2. PATHOLOGY and BIOLOGY


2.1 Biological data

2.1.1
Soft tissue sarcomas arise from mesodermic tissues. However, malignant schwannoma is included as well, which has an ectodermic origin.

2.1.2
The p53 gene seems altered in at least one third of sarcoma patients. In another third of patients the MDM2 gene is amplified, with inhibition of the p53 as a result.

2.1.3
Some chromosomal translocations are typical of some histological types, with specific gene fusions as a consequence.


2.2 Histological types

2.2.1
The following histotypes are considered in this chapter and constitute the "typical" soft tissue sarcomas of the adults. The ICD-O ("International Classification of Diseases for Oncology") morphology code is provided in brackets.

alveolar soft-part sarcoma (M-9581/3)
angiosarcoma (M-9120/3)
chondrosarcoma, extraskeletal c. (M-9220/3)
chondrosarcoma, dedifferentiated c. (M-9240/3)
clear-cell sarcoma (M-9044/3)
dermatofibrosarcoma protuberans (M-8832/3)
desmoplastic small cell tumor of children and young adults (ICD-O code not available)
epithelioid sarcoma (M-8804/3)
fibrosarcoma (M-8810/3)
granular cell tumor, malignant g.c.t. (M-9580/3)
hemangiopericytoma, malignant h. (M-9150/3)
haemangioendothelioma, malignant h. (M-9130/3)
haemangioendothelioma, malignant epithelioid h. (M-9133/3)
leiomyosarcoma (M-8890/3)
leiomyosarcoma, epithelioid l. (M-8891/3)
liposarcoma, dedifferentiated l. (M-8858/3)
liposarcoma, myxoid l. (M-8852/3)
liposarcoma, pleomorphic l. (M-8854/3)
liposarcoma, round cell l. (M-8853/3)
liposarcoma, well-differentiated l. (M-8851/3)
lymphangiosarcoma (M-9170/3)
malignant fibrous histiocytoma (M-8830/3)
malignant mesenchymoma (M-8990/3)
mesenchymoma, malignant m. (M-8990/3)
osteosarcoma, extraskeletal o. (M-9180/3)
rhabdoid, malignant r. tumor (M-8963/3)
schwannoma, malignant s., neurofibrosarcoma, malignant peripheral nerve sheath tumor (M-9540/3)
schwannoma, malignant melanotic s. (M-9560/3)
"synovial" sarcoma (M-9040/3)
sarcoma, NOS (M-8800/3)
tenosynovial giant cell tumor, malignant t.g.c.t. (ICD-O code not available)


2.3 Grading

2.3.1
Most frequent histotypes can be both low grade and high grade. Overall, high grade tumors are much more frequent than low grade ones. Malignancy grade clearly distinguishes patients with different prognoses and natural histories, so that different histotypes with the same malignancy grade basically display the same clinical behaviour, while different malignancy grades may be consistent with one histotype. This is the reason why histotype is generally less useful for the clinician than grading. In addition, treatment of soft tissue sarcomas is dictated much more by the malignancy grade than by the histotype. Basically, low grade soft tissue sarcomas should be distinguished from high grade ones, even if grading systems generally distinguish more than two grades. grade 1 sarcomas are low grade tumors, while grade 2 and 3 tumors are generally included in the high grade group.

2.3.2
More than one grading system is currently employed. The most important ones are the American, by Costa et al, and the European, by Trojani et al. Both distinguish three malignancy grades. The former is founded on the histotype and the degree of tumor necrosis, while the latter is based on the degree of necrosis, the degree of morphological differentiation, and the mitotic index.

2.3.3
It is recommended that the pathologist always provides the clinician with the indication of the malignancy grade. Nonetheless, there are some histotypes which are "automatically" grade 1: myxoid or well differentiated liposarcoma, dermatofibrosarcoma protuberans. Mixoid fibrous histiocytoma is usually a grade 2 sarcoma. Other histotypes are "automatically" grade 3: pleiomorphic liposarcoma, mesenchymal extraskeletal chondrosarcoma, and alveolar sarcoma. The following histotypes are always grade 2 or 3: synovial sarcoma, epithelioid schwannoma, malignant fibrous histiocytoma, angiosarcoma, epithelioid sarcoma. However, since grading should be attributed by the pathologist to the individual tumor by considering some standardized criteria and possibly individual characteristics, it is recommended that the pathological report explicitly provides the clinician with both the histotype and the malignancy grade.


2.4 Accuracy and reliability of pathological diagnosis

2.4.1
The diagnosis of a soft tissue sarcoma may be difficult and the rarity of soft tissue sarcomas adds to such difficulties. In 5-20of cases a second pathological opinion does change the diagnosis from sarcoma to a non sarcoma. It is recommended that the histopathological evaluation be performed by a pathologist who is experienced with soft tissue sarcomas.

2.4.2
The reproducibility rate among different pathologists with regard to the histotype averages >45-60%. The reproducibility rate with regard to the malignancy grade seems higher, around 75%.

2.4.3
Cytogenetics and electron microscopy may allow the specification of the histotype in those cases in which it otherwise would not be specified.


2.5 Particular histological types considered elsewhere

2.5.1
Rhabdomyosarcoma, extraskeletal Ewing's sarcoma and peripheral neuroepithelioma (peripheral neuroectodermic tumor). These are aggressive tumors which are typical in childhood and are very responsive to chemotherapy and radiotherapy. The approach to them is basically the same in children and in adults, and differs widely from "typical" soft tissue sarcomas. They are therefore considered in separate chapters (Rhabdomyosarcoma and Ewing's Sarcoma and Peripheral Neuroectodermic Tumors). This chapter does not apply to these tumors.

2.5.2
Clear-cell sarcoma. Clear cell sarcoma has a different natural history resembling that of malignant melanoma, in particular for its lymphotropism. It is possible that some therapeutic principles which apply to malignant melanoma are of value also for clear-cell sarcoma.

2.5.3
Aggressive fibromatosis, or desmoid tumor. This is a locally aggressive tumor, without the potential for metastatic spread, and has a different natural history from soft tissue sarcomas, even from low grade fibrosarcomas. It is therefore considered in a different chapter (Desmoid Tumors).

2.5.4
Pediatric non rhabdomyosarcoma sarcomas. The rare pediatric tumors belonging to the "typical" histotypes of adults have a natural history which is similar to the natural history in adults and so should be basically dealt with in the same way as in adults. The reader should therefore consult this chapter for these tumors if occurring in childhood. Note, however, that some problems related to the clinical approach to a soft tissue tumor in a child (in particular with regard to surgery and radiotherapy) will be found in the chapter Rhabdomyosarcoma.


References

2.I
Fletcher JA. Cytogenetics and experimental models of sarcoma. Curr Opin Oncol 1994; 6: 367-371.

2.II
ICD-O. International Classification of Diseases for Oncology, Second Edition. C Percy, V Van Holten, C Muir (eds), Geneva, World Health Organization, 1990.

2.III
Costa J, Glatstein WE, Rosenberg SA. The grading of soft tissue sarcomas. Results of a clinicopathologic correlation in a series of 163 cases. Cancer 1984; 53: 530-541.

2.IV
Presant CA, Russell WO, Alexander RW, Fu YS. Soft-tissue and bone sarcoma histopathology peer review: the frequency of disagreement in diagnosis and the need for second pathology opinions. The Southeastern Cancer Study Group experience. J Clin Oncol 1986; 4: 1658-1661.

2.V
Shiraki M, Enterline HT, Brooks JJ, Cooper NS, Hirschl S, Roth JA et al. Pathologic analysis of advanced adult soft tissue sarcomas, bone sarcomas, and mesotheliomas. The Eastern Cooperative Oncology Group (ECOG) experience. Cancer 1989; 64: 484-490.

2.VI
Trojani M, Contesso G, Coindre JM, Rouesse J, Bui NB, de Mascarel A et al. Soft-tissue sarcomas of adults: study of pathological prognostic variables and definition of a histopathological grading system. Int J Cancer 1984; 33: 37-42.

2.VII
Coindre JM, Trojani M, Contesso G, David M, Rouesse J, Bui NB et al. Reproducibility of a histopathologic grading system for adult soft tissue sarcoma. Cancer 1986; 58: 306-309.

2.VIII
Weiss SW. WHO International Histological Classification of Tumours. Histological Typing of Soft Tissue Tumours. Berlin Heidelberg; Springer-Verlag, 1994, Second Edition.



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European School of Oncology, 1996

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