Assessment of MUC4 Expression in Primary Bone Sarcomas
Roberto Tirabosco, Fitim Berisha, Dina Halai, Hongtao Ye, Anupama Swamy, Maria Fernanda Amary, Adrienne Flanagan. Royal National Orthopaedic Hospital, Stanmore - London, United Kingdom
Background: Mucin 4 (MUC4), a glycoprotein expressed in various types of carcinomas, has been recently highlighted as a specific and sensitive immunohistochemical marker of low grade fibromyxoid sarcoma (LFS), a soft tissue tumor the hallmark of which is the t(7;16)(q33;p11). Since it is recognised that osteosarcoma - the most frequent primary bone sarcoma - can mimic virtually all other tumors thereby making them difficult to diagnose, particularly on needle cores, we sought to analyse the expression of MUC4 on a series of primary malignant bone tumors, as such data are not available in the literature. Review of our pathology archive revealed that we had previously reported 2 tumors with morphological features consistent with LFS and the closely related epithelioid sclerosing fibrosarcoma (ESF), a tumor which has been rarely reported as occuring in bone.
Design: To address the sensitivity and specificity of MUC4 expression in sarcomas, in addition to primary bone tumors we included a series of soft tissues neoplasms, some of which may rarely arise in bone. Tissue microrrays, prepared at our Institution, including 120 osteosarcomas, 220 chondrosarcomas, 45 chordomas, 60 myxofibrosarcomas, 54 solitary fibrous tumors, 59 leiomyosarcomas and 90 synovial sarcomas were studied. Whole tissue sections of 8 ossifying fibromyxoid tumors and the 2 cases with features consistent with ESF (FUS-rearrangement negative) and LFS (FUS-rearrangement not informative) were analyzed. For comparison, 8 cases of ESF of soft tissue (FUS-rearrangement negative) were added. Ten FUS-rearrangement positive LFS were used as control. Immunohistochemistry was performed using standard methods.
Results: All LFS with the characteristic t(7;16) expressed MUC4 diffusely. The 2 primary ESF/LFS of bone were diffusely positive for MUC4. Three out of 8 ESF of soft tissue (37.5%) were diffusely immunoreactive for MUC4 and 22/90 SS (24.4%) were focally positive. All the remaining tumors were negative for MUC4.
Conclusions: We have identified 2 cases of bona fide primary malignant bone tumors that displayed morphological features consistent with LFS (scapula) and ESF (femur), which diffusely express MUC4. 25% of SS expressed MUC4 focally, mostly byphasic type, thereby confirming previously published data. We conclude that once a diagnosis of SS is excluded, it is very unlikely that tumors in bone other than LFS and ESF, express MUC4. We recommend that MUC4 expression is studied in all fibromyxoid and sclerosing tumors of bone, in order to improve the classification of primary bone tumors, as this may help stratify patients for neo-adjuvant treatment.
Category: Bone & Soft Tissue
Monday, March 19, 2012 1:00 PM
Poster Session II # 16, Monday Afternoon