Tumour-like calcinosis causing reversible tetraparesis in a patient on continuous ambulatory peritoneal dialysis
Matthew Davies1,
Paul Griffiths2,
Philip White3 and
Kieron Donovan1,
1 Departments of Renal Medicine
2 Histopathology
3 Radiology, Morriston Hospital, Swansea, UK
Keywords: Ectopic calcinosis; tetraparesis
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Introduction
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Extra-osseous calcinosis in chronic renal failure can affect a wide spectrum of organs and leads to considerable morbidity. We describe a devastating and unusual consequence of this problem, whose prompt diagnosis and treatment led to an excellent recovery from a life-threatening condition.
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Case
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A 46-year-old woman with severe deforming sero-positive rheumatoid arthritis (RA) and end-stage renal failure (ESRF) treated by continuous ambulatory peritoneal dialysis (CAPD) presented with a sudden deterioration in mobility, after a slow deterioration over the previous 6 months. She was already bed-bound for much of the day 1 month before admission, when she noticed a nuchal lump associated with a dull ache in the back of her neck, which she attributed to a flare-up of her arthritis. The lump disappeared suddenly 4 days before admission, at the same time as her neck pain worsened, upper limb function deteriorated bilaterally, paraesthesiae developed in both hands and she became numb to the level of her buttocks. At the time of admission she had not opened her bowels for at least 2 days, but was passing normal volumes of urine. She gave no recent history of trauma. On examination, higher mental faculties were intact and there were no abnormalities of the cranial nerves. She had no voluntary movement below the neck, except for a flicker of movement in both hands. There was sensory impairment to the level of C5. Reflexes were symmetrical and brisk with clonus at the left ankle. Babinski's sign was present bilaterally. Other than the presence of a Tenckhoff catheter for dialysis and joint deformities consistent with RA, the remainder of the examination was normal. A clinical diagnosis of cervical cord compression was made, the most likely cause of which was thought to be atlanto-axial instability caused by RA.
The patient had developed ESRF secondary to chronic pyelonephritis and congenital urogenital malformations, and had been established on CAPD for 18 months at the time of admission. For 18 months prior to this she had biochemical evidence of hyperparathyroidism, with a peak parathyroid hormone (PTH) level of 1300 ng/l (reference range 550 ng/l). This failed to respond to medical therapy comprising alfacalcidol and calcium carbonate, and a parathyroidectomy was successfully performed 6 months prior to admission, after which her PTH level remained within the reference range. Histology of the excised glands was consistent with tertiary hyperparathyroidism. Throughout this period her calcium-phosphate product had remained high, and parathyroidectomy had no impact on this. Due to post-operative hypocalcaemia (trough level 1.63 mmol/l for a reference range of 2.202.60 mmol/l 1 month post-parathyroidectomy) she continued on alfacalcidol at a dose of up to 3 µg three times daily. Unfortunately this gradually led to hypercalcaemia (peak level 3.18 mmol/l) over the following 5 months, despite progressive reduction in dosage, until finally this medication was discontinued.
The tetraparesis was investigated urgently: magnetic resonance imaging showed posterior cord compression from C2/3 to C4/5 by an extradural mass (Figure 1
). Computed tomography (CT) images demonstrated calcification within the mass, facet joint destruction and calcification of adjacent soft tissues (Figure 2
). The atlanto-axial joint appeared normal. Surgical decompression was performed, with C3 laminectomy and T1-frame fixation of C2, 4 and 5. Necrotic purulent fluid was evacuated from the extradural space, the histology of which showed fragments of calcified debris surrounded by macrophages and giant cells. No organisms were seen and there was no subsequent growth on culture. Von Kossa staining confirmed the presence of calcium phosphate in the debris.

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Fig. 1. T2-weighted sagittal magnetic resonance image showing extradural mass with low signal intensity at C2/3 (arrows).
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Fig. 2. CT section at C3/4 showing calcification within the extradural mass (black arrow), erosion of left facet joint (white arrow) and soft tissue calcification around the joint.
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Following surgery and rehabilitation, sensation normalized and mobility improved to levels previously not attained for years.
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Discussion
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Soft tissue calcification is a well recognized finding in patients with ESRF and renal osteodystrophy, most commonly diffuse, involving the vascular tree, periarticular soft tissues and viscera [1]. The finding of a single extradural calcific mass is, in contrast, extremely unusual. We have found only one other case described in a search of the medical literature [2]. In common with our case this patient had ESRF, hyperparathyroidism requiring parathyroidectomy, a persistently high calcium-phosphate product, and presented with a posterior cervical swelling that progressed over a similarly short time-course. The histological features of the mass were also similar: an extradural calcified mass with a purulent consistency containing macrophages and multinucleate giant cells. In contrast the patient was on haemodialysis, had no history of RA, and underwent parathyroidectomy only after decompression of the cervical cord.
The mechanisms of extraosseous calcinosis are not well understood, but it is generally agreed that an elevated calcium-phosphate (Ca/P) product is a prerequisite [1]. In this case the Ca/P product was persistently raised. The optimum level, however, is not clear. The saturation point of (Ca2+xPO4) is
5.6, but under physiological conditions in vivo, calcification may occur at much lower levels than this. It has been estimated that a Ca/P product of <4.2 should be aimed for to minimize the risk of soft tissue calcification [3]. Current UK Renal Association guidelines recommend a serum calcium within the normal range of the laboratory in question, and a phosphate of 1.7 mmol/l or less [4], giving a maximum desirable Ca/P product for this patient of 4.4. This was persistently exceeded in our patient. The major cause for this was a persistently high phosphate level >2.0 mmol/l, almost certainly due to poor patient compliance with dietary advice and phosphate binders. However, in addition she was hypercalcaemic for a period following her parathyroidectomy due to the continued use of alfacalcidol, and this may have been important in the progression of her symptoms. In our patient the calcification itself was purulent rather than solid, as is described in tumour-like calcinosis. Explanation for this phenomenon, described in three haemodialysis patients with hyperphosphataemia [6], is attributed to the relatively high ratio of phosphate to calcium in the raised Ca/P product by the authors; however this remains speculative.
The role of PTH is less clear. Elevated levels of PTH have been suggested to sensitize the calcification process in some way [5], although the mechanism of this is not understood, and in our case parathyroidectomy had already been successfully performed. Extraosseous calcinosis occurring after parathyroidectomy has been described previously in two patients with ESRF and a raised Ca/P product [6]. Although elevated PTH may have a role in the process of tumoural calcinosis, it should be remembered that hypoparathyroidism also favours the development of soft tissue calcification. Other factors that may be contributory in some cases include local or systemic alkalosis, local trauma and aluminium toxicity [1], none of which are relevant in this case.
Histologically, the mass is morphologically similar to tumoural calcinosis [7], a condition characterized by painless calcified masses in periarticular soft tissues, especially on extensor surfaces, usually occurring at multiple sites in adolescents. However it is usually associated with normal serum calcium, dihydrocholecalciferol and PTH levels, although hyperphosphataemia is a consistent feature. The singular nature of this mass, its site, the age of the patient and the abnormalities of calcium metabolism that were present argue against this diagnosis.
The role of RA, if any, is not clear, although it did feature in the initial differential diagnosis as a cause for tetraparesis. Extraosseous calcinosis in RA is usually periarticular, but there was no evidence of calcinosis in this distribution at other sites in our patient, despite widespread joint involvement of RA. Similar radiographic appearances of intra- and para-spinal calcification have been described in cases of scleroderma [8] and calcium pyrophosphate disease [9]; however, there is no clinical, serological or histological evidence to support these diagnoses in this case.
In summary, we describe an unusual case of extradural tumour-like calcinosis leading to the rapid onset of tetraparesis. The aetiology appears to have been primarily uncontrolled hyperphosphataemia, with a brief period of hypercalcaemia in addition, leading to a persistently high calcium-phosphate product that was not influenced by parathyroidectomy. We emphasize the importance of good calcium and phosphate control.
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Acknowledgments
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We thank Dr Andar Gunneberg, Department of Chemical Pathology, Morriston Hospital, for advice concerning bone metabolism, and the Department of Neurosurgery, Morriston Hospital, for surgical management of the case.
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Notes
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Correspondence and offprint requests to: Dr Kieron Donovan, Department of Renal Medicine, Morriston Hospital, Swansea SA6 6NL, UK 
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References
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Received for publication: 14.12.99
Revision received 25. 9.00.