Giant cell tumor (GCT) of bone accounts for 4% to 5% of primary bone tumors1. Distant metastasis occurs most commonly in the lung, reported at a rate of 2% to 5%2,3, although the overall outcome of metastatic GCT is favorable2. Recently, it was reported that the receptor activator of nuclear factor kappa-B ligand (RANKL) might play a pivotal role in osteoclast differentiation in the genesis of GCT4. However, the precise mechanism of GCT development remains obscure.
Multicentric giant cell tumor (MGCT) of bone is exceedingly rare, affecting approximately 1% of all patients with GCT5. There is no substantial difference between solitary GCT and MGCT regarding the clinicopathological features6,7.
We report the case of a twenty-year-old man with both MGCT and paraganglioma, who developed multiple distant metastases from each lesion. The patient’s parents were informed that data concerning the case would be submitted for publication, and they provided consent.
A twenty-year-old man was referred to us because of a six-month history of pain in the left knee. The pain was recurrent, but remission of the pain was present at times, although the pain gradually increased in severity. There was no history of trauma. The medical history was otherwise unremarkable. Physical examination revealed no inflammation, swelling, local heat, or tenderness. The patient’s temperature, pulse rate, and blood pressure were normal.
Radiographs of the affected knee showed expansile lytic lesions with trabeculation and cortical thinning in the epiphysis and metaphysis of the distal part of the femur, the proximal part of the tibia, and the proximal part of the fibula. These lesions showed no periosteal reaction or mineralized matrix. A lytic bone lesion with trabeculation was also observed in the distal part of the ipsilateral tibia (Figs. 1-A through 1-D). Computed tomography (CT) of the affected leg revealed that these lesions were isolated, and cortical destruction was not observed. Magnetic resonance imaging also demonstrated no extraosseous lesions. On bone scintigraphy, increased uptakes were seen in multiple areas, including the distal part of the left femur, the proximal part of the left tibia and fibula, and the distal part of the left tibia (Fig. 2). Serum alkaline phosphatase and C-reactive protein levels were slightly increased, although calcium, phosphate, and intact parathyroid hormone levels were in the normal range, ruling out hyperparathyroidism. A diagnosis of multiple GCT of bone was considered from these studies.
After confirmation of the pathological diagnosis by needle biopsy, surgical treatments were performed with tumor curettage, burring, and bone cement application in the lesions of the distal part of the femur and the proximal part of the tibia (Fig. 3-A); open biopsy was performed in the lesion of the distal part of the tibia; careful observation was chosen for the fibular lesion because of the lack of symptoms. Histopathological findings of these three lesions showed that numerous multinucleated giant cells were scattered throughout a background of oval and spindle stromal cells without nuclear atypia, compatible with GCT of bone (Fig. 4-A).
Ten months after the operation, although the fibular and distal tibial lesions had never progressed, there was sustained elevation of the patient’s temperature and the serum C-reactive protein level. CT revealed the existence of a retroperitoneal tumor located posterior to the bladder, leading to bilateral hydronephroses, and a solitary pulmonary metastasis at the right lower lobe (Figs. 5-A and 5-B). Thus, a low anterior resection of the retroperitoneal tumor was planned. During this procedure, acute episodes of alternating hyper and hypotension were observed, and we considered a diagnosis of pheochromocytoma. Postoperatively, the serum norepinephrine level was markedly reduced (217 pg/mL) from the intraoperative level (1516 pg/mL). Histologically, the retroperitoneal tumor consisted of polygonal cells with oval nuclei and eosinophilic granular cytoplasm, arranged in an alveolar pattern separated by vascular septa. Limited foci of necrosis and minimal vascular invasions were observed. Immunohistochemistry showed positive staining for synaptophysin and weak positivity for chromogranin A, lacking S-100 positive sustentacular cells. The MIB-1 index was approximately 6%. The presence of necrosis and a relatively high MIB-1 index led us to the diagnosis of extra-adrenal paraganglioma with a malignant potential (Fig. 4-B). Radioisotope 131I-MIBG scintigraphy showed no residual disease after the operation.
Four months after the abdominal surgery (fourteen months after the first surgery), sclerotic change was partially observed at the fibular lesion (Fig. 3-B), suggesting spontaneous improvement. However, new lesions appeared in both lungs. A right thoracotomy was performed, and histological examination verified that these lesions were the metastases of a GCT of bone.
Six months after the lung surgery (twenty months after the first surgery), lytic change of the fibular lesion increased (Fig. 3-C); three months later, a liver tumor was detected on follow-up abdominal CT, confirmed by 131I-MIBG scintigraphy. The serum norepinephrine level also increased. Surgical resection of the liver tumor was performed, and a histological diagnosis of metastatic paraganglioma was made.
Six months after the liver surgery (twenty-six months after the first surgery), new lytic change was observed in the left femoral head. A tumor specimen obtained by surgical resection revealed a metastasis of a GCT of bone.
Five months after the bone surgery (thirty-one months after the first surgery), multiple liver, lung, and bone metastases were detected by CT scan and 131I-MIBG scintigraphy. The patient died from respiratory obstruction four years after the first surgery.