MDM2 and CDK4 Immunoreactivity Distinguishes Low-Grade Osteosarcoma from Benign Mimics
A Yoshida, T Ushiku, T Motoi, M Fukayama, H Tsuda. National Cancer Center Hospital, Tokyo, Japan; University of Tokyo, Tokyo, Japan; Teikyo University, Tokyo, Japan
Background: Parosteal osteosarcoma (POS) and low-grade central osteosarcoma (LGCOS) show similar histological appearance and clinical behavior. Recent studies have also shown that these two types of low-grade osteosarcoma (LGOS) even share a genetic background: amplified sequences of 12q13-15 including MDM2 and CDK4. The histological diagnosis of LGOS is often challenging. Because of the bland cytology and mature bony trabeculae, LGOS tends to be confused with benign lesions. POS, for example, may be mistaken as myositis ossificans (MO), osteochondroma (OC), and other surface lesions, while LGCOS may simulate fibrous dysplasia (FD) among others. The accurate diagnosis is mandated to allow appropriate management. Since benign mimics of LGOS are not expected to harbor the characteristic gene amplification of sarcoma, we reasoned MDM2 and CDK4 immunostains may aid in this difficult differential diagnosis.
Design: Twenty-two cases of LGOS from 20 patients (14 POSs, 7 LGCOSs, 1 LGOS of undetermined subtype), and 38 cases of benign histological mimics of LGOS (11 MOs, 14 FDs, 6 OCs, 1 desmoplastic fibroma, 4 florid reactive periostitides, 1 Nora's lesion, and 1 Turrett exostosis) were retrieved from the hospital files. A representative section of each case was immunostained with antibodies against MDM2 and CDK4. The results were expressed with intensity graded from 1 (weak) to 3 (strong), and with extent being either focal (1-10%) or diffuse (11-100%).
Results: Fourteen LGOSs labeled for MDM2 (14/22, 64%); and 19 cases (19/22, 86%) labeled for CDK4. All the LGOSs (22/22, 100%) expressed one or both of the markers, with 11 cases expressing both (11/22, 50%). In the majority of the cases, staining was diffuse (20/22, 91%) and in moderate or strong intensity (15/22, 68%) for either antibody. In contrast, none (0%) of 38 benign lesions demonstrated immunoreactivity for MDM2 or CDK4. The combination of these two markers thus made both sensitivity and specificity reach 100% for the diagnosis of LGOS.
Conclusions: All the LGOSs labeled for MDM2 and/or CDK4, while none of benign histological mimics expressed these markers in this analysis. MDM2 and CDK4 immunostaining may hence serve as a useful adjunct for the diagnosis of POS and LGCOS.
Category: Bone & Soft Tissue
Tuesday, March 23, 2010 9:30 AM
Poster Session III # 12, Tuesday Morning