A 55-year-old man presents to the emergency department because he fell on his left arm two hours ago and believes it is broken. He states that his left arm and back have been aching for the past six weeks, so he has been taking acetaminophen daily. The rest of his past medical history is unremarkable. Physical examination reveals swelling and tenderness to palpation over the left upper arm. Distal pulses and sensation are intact. Radiographs of the left humerus show that the left humerus is bright white and wider than the right, bowed, and has a fracture that goes straight through horizontally with no chipping. Laboratory tests show elevation of serum alkaline phosphatase with serum calcium and serum phosphate in normal ranges. A histological sample of the bone shows a bizarre jigsaw pattern.
B) Gene mutation causing an increase in NFkB
The increase in NFkB results in increased osteoclast bone breakdown followed by increased osteoblast bone formation with irregular mosaic pattern. Paget’s disease produces highly sclerotic (bright white) wide bone that is often bowed. It is more prone to chalk stick fractures as described in the question stem. An increase in serum alkaline phosphatase is very consistent with the increased bone breakdown caused by Paget's disease.
Answer choice A: EWSR1 gene mutation resulting in cells expressing high levels of CD99, is incorrect. EWSR1 gene mutation resulting in cells expressing high levels of CD99 is consistent with Ewing sarcoma which is very similar to osteosarcoma on x-rays. The histologic sample would stain very positively for CD99 and have uniform cells with scant blue cytoplasm and round nuclei.
Answer choice C: Gene mutation causing a decrease in NFkB, is incorrect. This is the opposite mechanism seen in Paget’s disease of bone.
Answer choice D: Inactivation of P53 and Rb leading to malignant osteoid deposition, is incorrect. Inactivation of p53 and Rb leading to malignant osteoid deposition is consistent with osteosarcoma. While osteosarcoma can be related to Paget’s disease, the disease process is different. Osteosarcoma would show a sunburst pattern and Codman's triangle (raising of periosteum) on x-rays. Histology would show osteoid matrix unconnected by cartilage.
Answer choice E: Malignant giant cells expressing RANKL, is incorrect. Malignant giant cells expressing RANKL is consistent with giant cell carcinoma. While the increase in RANKL would increase osteoclast activity like Paget's disease, there would be no sclerosis (bright white) on x-rays. Histology would show multinucleate giant cells in a background of uniform mononuclear cells.
