Fig. 3
From: Somatic activating mutations in MAP2K1 cause melorheostosis

Intense bone remodeling and abnormal mineralization in melorheostosis. a Light microscopy images of cortical bone from patient Melo-2 showing the orientation of the collagenous matrix. Goldner’s trichrome staining is viewed under polarized light. Affected bone tissue shows in the periosteal regions appositional growth through deposition of layers of compact primary lamellar bone oriented parallel to the periosteal surface (open arrows). Subsequently these regions become highly remodeled. The solid arrows point towards large canals traversing the parallel layers of primary bone. Note the thick osteoid seams (red, unmineralized matrix) in affected bone tissue, whereas no osteoid is seen in unaffected bone (asterisks). b A backscattered electron image (BEI) of affected bone tissue from patient Melo-18. Gray represents the mineralized bone tissue, black is non-mineralized tissue. Note the extreme porosity of the bone tissue as a consequence of an intense bone remodeling activity (solid arrows). The open arrow is the same area labeled by the open arrow in a. c Bone histomorphometry. Comparison of indices of bone formation and bone resorption of affected vs. unaffected bone tissue from six patients with MAP2K1 mutations. All indices of bone formation and bone resorption are significantly increased in affected bone tissue compared to unaffected bone of the same patient. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001 vs. values of unaffected bone tissue (paired t-test). Unaff: unaffected bone tissue, Aff: affected bone tissue. d Overviews of unaffected and affected bone tissue obtained from patient Melo-9. Affected bone can be easily recognized by its porosity and by the substantial portions of unmineralized matrix (solid arrows), while osteoid formation is not seen around osteonal canals in the unaffected bone sample (asterisks). Goldner’s trichrome staining followed by light microscopy in the bright-field mode. Green indicates mineralized bone matrix and red indicates unmineralized matrix