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2010—May Case of the Month

Posted May 05, 2010

CLINICAL SUMMARY: BONE, RIGHT ILIUM  

CAP Foundation April 2010 Online Case of the Month

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After reading the summary, try answering the three related multiple-choice questions below.

A 78-year-old man with a history of Paget disease of bone involving both hips, complained of increasingly severe pain in his right hip for about six weeks. He was admitted for total hip arthroplasty. During surgery a large mass was identified, arising from the iliac crest and wrapping around the sciatic nerve. Multiple fragments of yellow/pink, fleshy tissue measuring 9.0 x 7.0 x 2.5 cm in greatest dimensions were submitted for examination.

Archive Case and Diagnosis: This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2007, Case 20 and is an osteosarcoma.

Criteria for Diagnosis and Comments: The diagnosis is osteosarcoma. Osteosarcomas are malignant tumors of mesodermal origin within which the tumor cells produce bone or osteoid (also referred to as "tumor osteoid/ bone"). They usually produce other matrices as well, which in some cases can dominate the neoplastic cell population. However, osteoid production is, by definition, present and must be identified to make the correct diagnosis. Depending on the predominant cell type and matrix (more than 50% of the tumor) conventional osteosarcomas can be divided into osteoblastic, chondroblastic, and fibroblastic subtypes. This is arbitrary since most osteosarcomas will produce varying amounts of all three types.

Osteosarcomas usually involve the metaphyseal region of long bones and are more common in the second and third decades of life when presenting de novo and without an underlying pathologic process. However, a second peak of activity occurs in the sixth and seventh decades. Here, the osteosarcoma is seen to be secondary to other conditions such as fibrous dysplasia, previous irradiation to the site, or Paget disease of bone.

Ninety percent of osteosarcomas are high grade tumors (grade 3 or 4) of conventional (intraosseous) type. Histologically, they are comprised of lace-like seams of osteoid distributed in a sarcomatous stroma. The malignant cells are polygonal to spindled and show marked nuclear pleomorphism. Abnormal mitotic figures are readily identifiable. Areas of chondroblastic differentiation, when present, show islands of cartilage with atypical chondrocytes having open-faced nuclei. Malignant fibrous histiocytoma and aneurysmal bone cyst-like patterns can also be found in conventional osteosarcomas. However, a total or near total aneurysmal vascular pattern should be regarded as telangiectatic osteosarcoma rather than a conventional type.

The importance of radiographic studies in the diagnosis of osteosarcoma cannot be over-emphasized. The lesion classically appears as a poorly circumscribed medullary lucency with mottled areas of radiodensity. Cortical destruction is usually present and focal invasion of the overlying soft tissue by mineralized tumor is not unusual. Periosteal reactive bone formation is appreciated as Codman's [tri]angle, at the interface with the soft tissue mass. Ancillary radiographic studies (CT, MRI) are often not necessary in the diagnosis of osteosarcoma. Nevertheless, they can be extremely useful in evaluating the extent of disease and/or presence of skip metastases, which occur in 5-10% of patients.

Sarcomas of bone are known to complicate long standing osteitis deformans (Paget disease) albeit at a very low frequency of less than 1%, although some authors report that the incidences as high as 12.5%. Nevertheless, this is a significantly higher risk than that to the general population. The majority of sarcomas arising in the background of Paget disease of bone are osteosarcomas although other types are well documented. Virtually all bones have been described as being susceptible to this transformation but the axial skeleton and the bones of the pelvis appear to be over-represented. Older men are more often seen to be affected. It is recognized that these older patients often have a worse prognosis than many patients with de novo osteosarcomas The survival rate is extremely poor with a 5 year survival of less than 10%. Molecular genetic and cytogenetic evaluation has shown Pagetic osteosarcomas [like sporadic conventional osteosarcomas] have loss of heterozygosity at the distal portion of chromosome 18q, which is thought to contain a tumor suppressor locus.

Fibrous dysplasia is a neoplastic lesion of bone characterized by proliferation of fibroosseous tissue in the medullary canal which usually occurs during skeletal growth but may first come to attention shortly after birth or in old age. Histologically, fibrous dysplasia shows irregular seams of woven new bone in a fibrous stroma of varying cellularity. The bony spicules are thin, discontinuous and arranged in curved shapes. Osteoblastic rimming is usually not identified outside the jaws and, although occasionally cellular, the stroma does not exhibit any atypia. Monostotic and polyostotic forms of fibrous dysplasia exist and, when associated with McCune-Albright syndrome, a genetic complex characterized by café au lait spots and endocrine abnormalities, or Mazaubraud disease; an increased risk of malignant transformation including development of osteosarcoma exists.

Malignant fibrous histiocytoma of bone is a rare tumor representing approximately 2% of all malignant lesions of the skeleton. It can be primary (exceedingly rare) or secondary, arising as a "dedifferentiated" focus in a background of chordoma, chondrosarcoma, giant cell tumor, or in pre-existing non-neoplastic bone conditions such as bone infarct, around foreign bodies, and Paget disease. It, like osteosarcoma, can also arise at sites of previous therapeutic irradiation for other pathologic processes including malignancies. It has a predilection for the long bones of the lower extremities, the femur being the most commonly affected (30-45%), followed by tibia. It is usually a diagnosis of exclusion and only when thorough sampling reveals no areas suggestive of another primary bone tumor will the diagnosis be supported. Histologically, malignant fibrous histiocytoma of bone is a poorly differentiated pleomorphic sarcoma having the same features as its soft tissue counterpart.

Mesenchymal chondrosarcoma is a small, round, blue cell neoplasm with foci of cartilaginous differentiation. The tumor is most common between the first and fourth decades of life and has a predilection for bones of the face, ribs, pelvis, and femur. Radiologically these are poorly circumscribed lytic lesions showing faint stippled calcifications. Histologically, the main feature of mesenchymal chondrosarcoma is the presence of sheets of small round cells with scant cytoplasm expressing Vimentin, CD57, and CD99. The small blue cell morphology together with expression of CD99 may make the mesenchymal component of this tumor difficult to differentiate from Ewing sarcoma/PNET or small cell osteosarcoma whereas the cartilaginous component can be misdiagnosed as chondroblastic osteosarcoma. The absence of tumor osteoid is critical for the diagnosis.

Osteoid osteoma is a benign bone-forming tumor characterized by small size (less than 2 cm), limited growth potential, pain, and a tendency to cause extensive reactive changes in adjacent tissues. It can occur in any bone but the most common site of involvement is the femur, followed by tibia. The radiographic appearance of osteoid osteoma is very characteristic: a radiolucent space (nidus) is surrounded by dense reactive bone. Histologically the nidus is comprised of interconnecting thin bands of osteoid or woven bone separated by loose fibrovascular stroma and lined by osteoblasts (osteoblastic rimming). The nidus is sharply demarcated from the surrounding reactive bone.

Reactive changes secondary to infection are seen in long standing osteomyelitis. Radiographically, osteomyelitis is characterized by lytic lesions in a background of bone sclerosis. Histologically, there is replacement of bone marrow by inflammatory cells, and reactive new bone formation. The nature of the inflammatory infiltrate is slightly different in acute versus subacute or chronic osteomyelitis. However, as with most of the bone lesions, osteomyelitis is a diagnosis that requires proper clinical and radiologic correlation.

Supplementary Questions For each of the following, select the most likely diagnosis from the diagnostic set (an answer may be used once, more than once, or not at all).

Question Diagnostic Set
1. Which entity is a well circumscribed lesion composed of various proportions of fibrous and osseous elements? The osseous component is represented by irregular, curvilinear, discontinuous trabeculae of woven (or rarely lamellar) bone with no osteoblastic rimming: A. Fibrous dysplasia
B. Malignant fibrous histiocytoma of bone
C. Mesenchymal chondrosarcoma
D. Osteoid osteoma
E. Osteosarcoma
F. Reactive changes secondary to infection
2. Which entity frequently complicates preexisting osseous lesions (i.e. radiation damage, Paget disease, cartilaginous neoplasms, and rarely bone infarcts) and is microscopically composed of pleomorphic spindle cells arranged in a storiform pattern and not associated with tumoral osteoid formation? A. Fibrous dysplasia
B. Malignant fibrous histiocytoma of bone
C. Mesenchymal chondrosarcoma
D. Osteoid osteoma
E. Osteosarcoma
F. Reactive changes secondary to infection
3. Which entity is most often associated in later life with an underlying primary pathologic condition of bone such as fibrous dysplasia or Paget disease? A. Fibrous dysplasia
B. Malignant fibrous histiocytoma of bone
C. Mesenchymal chondrosarcoma
D. Osteoid osteoma
E. Osteosarcoma
F. Reactive changes secondary to infection

References

  1. Fletcher CDM, Unni KK, et al. Pathology and genetics of tumours of soft tissue and bone. Lyon, IARC Press; 2002.
  2. Hansen, MF, Nellissery MJ, Bhatia P. Common mechanisms of osteosarcoma and Paget's disease. J Bone Mineral Res. 1999;14:39-44.
  3. Huvos AG, Butlerr A, Bretsky SS. Osteogenic sarcoma associated with Paget's disease of bone. A clinicopathologic study of 65 patients. Cancer. 1983;52:1489-1495.
  4. Klein MJ, Siegal GP. Osteosarcoma: anatomic and histologic variants. Am J Clin Pathol. 2006;125: 555-581.
  5. Lopez-Ben R, Pitt MJ, et al. Osteosarcoma in a patient with McCune Albright Syndrome and Mazabraud's Syndrome. Skel Radiol. 1999;28:522-526.
  6. McCarthy EF, Frassica FJ. Pathology of bone and joint disorders with clinical and radiographic correlation. Philadelphia, Saunders; 1998.
  7. McNairn JD, Damron TA, et al. Inheritance of osteosarcoma and Paget's disease of bone: a familial loss of heterozygosity study. J Mol Diagn. 2001;3: 171-177.
  8. Wick MR, Siegal GP, et al. Sarcomas of bone complicating osteitis deformans (Paget's Disease): Fifty years experience. Am J Surg Pathol. 1981;5:47-59.

Author:
2007
Luminita Rezeanu, MD
Fellow in Musculoskeletal Pathology
University of Alabama at Birmingham

Gene P. Siegal, MD, PhD
Surgical Pathology Committee
University of Alabama at Birmingham
Birmingham, AL