A 35-year-old African-American man presented with a several-month history of right buttock pain, especially on ambulation, and a tingling sensation on his right lateral leg. His medical history was significant for hypertension for the last 8 years, chronic kidney disease requiring dialysis 3 times/wk for the last 2 years, morbid obesity, and sleep apnea. Medications included amlodipine, 10 mg/d; cinacalcet, 30 mg/d; and a daily multivitamin (Nephplex Rx Oral; Nephro-Tech, Inc, Shawnee, KS). On physical examination, he had a large firm mass on the right buttock, mildly tender on palpation, with reduced range of motion of the right hip. The following laboratory data were notable: serum urea nitrogen, 24 mg/dL (8.6 mmol/L); serum creatinine, 8.0 mg/dL (707 μmol/L); calcium, 9.8 mg/dL (2.5 mmol/L); phosphate, 6.3 mg/dL (2.0 mmol/L); white blood cell count, 31.8 × 103/μL with 93.7% neutrophils; and parathyroid hormone, 1,488.5 pg/mL. The mass was surgically excised and submitted for gross and histological analysis. Sectioning of the soft-tissue mass showed white-tan collagen-like bundles with abundant chalky pus-like material and areas of calcification, as shown in Fig 1. Selected areas of the mass were submitted for histological examination, as shown in low and high power in Figure 2, Figure 3, respectively.
Figure 3. Hematoxylin and eosin staining; original magnification ×400.
■ What do these light micrographs show?
■ What is your clinicopathologic diagnosis?
Discussion
What do these light micrographs show?
Low power shows calcified cavities and regions of fibrous tissue with numerous inflammatory cells (Fig 2). The high-power image shows a papillary structure with multinucleated giant cells and foamy histiocytes surrounded by calcified granules (Fig 3).
What is your clinicopathologic diagnosis?
This patient has tumoral calcinosis, a rare disease classically defined as the deposition of dense nodular calcium-containing masses in the tissue surrounding the large joints of the body.1 Generally, this must exist in the setting of normal blood calcium levels. In the setting of increased calcium levels, this picture is attributed to the underlying disease. Risk factors for tumoral calcinosis include kidney disease, African descent, and increased blood phosphate levels. Two forms of tumoral calcinosis exist: familial and idiopathic. The familial type is inherited in an autosomal dominant manner and is caused by a mutation in one of several possible genes, including GALNT3 and FGF23. In the case of FGF23, the disease is caused by a gain-of-function mutation.2 Interestingly, a loss-of-function mutation in the same gene is the cause of autosomal dominant hypophosphatemic rickets. The pathogenesis of the familial type includes bleeding followed by the collection of foamy histiocytes that form a cavity.3 Large cytoplasmic vesicles form within osteoclast-like giant cells, and the cavities fill with calcified material and become encapsulated by fibrous tissue.4 The idiopathic type is believed to be caused by an error in phosphate metabolism, leading to calcium deposition despite normal calcium levels. The pathogenesis of idiopathic tumoral calcinosis is not fully characterized; however, the general occurrence of hyperphosphatemia in patients with end-stage renal disease (ESRD) is better understood. During the early stages of chronic kidney disease, reabsorption of phosphate by the sodium phosphate cotransporter in the proximal tubule becomes poorly regulated. However, serum phosphate is maintained at relatively normal levels because of an important adaptive mechanism: the binding of calcium to phosphate to form a less soluble salt that is more easily excreted by nonrenal mechanisms, especially in the intestines. The calcium required for this process is made available by increased parathyroid hormone secretion, often leading to parathyroid hyperplasia. By the late stages of chronic kidney disease, this parathyroid hyperplasia has become irreversible, phosphate levels have increased, significant bone loss has usually occurred, and, in some cases, soft-tissue deposition of calcium has taken place.5 Multiple cases of the idiopathic type of tumoral calcinosis in the context of ESRD have been described, with multiple causes for the ESRD, including hypertension, uncontrolled diabetes, and immunoglobulin A deposition.
Final Diagnosis
Tumoral calcinosis, with cystic cavities within a fibromuscular stroma that are filled with granular calcific material. Cyst walls consist of foamy histiocytes and multinucleated giant cells.
References
1. 1Smit GG, Schmaman A. Tumoral calcinosis. J Bone Joint Surg. 1967;49B:698–703.
2. 2Benet-Pages A, Orlik P, Strom TM, Lorenz-Depiereux B. An FGF23 missense mutation causes familial tumoral calcinosis with hyperphosphatemia. Hum Mol Genet. 2005;14:385–390. MEDLINE |
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3. 3Slavin RE, Wen J, Kumar D, Evans EB. Familial tumoral calcinosis (A clinical, histopathologic, and ultrastructural study with an analysis of its calcifying process and pathogenesis). Am J Surg Pathol. 1993;17:788–802. MEDLINE |
CrossRef
4. 4Pakasa NM, Kalengayi RM. Tumoral calcinosis: A clinicopathological study of 111 cases with emphasis on the earliest stages. Histopathology. 1997;31:18–24. MEDLINE
5. 5McCarron DA. Protecting calcium and phosphate balance in chronic renal disease. J Am Soc Nephrol. 2004;15:770–779. MEDLINE |
CrossRef
Case provided and authorized bySanjiv Prabhu, MD, Yiqing Chi, MD, Suman Setty, MD, PhD, and Gregorio Chejfec, MD, Department of Pathology, University of Illinois at Chicago, IL.
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