC without
underlying metabolic disorders.
Case report
A 68-year-old woman, a shamisen (a three-stringed Japanese musical instrument)
player, presented with large subcutaneous masses on her abdomen and extremities.
She substained a bruise to her abdomen in a traffic accident 21 years
ago. One year later, she noticed subcutaneous hard masses on her lower
abdomen and thighs. Thereafter the lesions gradually increased in size.
During the last six months, several nodules appeared on the extremities
and right hip.
On examination, she had large subcutaneous masses on her lower abdomen
and thighs (Fig.
1). There were several egg-sized nodules on the left upper arm,
left lower leg and right hip. She felt severe pain in both thighs when
sitting up straight, Japanese style, while playing the shamisen.
The results of routine laboratory examination including serum levels
of calcium and phosphate were normal. Thorough examinations ruled out
hyperparathyroidism and collagen diseases. X-ray examinations of her thighs
revealed the subcutaneous masses to be calcium deposits.
A biopsy was performed on a subcutaneous nodule on the right hip, and
a white milky fluid exuded from the incision. Histological examination
revealed amorphous basophilic materials in the entire dermis positively
stained with von Kossa's stain and determined to be calcified tissue that
was then partially stained with alcian-blue showing metachromasia in toluidine-blue.
Lymphohistiocytic cell infiltrate surrounding the calcified tissue was
observed. Multinucleated, osteoclast-like giant cells were also seen (Fig.
2). There were mild perivascular lymphohistiocytic infiltrates
in the dermis. The walls of the dermal vessels showed thickening (Fig.
3).
On electron microscopy, the calcified tissue was revealed to be an accumulation
of stick-like, electron-dense, crystalline materials, presumably the deposit
of hydroxyapatite crystals. Some of which were in the infiltrating histiocytes
(Fig. 4). The crystals
were embedded flocculent material made up of small, electron-dense, star-shaped
granules, which were probably of proteoglycan (Fig.
5). And in a vessel wall, a thick, layered basement membrane was
observed (Fig. 6).
The diagnosis of TC was made for which the patient received a partial
resection of the calcified tissue to relieve the pain and swelling so
that after the operation, she was able to sit up straight without difficulty
throughout the subsequent six years.
Discussion
The present case showed characteristic clinical and histopathological
features of TC without underlying metabolic disorders. Electron microscopic
study revealed that the calcified tissue was composed of an accumulation
of crystals that seemed to be formed by a deposit of hydroxyapatite.
The mechanism of TC remains unknown. In CREST syndrome, Brazzelli observed
electron microscopically star-shaped matrix granules in the dermis and
mentioned that they were like proteoglycan usually observed in cartilage,
elastic arteries and in the matrix of connective tissue but not in the
dermis. They suggested that the morphological alteration of the proteoglycan
occurred because of lowered pO2 caused by the thickening of the
capillary wall [5]. We observed electron-dense, star-shaped proteoglycan
in the dermis as well as in the vessel walls, the basement membranes of
which were thick and layered. These findings suggest that vascular injury
and subsequent hypoxia play a role in the mechanism of TC. Furthermore,
hydroxyapatite crystals deposited on proteoglycan aggravate vascular injury,
a process that may contribute to the development of new lesions [6]. Recently
Kajander and Ciftcioglu reported a role of infections in tissue calcifications
[7]. They found in in vitro studies intracellular calcifications
in nanobacteria-infected fibroblasts and nanobacteria coated in needle-like
apatite crystals. Though we could not find any morphological alterations
of fibroblasts on electron microscopy, their findings provide evidence
that nanobacteria can act as crystallization centers for the formation
of biogenic apatite structures and that nanobacteria may also be involved
in the mechanism of tissue calcification in TC.
Surgical excision has been the recommended treatment of tumoral calcinosis.
Though removal of larger masses is often incomplete and followed by recurrence,
resection of the masses can be helpful when calcium deposits are large
and symptomatic [8]. In this case, we performed a partial resection with
good results in alleviating the patient's pain.
Article accepted on 16-9-99.
REFERENCES
1. Knowles SAS, Declerck G, Anthony PP. Tumoral calcinosis. Br
J Surg 1983; 70: 105-7.
2. Baldurrson H, Evans EB, Dodge WF, et al. Tumoral calcinosis
with hyperphosphatemia. A report of a family with incidence in four siblings.
J Bone Joint Surg 1969; 51A: 913-25.
3. Mckee PH, Liomba NG, Hutt MSR. Tumoral calcinosis: a pathological
study of sixty-six cases. Br J Dermatol 1982; 107: 669-74.
4. Suzuki K, Takahashi S, Ito K, et al. Tumoral calcinosis
in a patient undergoing hemodialysis. Acta Orthop Scand 1979; 50:
27-31.
5. Brazzelli V, Dell'Orbo C, Borroni G, et al. The role
of the intercellular matrix in the dermal calcinosis of CREST syndrome.
Am J Dermatopathol 1992; 14: 42-9.
6. Slavin RE, Julie W, Dhruv K, et al. Familial tumoral
calcinosis: a clinical, histopathologic, and ultrastractural study with
an analysis of its calcifying process and pathogenesis. Am J Surg Pathol
1993; 17: 788-802.
7. Kalander EO, Ciftcioglu N. Nanobacteria: an alternative mechanism
for pathogenic intra- and extracellular calcification and stone formation.
Proc Natl Acad Sci USA 1998; 95: 8274-9.
8. Serdar T, Allan ES, Quan-Yang D, et al. Tumoral calcinosis:
controversies in etiology and alternatives in the treatment. Arch Surg
1993; 128: 737-45.
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