FIGURE 12.1

Normal bone structure and function. (A) Cortical bone is arranged in concentric cylindrical structures – Haversian systems – here seen in cross-section. (B) Polarization microscopy shows the lamellar structure well. (C) Bone within the medulla forms a meshwork of trabeculae, this is known as cancellous bone; this is also lamellar in type. (D) The cellular composition of bone shown in this photomicrograph is of rapidly formed woven bone with a random arrangement of the collagen fibres. A row (or sheet in three dimensions) of osteoblasts covers the upper surface of the bone: the perinuclear vacuoles are the prominent Golgi apparatus of protein synthesizing and exporting cells. Osteocytes are seen within their lacunae within the bone trabecula. Three active multinucleated osteoclasts lie within resorption cavities on the lower surface.

FIGURE 12.2

The cycle of bone turnover. Various agents promote bone resorption by stimulating osteoclast formation and maturation. As these cells resorb bone, cytokines are released which in turn promote osteoblastic activity, thus completing the cycle.

FIGURE 12.3

Osteoclast precursors (monocyte/macrophage lineage cells) are stimulated to become osteoclasts by receptor activator of nuclear factor κB ligand (RANKL). This molecule is upregulated on the surface of marrow stromal cells by vitamin D (Vit D), parathyroid hormone (PTH) and other factors. Overactivity of RANK L is normally prevented by the soluble protein osteoprotegerin (OPG). In the process of removing bone, osteoclasts produce cytokines such as transforming growth factor β (TGFβ) which both stimulate osteoblasts to produce new bone and inhibit osteoclasts. Unwanted osteoclasts undergo apoptosis under the influence of oestrogens and bisphosphonates.

FIGURE 12.4

The vicious cycle of bone destruction. Osteoclasts produce growth factors that stimulate tumour cells in the marrow to grow and proliferate. More tumour cells produce more osteoclast activating factors and the vicious cycle is completed. TGFβ = transforming growth factor β; PTHrP = parathyroid hormone-related peptide.

FIGURE 12.5

Osteoporosis. This section is taken from the spine of a patient with steroid-induced osteoporosis. The bone trabeculae are thinned and some appear disconnected from each other. It is easy to see why vertebral collapse has occurred.

FIGURE 12.6

Changes in bone mass with age. This line diagram shows the rapid acceleration in bone growth during puberty to reach peak bone mass. This is followed by a slow decline in both sexes, the more rapid fall in post-menopausal women accounting for the greater risk of osteoporosis than in men.

FIGURE 12.7

Osteomalacia. Histological examination of undecalcified sections shows that most of the bone (purple) surfaces are covered by a thick layer of nmineralized osteoid (pale blue), reflecting the delay in mineralization.(Toluidine blue.)

FIGURE 12.8

Brown tumour of hyperparathyroidism. The patient was a middle-aged woman with a past history of two malignant tumours who developed a destructive lesion of the distal humerus. Biopsy shows numerous osteoclasts among fibrous stroma and some reactive new bone formation. She was also known to have chronic renal failure. The lytic lesion rapidly filled-in following removal of an enlarged parathyroid gland.

FIGURE 12.9

Pathophysiology of renal osteodystrophy.

FIGURE 12.10

Paget’s disease of bone. Characteristic thickening of the skull with loss of distinction between the tables.

FIGURE 12.11

Paget’s disease of bone. (A) The active phase is characterized by numerous large osteoclasts eroding bone, followed by new bone formation by sheets of osteoblasts. The marrow is replaced by vascular fibrous tissue. (B) Repeated episodes of irregular resorption and synthesis result in a jigsaw or mosaic pattern of cement (reversal) lines.

FIGURE 12.12

Osteonecrosis (avascular necrosis) of the femoral head. The articular surface of the femoral head shows a crescent-shaped depression (A) which, on the cut section (B) is seen to be due to a subchondral fracture. The yellow tissue (*) is necrotic bone.

FIGURE 12.13

Osteomyelitis is often due to haematogenous spread from foci elsewhere. The bacteria lodge within metaphyseal (hairpin) blood vessels and set up an inflammatory reaction in the medullary canal, which spreads through the cortex, elevates the periosteum and may spread locally into an adjacent joint, causing septic arthritis, or into blood vessels leading to bacteraemia or septicaemia. Interference with blood supply leads to bone death, with formation of a ‘sequestrum’; meantime, the periosteum lays down a shell of new bone, the involucrum. Pus may track to the skin surface forming a discharging sinus.

FIGURE 12.14

Septic arthritis. Humeral head showing marked destruction of the articular cartilage by acute inflammation.

FIGURE 12.15

Tuberculosis of spine: there is involvement of at least two vertebrae, one of which has collapsed. The discs are better preserved than is typically seen. The differential diagnosis includes metastatic carcinoma.

FIGURE 12.16

Metastatic carcinoma in bone. This proximal humerus with adjacent shoulder joint and glenoid was resected for metastatic renal carcinoma. A large tumour mass occupies the medulla and has extended into adjacent soft tissue particularly medially.

FIGURE 12.17

Osteoid osteoma. This shows a transverse section of an  excised length of fibula containing a nidus of an osteoid osteoma both on naked eye (A) inspection and histology (B). The nidus is well defined and is surrounded by sclerotic bone.

FIGURE 12.18

Osteocartilaginous exostosis. This small exostosis consists of a thin cartilaginous cap with underlying cancellous bone.

FIGURE 12.19

Giant cell tumour of bone. The tumour consists of large multinucleated osteoclasts of reactive nature interspersed with ovoid mononuclear tumour cells.

FIGURE 12.20

Osteosarcoma. A delicate meshwork of eosinophilic osteoid matrix has been formed directly by large ovoid malignant cells.

FIGURE 12.21

Osteosarcoma. This large tumour has arisen in the metaphysis of the proximal tibia and has penetrated the cortex to extend through the periosteum forming a circumferential soft tissue extension. The growth plate is closed, but the tumour has penetrated through its scar to involve the epiphysis.

FIGURE 12.22

This radiograph shows a destructive lesion in the distal femoral metaphysis with cortical destruction and soft tissue extension. A periosteal reaction is present (Codman’s triangle). The features are of a malignant tumour and in this age group osteosarcoma is the likeliest diagnosis.

FIGURE 12.23

Biopsy of femur. The tumour shows large cells with pleomorphic nuclei, and numerous mitotic figures including one abnormal one. Although osteoid is not present in this biopsy, it was seen elsewhere and the features are those of an osteosarcoma.

FIGURE 12.24

Resection of distal femur. The gross appearances reflect those of the radiograph in Figure 12.22. There is a large tumour occupying much of the medullary canal; it has penetrated through the cortex into soft tissue. This extraosseous mass has shrunk, representing a good response to preoperative
chemotherapy. Tumour has also penetrated the physeal plate to extend into the epiphysis, indicating this is an incomplete barrier to tumour spread.

FIGURE 12.25

This section from the medullary canal shows two large bony trabeculae separated by loose fibrovascular tissue. Compared with Fig 12.23 almost all the tumour cells have been killed and there are only occasional residual cells which have been severely damaged by chemotherapy.

FIGURE 12.26

Chondrosarcoma. This advanced tumour of the proximal humerus has arisen within the medullary canal, but has extended through the medial humeral cortex to form a large soft tissue mass.

FIGURE 12.27

Chondrosarcoma. This tumour is clearly cartilaginous as the cells lie within lacunae in a chondroid matrix, but there is considerable variation in nuclear size and three mitotic figures are present. This is therefore a high-grade tumour.

FIGURE 12.28

Ewing’s sarcoma. This is a malignant round cell tumour whose cells have clear cytoplasm due to the presence of glycogen. The nuclei are regular and mitotic figures are sparse for such an aggressive tumour.

FIGURE 12.29

Fibrous dysplasia. Irregularly orientated trabeculae of woven bone are formed from a vascular fibroblastic stroma.

FIGURE 12.30

Aneurysmal bone cyst. The lesion consists of septa containing some steoclasts, fibroblasts and osteoid, but there is no endothelial lining, indicating that this is not a haemangioma.

FIGURE 12.31

Normal joint structure. (A) Structure of a synovial joint (knee). (B) Articular cartilage is a smooth-surfaced material covering the bone ends. Small uniform chondrocytes lie in lacunae within a hyaline matrix. (C) In health, the synovial membrane consists of fibrovascular tissue covered by a thin layer of flattened cells, which on ultrastructure can be shown to be a mixture of fibroblasts and histiocytes.

FIGURE 12.32

Osteoarthritis. (A) The articular cartilage is lost from the weightbearing surface of this femoral head; if the acetabular cartilage is similarly lost, then it is easy to see why the joint space becomes narrowed on radiology. The underlying bone so exposed becomes thickened and polished. Osteophytes, protruding pieces of cartilage and bone have formed at the joint margin. (B) The articular cartilage is progressively thinned from right to left and is finally lost completely. To the left of this, bone provides the articular surface and it is noticeably thicker (sclerotic) in this area.

FIGURE 12.33

Rheumatoid arthritis. The knee joint (A) has been opened to show the distal femur whose articular cartilage has been eroded from the periphery by haemosiderin-stained pannus. Low-power microscopy (B) demonstrates that the pannus grows over and erodes the cartilage. The synovium (C) shows a villous architecture, the fronds are densely infiltrated by chronic inflammatory cells and there is fibrinous exudate.

FIGURE 12.34

Rheumatoid nodule. The lower half of the illustration consists of necrobiotic collagen with basophilic (blue) staining. Above, and surrounding this, is a reaction of histiocytic cells whose nuclei are oriented in a parallel manner known as palisading.

FIGURE 12.35

Pathogenesis of rheumatoid arthritis.

FIGURE 12.36

Gout. (A) This small toe was amputated for persistent pain. Cut section shows extensive deposition of chalky, white crystalline material within the distal phalanx and in adjacent soft tissue. On polarization microscopy (B), large sheaves of brilliantly birefringent crystals are seen.

FIGURE 12.37

Pseudogout. Numerous rod-shaped crystals can be seen on polarization microscopy in fluid aspirated from the knee of an elderly man.

FIGURE 12.38

Reaction to a joint prosthesis. (A) Foreign body giant cells surround a pool of acrylic cement (right) and fragments of high-molecularweight polyethylene (left). On polarization (B), the cement is not birefringent, but unsuspectedly large amounts of polyethylene are revealed.

FIGURE 12.39

Tenosynovial giant cell tumour (pigmented villonodular synovitis). The radiograph of the left hip (A) and gross photograph of the resected specimen (B) show extensive erosion of the bone of the neck and inferior surface of the head of the femur. The lesional tissue is brown/tan and multinodular.

FIGURE 12.40

High-grade sarcoma. This tumour arising in the right vastus intermedialis was resected en bloc. The apparent degree of circumscription is deceptive as the tumour had an infiltrative pattern on histology.

FIGURE 12.41

Myxoid/round cell liposarcoma. Myxoid liposarcoma consists of small cells in a loose myxoid background with occasional cells whose vacuolated cytoplasm contains lipid (A). Round cell liposarcoma (B) consists of closely packed and more hyperchromatic cells, some showing vacuolation. Within one tumour these two patterns may be seen as in this case. The round cell component confers a much worse prognosis.

FIGURE 12.42

Alveolar rhabdomyosarcoma. The tumour is composed of sheets of round cells which show central discohesion with the formation of an alveolar or honeycomb pattern. Insert (lower left) shows that the nuclei stain with an antibody directed against myogenin, a nuclear regulatory protein involved in skeletal muscle differentiation, helping to confirm the diagnosis.

FIGURE 12.43

Biphasic synovial sarcoma. As the name suggests, there are two patterns to this tumour, namely well-differentiated glandular structures and closely packed spindle-shaped cells.

FIGURE 12.44

(A) Karyotype showing a reciprocal translocation between chromosomes 11 and 22 as seen in Ewing’s Sarcoma. (B) Chromosome ideograms showing the t(11;22) translocation with chromosome 11 in black and 22 in blue. The red and green regions represent the EWSR1 break apart probe (Vysis) for the Ewing’s gene. (C) Diagram showing interphase FISH pattern with the split signal indicating a translocation involving the Ewing’s gene. (D) Interphase FISH image showing the pattern illustrated in C.

FIGURE 12.45

Nodular fasciitis. Loosely arranged fibroblasts lie randomly arranged like cells in tissue culture. While there are two mitotic figures (arrows) these are of normal appearance and although the cells vary in size the nuclei are not hyperchromatic.

FIGURE 12.46

Normal muscle stained to show ATPase activity at pH9.4. Type 1 fibres are pale staining and type 2 are dark.

FIGURE 12.47

Polymyositis. Necrosis and regeneration of muscle fibres are accompanied by focal chronic inflammation and fibrosis.

FIGURE 12.48

McArdle’s disease. Muscle stained for the presence of myophosphorylase activity. Normal (left) shows abundant dark blue reaction product, which is absent in the biopsy from an affected individual (right).

FIGURE 12.49

Becker-type muscular dystrophy. Staining for dystrophin shows patchy and variable staining (A) at the periphery of the fibres compared with the regular pattern of normal muscle (B). Staining is typically absent in Duchenne’s dystrophy.

FIGURE 12.50

Duchenne’s muscular dystrophy. This biopsy from advanced disease shows muscle fibres, many of which are atrophic, lying among adipose tissue.

FIGURE 12.51

Neurogenic atrophy. The majority of muscle fibres are denervated and have atrophied to small fibres whose nuclei appear large. A few large hypertrophied fibres are present.