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USMLE Step 1 – Question of the Week#1

Q1. A 27-year-old man presents to physician with complain of pain in left thigh for last one month. Physical examination shows presence of a painful swelling just above left knee joint. Radiogram of left leg shows a radio-lucent lesion which is located eccentrically near lower end of femur. The lesion is surrounded by a thin rim of bone and soap-bubble appearance is present.


After necessary evaluation, en bloc resection of the lesion is performed and is sent for microscopic examination. Histology of the lesion shows multi-nuclear giant cells in network of sheets of oval mononuclear cells. Necrosis and mitotic activity are present in the lesion and reactive bone is present at the periphery.

Which of the following mechanisms best describe pathogenesis of the bone lesion?

A. Dysregulation of RANKL-RANK signaling cascade

B. Increased production of 2-hydroxyglutarate

C. Defective diffusion of Indian hedgehog factor

D. Inactivating mutation of a tumor suppressor gene

E. Activation of Gs protein and increased production of cyclic adenosine monophosphate (cAMP)