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Musculoskeletal Pathology
LABORATORY 2


Reading Assignments (Robbins: Pathologic Basis of Disease, 8th Ed.)
1235 - 1240 Osteoarthritis and rheumatoid arthritis
1242 - 1246 Gout and gouty arthritis
516-517 Wegener granulomatosis

LEARNING OUTCOMES: Students will be able to...

  1. Compare and contrast the histopathologic features of degenerative joint disease with those seen in rheumatoid arthritis.

  2. Recognize the features of inflammatory pannus and describe the progression of joint damage to development pf ankylosis in rheumatoid arthritis.

  3. Describe how the pathologic changes relate to the clinical symptoms in rheumatoid arthritis.

  4. Describe the histopathologic features of a gouty tophus and how crystal deposition leads to joint damage and clinically symptoms.

  5. Explain the difference between primary and secondary gout.

  6. Recognize the salient histologic features of granulomatosis polyangiitis (Wegener granulomatosis).


Slides 193 [WebScope] [ImageScope] and 197 [WebScope] [ImageScope]

Rheumatoid synovitis with rheumatoid nodule and rheumatoid arthritis

These tissues were removed from patients with severe deforming arthritis and/or joint movement limitation. The surgery was a form of reconstruction to improve function.

Both of the slides illustrate the involvement of synovium, articular cartilage, and underlying bone in rheumatoid arthritis. Slide 193 depicts synovium removed from a patient's wrist in the process of reconstructive surgery to improve the function of severely affected joints. This is a particularly good illustration of the increased length and thickness of synovial villi caused by an inflammatory infiltrate (primarily lymphocytes, plasma cells, and macrophages), hyperplasia of synovial lining cells (synoviocytes), and accumulation of fibrin on the surfaces and within the tissues. In several areas, there is fibrinoid necrosis of the synovium, sometimes involving the surface and sometimes involving the deeper areas. These areas represent "rheumatoid nodules" that are commonly found in soft tissues around joints, but which may also extend to the synovium and other tissues. There is excellent "palisading" of macrophages around the areas of necrosis.

Slide 197 is a portion of articular cartilage with underlying bone. There is little cartilage in the slide, but the purpose of the slide is to demonstrate further the inflammatory nature of the rheumatoid process. The inflammatory tissue of the synovium has extended to eventually destroy much of the articular cartilage and erode into the subchondral bone. What you see is bone with irregular trabeculae and some new bone formation. Inflammatory tissues resembling that seen in the synovium have replaced the normal marrow. There are aggregates of lymphocytes, scattered plasma cells, and there are areas of necrosis surrounded by fibroblasts, macrophages, and other inflammatory cells. It should be evident that there is significant destruction of the joint.

  1. Which joints are characteristically involved in rheumatoid arthritis?

  2. What is inflammatory pannus?

  3. What is the eventual outcome of joints affected by unabated rheumatoid arthritis?

  4. What are rheumatoid nodules?

  5. Rheumatoid arthritis is considered to be an autoimmune process, the etiology of which is still somewhat uncertain. How do the various cells in the inflammatory tissues in your slides contribute to the destruction of the joints?

  6. How would you histologically differentiate rheumatoid arthritis from degenerative joint disease (osteoarthritis)?


Slide 196 [WebScope] [ImageScope]

Osteoarthritis

These sections are from the femoral head of a 64-year-old man who had noted increasing pain and stiffness of his hips for the past two to three years. He found it very difficult to "get moving" in the morning and noted increased pain, particularly on the left side, as the day progressed.

The slide consists of two sections of the articular surface of the femoral head. The articular cartilage should be of relatively uniform thickness. In both of the pieces, a variety of abnormalities is evident. The cartilage is frayed on the surface, the chondrocytes are grouped together, a portion of the cartilage is abruptly thinned, and the adjacent subchondral bone is sclerotic (abnormally thickened trabeculae) and has a smooth surface. Note that in the areas where the cartilage is completely eroded there are many abnormal changes in the adjacent bone. The changes are due to the chronic trauma of bone moving against another bone in a joint where the cushioning function of the articular cartilage is absent. The changes are similar to those of fracture callus. There is reactive new bone formation and lobules of cartilage and fibrous tissue with some cystic degeneration. Characteristically, the "bare" bone at the bone ends becomes altered, shifting the stress points, and stimulating new bone and cartilage to proliferate within the synovium at the margins of the joints forming irregular nodules termed osteophytes.

  1. What joints are involved in degenerative joint disease?

  2. What are the changes noted in the cartilage that are considered degenerative?

  3. The patient likely had primary osteoarthritis of the hip. Please mention several risk factors for this disorder.

  4. What disorders can cause secondary osteoarthritis of the hip?

  5. How do you explain the bone changes in the areas where the articular cartilage is absent?

  6. What is the eventual course of degenerative joint disease?


Slide 12 [WebScope] [ImageScope]

Gouty tophus

This para-articular mass was removed from a patient who had a long history of intermittent acute bouts of arthritis. He carried the diagnosis of gout.

This slide is a section of the pathognomonic lesion of gout, the tophus. The specimen was fixed in alcohol so that the water soluble urate crystals were preserved. They appear as brownish, needle-shaped crystals deposited in irregular masses and surrounded by unusual multinucleated giant cells. If you could examine your slide with polarizing lenses, the crystals would be brightly anisotropic. Even when the crystals are dissolved by ordinary formalin fixation, the residual pattern of deposition and the characteristic giant cells are good presumptive evidence of gout.

The diagnosis of gout is usually made on the basis of the clinical symptoms, hyperuricemia, and/or the presence of urate crystals in neutrophils within synovial fluid of the affected joint. Treatment is generally effective in controlling the acute symptoms and in preventing chronic changes. The chronic disease is caused by urate deposition in synovium, with reactive inflammation, pannus formation, and destruction of articular cartilage. Occasionally, a surprise diagnosis is made when tophi are seen in joint tissue that is removed from a patient having the diagnosis of degenerative joint disease.

  1. What are the diagnostic features of gout in synovial fluid?

  2. What are the usual histopathologic features of a tophus that involves the synovium?

  3. What joints are involved in gout?

  4. What are the renal complications of chronic gout?

  5. What is the difference between primary and secondary gout?


Slide 100 [WebScope] [ImageScope]

Granulomatosis polyangiitis (Wegener granulomatosis)

This slide illustrates a classic example of nasal involvement in granulomatosis polyangiitis (GPA), formerly Wegener granulomatosis. This is a large nasal biopsy in a 52 year old man with weight loss, fevers, epistaxis and cough with hemoptysis. On exam, rhinitis with a nasal septal perforation was identified. The slide is quite busy but several salient histologic features of GPA are easily identified. In areas, the surface mucosa is intact next to areas demonstrating ulcer and underlying mixed acute and chronic inflammation. At low power, throughout the specimen, areas of serpiginous necrosis are identified (pinker areas). Look at higher magnification in these areas and identify cells in various stages of cellular necrosis. Some appear intact; others demonstrate coagulative necrosis (‘ghost’ cells) and others are just nuclear fragments (karyorrhexis). This type of necrosis is typical of the stromal necrosis seen in GPA. In other areas, microabscess are also present and are also typical of GPA. Although well-formed granulomas are not present in most cases of GPA, the ‘granulomas’ that are seen in GPA are comprises of loose clusters of multinucleated giant cells. Many blood vessels are present in this specimen and most show at least segmental involvement by a destructive vasculitis. The easiest to recognize are the small muscular arteries.

  1. What organs are typically affected in granulomatosis polyangiitis (GPA)?

  2. What is the histologic triad in GPA?

  3. What sized vessels are involved in GPA?

  4. What laboratory test would help in supporting a diagnosis of GPA?

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 there will be a folder called 'Path Lab Resources'


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