Review Question - QID 213025

The lesions present in this patient are consistent with a diagnosis of multiple hereditary exostosis (MHE). In patients with MHE, there is a 10% risk of malignant transformation to chondrosarcoma. Figure D demonstrates histopathology consistent with a low-grade chondrosarcoma.

MHE is an autosomal dominant disorder characterized by the development of multiple skeletal osteochondromas. This disease process results from mutations in the EXT-1, EXT-2, and EXT-3 tumor suppressor genes. Patients with the EXT-1 mutation have the greatest disease severity and as a result the highest risk of malignant transformation. Although the resulting osteochondromas can appear at any location associated with a physis, the lesions typically occur in the distal femur, proximal tibia, proximal femur, and proximal humerus.

Czajka et al. investigated the proportion of patients undergoing malignant transformation among a large international, heterogeneous cohort of patients with MHE. They reported a 2.7% rate of malignant degeneration, at a mean age of 28.6 years and reported that the most common sites of malignant change from benign exostoses were the pelvis and scapula. The authors concluded that MHE is a progressive disease associated with an ongoing risk of chondrosarcoma, and therefore patients with this diagnosis should be monitored regularly throughout their lifetime.

Sonne-Holm et al. published a systematic review on MHE and the development of chondrosarcoma. They reported that there is a wide range in the frequency (1-25%) of malignant transition of MHE into sarcomas, and that the exostoses in the axial skeleton are more prone to develop into chondrosarcomas than peripheral exostoses. They recommend a screening program be launched with clinical examination by MR imaging or bone scintigraphy every two years for surveillance.

Figures:
Figure A depicts a sessile osteochondroma of the left proximal humerus, proximal tibia and fibula.
Figure B, C, D, E, and F depict the histological sections of chrondromyxoid fibroma, osteochondroma, chondrosarcoma, osteosarcoma, and synovial sarcoma, respectively.

Incorrect Answers:
Answer 1: Figure B depicts a chondromyxoid fibroma, with the typical stellate-shaped cells within a myxoid stroma. These lesions are not associated with MHE.
Answer 2: Figure C is the histology of a benign osteochondroma, demonstrating a large benign-appearing cartilage cap and underlying osseous element.
Answer 4: Figure E is a histological section of an osteosarcoma. There are characteristic atypical spindle cells with high nuclear-to-cytoplasm ratio associated with lacey osteoid. MHE patients are more likely to undergo malignant transformation of existing osteochondromas into chondrosarcoma.
Answer 5: Figure F depicts histology consistent with a synovial sarcoma. There is a classic biphasic pattern of spindle and epithelial cells. MHE patients are more likely to develop chondrosarcoma.