1. Molecular Pathology of Bone Tumors
Suk Wai Lam, David G.P. van IJzendoorn, Anne-Marie Cleton-Jansen, Karoly Szuhai, Judith V.M.G. Bovée 
The Journal of Molecular Diagnostics 
Volume 21, Issue 2, Pages (March 2019)
DOI: /j.jmoldx
Copyright © 2019 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions

2. Figure 1
A: Giant cell tumor of bone (hematoxylin and eosin; H&E), showing mononuclear cells admixed with giant cells. B: Nuclear staining with H3F3 G34W mutant antibody, highlighting the mutant mononuclear cells, whereas the giant cells are negative. C: Next-generation sequencing (NGS) data showing the point mutation in H3F3A c.103G>T, p.Gly34Trp. D: Chondroblastoma (H&E) showing small chondroblast-like cells admixed with giant cells, and focal matrix deposition. Note the morphologic overlap with giant cell tumor of bone. E: Nuclear staining, with H3F3 K36M mutant antibody staining of the mutant chondroblast-like tumor cells. F: NGS data showing the point mutation in H3F3B c.110A>T, p.Lys36Met. Scale bars = 50 μm.
The Journal of Molecular Diagnostics  , DOI: ( /j.jmoldx )
Copyright © 2019 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions

3. Figure 2
As a conceptual framework, molecular alterations of bone tumors can be divided into two categories: simple or complex karyotype. Simple karyotypes include recurrent translocations, such as those predominantly seen in round cell tumors (Table 1). A and B: The prototypical example is Ewing sarcoma (A), harboring fusions with mostly EWSR1 and ETS family members, as can be demonstrated using fluorescence in situ hybridization (FISH), with split-apart probes flanking EWSR1 and showing distantly located red-green signals, which indicate the presence of a break in the EWSR1 locus (B). C: Bone tumors carrying specific point mutations also fall into the category of simple karyotypes. A tumor with a simple karyotype is, for example, fibrous dysplasia, which shows bland fibroblastic spindle cells with areas of woven bone on hematoxylin and eosin (H&E) staining. D: Next-generation sequencing can be used to demonstrate the specific point mutation in GNAS c.602G>A, p.Arg201His. Tumors with complex karyotypes lack specific alterations that can be used in routine diagnostics. E: A prototypical example includes conventional osteosarcoma, which on H&E staining shows atypical hyperchromatic cells producing tumor osteoid. F: Combined binary ratio labeling–FISH illustrates a complex chaotic karyotype, with numerous regions of amplification and deletions, combined with many translocations. Scale bars = 50 μm. Original magnification: ×400 (B); ×630 (F).
The Journal of Molecular Diagnostics  , DOI: ( /j.jmoldx )
Copyright © 2019 American Society for Investigative Pathology and the Association for Molecular Pathology Terms and Conditions