On histological observation of the present cases, osteochondroma showed increased endochondral ossification with overgrowth of hypertrophic chondrocytes, while BPOP showed abortive endochondral ossification. The immature cartilaginous tissue of BPOP abruptly produced the trabecular bones that were elongated linearly in a radiating fashion from the core cartilage. While the hypertrophic chondrocytes of osteochondroma produced trabecular bones that were subsequently connected with the original bone marrow, the cartilaginous tissue of BPOP, probably derived from the parosteal mesenchyme, produced trabecular bones in the external direction from the core cartilage, resulting in marrow discontinuity between BPOP and the original bone. However, the trabecular bone growth of BPOP was more active and extensive than that of osteochondroma, and BPOP had multiple cartilaginous tissues which were immature and diffusely scattered, while osteochondroma had a thick cartilage cap on the condylar head. These findings directly indicate that BPOP may have higher recurrence rate than osteochondroma.
In the IHC stains, BPOP showed more intense expression of osteogenic proteins (BMP-2, BMP-4, RUNX2, OC, AP, OPG, RANKL, CTGF, and bFGF) than the ostoeochondroma. BMP-2 and BMP-4, which are markers of osteogenesis and chondrogenesis, respectively, were consistently positive in BPOP but only weakly positive in osteochondroma. Furthermore, the biomarkers of ossification (RUNX2, OC, AP, OPG, and RANKL) and the biomarkers of mesenchymal growth (bFGF and CTGF) were much stronger in BPOP than in osteochondroma. It was thought that BPOP grew more actively than osteochondroma by producing immature cartilage and bone.
The higher expression of osteogenic proteins in BPOP than in osteochondroma was coincident with increased expression of PCNA in the perichondral spinous cells and marrow osteogenic cells of BPOP. Osteochondroma was rarely positive for PCNA. The present study also performed IHC examination for different oncogenic proteins (p53, β-catenin, BCL2, pAKT, and survivin) and the biomarkers of chondrosarcoma (CEA, EMA, pan-K, and S-100) in BPOP and osteochondroma. For the surgical approach for the osteochondroma, not like that for BPOP, several factors, such as complete excision with condylar reconstruction, mandibular contouring, and reconstruction of normal occlusion, must be considered. Virtual surgical simulation for guidance of excision of the mandibular condyle and combined correction of dentofacial deformities can be recommended recently [29].
The oncogenic protein expression of perichondral spindle cells and marrow osteoblasts/fibroblasts of BPOP was strongly positive for p53, β-catenin, BCL2, pAKT, and survivin, while osteochondroma was weakly positive for β-catenin and 14-3-3 and rarely positive for p53, BCL2, pAKT, and survivin. Furthermore, BPOP was consistently positive for CEA, EMA, pan-K, and S-100, while osteochondroma was rarely positive for these proteins.
Immunohistochemically, BPOP showed the expression of bFGF and vascular endothelial growth factor (VEGF), similar to those occurring in endochondral ossification in the growth plate. Thus, BPOP is considered as a reparative process which is occasionally confused with other benign or malignant conditions [30]. It was presumed that BPOP was more strongly activated by the oncogenic proteins (p53, β-catenin, BCL2, pAKT, and survivin) than osteochondroma; BPOP might be affected by oncogenic signaling of cellular proliferation and survival. Eventually, BPOP produced CEA, EMA, pan-K, and S-100, implying that BPOP might have higher potential for malignant transformation than osteochondroma. Since BPOP still showed no cellular atypia and expressed only low levels of embryonic chondrocyte proteins (CEA, EMA, pan-K, and S-100), it was also presumed that the growth of BPOP was primitive and immature, similar to the embryonal development of cartilage and bone, i.e., Meckel’s cartilage in mandible development, rather than to the progression of malignant transformation.