Kamran M. H. Karimi, Clinical Instructor, Department of Surgery; Alison M. Wilson, Assistant Professor, Chair, Department of Trauma and Surgical Critical Care; H. James Williams, Professor, Department of Anatomic Pathology, West Virginia University Hospital, Morgantown, WV
Kamran M. H. Karimi, MD
Department of Surgery
Alison M. Wilson, MD
Assistant Professor, Chair
Department of Trauma
and Surgical Critical Care
H. James Williams, MD
Department of Anatomic
West Virginia University
Introduction: Tumoral calcinosis is a rare but well-recognized clinical and pathologic entity that is characterized by tumor-like periarticular deposits of calcium, which are most often observed in the regions of the shoulders, elbows, and hips.
Results and discussion: This paper describes the case of a patient who presented to the hospital with a 2-year history of swelling and firmness in his right prepatellar region, which was identified after excision as tumoral calcinosis. It also examines the three distinct clinical entities of the disease and the appropriate treatment for each one.
Conclusion: Patients with tumoral calcinosis usually present with a solitary, painless, periarticular mass that may interfere with joint motion. To provide appropriate treatment, it is important to differentiate this condition from other, more common, calcium-deposition disorders of the joints. In the absence of a demonstrable metabolic derangement and in cases of severely symptomatic masses, surgical excision is the treatment of choice.
Tumoral calcinosis is a rare but well-recognized clinical and pathologic entity characterized by tumor-like periarticular deposits of calcium, which are most often observed in the regions of the shoulders, elbows, and hips. This calcification typically takes the form of calcium hydroxyapatite crystals surrounded by a foreign body giant cell reaction and histiocytes. When Inclan and associates coined the term "tumoral calcinosis" in 1945, it was thought that this disease exclusively afflicted familial clusters and people of African descent.1 Increasing experience with tumoral calcinosis has demonstrated a more diverse clinical picture. We report a case of tumoral calcinosis in a white man who presented with a longstanding history of swelling and firmness in his right prepatellar area. We also discuss the literature regarding this condition.
A 52-year-old white man presented with a 2-year history of swelling and firmness in his right prepatellar region. He had experienced no trauma to that area and had no similar lesions in any other part of his body. He also reported no recent pain, fevers, chills, travels, or exposure to sickness. His family, medical, surgical, and medication histories were noncontributory. His social history was remarkable for smoking a half pack of cigarettes daily.
On physical examination, the patient was afebrile and did not appear to be in any distress. Cardiovascular, respiratory, neurologic, and abdominal examinations were unremarkable, and there was no adenopathy. Examination of his right lower extremity revealed a firm, nontender, mobile prepatellar mass, which demonstrated superficial skin ulceration. Range of motion was limited at this joint. No additional masses or skin lesions were identified anywhere else on the patient's body.
Laboratory data included complete blood counts, chemistries with renal functions, and calcium and phosphate levels, all of which were normal. A three-view plain radiograph showed heterogeneous, amorphous calcification in the soft tissue anterior and inferior to the patella (Figure 1). There was no radiographic evidence of bony trauma, osseous erosion, joint involvement, or effusion.
The patient underwent excision of the mass with primary closure. The operative specimen measured 6.3 x 4.0 x 1.8 cm and did not directly involve the knee or the patellofemoral joint. The gross specimen consisted of an ellipse of tan-gray skin with a centrally located, 1.5-cm raised lesion and associated underlying soft tissue, which was fibrotic, with grossly evident calcifications in need of decalcification. Microscopic examination revealed multiple discrete areas of amorphous calcifications surrounded by histiocytes and multinucleated giant cells (Figure 2). Numerous calcific particles involving the overlying skin were noted (Figure 3). At 2-year follow-up, the patient was free of recurrences and exhibited no new growths anywhere on his body.
Tumoral calcinosis is a rare disease that has been recognized since 1899.2 Several terms in the literature are synonymous with this condition, including calcifying collagenolysis, calcifying bursitis, tumoral lipocalcinosis, Teutschlaender disease, kikuyu bursa, hip-stone disease, hydroxyapatite disease, and pseudotumoral calcinosis.1,3 Slightly more than 300 cases of this condition have been documented in the world literature.4
The majority of patients present with a solitary, painless, periarticular mass that can interfere with joint motion. Dystrophic periarticular soft tissue calcification with sparing of the joint is a universal finding. The lack of joint calcification helps differentiate tumoral calcinosis from calcium pyrophosphate dihydrate crystal deposition disease (pseudogout) and the intra-articular radiodense deposits of idiopathic synovial chondromatosis. The overlying skin is usually intact, but soft tissue ulceration may be seen.5
Tumoral calcinosis can manifest in three distinct clinical settings: (1) in patients with renal disease who are dependent on dialysis; (2) as a familial disorder in patients who have a phosphorus and vitamin D metabolism disorder; and (3) sporadic cases in which there is no demonstrable evidence of renal or vitamin D?related abnormalities.6 Of these three situations, renal failure and its attendant disorder of calcium and phosphorus homeostasis is the most common. Tumoral calcinosis affects men more often than women and African Americans more often than whites.7 The patient's age at presentation varies, with the condition reported in patients ranging in age from 5 months to 83 years.
Radiographs reveal the periarticular calcified masses. Laboratory findings include derangements of serum phosphorus levels and increased serum 1,25-dihydroxy— vitamin D concentration. In sporadic cases, serum chemistries are within normal range. Definitive diagnosis is made using light microscopic examination of tissue, which shows cysts containing deposits of calcium bordered by granulation or dense fibrous tissue.2 Slavin and colleagues proposed a stage classification of the disease: stage 1 disease consists of cellular lesions without calcification; stage 2 shows cellular cystic lesions with evolving calcifications; and stage 3 reveals inactive calcifying lesions without an accompanying cellular response.8
Franco and colleagues' study of 254 hemodialysis patients identified 3 cases of tumoral calcinosis, indicating an incidence of approximately 1% in the dialysis-dependent population.9 Secondary hyperparathyroidism has been touted as an essential pathogenic factor by some authors and found by others to be noncontributory.9,10 Hyperphosphatemia seems to be present more consistently in dialysis-dependent patients, and the actual calcium/phosphorus level product has been implicated as the inciting factor in crystal deposition.
Apostolou and colleagues reported successful treatment of ischial tumoral calcinosis in a dialysis-dependent patient with reduced calcium dialysate and administration of vitamin D.10 Hamada and colleagues noted this treatment method to be more effective for patients with solitary lesions and ineffective in those with multiple ones.11 Tumoral calcinosis that fails to respond to medical treatment or occurs without demonstrable metabolic derangement requires surgical excision. While surgical excision also may be necessary for severely symptomatic masses, phosphate binders that lower serum phosphorus levels have proven quite effective in treating this condition.12,13
Cases of familial metabolic calcinosis generally are observed in younger patients, who tend to have multiple areas of calcification. A positive family history is encountered in 30% to 40% of cases.14 The literature includes about 100 reports of familial tumoral calcinosis.3 In these reports, the disease results from disruptions in phosphate metabolism and is characterized by a high serum phosphate level and elevated 1,25-dihydroxyvitamin D. Normal renal function, elevated vitamin D levels, and an autosomal recessive inheritance pattern differentiate this variety of tumoral calcinosis from the type observed in dialysis patients. Recently, the genetic basis of familial tumoral calcinosis has been clarified. The kidneys' ability to excrete excess phosphorus from the body depends on the phosphaturic factor known as fibroblast growth factor 23 (FGF23).12 Secretion of intact FGF23 requires O-glycosylation by polypeptide N-acetylgalactosaminyltransferase 3 (GalNAc-T3) isoform.13 A mis-sense mutation in the GalNAc-T3 gene is thought to constitute the genetic basis of this disorder.
In cases of sporadic tumoral calcinosis, trauma may be an inciting factor. Some clinicians think that elevated stromal hemosiderin levels implicate hemorrhage-related histogenesis.2 There do not appear to be any associated metabolic abnormalities, and these patients tend to be older than those with familial tumoral calcinosis. Surgical excision is the mainstay of treatment in this group of patients.
Our case report highlights certain salient features of tumoral calcinosis. First, it recognizes the condition as a clinical diagnosis. Second, it differentiates it from other, more common, calcium-deposition disorders of the joints. Third, it highlights the importance of classifying patients into one of the three distinct clinical settings of this disease, because treatments may differ based on its biochemical pathogenesis, with medical treatment being sufficient in some cases and surgery required for others.
The authors have no relationship with any commercial entity that might represent a conflict of interest with the content of this article and attest that the data meet the requirements for informed consent and for the Institutional Review Boards.