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Musculoskeletal Pathology

Reading Assignments (Robbins: Pathologic Basis of Disease, 8th Ed.)
1206 - 1210 Introduction - normal bone, modeling and remodeling, growth and development
1219- 1220 Fractures
1221 - 1222 Infections
1218 - 1219 Rickets and osteomalacia; hyperparathyroidism; renal osteodystrophy
1216 - 1218 Paget's disease

Reading Assignments (Robbins: Pathologic Basis of Disease, 7th Ed.)
1274 - 1278 Introduction: normal bone, modeling and remodeling, growth and development
1288 - 1289 Fractures
1290 - 1291 Infections
1287 - 1288 Rickets and osteomalacia; hyperparathyroidism; renal osteodystrophy
1284 - 1286 Paget's disease

LEARNING OUTCOMES: Students will be able to...

  1. Compare and contrast the histological features of the reparative response of bone as exemplified in a healing fracture with neoplastic processes.

  2. Recognize the tissues that constitute a fracture callus (i.e., fibrous tissue, cartilage, new bone).

  3. Describe the changes in bone that result from pyogenic bacterial infection.

  4. Describe the clinical manifestations and complications of osteomyelitis.

  5. Recognize the histopathologic changes of renal osteodystrophy in bone and explain the relationship(s) between renal failure, secondary hyperparathyroidism, and osteomalacia.

  6. Explain the relationship between the histopathologic features of Paget's disease and the process of exaggerated bone remodeling.

  7. Correlate the radiographic and clinical findings in Paget's disease with the pathologic features.

  8. Differentiate the nonspecific reactions to injury of bone (e.g., bone remodeling due to fracture) from the pathologic features that are characteristic of osteomyelitis, osteomalacia, renal osteodystrophy, and Pagetís disease.

  9. Explain potential complications for each of the disorders of bone discussed in lab.

The slides for this session have been selected because they illustrate typical bone responses to physical injury, metabolic abnormalities, and unknown stimuli.

The changes you see in the fracture recapitulate features of developing bone: endochondral bone formation, intramembranous bone formation, remodeling, fibrous proliferation, etc. There is abundant woven bone that you can compare with lamellar bone. The osteoblasts, osteocytes, and osteoclasts are recognizable and are often seen in a histologic setting that is indicative of their function. Many of these same features are seen in the other slides for today's exercise but they are frequently exaggerated. Try to envision the effects of such changes on the x-ray appearances and on the signs and symptoms in a patient's clinical presentation. Reparative and/or responsive changes in bone are somewhat unique in their appearance because of the mineralized nature of bone and the often complex features of the healing process in such tissue. Studying these slides should help you understand and recognize a range of cytologic and histologic changes in reactive bone so that you will be able to better appreciate how abnormal processes and neoplasms exceed these ranges or otherwise vary from normal.

In the more acute phase of osteomyelitis, there is often marked lysis of bone, so areas with many osteoclasts are commonly observed. Eventually, bone formation attempts to heal the damage or "wall off" the areas of inflammation, resulting in irregular and often excessive bone formation.

Several factors are at work in renal osteodystrophy. Hyperparathyroidism causes exuberant remodeling. "Cutting cones" are collections of increased numbers of osteoclasts that invade bone trabeculae and are in turn replaced by granulation tissue. Peritrabecular fibrosis often forms. Features of osteomalacia may be seen as focally excessive osteoid (uncalcified "bone").

Paget's disease is manifested by exaggerated bone remodeling. In contrast to normal remodeling, Pagetís disease produces greater irregularity of bone trabeculae, larger osteoclasts, and a mosaic pattern of bone due to prominent cement lines.

Slide 181 [WebScope] [ImageScope]

Healing fracture

This 43-year-old man noted a painful rib mass that gradually enlarged over a period of approximately three weeks. An x-ray revealed a fracture with adjacent bony callus. As the patient did not remember a specific injury, the lesion was removed because of the question of a possible pathologic fracture.

This slide manifests well-formed osteoid and bone, cartilage, periosteal bone formation, and scar around bits of necrotic bone. This collection of features is characteristic of a callus. In fact, the callus recapitulates the normal growth and development of bone.

  1. What processes are at work in this callus that remind you of growing bone?

  2. What different tissues can you recognize?

  3. What histologic features indicate that this is a reparative rather than a neoplastic process?

  4. What factors or variables affect the reparative processes manifested by this slide?

Slide 182 [WebScope] [ImageScope]

Chronic osteomyelitis

This tissue was removed from the right humerus of a man who had injured his arm several years before and had had recurrent purulent drainage from the area, sometimes accompanied by systemic symptoms, such as chills and fever. The skin about the draining area was thickened, red, and irregular.

The tissue on the slide is somewhat variable, but consists, in some areas, of bone with irregular trabeculae (irregular because of exaggerated remodeling Ė note focal areas with many osteoclasts and prominent Howship's lacunae). In other areas of the slide, the trabeculae are thickened because of appositional bone formation, a result of chronic inflammation. The marrow is replaced by fibrous tissue containing polymorphous inflammatory cells, including neutrophils. Necrotic bone may also be seen. In addition to the bone, there is scar tissue and squamous epithelium. This is the epithelium that lined a sinus tract responsible for the clinical drainage. The tract extended from the inflamed bone to the skin surface.

  1. What bacteria are commonly encountered in hematogenously disseminated osteomyelitis? Sickle cell osteomyelitis? What other types of infective agents can cause osteomyelitis?

  2. What are the clinical and radiographic manifestations of osteomyelitis?

  3. How is the diagnosis of osteomyelitis established?

  4. What are the histopathologic features of osteomyelitis?

  5. The patient was diagnosed with chronic osteomyelitis. Which persons are at increased risk for developing chronic osteomyelitis?

  6. Predict the histopathologic features produced by tuberculous osteomyelitis.

Slide 183 [WebScope] [ImageScope]

Renal osteodystrophy

This section is taken from the vertebrae of an adult with renal failure who had undergone long-term hemodialysis. She died of pneumonia.

This is a striking example of secondary hyperparathyroidism (osteitis fibrosa cystica) involving bone, a process of high turnover osteodystrophy. The primary change is that of exaggeration of osteoclastic lysis of bone. Osteoclasts erode into bone trabeculae, followed by loose fibrous tissue. The osteoclasts and fibroblasts form a "cutting cone," a hyperreactive process seen on a much smaller scale in normal remodeling of bone. Note the irregularity of trabeculae, the many Howship's lacunae, and the loose fibrous tissue within and around bone trabeculae. Although there is probably an element of osteomalacia in this slide as well (a feature of renal failure), it is not recognizable since the tissue has been decalcified. Renal osteodystrophy is complex and usually manifests a combination of bone changes.

  1. What are the bone changes of renal osteodystrophy?

  2. How does chronic renal failure often lead to these bone changes?

  3. What are the clinical and radiographic manifestations of renal osteodystrophy?

Slide 184 [WebScope] [ImageScope]

Paget's disease of bone

A 60-year-old man had severe back pain. X-rays of his spine revealed a vertebral compression fracture and irregular lucencies of several vertebrae. An operation was performed to relieve nerve compression. Metastatic carcinoma was suspected.

The tissue consists of multiple, fairly large, pieces of bone, most of which demonstrate exaggerated bone remodeling. Very large osteoclasts reside in large Howship's lacunae, resulting in marked bone distortion. Pronounced osteoblastic activity involves the same trabeculae being resorbed by the osteoclasts. The result of excessive lysis and active bone formation is an irregular pattern of bone resembling a jigsaw puzzle or a mosaic of irregular bone plates outlined by prominent cement lines. There is fibrosis, but it tends to replace marrow in affected areas and is not characteristically peritrabecular as in hyperparathyroidism (osteitis fibrosa cystica). The giant osteoclasts present are characteristic of this disease. Some osteoclasts may have over a hundred nuclei. Another characteristic feature is the very prominent vascularity and telangiectasia of the involved sites. This disorder is initially primarily lytic due to very active osteoclasts. It then has a lytic-blastic phase when lysis and bone production tend to balance each other. Eventually, osteoclastic activity decreases and the bone production results in irregular dense bone.

  1. What clinical laboratory tests may aid in the diagnosis?

  2. What radiologic changes may indicate the diagnosis?

  3. What is the usual clinical presentation for this disorder? Describe the geographic distribution of this disorder.

  4. What are the theories of pathogenesis?

  5. What are the complications of Pagetís disease?

  6. How do the pathologic features differ from renal osteodystrophy?

The answers to the path lab questions will be posted approximately 48-72 hours after the lab sessions. These are abbreviated answers, not a full discussion of the topics. You can find them in the M2 CTools site resources. In the folder for each sequence the will be a folder called 'Path Lab Resources'


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