Calcaneal Brown Tumor With PrimaryHyperparathyroidism Causedby Parathyroid Carcinoma:An Atypical Localization

Ali Dogan, MD,1 Ekrem Algun, MD,2 Erol Kisli, MD,3 Mustafa Harman, MD,4

Mustafa Kosem, 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-oldwoman with primary hyperparathyroidism caused by parathyroid carcinoma with an unusual location ofa brown tumor in the calcaneus. She first presented with pain and swelling over the heel and ankle, andthe 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 wastreated with immobilization of the foot. (The Journal of Foot & Ankle Surgery 43(4):248-251, 2004)

Key words: brown tumor, calcaneus, primary hyperparathyroidism

Brown tumors in primary hyperparathyroidism (PHPT)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, vas-cular, proliferating fibrous tissue replace the normal marrowcontents. It represents localized accumulations of fibroustissue and giant cells, which can replace bone and may evenproduce osseous expansion (1, 2).

Brown tumors appear as single or multiple well-definedlesions of the axial or appendicular skeleton, frequentlyeccentric or cortical in location. Common sites of involve-ment are the facial bones, pelvis, ribs, femur, and other longbones. Other manifestations of PHPT are generally appar-ent, although occasionally a brown tumor is the presentingfinding in the disease (3). We report case of a brown tumorinvolving the calcaneus in a patient with PHPT caused byparathyroid carcinoma.

From the School of Medicine, Yuzuncu Yıl University, Van, Turkey.Address correspondence to: Ali Dogan, MD, Yuzuncu Yıl Universitesi, TıpFakultesi Ortopedi ve Travmatoloji AD, 65200 Van, Turkey. E-mail:alidogan67@hotmail.com

1Assistant Professor, Department of Orthopedics and Traumatology.2Associated Professor, Department of Endocrinology.3Assistant Professor, Department of General Surgery.4Assistant Professor, Department of Radiology.5Assistant Professor, Department of Pathology.6Associated Professor, Department of Orthopedics and Traumatology.Copyright © 2004 by the American College of Foot and Ankle Surgeons1067-2516/04/4304-0008$30.00/0

doi:10.1053/j.jfas.2004.05.001

248 THE JOURNAL OF FOOT & ANKLE SURGERY

Case Report

A 50-year-old woman was admitted to the orthopaedicclinic with a 2-year history of pain over the right ankle andheel. There were no prior signs or symptoms of hyperpara-thyroidism. She was otherwise healthy and there was nohistory of trauma.

Physical examination showed diffused swelling on bothsides of the ankle. There were no changes of the overlyingskin. Range of motion of the ankle was minimally limited.Radiographs of right foot showed a septated, radiolucentlesion that involved most of the posterior portion of thecalcaneus (Fig 1). Magnetic resonance images (MRI)showed hyperintense signal intensity caused by solid andcystic changes on T2-weighted images and hypointensesignal intensity caused cystic changes in the calcaneus onT1-weighted images (Fig 2).

A whole-body bone scan was performed and multiple hotspots were observed in the calcaneus. Results of a fine-needle aspiration biopsy were unsatisfactory, so an inci-sional biopsy was procured by curetting through the lateralcortex of the calcaneus. The pathologic examinationshowed bone tissue with multinucleated giant cells, a clusterof hemosiderin-laden macrophages, and a combination ofosteoblastic and osteoclastic activity compatible with browntumor of PHPT (Fig 3). The patient was referred to theendocrinology clinic for further evaluation. The results of aninitial blood chemistry evaluation were serum calciumlevel, 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

of involvement.

sagittal MRI showing septated cystic hyperintense lesion and thinning o

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pg/mL); urinary calcium/creatinine ratio, 0.22; and alkalinephosphatase level, 873 U/L (NR, 0 to 270 U/L). Ultrasono-graphic examination showed a 30-mm diameter mass in theright lower parathyroid gland. A dual-phase technetiumTc99m sestamibi parathyroid scintigraphy was also compat-ible with a right lower parathyroid adenoma. A diagnosis ofPHPT was established.

She underwent a surgical exploration of the neck. Theright lower parathyroid gland was removed along with aright total, left subtotal thyroidectomy. Histopathologic ex-amination confirmed the lesion as a parathyroid carcinoma.Focal trabecular arrangement, dense fibrous bands, and cap-sular and areas of intrathyroidal invasion were seen inhistopathologic examination of the parathyroid gland. Post-operatively, parathormone levels were within the normalrange and she experienced a short course of hypocalcemia(ie, hungry bone syndrome). Oral calcitriol and calciumsupplement treatment was administered.

Eighteen months later, there was no recurrence of theparathyroid lesion. Serum calcium and parathormone levelsremained within the normal range. Follow-up radiographs

intense septated cystic lesion within the calcaneus. (B) T2-weighted

FIGURE 1 Lateral foot radiograph showing expansion and in-creased radiolucency of the calcaneus. Arrows indicate the extent

FIGURE 2 (A) T1-weighted sagittal MRI showing expansion and a hypo

f the calcaneal cortex.

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(Fig 4) and MRI (Fig 5) of the calcaneus showed hyper-dense 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 secre-tion occurring as a result of a variety of causes, includingdiffuse hyperplasia, adenomas, and, rarely, carcinoma. It isa relatively common condition; it is the third most commonendocrine disorder after diabetes and thyroid disease. Thedisease may involve many systems. Prominent changes aredetected especially in the skeletal system (4).

Initial bone changes may be so slight as to be impercep-

FIGURE 3 (A) Bone tissue with osteoblastic and osteoclastic activstain, �50.) (B) Bone tissue with cluster of hemosiderin-laden macrostain, �50.)

FIGURE 4 Lateral radiograph of the calcaneus 1 year after surgi-cal removal of the parathyroid tumor. Note the new bone formationin the calcaneus.

tible on radiographic examination. In this stage, bone-min-

250 THE JOURNAL OF FOOT & ANKLE SURGERY

eral measurement methods may have diagnostic values.Subsequently, more prominent skeletal changes such asincreased bone resorption (subperiosteal, endosteal, sub-chondral, 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 secondaryhyperparathyroidism (5, 6). They represent localized accu-mulations of fibrous tissue and giant cells, which can re-place bone and may even produce osseous expansion. Thesetumors may subsequently undergo necrosis and liquefac-tion, producing cysts. Common sites of involvement are the

d multinucleated giant cells (small arrows). (Hematoxylin and eosines and multinucleated giant cells (arrows). (Hematoxylin and eosin

FIGURE 5 Fat-saturation T2-weighted sagittal MRI shows recov-ery of the lesion in the calcaneus 18 months postoperatively.

ity anphag

facial bones, pelvis, ribs, and femur (3); it is rarely seen on

the axial skeleton (7, 8). Spinal-cord compression has beenreported (9). Pathologic fracture may occasionally occurwith PHPT (10).

Our patient had an atypical location for a brown tumor.Other primary or metastatic tumoral involvement was sus-pected as the initial differential diagnosis. Histologically,brown tumors are hard to distinguish from giant cell tumors,reparative granuloma, aneurysmal bone cysts, and telangi-ectatic osteosarcoma. Nevertheless, expansile, well-definedlytic lesions, especially when numerous, in a patient withknown HPT are more likely to be brown tumors than giantcell tumors (1).

Parathyroid carcinoma is a rare malignant neoplasm thatcharacteristically pursues an indolent course. En block re-section of the tumor is often curative, but local recurrencesare common. Metastases are uncommon and are a latemanifestation of the disease. Bone metastases appear to berare, having been reported in only 2.2% of cases. In con-trast, radiographic bone disease, including the localizedlytic lesions of hyperparathyroidism (brown tumor), is fre-quent, occurring in up to 76% of patients with parathyroidcarcinoma (11). After resection of the parathyroid lesion,brown tumors heal with increased radiographic density.Persistence of the fibroosseous lesions after such surgerymay indicate that they are not the brown tumors of hyper-parathyroidism but may be related to some other cause (2).

Essentially, brown tumors are benign, but surgical treat-ment is indicated when the lesion is located in a problematicsite such as the calcaneus (12, 13). The risk of pathologicfracture should be assessed. Our patient did not undergosurgery for the calcaneal lesion because the symptoms im-proved after the excision of the parathyroid tumor. One yearlater, the calcaneal lesion disappeared and there were noother biochemical or roentgenographic manifestations ofPHPT.

In conclusion, an uncommon case of a brown tumor

involving the calcaneus in a patient with PHPT has been

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presented. Presence of a mass or swelling in any bone in apatient with high serum levels of calcium and parathormoneshould create suspicion of a brown tumor and PHPT.

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