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Musculoskeletal Pathology
LABORATORY 3


Reading Assignments (Robbins: Pathologic Basis of Disease, 8th Ed.)
1227 Osteochondroma
1229 - 1230 Chondrosarcoma
1224 - 1229 Bone forming tumors
609 - 611 Multiple myeloma (plasmacytoma)
1235 Metastatic carcinoma

Reading Assignments (Robbins: Pathologic Basis of Disease, 7th Ed.)
1296 Osteochondroma
1298 - 1299 Chondrosarcoma
1293 - 1296 Bone forming tumors
679 - 681 Multiple myeloma (plasmacytoma)
1302 - 1303 Metastatic carcinoma

LEARNING OUTCOMES: Students will be able to...

  1. Compare and contrast the clinical presentation, radiographic findings, gross and microscopic pathologic findings, and general treatment options for bone neoplasms.

  2. Differentiate the gross and histopathological features favoring a malignant process and those features favoring a benign process of bone.

  3. In patients with abnormalities of bone, develop a differential diagnosis based on clinical presentation, radiographic findings and gross and histopathologic features.


In this laboratory you will be able to review a sampling of the many neoplasms that may involve bone either primarily or secondarily. These include a range of chondroid, osteogenic, hematopoietic, and metastatic neoplasms. When you are studying these neoplasms, compare the features with the reactive changes seen in the previous laboratories. Note the histopathologic similarities and differences and develop an appreciation for the different types of information required for an accurate pathologic diagnosis.

There is little information in your text about metastatic neoplasm to bone and yet metastases far outnumber primary bone tumors approximately 25 to 1. More than 80% of metastases are from carcinomas of breast, prostate, lung, kidney, and thyroid. X-rays of metastases may be lytic (entirely destructive of bone), blastic (causing bone production), or manifest a combination of these features. Metastatic carcinoma from kidney and thyroid are usually purely lytic, carcinoma of prostate is most often blastic, and carcinoma of breast and lung often are mixed. This slide is an excellent example of an osteoblastic prostate carcinoma metastasis. Metastases may induce a variety of pathologic features, including periosteal bone formation, fractures with callus formation, and inflammation. The clinical history is very important; the average age of patients with metastasis is 55 and the most commonly involved bones are those of the spine.


Slides 185 [WebScope] [ImageScope]

Osteochondroma

The specimen was removed from the fibula of a 22-year-old woman because she continually hit it and it had become tender. It was on the lateral side of her knee and presented as a small bump that had been present for many years and had not changed in size.

This slide shows a very unexciting example of this lesion that was selected because the entire specimen could fit on one slide. It was simply sliced off of the fibula. The lesion consists of cortical and cancellous bone and fatty marrow. On one surface there is a small cartilaginous cap which is covered by a thin layer of fibrous tissue. This is the typical appearance of this lesion. A small area of the growth plate breaks through the cuff of periosteal bone that normally surrounds the growth plate and grows in a different direction from that of the parent bone. It usually ends up at about a 45-degree angle to the parent bone and attaches smoothly to the cortex of that bone. The marrow is continuous with the bone from which it arises. The cartilage cap is merely part of the cartilaginous growth plate analogous to the articular cartilage in the normal adult bone. The layer of fibrous tissue over the cartilage is really periosteum since the lesion grows right out the side of the parent bone. There are all sizes and shapes of this common lesion and it may be painful or deforming. The lesion enlarges as the bone grows in length and stops growing when the parent bone no longer grows. This lesion needs to be distinguished from parosteal osteosarcomas, myositis ossificans, and other bone surface tumors. Sarcomatous transformation to chondrosarcoma is seen rarely. There is a syndrome of hereditary multiple osteochondromas. Malignant transformation is more commonly seen in the setting of this syndrome.

  1. What clinical features would lead you to examine, x-ray, and consider removing such a lesion?


Slide 186 [WebScope] [ImageScope]

Chondrosarcoma

This tissue was part of a relatively large neoplasm involving the pelvis in a 60-year-old woman. X-rays showed a destructive mass involving the pubic bone. Spotty calcification was also seen.</p>

This slide is mostly neoplasm (except for strands of fibrous tissue and skeletal muscle) that consists of lobules of tissue that are quite cellular, particularly at the outer edges of the lobules. The cells mature slightly towards the center of the lobules, where the hyaline matrix is more abundant, and the cells rest in clear lacunar spaces. These features resemble cartilage. There are also foci of calcification but no evidence of bone formation from malignant cells. This appears to be a purely cartilaginous neoplasm. It is malignant for the following reasons: clinical and x-ray evidence, hypercellularity, cell nuclei manifesting hyperchromatism and pleomorphism, and areas with numerous mitotic figures. For a cartilaginous tumor, these features indicate a moderately high grade of malignancy.

  1. Is the clinical history in this case typical?

  2. Are these neoplasms usually regarded as high grade or low grade neoplasms?

  3. How does the histologic grade affect prognosis and treatment?

  4. How would your diagnosis change if bone or osteoid were produced directly from malignant cells in a small area of the neoplasm?


Slide 192 [WebScope] [ImageScope]

Osteoid osteoma

This specimen was removed from a 16-year-old girl who had complained for several months of pain in her left leg. The pain was more severe at night but responded very well to aspirin or other mild analgesics. Her doctor had interpreted her complaints as "growing pains" but finally obtained an x-ray. A dense area was noted that involved the tibial diaphyseal cortex, and in the center of the density was a small lucency.

This section is the surgical specimen. Note that in the center of rather dense bone there is a small well-circumscribed area called a nidus that appears to consist of osteoid or bone trabeculae rimmed by osteoblasts. The nidus has the appearance of reactive new bone and appears similar to a bony callus or area of periosteal reactive new bone. The osteoblasts are plump and numerous. Osteoclasts should also be readily apparent. The tissue surrounding the new bone spicules is very vascular and fibrous. Cartilage is not seen. This is a very typical appearance of a benign bone-forming lesion known as an osteoid osteoma. The exact nature of the lesion is still somewhat controversial, since it does not grow larger and, if near a joint, may be associated with chronic synovitis. A lesion that is histopathologically similar but is larger and without surrounding bony sclerosis is a benign neoplasm known as an osteoblastoma.

  1. What features indicate that this lesion is benign?


Slide 187 [WebScope] [ImageScope]

Osteogenic sarcoma

This specimen was taken from a larger neoplasm that involved the distal femur of a 16-year-old male. The patient had noted vague but rather persistent pain for a few weeks; he had come to the doctor because his knee was swollen and he had begun to limp.

The slide shows a very invasive and destructive neoplasm that involves the normal bone trabeculae and replaces the marrow completely. One side of the specimen is residual cortex, but it has been completely invaded by the neoplasm and is partially destroyed. The neoplasm is relatively typical, with sheets of poorly differentiated malignant cells that appear to produce osteoid. There is a complete lack of the normal organized bone production in which osteoblasts line the trabeculae in a regular fashion. There are a few areas of the neoplasm in which malignant cartilage is also seen resembling chondrosarcoma. It has been said that the most constant feature of this neoplasm is its variability, so it is difficult to cover all features of this neoplasm in one case. The most important histopathologic feature is the finding of osteoid or bone being produced by the malignant cells. This feature is the diagnostic sine qua non.

  1. Who is the typical patient with this neoplasm?

  2. Are there known etiologic factors?

  3. What are some other histologic subtypes of osteogenic sarcom?

  4. What x-ray changes are typical?


Slide 48 [WebScope] [ImageScope]

Metastic prostate carcinoma

This is a section of vertebra taken at the autopsy of a man with prostatic carcinoma. He had had a high serum PSA and evidence of bony involvement with multiple osteoblastic metastases. Despite radiation and chemotherapy, his disease progressed and he and his family asked that there be no further treatment attempts. He died shortly after that decision.

This slide is an example of the most common of all malignant tumors involving bone-metastatic carcinoma. The ratio of skeletal metastases to primary bone tumors is about 25 to 1. Of carcinomas that metastasize to bone, the most common primary sites are breast, prostate, and lung. Kidney, thyroid, and GI tract are also important primary sites. Note that in this slide the marrow is replaced by fairly well differentiated adenocarcinoma, often having cribriform (glands within glands) glands surrounded often by dense fibrosis. Note appositional bone formation, probably stimulated by the neoplasm. This feature is commonly seen with metastases from prostate and quite often with breast carcinoma as well. This is a good specimen to note the difference between mature lamellar bone and the newly formed woven bone. Woven bone is abnormal in the adult; it is always caused by some abnormal stimulus, such as trauma, infection, or neoplasm.

  1. What would you expect the x-ray to look like in this case?

  2. What would be the most likely primary site if the patient were a woman? A man?


Slide 176 [WebScope] [ImageScope]

Multiple myeloma

This specimen is from the rib of a 64-year-old man who had complained of increasingly severe back pain and generalized weakness. X-rays revealed lytic lesions of his spine, skull, and ribs.

The rib marrow is uniformly replaced by recognizable plasma cells. The extent of the plasma cell infiltration is strong evidence for multiple myeloma, but serum protein evaluation and x-rays also constitute important data for a firm diagnosis. There is frequently severe loss of bone at the sites of involvement and pathologic fractures are not uncommon.

  1. What other diagnoses might be considered, given the history and x-rays?

  2. Does the presence of plasma cells in a marrow always indicate myeloma?

  3. What is the usual effect on the bone of a myeloma lesion?


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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