Primary hyperparathyroidism having multiple Brown tumors mimicking malignancy.

Primary hyperparathyroidism is a disease characterized by excessive secretion of parathormone. During the course of this disease, bone loss occurs, particularly depending on resorption of the skeletal system. One of the complications of primary hyperparathyroidism is fibrotic, cystic bony changes which is called Brown tumor. Skeletal manifestations in the form of Brown tumors are rare and according to literature occur in less than 2% of patients suffering from any form of hyperparathyroidism. Such rare and multiple benign lesions may simulate a malignant neoplasm and pose a real challenge for the clinician in its differential diagnosis. We present a case of a 23-year-old Indian woman who was evaluated for multiple lytic expansile lesions with a strong suspicion of malignancy and fibrous dysplasia but turned out to be a case of primary hyperparathyroidism.

INTRODUCTION

Hyperparathyroidism is a condition characterized by increased parathormone secretion. Due to parathormone hyper-secretion, several consequences occur, such as excess calcium reabsorption from kidneys, phosphaturia, increased vitamin D synthesis and bone resorption. Parathormone increases osteoclastic activity in the bones. While renal calculi have been reported in 10-25% of the primary hyperparathyroidism cases, the frequency of bone disease has been reported to be around 10-20%.

The Brown tumor is a localized bone cyst. In histological perception, it is a benign lesion. Although bone findings are rarely seen in primary hyperparathyroidism, they are frequent in the carcinomas or in the case of secondary hyperparathyroidism. The Brown tumor may cause swelling, pathological fracture, and bone pain in the skeletal system. Multiple Brown tumors in the setting of primary hyperparathyroidism is very rare.[1] Only six cases have been reported in the English medical literature.[2-7]

In this article, we present the radiological and clinical features of a case with primary hyperparathyroidism caused by parathyroid adenoma.

CASE REPORT

A 23-year-old woman of Asian Indian origin was admitted to the orthopedic emergency department; she was having a clinical presentation of pain in her left shoulder region, right knee, and left thigh following a trivial trauma. The patient had a history of pain in the left shoulder region for about 5 months and was bedridden for the last 3 months due to a fractured femur. She was being evaluated for malignancy and polyostotic fibrous dysplasia in a tertiary care center.

On physical examination of the patient, tenderness was found to be present in the left shoulder, right knee, and left thigh. No other significant clinical abnormality was observed. On laboratory analysis, serum calcium level was 11.4 mg/dl (normal 8.4-10.7 mg/dl), serum albumin level was 5 g/dl (normal 3.4-4.8 g/dl), serum alkaline phosphatase level was 780 IU/l (normal 50-240 IU/l), serum acid phosphatase level was 11.36 IU/l (normal 0-5.5 IU/l), serum parathyroid hormone level was 456 pg/ ml (normal 7-53 pg/ml), vitamin D3 (1,25-dihydroxy cholecalciferol) was 32 pg/ml (normal 25-45 pg/ml) and vitamin D3 (25-hydroxy cholecalciferol) was 37 ng/ml (normal 15-80 ng/ml).

A plain digital radiograph of the affected left shoulder region and right knee, revealed multiple lytic expansile lesions with evidence of pathological fractures in the upper one-third of left humerus and right tibia as well as in the fifth posterior rib on the left side and lower one-third of the right femur with sparing of epiphyseal region [Figure 1].

Figure 1

(a) Radiograph left shoulder AP view shows geographic lytic expansile lesion with pathological fracture in metadiaphyseal region of left humerus with similar lesion in the fifth posterior rib in the left side of the chest with sparing of epiphysis. (b) Radiograph of both hands AP view shows lytic expansile lesion with no evidence of calcification in the third metacarpal of the right hand and the fifth metacarpal of the left hand

Later, further evaluation of the patient was done to rule out malignancy, some more plain digital radiographs were recommended to the patient including those for both the hands, skull, and pelvis regions [Figure 2]. The radiographs all showed similar lytic expansile lesions in the third metacarpal on the right side, fifth metacarpal on the left side, but with no evidence of calcification in the lesions. Similar lesions were seen in the pelvis with a ground-glass appearance [Figure 1]. The radiograph of the skull was found to be normal. An ultrasound scan of the neck was also done which showed a well-defined homogenous hypoechoic solid soft tissue lesion in relation to the posterior aspect of the inferior pole of the left lobe of the thyroid [Figure 3].

Figure 2

(a) Radiograph of pelvis with both hips. AP view shows multiple lytic expansile lesions with ground glass appearance in whole pelvis with fixation device in situ for pathological fracture in diaphysis of right femur. (b) Radiograph of right knee anterioposterior view and lateral view shows lytic expansile lesions in the metadiaphyseal region of lower third right femur and upper third of right tibia

Figure 3

Ultrasound neck shows well-defined homogenous hypoechoeic solid mass lesion in relation to the posterior aspect of the inferior pole of the left lobe of thyroid

To arrive at conclusive diagnosis, pathological analysis was essential. At the same time, the impending pathological fracture of the patient's left femur was a matter of concern. An elective surgery was therefore performed for the following two reasons: (1) to obtain some tissue from the lesions for a definite diagnosis; (2) to provide a rigid internal fixation to prevent any fracture. A subsequent pathological analysis confirmed the diagnosis of Brown tumor. After successful internal fixation was performed, the patient was able to ambulate with normal gait and without pain.

Later, an opinion was sought from the General surgeon who then advised and performed a left-side parathyroidectomy. Two weeks postoperatively, the serum levels of calcium and PTH had declined to a level within their respective normal limits. The last follow-up visit which was conducted after about 6 months showed marked improvement in the patient's clinical condition and radiological findings.

HISTOPATHOLOGICAL EVALUATION

Histopathological examination showed the presence of hypercellular nodules with chief cell hyperplasia and surrounded by a thin capsule. The pattern of growth of chief cells was diffused, acinar/pseudoacinar and pseudopapillary. The pathological diagnosis revealed parathyroid adenoma.

DISCUSSION

Primary hyperparathyroidism is characterized by the hyper functioning of parathyroid glands. The female:male ratio is 5:2. According to our literature reviews, multiple Brown tumor cases associated with primary hyperparathyroidism were initially reported by Joyce et al. in 1994.[24] Also five more cases have been observed since then. Such rare and multiple benign lesions may simulate a cancer and pose a real challenge for the clinician during its differential diagnosis. Lytic lesions caused by hyperparathyroidism are called Brown tumors. The term “Brown tumor” is a misnomer because it is not a true neoplasm. Although Brown tumor is generally seen more frequently in the cases of serious secondary hyperparathyroidism, it is fairly characteristic for primary hyperparathyroidism. Brown tumors may be observed in the facial bones, pelvis, ribs and femur. In the case of hyperparathyroidism, the early findings are seen on the bones of the hands. They may be multiple in the terminal stage of hyperparathyroidism or in the parathyroid carcinomas. They may cause swelling, pathological fracture, and bone pain.[1] USG is one of the most common imaging methods used for neck evaluation and it is practically the first option in the primary hyperparathyroidism assessment. On USG, parathyroid adenoma is seen typically as a round or oval homogenous, hypoechoic nodule localized behind the thyroid gland and at the lower aspect of paratracheal or paraeosophageal region. It is clearly separated from the thyroid gland due to its capsule. Morphological differences such as hyperechoic component, cystic changes, and calcification may be seen particularly in large adenomas. More than 90% of parathyroid adenomas include intra parenchymal hypervascular pattern in the color flow imaging. A diagnostic confusion arises mainly when the clinician encounters multiple lytic lesions involving different areas of the skeleton as was the case in our patient. About 90% of the patients with skeletal metastases present with multiple lesions.[6] In the case of hypercalcemia and radiographic evidence of multiple lytic lesion, primary hyperparathyroidism should always be kept in differential diagnosis and should be looked into once more common causes such as malignancy has been excluded. A high index of suspicion will lead to an early diagnosis.