Soft tissue sarcomas include all sarcomas except those that arise from bone, the pretext giving the tissue of origin thus: leiomyosarcoma (for sarcomas arising from smooth muscle), neurofibro-sarcoma (for those arising from neural sheaths), fibro-sarcoma (for those arising from fibrous cells – and malignant fibrous histiocytoma is a variant of this type), rhabdomyosarcoma (for those arising from voluntary muscle cells), liposarcoma (for those arising from fat cells), synovial sarcoma (for those arising from the synovium of joints), angiosaarcoma (for those arising from blood vessel tissue) etc…
It is clear that the group is a very heterogeneous one but enough similarity exists for us to consider the group together.
Sarcomas are malignant tumours of the mesenchyme - the background matrix tissues of the body (the third germ layer). Where the sarcoma is resembles the tissue of origin (e.g. long stranded cells, perhaps even demonstrating the cross striations of voluntary muscle and indicating rhabdomyosarcoma) the diagnosis is easily reached by the histologist.
However, many sarcomas are poorly differentiated and down the microscope it is difficult for the histologist to tell whether such a tumour has a sarcomatous origin. Here the recent explosion of special staining methods and immunocytogenetics has assisted greatly. Thus sarcomas frequently stain for desmin and vimentin (whereas poorly differentiated melanomas stain for melanin and S-100 [although some sarcomas can also stain for S-100], lymphomas stain for leucocyte common antigen – LCA- and carcinomas stain for cytokeratin).
Furthermore, there are well recognised cytogenetic abnormalities such as the expression of t[X;18][p11.2;q11.2] in the tumour cells of synovial sarcoma, t[11:12]]q24;q12] in Ewing’s sarcoma, and t[12;16][q13;p11] in myxoid sarcoma – all of which may help the histologist to identify the tissue of origin of a poorly differentiated tumour.
Overall, the rhabdomyosarcomas predominate in childhood and in adults the distribution of frequency is: Malignant fibrous histiocytoma 20-25%, fibrosarcoma 15%, liposarcoma 15%, leiomyosarcoma 10%, rhabdomyosarcoma 8%, synovial sarcoma 7%, neurofibrosarcoma 7%, others 12%.
Lastly it is now the histologist’s job to grade the sarcoma, as it has been firmly established that the tumour’s grade is strongly related to overall outcome/prognosis.
The grading is based on tumour differentiation (a point we have already alluded to with regard to well differentiated tumours resembling the tissue of origin and poorly differentiated tumours having no such distinguishing foot-prints), pleomorphism, which refers to heterogeneity of appearance of different cells within the sarcoma, cellularity (density of cellular composition within the tumour), number of mitoses (i.e. the number of cells in division when viewed at the moment of preservation of the histological specimen – a modern method of assessing this is by the use of a special stain called the Ki-676 stain which picks up a nuclear antigen that is only present in mitosing cells) and various other factors such as vascular (blood vessel) formation and invasion of such vessels – all to suggest a scoring system which predicts the aggressiveness of behaviour of the tumour. The final score would segregate the sarcoma into a low, intermediate or high grade cancer (sometimes graded 1-4 respectively).
A low grade tumour would resemble the tissue of origin, most of the cells would conform to this picture; it would have a low number of mitoses per high power microscope field and no vascular invasion.
Symptoms of soft tissue sarcomas
The main initial complaint to the doctor is because of the development of a lump. This is difficult for the doctor as many similar lumps will be benign but the appearance and progression of such a lump should alert physicians to the possibility of a sarcoma.
Of course, when the lump has grown to a large size it causes secondary pressure symptoms that may cause presentation complaints depending on the situation of the growth.
Occasionally, the patient may present with symptoms of metastatic disease; it is noteworthy that sarcomas metastasise to the lungs in the first instance in most cases, although regional node metastatic disease is a feature of some (e.g. synovial sarcoma).
Treatment of soft tissue sarcomas
Where the tumour is localised, wide excision (which implies that the surgeon cuts cleanly around the tumour, never through it, and with generous margins of safety) is recommended. Sometimes this requires amputation to achieve this goal but nowadays more often than not the requirement can be fulfilled by subablative surgery, perhaps supplemented by radiotherapy to the area post-operatively.
Where the sarcoma is localised to one muscle group (e.g. hamstrings of the thigh) such wide excision implies the resection of the whole muscle compartment (operation nicknamed, compartmentectomy), which can be a large and functionally disabling operation. Nevertheless, as an alternative to amputation, it is an advance over what was recommended twenty years ago, and with modern orthopaedic rehabilitation it is often less disabling than initially envisaged.
Where the operation is less than ablative, it is clear that the delivery of high radiotherapy to the region will further lessen the chances of relapse, and most patients will be recommended to receive a five to six week course of fractionated radiotherapy on modern equipment preceded by careful planning.
However, radiotherapy should not substitute a larger operation if the surgeon cannot achieve clear margins (i.e. the histologist is not able to identify any tumour at the edges of the operation specimen) as this does not achieve the good results that can be achieved by a good, clear surgical result before radiotherapy.
For many soft tissue sarcomas of the body, it is not possible to achieve even the modest margins achieved by a compartmentectomy in the limbs; here radiotherapy in the post-operative period is even more important. Sometimes, the radiotherapy precedes the surgery to try to effect shrinkage and facilitate curative resection.
The subject of adjuvant chemotherapy (i.e. the delivery of chemotherapy in the post-operative period in patients who have ostensibly localised disease but are at high risk of subsequent relapse; see breast cancer section) is highly controversial in this disease.
Some trials demonstrate that the delivery of the best agents known against this disease (e.g. doxorubicin/adriamycin and cyclophosphamide/iphosphamide) for a finite number of exposures (e.g. six) immediately after the operation can lead to a reduced risk of subsequent relapse.
However, the risk reduction is not as well validated as for example in node positive breast cancer (see breast cancer section) and many other trials only show a relapse free survival advantage (c.f. an overall survival advantage) or no advantage at all. Thus whilst there is now good evidence to support the routine delivery of adjuvant chemotherapy to children and young adults with resected rhabdomyosarcomas, this practice is not well validated and is not standard best care for many or most of adult soft tissue sarcomas encountered in the clinic.
Chemotherapy is so much better established in the childhood rhabdomyosarcoma practice that it is common for therapy to commence with chemotherapy here and surgery to come in later when the tumour has shrunk right down.
Where the patient presents with metastatic disease, the use of chemotherapy is obviously more in demand and there is a method of auditing the response by serial scans. The same drugs are used.
Occasionally, a single metastasis occurs (e.g. in the lungs) and surgery to this and the primary is considered, but this is very much a minority of cases and usually the patient who presents with metastatic disease is treated with chemotherapy to try to contain the disease for as long as possible.