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Histology of bone sarcoma

The most common types of bone sarcoma are:

  • Osteosarcoma
  • Ewing`s sarcoma
  • Chondrosarcoma
  • Chordoma

Osteosarcoma

Osteosarcoma is the most common type of sarcoma in the bone. Microscopically malignant (atypical) cells produce bone or osteoid in this tumor type. There are many subtypes based on localization, clinical, radiological and microscopic findings.

Femur bone specimen with osteosarcoma. Click to enlarge. Photomicrograph of an osteoblastic osteosarcoma. Click to enlarge. Photomicrograph of a cytological specimen from an osteoblastic osteosarcoma. Click to enlarge.

Classical osteosarcoma

Classical osteosarcoma is seen in young people between 10 and 30 years old and it is located in the metaphysis of long bones typically around the knee joint or upper part of the arm. This tumor consists of malignant cells producing osteoid or bone with calcification. There is often areas with chondroblastic or fibroblastic differentiation. Thus, in small biopsies (not representative), incorrect diagnosis such as chondrosarcoma or fibrosarcoma can be concluded .

Well differentiated intraosseous osteosarcoma

Well differentiated intraosseous osteosarcoma is a spindle cell osteosarcoma. Slightly atypical spindle cells and very few mitotic figures are seen. There is a varying amount of bone trabeculas.

Teleangiectatic osteosarcoma

Teleangiectatic osteosarcoma is a relatively uncommon variant of osteosarcoma that radiologically can appear like an aneurysmal bone cyst (a benign condition). This tumor demonstrate large, blood-containing cysts with expansion of the cortex. Microscopically, a classical high grade osteogenic sarcoma is seen in addition to cysts and multinucleated giant cells are seen. Sometimes it can be difficult to demonstrate osteoid.

Parosteal osteosarcoma 

Parostealt osteosarcoma is situated on the bone surface usually distally on the femur and show a low grade fibroblastic growth pattern with bone production. About 50% of these tumors demonstrate chondroid differentiation. In single cases the underlying cortex and bone marrow might be infiltrated. In some cases also high grade components can appear and they are then designated as dedifferentiated parostealt osteosarcomas. These have worse prognosis compared to the ordinary type. Cytogenetic investigation may demonstrate ring chromosomes in this type a finding, separating it from classical osteosarcoma.

Ewing`s sarcoma

Ewing`s sarcoma, PNET (primitive neuroectodermal tumor) and Askin's tumor, belongs to a family of small cell tumors (”the Ewing family of tumors”) which demonstrate varying degree of neuroectodermal differentiation. These tumors can appear in soft tissue or bone.

Histologically, they consist of small round cells with sparse cytoplasm containing glycogen (glycogen can be demonstrated by histochemical PAS staining). A few cases show more pleomorphic cells. There is no matrix production and rosettes can sometimes be seen and is related to neuroectodermal differentiation. This tumor is, by definition, highly malignant and grading meaningless.

There are several differential diagnosis such as malignant lymphoma, mesenchymal chondrosarcoma, small cell carcinoma, and neuroblastoma. A number of special analysis are performed to exclude other diagnoses such as immunhistochemistry, cytogenetic or molecular methods (RT-PCR and FISH) and sometimes electron microscopy.

Immunhistochemical analysis demonstrates positivity for vimentine, CD99 (sensitive, but not specific) and FLI-1. It is important to include an extensive panel to exclude the differential diagnosis. Ewing`s sarcoma/PNET has positive findings for some neuroectodermal markers, such as synaptophysin, S-100 protein and chromogranin.

Specimen from humerus with Ewing`s sarcoma. Click to enlarge. Photomicrograph demonstrating Ewing sarcoma. Click to enlarge. Photomicrograph demonstrating Ewing sarcoma in a cytological specimen. Click to enlarge.

Ewing`s sarcoma/PNET has diagnostic genetic findings. The most common translocation is t(11;22)(q24;q12) with an EWSR1-FLI1 gene fusion (more than 90 %). There are several variants of translocations in Ewing's sarcoma/PNET where the EWSR1 gene is involved. EWSR1 rearranging (gene fusions) can appear in other malignant tumors such myxoid liposarcoma, extraskeletal myxoid chondrosarcoma and clear cell sarcoma, but then with other fusion partners. This can be determined by cytogenetic analysis, RT-PCR and FISH .

Example of tumors where EWSR1 is involved
Chromosome rearrangement Gene fusion Tumortype
t(2;22)(q35;q12) EWSR1-FEV Ewing sarcoma
t(7;22)(p21;q12) EWSR1-ETV1 Ewing sarcoma
t(11;22)(q24;q12) EWSR1-FLI1 Ewing sarcoma
t(17;22)(q21;q12) EWSR1-ETV4 Ewing sarcoma
inv(22)(q12;q12) EWSR1-PATZ1 Ewing sarcoma
t(2;22)(q33;q12) EWSR1-CREB1 Angiomatoid fibrous histiocytom/Clear cell sarcoma in soft tissue
t(12;22)(q13;q12) EWSR1-ATF1 Angiomatoid fibrous histiocytom/Clear cell sarcoma in soft tissue
t(9;22)(q22;q12) EWSR1-NR4A3 Extrasceletal myxoid chondrosarcoma
t(11;22)(p13;q12) EWSR1-WT1 Desmoplastic small round cell tumor
t(12;22)(q13;q12) EWSR1-DDIT3 Myxoid liposarcoma

Chondrosarcoma

Chondrosarcoma is a malignant tumor containing cartilage substance and chondrocytes. Production of osteoid is not part of this tumors, but reactive bone tissue can appear.

Chondrosarcoma can be divided based on localization (central, peripheral or juxtacortical) on the presence of preexisting lesion (de novo or secondary developed from preexisting osteochondroma), cell differentiation (low/moderate/high grade) or histological variant (Clear cell, mesenchymal or dedifferentiated).

Chondrosarcoma differ from enchondromas by being more cellular and pleomorphic. There is an increased variation in cell size, and often binucleated cells. Mitotic figures are rare. Myxoid and cystic areas indicate malignancy. Calcification and bone tissue can be seen. These tumors often filtrate into cortex or into surrounding soft tissue. Forkalkninger Higher grade chondrosarcomas can show severe atypia and abundant myxoid tissue. The growth pattern are charactarized by filling the bone marrow growing and sourrounding bone trabeculas. Cartilage is then seen on both sides of the bone trabecle (so called "permeation"). Immunohistochemistry show positive for vimentin and protein S-100, but negative for cytokeratin and EMA.

Dedifferentiated chondrosarcoma show well differentiated chondrosarcoma with areas with abrupt transition into high grade chondrosarcoma without  chondroid differentiation. These component is often spindle cell.

Chondrosarcoma is graded  1–3. Grade 4 is reserved for dedifferentiated and mesenchymal chondrosarcoma.

Humerus specimen with a chondrosarcoma. Click to enlarge. Photomicrograph of a low grade chondrosarcoma. Click to enlarge. Photomicrograph of a high grade chondrosarcoma. Click to enlarge.

Chordoma

Chordoma is a low grade malignant tumor that is locally aggressive and originates from chorda dorsalis. This type of tumor comprise 4% of malignant bone tumors. Tumor is characterized by a lobular growth pattern. The cells is growing in rows with vacuolated cells ("physaliphorous") in a myxoid substance. Immunohistochemistry is positivite for vimentin, cytokeratin, protein S-100 and EMA (in differential diagnosis to chondrosarcoma).

Specimen from sacrum with chordoma. Click to enlarge. Photomicrograph of a chordoma. Click to enlarge. Photomicrograph of a chordoma in a cytological specimen. Click to enlarge.

Evaluation of specimen

The operation specimen is studied to:

  • confirm preoperative diagnosis
  • evaluate extension of tumor, vessel invasion and necrosis
  • evaluate resection borders
  • evaluate treatment effect

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