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Calcaneal brown tumor with primary hyperparathyroidism caused by parathyroid carcinoma: An atypical localization
Calcaneal Brown Tumor With Primary Hyperparathyroidism Caused by Parathyroid Carcinoma: An Atypical Localization Ali Dog˘an, MD,1 Ekrem Algu¨n, MD,2 Erol Kisli, MD,3 Mustafa Harman, MD,4 Mustafa Ko¨sem, MD,5 and Nihat Tosun, MD6 Brown tumors are one of the characteristics of primary hyperparathyroidism, although, in some cases, they are noted with secondary hyperparathyroidism as well. The authors present a case of a 50-year-old woman with primary hyperparathyroidism caused by parathyroid carcinoma with an unusual location of a brown tumor in the calcaneus. She first presented with pain and swelling over the heel and ankle, and the diagnosis was suspected by radiographs. Biopsy of the calcaneal lesion confirmed a brown tumor. After the parathyroid lesion was removed surgically, her symptoms were relived. The calcaneal lesion was treated with immobilization of the foot. ( The Journal of Foot & Ankle Surgery 43(4):248-251, 2004) Key words: brown tumor, calcaneus, primary hyperparathyroidism
B rown tumors in primary hyperparathyroidism (PHPT)
Case Report
are caused by localized, rapid osteoclastic turnover of bone, secondary to a direct effect of parathormone. As a result, hemorrhage, reparative granulation tissue, and active, vascular, proliferating fibrous tissue replace the normal marrow contents. It represents localized accumulations of fibrous tissue and giant cells, which can replace bone and may even produce osseous expansion (1, 2). Brown tumors appear as single or multiple well-defined lesions of the axial or appendicular skeleton, frequently eccentric or cortical in location. Common sites of involvement are the facial bones, pelvis, ribs, femur, and other long bones. Other manifestations of PHPT are generally apparent, although occasionally a brown tumor is the presenting finding in the disease (3). We report case of a brown tumor involving the calcaneus in a patient with PHPT caused by parathyroid carcinoma.
A 50-year-old woman was admitted to the orthopaedic clinic with a 2-year history of pain over the right ankle and heel. There were no prior signs or symptoms of hyperparathyroidism. She was otherwise healthy and there was no history of trauma. Physical examination showed diffused swelling on both sides of the ankle. There were no changes of the overlying skin. Range of motion of the ankle was minimally limited. Radiographs of right foot showed a septated, radiolucent lesion that involved most of the posterior portion of the calcaneus (Fig 1). Magnetic resonance images (MRI) showed hyperintense signal intensity caused by solid and cystic changes on T2-weighted images and hypointense signal intensity caused cystic changes in the calcaneus on T1-weighted images (Fig 2). A whole-body bone scan was performed and multiple hot spots were observed in the calcaneus. Results of a fineneedle aspiration biopsy were unsatisfactory, so an incisional biopsy was procured by curetting through the lateral cortex of the calcaneus. The pathologic examination showed bone tissue with multinucleated giant cells, a cluster of hemosiderin-laden macrophages, and a combination of osteoblastic and osteoclastic activity compatible with brown tumor of PHPT (Fig 3). The patient was referred to the endocrinology clinic for further evaluation. The results of an initial blood chemistry evaluation were serum calcium level, 11.6 mg/dL (normal range [NR], 8.4 to 10.3 mg/dL); inorganic phosphorus level, 2.2 11.6 mg/dL (NR, 2.7 to 4.5 mg/dL); parathormone level, 347 pg/mL (NR, 12 to 72
From the School of Medicine, Yuzuncu Yıl University, Van, Turkey. ¨ niversitesi, Tıp Address correspondence to: Ali Dog˘an, MD, Yu¨zu¨ncu¨ Yıl U Faku¨ltesi Ortopedi ve Travmatoloji AD, 65200 Van, Turkey. E-mail: [email protected] 1 Assistant Professor, Department of Orthopedics and Traumatology. 2 Associated Professor, Department of Endocrinology. 3 Assistant Professor, Department of General Surgery. 4 Assistant Professor, Department of Radiology. 5 Assistant Professor, Department of Pathology. 6 Associated Professor, Department of Orthopedics and Traumatology. Copyright © 2004 by the American College of Foot and Ankle Surgeons 1067-2516/04/4304-0008$30.00/0 doi:10.1053/j.jfas.2004.05.001
248
THE JOURNAL OF FOOT & ANKLE SURGERY
FIGURE 1 Lateral foot radiograph showing expansion and increased radiolucency of the calcaneus. Arrows indicate the extent of involvement.
pg/mL); urinary calcium/creatinine ratio, 0.22; and alkaline phosphatase level, 873 U/L (NR, 0 to 270 U/L). Ultrasonographic examination showed a 30-mm diameter mass in the right lower parathyroid gland. A dual-phase technetium Tc99m sestamibi parathyroid scintigraphy was also compatible with a right lower parathyroid adenoma. A diagnosis of PHPT was established. She underwent a surgical exploration of the neck. The right lower parathyroid gland was removed along with a right total, left subtotal thyroidectomy. Histopathologic examination confirmed the lesion as a parathyroid carcinoma. Focal trabecular arrangement, dense fibrous bands, and capsular and areas of intrathyroidal invasion were seen in histopathologic examination of the parathyroid gland. Postoperatively, parathormone levels were within the normal range and she experienced a short course of hypocalcemia (ie, hungry bone syndrome). Oral calcitriol and calcium supplement treatment was administered. Eighteen months later, there was no recurrence of the parathyroid lesion. Serum calcium and parathormone levels remained within the normal range. Follow-up radiographs
FIGURE 2 (A) T1-weighted sagittal MRI showing expansion and a hypointense septated cystic lesion within the calcaneus. (B) T2-weighted sagittal MRI showing septated cystic hyperintense lesion and thinning of the calcaneal cortex.
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FIGURE 3 (A) Bone tissue with osteoblastic and osteoclastic activity and multinucleated giant cells (small arrows). (Hematoxylin and eosin stain, ⫻50.) (B) Bone tissue with cluster of hemosiderin-laden macrophages and multinucleated giant cells (arrows). (Hematoxylin and eosin stain, ⫻50.)
FIGURE 4 Lateral radiograph of the calcaneus 1 year after surgical removal of the parathyroid tumor. Note the new bone formation in the calcaneus.
(Fig 4) and MRI (Fig 5) of the calcaneus showed hyperdense areas caused by new bone formation at the calcaneus. She had no symptoms in the foot, and gait was normal. Discussion PHPT is characterized by increased parathormone secretion occurring as a result of a variety of causes, including diffuse hyperplasia, adenomas, and, rarely, carcinoma. It is a relatively common condition; it is the third most common endocrine disorder after diabetes and thyroid disease. The disease may involve many systems. Prominent changes are detected especially in the skeletal system (4). Initial bone changes may be so slight as to be imperceptible on radiographic examination. In this stage, bone-min250
THE JOURNAL OF FOOT & ANKLE SURGERY
FIGURE 5 Fat-saturation T2-weighted sagittal MRI shows recovery of the lesion in the calcaneus 18 months postoperatively.
eral measurement methods may have diagnostic values. Subsequently, more prominent skeletal changes such as increased bone resorption (subperiosteal, endosteal, subchondral, trabecular, or subligamentous), brown tumors, bone sclerosis, and chondrocalcinosis may be seen. Brown tumors are commonly associated with PHPT but, occasionally, are also reported in patients with secondary hyperparathyroidism (5, 6). They represent localized accumulations of fibrous tissue and giant cells, which can replace bone and may even produce osseous expansion. These tumors may subsequently undergo necrosis and liquefaction, producing cysts. Common sites of involvement are the facial bones, pelvis, ribs, and femur (3); it is rarely seen on
the axial skeleton (7, 8). Spinal-cord compression has been reported (9). Pathologic fracture may occasionally occur with PHPT (10). Our patient had an atypical location for a brown tumor. Other primary or metastatic tumoral involvement was suspected as the initial differential diagnosis. Histologically, brown tumors are hard to distinguish from giant cell tumors, reparative granuloma, aneurysmal bone cysts, and telangiectatic osteosarcoma. Nevertheless, expansile, well-defined lytic lesions, especially when numerous, in a patient with known HPT are more likely to be brown tumors than giant cell tumors (1). Parathyroid carcinoma is a rare malignant neoplasm that characteristically pursues an indolent course. En block resection of the tumor is often curative, but local recurrences are common. Metastases are uncommon and are a late manifestation of the disease. Bone metastases appear to be rare, having been reported in only 2.2% of cases. In contrast, radiographic bone disease, including the localized lytic lesions of hyperparathyroidism (brown tumor), is frequent, occurring in up to 76% of patients with parathyroid carcinoma (11). After resection of the parathyroid lesion, brown tumors heal with increased radiographic density. Persistence of the fibroosseous lesions after such surgery may indicate that they are not the brown tumors of hyperparathyroidism but may be related to some other cause (2). Essentially, brown tumors are benign, but surgical treatment is indicated when the lesion is located in a problematic site such as the calcaneus (12, 13). The risk of pathologic fracture should be assessed. Our patient did not undergo surgery for the calcaneal lesion because the symptoms improved after the excision of the parathyroid tumor. One year later, the calcaneal lesion disappeared and there were no other biochemical or roentgenographic manifestations of PHPT. In conclusion, an uncommon case of a brown tumor involving the calcaneus in a patient with PHPT has been
presented. Presence of a mass or swelling in any bone in a patient with high serum levels of calcium and parathormone should create suspicion of a brown tumor and PHPT. References 1. Blinder G, Hiller N, Gatt N, Matas M, Shilo S. Brown tumor in the cricoid cartilage: an unusual manifestation of primary hyperparathyroidism. Ann Otol Rhinol Laryngol 106:252–253, 1997. 2. Enneking WF. Clinical Musculoskeletal Pathology, ed 3, University of Florida Press, Gainesville, FL, 1990. 3. Resnick D, Niwayama G. Parathyroid disorders and renal osteodystrophy. In: Diagnosis of Bone and Joint Disorders. ed 3, pp 2012– 2075, edited by D Resnick, Saunders, Philadelphia, 1995. 4. Polat P, Kantarcı M, Alper F, Koruyucu M, Suma S, Onbas¸ O. The spectrum of radiographic findings in primary hyperparathyroidism. Clin Imaging 26:197–205, 2002. 5. Bereket A, Cesur Y, Firat P, Yordam N. Brown tumour as a complication of secondary hyperparathyroidism in severe long-lasting vitamin D deficiency rickets. Eur J Pediatr 159:70 –73, 2000. 6. Present D, Calderoni P, Bacchini P, Bertoni F. Brown tumor of the tibia as an early manifestation of renal osteodystrophy. A case report. Clin Orthop 231:303–306, 1988. 7. Heyman SN, Michaeli J, Brezis M, Gezlan L, Lernau O. Case report: primary hyperparathyroidism presenting as cervical myopathy. Am J Med Sci 291:112–114, 1986. 8. Barlow IW, Archer IA. Brown tumor of the cervical spine. Spine 187:936 –937, 1993. 9. Sarda AK, Arunabh VM, Kapur M. Paraplegia due to osteitis fibrosa secondary to primary hyperparathyroidism: report of a case. Surg Today 23:1003–1005, 1993. 10. Morgan G. Ganapathi M, Afzal S, Grant AJ. Pathological fractures in primary hyperparathyroidism: a case report highlighting diagnostic difficulties. Inj Int J Care Injured 33:288 –291, 2002. 11. Sulak LE, Brown RW, Butler DB. Parathyroid carcinoma with occult bone metastases diagnosed by fine needle aspiration cytology. Acta Cytol 33:645– 648, 1989. 12. Wilder R. Hyperparathyroidism: tumor of the parathyroid glands associated with osteotis fibrosa. Endocrinology 13:231–244, 1929. 13. Kulak CA, Bandeira C, Voss D, Sobieszczyk SM, Silverberg SJ, Bandeira F, Bilezikian JP. Marked improvement in bone mass after parathyroidectomy in osteitis fibrosa cystica. J Clin Endocrinol Metab 83:732–735, 1998.
VOLUME 43, NUMBER 4, JULY/AUGUST 2004
251
B rown tumors in primary hyperparathyroidism (PHPT)
Case Report
are caused by localized, rapid osteoclastic turnover of bone, secondary to a direct effect of parathormone. As a result, hemorrhage, reparative granulation tissue, and active, vascular, proliferating fibrous tissue replace the normal marrow contents. It represents localized accumulations of fibrous tissue and giant cells, which can replace bone and may even produce osseous expansion (1, 2). Brown tumors appear as single or multiple well-defined lesions of the axial or appendicular skeleton, frequently eccentric or cortical in location. Common sites of involvement are the facial bones, pelvis, ribs, femur, and other long bones. Other manifestations of PHPT are generally apparent, although occasionally a brown tumor is the presenting finding in the disease (3). We report case of a brown tumor involving the calcaneus in a patient with PHPT caused by parathyroid carcinoma.
A 50-year-old woman was admitted to the orthopaedic clinic with a 2-year history of pain over the right ankle and heel. There were no prior signs or symptoms of hyperparathyroidism. She was otherwise healthy and there was no history of trauma. Physical examination showed diffused swelling on both sides of the ankle. There were no changes of the overlying skin. Range of motion of the ankle was minimally limited. Radiographs of right foot showed a septated, radiolucent lesion that involved most of the posterior portion of the calcaneus (Fig 1). Magnetic resonance images (MRI) showed hyperintense signal intensity caused by solid and cystic changes on T2-weighted images and hypointense signal intensity caused cystic changes in the calcaneus on T1-weighted images (Fig 2). A whole-body bone scan was performed and multiple hot spots were observed in the calcaneus. Results of a fineneedle aspiration biopsy were unsatisfactory, so an incisional biopsy was procured by curetting through the lateral cortex of the calcaneus. The pathologic examination showed bone tissue with multinucleated giant cells, a cluster of hemosiderin-laden macrophages, and a combination of osteoblastic and osteoclastic activity compatible with brown tumor of PHPT (Fig 3). The patient was referred to the endocrinology clinic for further evaluation. The results of an initial blood chemistry evaluation were serum calcium level, 11.6 mg/dL (normal range [NR], 8.4 to 10.3 mg/dL); inorganic phosphorus level, 2.2 11.6 mg/dL (NR, 2.7 to 4.5 mg/dL); parathormone level, 347 pg/mL (NR, 12 to 72
From the School of Medicine, Yuzuncu Yıl University, Van, Turkey. ¨ niversitesi, Tıp Address correspondence to: Ali Dog˘an, MD, Yu¨zu¨ncu¨ Yıl U Faku¨ltesi Ortopedi ve Travmatoloji AD, 65200 Van, Turkey. E-mail: [email protected] 1 Assistant Professor, Department of Orthopedics and Traumatology. 2 Associated Professor, Department of Endocrinology. 3 Assistant Professor, Department of General Surgery. 4 Assistant Professor, Department of Radiology. 5 Assistant Professor, Department of Pathology. 6 Associated Professor, Department of Orthopedics and Traumatology. Copyright © 2004 by the American College of Foot and Ankle Surgeons 1067-2516/04/4304-0008$30.00/0 doi:10.1053/j.jfas.2004.05.001
248
THE JOURNAL OF FOOT & ANKLE SURGERY
FIGURE 1 Lateral foot radiograph showing expansion and increased radiolucency of the calcaneus. Arrows indicate the extent of involvement.
pg/mL); urinary calcium/creatinine ratio, 0.22; and alkaline phosphatase level, 873 U/L (NR, 0 to 270 U/L). Ultrasonographic examination showed a 30-mm diameter mass in the right lower parathyroid gland. A dual-phase technetium Tc99m sestamibi parathyroid scintigraphy was also compatible with a right lower parathyroid adenoma. A diagnosis of PHPT was established. She underwent a surgical exploration of the neck. The right lower parathyroid gland was removed along with a right total, left subtotal thyroidectomy. Histopathologic examination confirmed the lesion as a parathyroid carcinoma. Focal trabecular arrangement, dense fibrous bands, and capsular and areas of intrathyroidal invasion were seen in histopathologic examination of the parathyroid gland. Postoperatively, parathormone levels were within the normal range and she experienced a short course of hypocalcemia (ie, hungry bone syndrome). Oral calcitriol and calcium supplement treatment was administered. Eighteen months later, there was no recurrence of the parathyroid lesion. Serum calcium and parathormone levels remained within the normal range. Follow-up radiographs
FIGURE 2 (A) T1-weighted sagittal MRI showing expansion and a hypointense septated cystic lesion within the calcaneus. (B) T2-weighted sagittal MRI showing septated cystic hyperintense lesion and thinning of the calcaneal cortex.
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FIGURE 3 (A) Bone tissue with osteoblastic and osteoclastic activity and multinucleated giant cells (small arrows). (Hematoxylin and eosin stain, ⫻50.) (B) Bone tissue with cluster of hemosiderin-laden macrophages and multinucleated giant cells (arrows). (Hematoxylin and eosin stain, ⫻50.)
FIGURE 4 Lateral radiograph of the calcaneus 1 year after surgical removal of the parathyroid tumor. Note the new bone formation in the calcaneus.
(Fig 4) and MRI (Fig 5) of the calcaneus showed hyperdense areas caused by new bone formation at the calcaneus. She had no symptoms in the foot, and gait was normal. Discussion PHPT is characterized by increased parathormone secretion occurring as a result of a variety of causes, including diffuse hyperplasia, adenomas, and, rarely, carcinoma. It is a relatively common condition; it is the third most common endocrine disorder after diabetes and thyroid disease. The disease may involve many systems. Prominent changes are detected especially in the skeletal system (4). Initial bone changes may be so slight as to be imperceptible on radiographic examination. In this stage, bone-min250
THE JOURNAL OF FOOT & ANKLE SURGERY
FIGURE 5 Fat-saturation T2-weighted sagittal MRI shows recovery of the lesion in the calcaneus 18 months postoperatively.
eral measurement methods may have diagnostic values. Subsequently, more prominent skeletal changes such as increased bone resorption (subperiosteal, endosteal, subchondral, trabecular, or subligamentous), brown tumors, bone sclerosis, and chondrocalcinosis may be seen. Brown tumors are commonly associated with PHPT but, occasionally, are also reported in patients with secondary hyperparathyroidism (5, 6). They represent localized accumulations of fibrous tissue and giant cells, which can replace bone and may even produce osseous expansion. These tumors may subsequently undergo necrosis and liquefaction, producing cysts. Common sites of involvement are the facial bones, pelvis, ribs, and femur (3); it is rarely seen on
the axial skeleton (7, 8). Spinal-cord compression has been reported (9). Pathologic fracture may occasionally occur with PHPT (10). Our patient had an atypical location for a brown tumor. Other primary or metastatic tumoral involvement was suspected as the initial differential diagnosis. Histologically, brown tumors are hard to distinguish from giant cell tumors, reparative granuloma, aneurysmal bone cysts, and telangiectatic osteosarcoma. Nevertheless, expansile, well-defined lytic lesions, especially when numerous, in a patient with known HPT are more likely to be brown tumors than giant cell tumors (1). Parathyroid carcinoma is a rare malignant neoplasm that characteristically pursues an indolent course. En block resection of the tumor is often curative, but local recurrences are common. Metastases are uncommon and are a late manifestation of the disease. Bone metastases appear to be rare, having been reported in only 2.2% of cases. In contrast, radiographic bone disease, including the localized lytic lesions of hyperparathyroidism (brown tumor), is frequent, occurring in up to 76% of patients with parathyroid carcinoma (11). After resection of the parathyroid lesion, brown tumors heal with increased radiographic density. Persistence of the fibroosseous lesions after such surgery may indicate that they are not the brown tumors of hyperparathyroidism but may be related to some other cause (2). Essentially, brown tumors are benign, but surgical treatment is indicated when the lesion is located in a problematic site such as the calcaneus (12, 13). The risk of pathologic fracture should be assessed. Our patient did not undergo surgery for the calcaneal lesion because the symptoms improved after the excision of the parathyroid tumor. One year later, the calcaneal lesion disappeared and there were no other biochemical or roentgenographic manifestations of PHPT. In conclusion, an uncommon case of a brown tumor involving the calcaneus in a patient with PHPT has been
presented. Presence of a mass or swelling in any bone in a patient with high serum levels of calcium and parathormone should create suspicion of a brown tumor and PHPT. References 1. Blinder G, Hiller N, Gatt N, Matas M, Shilo S. Brown tumor in the cricoid cartilage: an unusual manifestation of primary hyperparathyroidism. Ann Otol Rhinol Laryngol 106:252–253, 1997. 2. Enneking WF. Clinical Musculoskeletal Pathology, ed 3, University of Florida Press, Gainesville, FL, 1990. 3. Resnick D, Niwayama G. Parathyroid disorders and renal osteodystrophy. In: Diagnosis of Bone and Joint Disorders. ed 3, pp 2012– 2075, edited by D Resnick, Saunders, Philadelphia, 1995. 4. Polat P, Kantarcı M, Alper F, Koruyucu M, Suma S, Onbas¸ O. The spectrum of radiographic findings in primary hyperparathyroidism. Clin Imaging 26:197–205, 2002. 5. Bereket A, Cesur Y, Firat P, Yordam N. Brown tumour as a complication of secondary hyperparathyroidism in severe long-lasting vitamin D deficiency rickets. Eur J Pediatr 159:70 –73, 2000. 6. Present D, Calderoni P, Bacchini P, Bertoni F. Brown tumor of the tibia as an early manifestation of renal osteodystrophy. A case report. Clin Orthop 231:303–306, 1988. 7. Heyman SN, Michaeli J, Brezis M, Gezlan L, Lernau O. Case report: primary hyperparathyroidism presenting as cervical myopathy. Am J Med Sci 291:112–114, 1986. 8. Barlow IW, Archer IA. Brown tumor of the cervical spine. Spine 187:936 –937, 1993. 9. Sarda AK, Arunabh VM, Kapur M. Paraplegia due to osteitis fibrosa secondary to primary hyperparathyroidism: report of a case. Surg Today 23:1003–1005, 1993. 10. Morgan G. Ganapathi M, Afzal S, Grant AJ. Pathological fractures in primary hyperparathyroidism: a case report highlighting diagnostic difficulties. Inj Int J Care Injured 33:288 –291, 2002. 11. Sulak LE, Brown RW, Butler DB. Parathyroid carcinoma with occult bone metastases diagnosed by fine needle aspiration cytology. Acta Cytol 33:645– 648, 1989. 12. Wilder R. Hyperparathyroidism: tumor of the parathyroid glands associated with osteotis fibrosa. Endocrinology 13:231–244, 1929. 13. Kulak CA, Bandeira C, Voss D, Sobieszczyk SM, Silverberg SJ, Bandeira F, Bilezikian JP. Marked improvement in bone mass after parathyroidectomy in osteitis fibrosa cystica. J Clin Endocrinol Metab 83:732–735, 1998.
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251