28 July 2005 – Case of the Week #14
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We thank Dr. Osama M. Al-Agha, SUNY Downstate, Brooklyn, New York for contributing this case and the discussion. We invite you to contribute a Case of the Week by emailing [email protected] with microscopic images (any size, we will shrink if necessary) in JPG or GIF format, a short clinical history and any other images (gross, immunostains, EM, etc.) that you have and that may be helpful or interesting. We will write the discussion (unless you want to contribute to it). We will list you as the contributor, and send you a check for $35 (US) for your time if we use the case. Please only send cases with a definitive diagnosis.
Case of the Week #14
A 17 year old woman presented to her dentist with a chief complaint of loosening of her lower incisors. She also had a cystic but painless swelling of the anterior jaw for 2 months. There was no history of trauma or other medical problems. The urinalysis and serum calcium phosphate, alkaline phosphatase and parathyroid hormone were within their reference ranges. An Xray of the jaw showed a 2.6 cm circular, unilocular, radiolucent area at the symphysis mandible (Figure 1, arrow points to the lesion). There was no peripheral bone sclerosis or periosteal reaction. The lesion was excised.
Microscopic examination revealed fibroblastic stroma with spindled mesenchymal cells and multinucleated osteoclast-like giant cells (Figure 2). There was extravasational hemorrhage throughout the lesion. The giant cells had < 20 nuclei and clustered around areas of hemorrhage (Figure 3a). Occasional intravascular giant cells were seen (Figure 3b). Osteoid trabeculae were present (Figure 4a) and were surrounded by rims of benign osteoblasts (Figure 4b). No similar lesions were present elsewhere in the body.
What is your diagnosis?
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Diagnosis: Central Giant Cell Granuloma of the Mandible
Central giant cell granuloma, also called giant cell reparative granuloma, is an uncommon (7% of benign jaw lesions), cystic, intraosseous lesion of the anterior mandible and maxilla. It can also appear in the tubular bones of the hands and feet (Int J Surg Path 2001;9:189). It affects children and young adults, predominantly females, and is often painless. On Xray, it is a unilocular or multilocular radiolucency that may cause marked thinning of the cortical plates and resorption or movement of teeth (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996;81:720). It may be caused by recurrent, slow, minute hemorrhages and an associated reparative reaction. Treatment is excision and thorough curettage. These tumors are benign, but may recur.
Histologically, central giant cell granulomas are characterized by spindle cells within fibrous stroma, with numerous multinucleated giant cells in a patchy distribution, usually near areas of hemorrhage. The giant cells usually contain < 20 nuclei per giant cell, and may be intravascular. The spindle cells have variable mitotic figures. Spicules of new woven or lamellar bone are found in 1/3 of cases, usually with benign osteoblastic rimming. Cartilage is absent. The giant cells are immunoreactive for CD68, a histiocytic marker.
The differential diagnosis includes peripheral giant cell granuloma, giant cell tumor, aneurysmal bone cyst, brown tumor of hyperparathyroidism, giant cell-rich osteosarcoma, and metaphyseal fibrous defect / nonossifying fibroma. Peripheral giant cell granuloma is primarily an extraosseous soft tissue lesion that very rarely affects the underlying bone. Giant cell tumors have more giant cells, which are generally evenly distributed without clustering and contain >20 nuclei per giant cell. Aneurysmal bone cysts contain blood-filled cystic spaces typically surrounded by giant cells. Giant cell-rich osteosarcomas have osteoid formation and osteoclast-like giant cells, but the osteoid is more eosinophilic, is composed of delicate stands or lace-like trabeculae, and is surrounded by atypical osteoblastic cells. Metaphyseal fibrous defects / nonossifying fibromas typically involve the distal tibia or femur and contain a spindle cell fibroblastic proliferation in a storiform pattern with scattered giant cells, but lack osteoid or woven bone formation. Brown tumor of hyperparathyroidism is histologically similar to central giant cell granuloma, and must be ruled out through laboratory testing.
A recent study has concluded that the giant cells in four giant cell lesions of the jaw - central giant cell granuloma, aneurysmal bone cyst, peripheral giant cell granuloma and cherubism, all have characteristics of osteoclasts, including positive enzyme histochemistry for tartrate resistant acid phosphatase, suggesting a similar pathogenesis (J Oral Pathol Med 2003;32:367)
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