Final Diagnosis -- Dedifferentiated chondrosarcoma

FINAL DIAGNOSIS   

Dedifferentiated chondrosarcoma

DISCUSSION

Chondrosarcomas are polarized by age and location. In the older patient population, they occur primarily in long tubular bones, whereas in the younger population they occur more often in flat bones. The current histologic grading scheme separates these tumors into 3 grades based on cellularity, cytologic atypia and mitotic activity. Compared to enchondromas, grade 1 chondrosarcomas have increased cellularity and contain plump nuclei with more open, vesicular chromatin. The cells tend to be of uniform size and binucleation is usually present. With increasing grade, chondrosarcomas become more cellular and develop large hyperchromatic nuclei with increasing degrees of nuclear atypia and mitotic activity.

Dedifferentiated chondrosarcomas have a malignant cartilaginous component that is juxtaposed with a divergent, high grade spindle cell sarcoma. These two cell populations are sharply demarcated, with no transition zone between them. In the case presented above, the cartilaginous component was represented by a grade 2 chondrosarcoma. Interestingly, the dedifferentiated component had features of an osteosarcoma, with true malignant osteoid formation. Johnson et al. reviewed a series of 26 cases of dedifferentiated chondrosarcoma and found that only 2 cases showed osteosarcomatous differentiation in the high grade spindle cell component. More commonly, this component showed a histologic appearance of fibrous or myoid differentiation.

The differential diagnosis for dedifferentiated chondrosarcoma is potentially extensive depending on the features of the dedifferentiated component and the location of the lesion. In this case, the differential diagnosis would include mesenchymal chondrosarcoma. Microscopically, mesenchymal condrosarcoma has a biphasic pattern of undifferentiated small round cells admixed with islands of hyaline cartilage, this could look microscopically similar to dedifferentiated chondrosarcoma. However, it will not show a sharp demarcation between components. In addition, the undifferentiated areas of mesenchymal chondrosarcoma typically simulate Ewing sarcoma, and a hemangiopericytomatous vascular pattern is common (this vascular pattern is not seen in dedifferentiated chondrosarcoma). The most common sites for mesenchymal chondrosarcoma include craniofacial bones, vertebrae, ilium, and ribs.

Other points:

• Patients usually older than 50 with M>F.
• Most common site is proximal femur. Other common sites include pelvis and humerus.
• Diagnosis carries poor prognosis, despite management with surgery +/- chemoradiation. Mortality is 90%, with distant metastases within 2 years.
• Low grade and dedifferentiated high grade share identical genetic aberrations,which suggests that they both arise from a common precursor cell.
• Several additional genetic aberrations that may provoke dedifferentiation include overexpression of p53, cyclin D1
• Ossification of anaplastic component has been shown to occur by both membranous and enchondral mechanisms.
• Metastases usually show only high grade anaplastic component.

REFERENCES

Dornauer, K., Söder, S., Inwards, C. Y., Bovee, Judith. V. M. G. and Aigner, T. (2010), Matrix biochemistry and cell biology of dedifferentiated chondrosarcomas. Pathology International, 60: 365-372. doi: 10.1111/j.1440-1827.2010.02530.x

Fletcher, Christopher D. M., K. Krishnan Unni, and Fredrik Mertens. "Chondrosarcoma." Pathology and Genetics of Tumours of Soft Tissue and Bone. Lyon: IARC, 2002. 247-54.

Gattuso, Paolo. Differential Diagnosis in Surgical Pathology. Philadelphia, PA: Saunders/Elsevier, 2010.

Johnson, S. et al. 1985. Chondrosarcoma With Additional Mesenchymal Component (Dedifferentiated Chondrosarcoma). Cancer. 58:278-286.

Kim, M., Cho, K., Ayala, A.,and Ro1, J.Y. 2011. Chondrosarcoma: With Updates on Molecular Genetics. Sarcoma. 2011: 405437.

Meijer, D., de Jong, D., Pansuriya, T. C., van den Akker, B. E., Picci, P., Szuhai, K. and Bovée, J. V.G.M. (2012), Genetic characterization of mesenchymal, clear cell, and dedifferentiated chondrosarcoma. Genes Chromosom. Cancer, 51: 899-909. doi: 10.1002/gcc.21974

QUESTIONS:

1. You have a 31 year old patient recently diagnosed with chondrosarcoma. Out of the following choices, at what location would you expect this lesion to arise?
   1. Mandible
   2. Metatarsal
   3. Scapula
   4. Femur

2. When comparing histologic features of grade 1 chondrosarcomas with features of enchondromas, which statement is false?
   1. Enchondromas have more vesicular nuclei.
   2. Chondrosarcomas are more cellular.
   3. Enchondromas have more hyperchromatic nuclei.
   4. Chondrosarcomas have larger nuclei.

3. In what patient population and location is dedifferentiated chondrosarcoma most common?
   1. Male patients older than 50; pelvis
   2. Male patients between 30 and 50; proximal femur.
   3. Male patients older than 50; proximal femur
   4. Male patients older than 50; distal femur

4. The dedifferentiated component can have histologic features of which three:
   1. Osteosarcoma, fibrosarcoma, angiosarcoma
   2. Fibrosarcoma, osteosarcoma, rhabdomyosarcoma
   3. Rhabdomyosarcoma, osteosarcoma, liposarcoma
   4. Osteosarcoma, rhabdomyosarcoma, liposarcoma

5. What distinguishes dedifferentiated chondrosarcoma from mesenchymal chondrosarcoma?
   1. Mesenchymal chondrosarcoma has a sharp demarcation between the cartilaginous and dedifferentiated components.
   2. Dedifferentiated chondrosarcoma has a hemangiopericytomatous vascular pattern.
   3. Mesenchymal chondrosarcoma is typically not biphasic.
   4. One of the most common sites for mesenchymal chondrosarcoma is the jawbone.

Answers: 1C (a flat bone), 2A, 3C, 4B, 5D

Contributed by Kate Serdy, MD and Alka Palekar, MD