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1 © 2015, Elsevier Inc., Heymann, Bone Cancer, Second Edition Chapter 23 Osteoclasts and bone cancers.

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Presentation on theme: "1 © 2015, Elsevier Inc., Heymann, Bone Cancer, Second Edition Chapter 23 Osteoclasts and bone cancers."— Presentation transcript:

1 1 © 2015, Elsevier Inc., Heymann, Bone Cancer, Second Edition Chapter 23 Osteoclasts and bone cancers

2 2 © 2015, Elsevier Inc., Heymann, Bone Cancer, Second Edition FIGURE 23.1 A distal femoral resection showing the macroscopic appearance of a giant cell tumor of bone. There is extensive hemorrhage and necrosis. Note the subarticular site in a long bone in which the epiphysis is closed (A). The radiographic appearance of a typical giant cell tumor of the proximal tibia: this expansile lytic tumor is sited in the subarticular area in a skeletally mature individual. Also note the absence of a periosteal reaction (B). These tumors generally are without a sclerotic margin (a narrow zone of transition) and, if present, is seldom complete. Septa may be seen in the lesion in 33–57% of patients; these represent non-uniform growth of the tumor rather than true septa.

3 3 Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 23.2 A high power magnification of a transmitted light photomicrograph showing a hematoxylin and eosin-stained section of an osteoclast in a giant cell tumor of bone. Note the presence of literally hundreds of nuclei.

4 4 Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 23.3 Transmitted light photomicrographs showing the wide range of appearances found in a giant cell tumor of bone. Predominantly osteoclasts are seen with a much less conspicuous number of mononuclear cells (A, B). In contrast, osteoclasts are present in significantly fewer numbers in C and almost undetectable in D, in which collections of foamy histiocytes are noted. A fibroblastic overgrowth is noted in E and there is considerable scarring in F. Focal areas of infarction are present in G. Secondary aneurysmal cyst formation, indistinguishable from that of a primary aneurysmal bone cyst also occurs in giant cell tumors (H). Focally, there is metaplastic osteoid deposition which makes giant cell tumors difficult to distinguish from osteosarcomas (I).

5 5 Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 23.4 Hematoxylin and eosin sections of pigmented villonodular synovitis/tenosynovial giant cell tumor. This osteoclast-rich tumor generally contains a more fibroblastic population compared to that seen in giant cell tumors and the osteoclasts (arrow head) are more scattered throughout the fibroblastic cells (A). Hemosiderin is also a common finding (arrow) (B).

6 6 Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 23.5 A non-ossifying fibroma in a young patient with neurofibromatosis type 1. In contrast to a giant cell tumor, the non- ossifying fibroma is sited in the metadiaphysis of the bone, has a sclerotic rim surrounding the central lytic area and most often presents in a growing child (skeletally immature) (A). Microscopic appearance of a non-ossifying fibroma showing bland fibroblastic cells in a storiform arrangement (B) in which clusters of foamy histiocytes are seen (arrow) (C).

7 7 Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 23.6 This radiographic image of a fine cut slab shows the typical appearance of a primary aneurysmal bone cyst (A). The findings consist of a central expansive lytic lesion, appearing cystic as a result of fine septa. The macroscopic appearance of an aneurysmal bone cyst involving the greater trochanter (B).

8 8 Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 23.7 The typical microscopic features of an aneurysmal bone cyst. Low power magnification shows the overall architecture of the tumor (A, B). Note, at higher magnification, the blood-filled spaces not lined by endothelial cells, the wall of which are composed of fibroblastic cells in which osteoclasts (arrows) line up in variable numbers (C). A characteristic feature is the presence of “blue” bone (arrow head) which represents calcified osteoid which is present in tumor septa (A, D).

9 9 Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 23.8 Activation of RAS-MAP kinase signaling is the molecular event that unites the overlapping phenotype occurring in cherubism, Noonan syndrome and neurofibromatosis type 1. Activation can either occur directly (mutations in SH3BP2, PTPN11, SOS1, K-RAS, CRAF) or indirectly by disabling negative regulators of Ras (mutations in NF1, PTPN11).

10 10 Copyright © 2013 Elsevier Inc. All rights reserved. FIGURE 23.9 A radiograph of the jaw of a child with a cherubism phenotype but who has a PTPN11 mutation (Noonan syndrome). Note the bilateral symmetric radiolucent bubbly appearance of the mandible and maxilla (arrows) (A). The histology shows an osteoclast- rich lesion with features not dissimilar to that of a non-ossifying fibroma: there is a fibroblastic population of cells in which osteoclasts are scattered (B).


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