A rare, low-grade appendiceal mucinous neoplasm (Pseudomyxoma peritonei) with ossification: A case report with morphoproteomic analysis of bone formation

Abstract

Heterotopic ossification occurring to low-grade appendiceal mucinous neoplasm (LAMN) (pseudomyxoma peritonei) is extremely rare. The pathogenetic mechanism of the tumor-related heterotopic bone formation remains as yet unconfirmed. Here, we describe a rare case of LAMN with ossification in a 72-year-old woman, and concentrate on the etiology of heterotopic ossification by the immunohistochemical evaluation of the novel markers such as BMP9, osteocalcin, and osteopontin. BMP9 is one of the most effective osteogenetic proteins. However, no researches associated with BMP9 in the heterotopic ossification occurring to LAMN have been performed. Consequently, we suggest the trustworthy hypothesis of tumor-associated heterotopic bone formation through this case. When osteoblastic markers such as BMP9, osteocalcin, and osteopontin are overexpressed in tumor cells, osteoblast-like transformation of such tumor cells occurs. In turn, these tumor cells increase secretion of interactive osteogenetic factors, such as BMP9, osteocalcin, and osteopontin, thus contributing to heterotopic bone formation through a microenvironmental change to mesenchymal stromal cells (osteoblastic differentiation). This phenomenon is considered a type of EMT. Patients should be followed closely because EMT-like transformed tumors have shown a tendency toward local recurrence. Our findings provide insight into the pathogenetic etiology of the heterotopic ossification in LAMN (pseudomyxoma peritonei).

Keywords: BMP9; Heterotopic ossification; Low-grade appendiceal mucinous neoplasm; Osteocalcin; Osteopontin; Pseudomyxoma peritonei.