Case 247 - Discussion

Uploaded: 2008-06-25, Updated: 2008-07-02

 

 

 

Diagnosis: low grade Chondrosarcoma of the humeral head.
- Histologic grade: 1/3.
- Maximum tumor dimension: 10.0 cm.
- Mitotic rate: 0-1/10HPF

 

Sections of the tumor show multiple lobules of immature cartilage varying in size and shape. The neoplastic chondrocytes reveal mild pleomorphism with enlarged hyperchromatic nuclei and frequent binucleation. The mitotic count is 0-1 per 10 hpf. The tumor infiltrates into the marrow spaces and the bony trabeculae, and the tumor permeates cortical bone into the soft tissue in the medial inferior side. No tumor necrosis or area of dedifferentiation is noted.

   
 

Chondrosarcoma

Clinical Futures

 
  • Third most common primary malignant bone tumor (myeloma, osteosarcoma);

  • Adulthood and old age;

  • Pain, most common presenting symptom;

  • Most common sites: pelvic, shoulder girdles, upper ends of femur and humor, >2/3 ( osteosarcoma most often around the knee);

  • Involve diaphysis and metaphysis, rarely epiphysis;

  • Imaging studies commonly show calcification/minialilzation;

  • Secondary chondrosarcoma: 25% of cases, malignant transformation from preexisting enchondroma or osteochondroma;

Gross Findings

 
  • Lobulated, light/gray blue or white masses with solid or sticky mucoid matrix;

  • Matrix may undergo liquefaction, producing cysts full of liquid;

  • Calcification, chalky white deposits;

  • Necrosis.

Microscopic Findings

 
  • Lobules of various sizes with hyaline/myxoid cartilage matrix;

  • Calcification and reactive bone formation may be present;

  • Malignant chondrocytes in lacunae;

  • Permeation and distruction of the cortical bone;

  • Permeation of the medullary bone.

  • Grading:  cellularity, matrix (solid or myxoid), cytology, and relationship to the bone (permeative or not)

    • Grade 1 (low-grade)
      Very similar to enchondroma. However, the cellularity is higher, and there is mild cellular pleomorphism. The nuclei are small but often show open chromatin pattern and small nucleoli. Binucleated cells are frequent. Mitoses are very rare. Grade 1 chondrosarcomas are locally aggressive and prone to recurrences, but usually do not metastasize.

    • Grade 2 (low-grade)
      The cellularity is higher than in Grade 1 tumors. Characteristic findings are moderate cellular pleomorphism, plump nuclei, frequent bi-nucleated cells, and occasional bizarre cells. Mitoses are rare. Foci of myxoid change may be seen. Unlike Grade 1 tumors, about 10% to 15% of Grade 2 chondrosarcomas produce metastases.

    • Grade 3 (high-grade)
      Characteristic findings are high cellularity, marked cellular pleomorphism, high N/C ratio, many bizarre cells and frequent mitoses (more than 1 per hpf). These are high grade tumors with significant metastatic potential

Subtypes

 

 - Dedifferentiated (high grade), 6-10%
          - rare type of high grade chondrosarcoma which arises from a low grade chondrosarcoma;
          - a high-grade spindle-cell sarcoma coexists with a lower-grade chondroid tumour;
          - histologically there will be areas c/w MFH, osteosarcoma, or fibrosarcoma;
          - high risk for metatastasis, only 5% of patients will survive more than 5 years;
- Myxoid type, 5%

- Msenchymal type, 2%

- Clear cell (intermediate grade), 2%
          - rare, slow growing, locally recurrent tumor easily confused w/ chondroblastoma but malignant;
                - tumor is especially rare in a child or adolescent;
                - may invade epiphysis;
                - most common in proximal femur (over 50%) followed by proximal humerus;
          - microscopically, sheets of cartilaginous cells in a lobular arrangement are mixed with scattered giant cells;
          - this radiolucent lesion is often misdiagnosed and undertreated;
 - Atypical enchondroma (juxtacortical chondroma), 2%
          - histologic exam of a low grade chondrosarcoma may show nodular cartilage tissue with mostly isomorphic tumor cells;
          - tissue samples show cellularity than is seen w/ enchondroma;
          - differentiating between this malignant tumor growth and an enchondroma can be extremely difficult;
          - an aysmptomatic, well circumscribed calcified lesion which has not changed in size is most consistent w/ an enchondroma;
          - more peripherally located lesions are also more likely to represent an enchondroma;
 

Differential Diagnosis

 
  • Enchondromas: usually have well defined borders with no evidence of invasion. Quite often you will see nodules of enchondroma surrounded by the bone marrow and reactive bone trabeculae. That should not be mistaken for invasion. On the contrary, malignant nodules of chondrosarcoma infiltrate between the lamellar bone obliterating the marrow. Separation of the nodules by fibrous bands would be another feature highly suggestive of malignancy.

  • Chondroblastic osteosarcoma: affects children, sheets of spindle cells with the formation of lace -like osteoid.

Immunohistochemistry Straining

 
  • p53 overexpression and high Ki-67 proliferation index correlate with clinically aggressive behavior in chondrosarcomas. Recent data suggest that these immunohistochemical stains may be particularly useful for determining the prognosis of patients with Grade 2 chondrosarcomas.

Cytogenetics

 
  • Extraskeletal myxoid chondrosarcomas have been demonstrated to be caused by chimeric genes generated by translocations. The translocation t(9;22)(q22;q12) results in fusion of the CSMF (NR4A3) and EWS genes, creating a chimeric EWS/CSMF oncogene. The translocation t(9;17)(q22;q11) results in fusion of the CSMF and RBP56 genes, creating a chimeric RBP56/CSMF gene in cases of extraskeletal myxoid chondrosarcomas.

Treatment and Prognosis

 
  • Low-grade (Grades 1 and 2) tumors are locally aggressive and prone to recurrences, but their metastatic potential is low. Recurrent tumors may show an increase in grade. High-grade (Grade 3) tumors metastasize to the lungs, skin, and soft tissues.

Reference

 
  • Hasegawa T, Seki K, Yang P, et al: Differentiation and proliferative activity in benign and malignant cartilage tumors of bone. Hum Pathol 26:838, 1995

  • Oshiro Y, Chaturvedi V, Hayden D, Nazeer T, Johnson M, Johnston DA, Ordonez NG, Ayala AG, Czerniak B. Altered p53 is associated with aggressive behavior of chondrosarcoma: a long-term follow-up study. Cancer 1998;83(11):2324-2334

  • Nawa G, Ueda T, Mori S, et al: Prognostic significance of Ki-67 (Mib1) proliferation index and P53 over-expression in chondrosarcomas. Int J Cancer 69:86, 1996

  • AFIP, series 4