Soft tissue tumours

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Contents

Introduction

Soft tissue tumours are diverse in aetiology and diagnostic possibilities. The commonest cause is a simple lipoma, the majority of which will not require surgical excision. However, there is a rare group of tumours of soft tissue, referred to as soft tissue sarcomas, all of which are individually rare but which need to be diagnosed and treated appropriately, and which therefore must be distinguished from the common lipoma. The key management issues therefore, for a patient presenting with a soft tissue tumour, are the diagnosis of the underlying lump and then its appropriate management, so that the rare but important soft tissue sarcoma is recognised and treated appropriately.

Incidence

Soft tissue sarcomas are rare and occur in roughly the same degree of frequency as testicular cancers. They represent slightly less than 1% of all malignant tumours and occur at a rate of 2 cases per 100,000 population per annum. There are approximately 1200 new cases per annum in the United Kingdom, 6000 in the United States and about 200 in Victoria.

Apart from a small peak in infancy, soft tissue sarcomas are progressively more common with age, most occurring in patients older than 50. There is a slight male preponderance in incidence.

The childhood soft tissue sarcomas should be considered as a separate group as their behaviour and treatment is markedly different from other soft tissue sarcomas. The tumour most commonly affecting infants is the rhabdomyosarcoma, which usually occurs in the head and neck or the retroperitoneum. Unlike other soft tissue sarcomas, this tumour is sensitive to chemotherapy.

However, there is a diverse range of benign soft tissue tumours that may mimic soft tissue sarcomas and collectively these tumours are relatively common. Because of this the diagnosis of soft tissue sarcoma may be unsuspected at the time of presentation and an inappropriate biopsy performed.

Classification

Benign soft tissue tumours

Overwhelmingly the simple lipoma is the commonest tumour occurring in any site.

Other common soft tissue benign tumours include non-neoplastic lesions such as hamartomas, sebaceous cysts, inclusion dermoids, haematomas, seromas, fat necrosis, implantation dermoids, fracture callus, granulomata, degenerative cysts and ganglia, gouty tophi, rheumatoid nodules, lipodystrophy and infective cysts.

In addition, there is an extensive range of benign neoplasms which may also present clinically as a soft tissue lump. These can be classified according to tissue of orgin. Common examples in addition to lipomas, include neurofibromas, dermatofibromas and AV malformations, such as haemangiomas and varieties of lymphangioma (Table 43, “Benign neoplastic soft tissue lumps”).

Table 43. Benign neoplastic soft tissue lumps
Tissue of origin Tumour
Adipocyte Lipoma
Fibroblast Fibroma
Blood vessel Haemangioma
Lymph vessel Lymphangioma
Smooth muscle Leiomyoma
Synovial cell Giant cell tumour of tendon sheath
Nerve cell sheath Neurilemmoma
Neurofibroma

Intermediate-grade soft tissue tumours

These tumours include the desmoid tumour (aggressive fibromatosis), atypical deep lipomas (welldifferentiated lipoma-like liposarcomas), and dermatofibrosarcoma protuberans.

These intermediate-grade tumours warrant separate classification from benign neoplasms and malignant neoplasms. They are analogous to basal cell carcinomas in the skin in the sense that they are locally malignant and recur locally, if inadequately excised. However, they do not metastasise.

Malignant soft tissue tumours

Classification

A classification of malignant soft tissue tumours is given in Table 44, “Malignant soft tissue tumours”. Approximately 40 histological subtypes of soft tissue sarcomas are currently recognised, but the commonest varieties are liposarcoma, malignant fibrous histiocytoma (MFH), rhabdomyosarcoma, leiomyosarcoma, and synovial cell sarcoma.

Table 44. Malignant soft tissue tumours
Soft tissue sarcomas Liposarcoma
Clear cell sarcoma
Haemangio-epithelioma
Epithelioid sarcoma
Extra-skeletal myxoid condrosarcoma
Fibrosarcoma
Haemangiosarcoma
Leiomyosarcoma
Malignant haemangio-pericytoma
Malignant fibrous histiocytoma
Malignant peripheral nerve sheath tumour (MPNST or neurofibrosarcoma)
Rhabdomyosarcoma
Synovial sarcoma
Sarcoma NOS (not otherwise specified)
Malignant soft tissue tumours other than soft tissue sarcomas Extra-lymphatic soft tissue lymphoma
Metastatic melanoma
Metastatic carcinoma
Extra-skeletal bone tumours

Although they occur at all age levels, different histological subtypes predominate at different ages. For example, rhabdomyosarcoma is commonest in childhood and malignant fibrous histiocytoma tends to occur in the elderly.

The anatomical site may dictate the likely histological subtype. For example, liposarcoma is the commonest sarcoma in the thigh. (Soft tissue sarcoma of the thigh.)

Soft tissue sarcoma of the thigh.

Soft tissue sarcomas develop in mesodermal tissues with a common histogenetic origin, although malignant peripheral nerve sheath tumours and primitive neuro-ectodermal tumours are of ectodermal origin. It is most useful to use a histogenetic classification of soft tissue sarcomas. Pathologists may have differing opinions about the exact histological subtype, and it is generally accepted that even in expert hands 10% of tumours are not classifiable histologically. For diagnosing these tumours, immunohistochemistry, electron microscopy and cytogenetics may be helpful.

Soft tissue sarcomas may be usefully defined as malignant neoplasms of supporting connective tissue and muscle other than cartilage or bone, but may arise in any site in the body, excluding tumours of viscera but including tumours of peripheral nerves and rami. The definition therefore excludes, in addition to bone and cartilage, the anatomical sites of sarcomas of lymphoid organs, lymph nodes, viscera and the central nervous system. Also excluded are patients with Kaposi's sarcoma because the clinical presentation and the management of this disorder differs from that of other soft tissue sarcomas. Importantly, soft tissue malignant tumours due to lymphoma, melanoma, metastatic carcinoma such as lung cancer and extra-skeletal bone tumours must always be considered in the differential diagnosis of soft tissue sarcomas.

Site and grade

A number of features of soft tissue sarcoma follow a two-thirds to one-third rule in terms of proportion. Two-thirds of soft tissue sarcomas occur in the limbs and of these two-thirds occur in the lower limbs. Of these, two-thirds occur in the proximal compared to the distal limb. Therefore the commonest site of soft tissue sarcoma is in the thigh. Two-thirds of soft tissue sarcomas in the limbs occur deep to the deep fascia and it is for this reason that any soft tissue mass deep to the deep fascia is more likely to be malignant than benign. Sarcomas occur in the soft tissue compared to bone in the ratio of 2 : 1. Two-thirds of soft tissue sarcomas are of high grade. Various grading systems are employed, but the most useful classification is high-grade versus low-grade. High-grade tumours have a worse prognosis for survival than low-grade tumours. The distinction is also important for treatment. For example all high-grade tumours will usually be treated by surgery as well as radiotherapy; however, for some low-grade tumours radiotherapy may be avoided.

Surgical pathology

Soft tissue sarcomas grow differently to infiltrative carcinomas. They tend to be expansive and form a pseudo-capsule which is partly a fibrous tissue reaction, but partly also surrounding compressed host tissue. The pseudo-capsule, however, always contains malignant cells. Nonetheless, this gives a false impression of a capsule through which a tumour can be enucleated. This should not be undertaken because it always results in tumour cells being left behind. Soft tissue sarcomas tend to infiltrate along the planes of the least resistance and if arising in the centre of a particular muscle, for example, the rectus femoris in the thigh, the tumour will for a considerable time expand within the muscle rather than breaking through the fibrous capsule. For the same reason, the tumour tends to spread along blood vessels and nerves rather than invading them. These macroscopic patterns of growth have important implications for surgery in that if a tumour is confined to one muscle or one compartment in the limb, it is possible by removing that compartment or muscle that a complete excision of the tumour can be achieved. Unfortunately, only 15% of soft tissue sarcomas are appropriately confined to a single muscle or a compartment. The concept of treatment by compartmentectomy is therefore only applicable to about 15% of tumours. Nonetheless, it is a useful concept in understanding the biology of these tumours. Furthermore, vessels and nerves are rarely invaded and therefore vessels and nerves do not need to be sacrificed surgically.

Spread

Soft tissue sarcomas only rarely spread to lymph nodes (less than 5% of cases). Soft tissue sarcomas spread via the haematogenous route, and therefore the commonest site of metastases is pulmonary.

Clinical features

A problem-oriented history and examination are required. The onset and duration of the lump may be important, and a lump which is increasing in size suggests a neoplastic growth. Pain suggests inflammation, but up to one-third of soft tissue sarcomas present with pain. A detailed physical examination is required. There are a number of elements to such an examination.

First, the general features of any clinical lump are noted. These include the site/region, plane or depth, the size in three dimensions, the shape - whether this is regular or irregular, the surface and contour, the edge, the consistency and changes in the overlying skin and underlying fixation.

Second, any special regional features of the lump are noted. For example, distant neurovascular function for a tumour in the thigh.

Third, regional lymph nodes are assessed and finally a complete general examination is always essential.

Features of the commoner soft tissue tumours

Lipomas

Lipomas are the commonest form of benign soft tissue tumour. They are usually subcutaneous and present as soft, fluctuant, lobulated masses which are neither fixed to skin nor deep tissue. The clinical feature of deep fixation is important. The classic feature of a lump deep to the deep fascia in a limb is that it becomes less obvious on contraction of the muscle. The majority of lipoma are small and asymptomatic and will not require removal. Possible indications for removal of a lipoma would include a lipoma which is painful (commonly seen in the variant angiolipoma), an enlarging lipoma, a lipoma causing pressure effects on adjacent structures, a lipoma with any clinical, radiological, cytological or histological feature of concern, a lipoma larger than 5 cm in maximal dimension, and a lipoma deep to the deep fascia. In the limbs, a tumour which occurs deep to the deep fascia is more likely to be malignant than to be benign.

Angiolipomas

Angiolipomas are less common, but typically present with pain and histologically are a mixture of fat and blood vessels.

Dermatofibromas

Dermatofibromas (sclerosing haemangiomas) are characteristic dome-shaped nodules usually found in the upper leg of the middle aged and elderly. They consist of a mixture of mature fibrous tissue, histiocytes and vascular elements. They are benign and require no specific treatment except for cosmetic reasons or if there is doubt about their diagnosis.

Haemangiomas

Haemangiomas are hamartomas and are present at birth, although initially this may not be clinically apparent. Characteristically, enlargement occurs within the first year of life representing proliferation of excessive numbers of mature vessel elements. The endothelial line spaces form either capillary or cavernous lesions according to their size.

In the skin, strawberry haemangiomas have the appearance to be expected by their name, presenting with an irregular pitted surface with protrusions in the form of capillary tufts. Their variant is a more solid, smooth cherry haemangioma.

Cavernous haemangiomas of the skin are more deeply placed, more widely spread and irregular in shape, with a blueish, rather than red, appearance. All three forms blanch with pressure as is expected from their structure. All are self limiting by progressive obliteration and are usually replaced by mature fibrous tissue, sometimes a haemosiderin staining by the age of 6 years. Treatment in the form of surgical excision or obliteration by laser therapy is rarely indicated except for cosmetic reasons in exposed areas or for avoidance of bleeding in areas subjected to frequent trauma.

Lymphangiomas

Lymphangiomas are also hamartomas rather than true tumours and occur in capillary or cavernous forms. The carvernous form is commoner and is seen in the form of cystic hygroma of the neck, axilla or groin. There are usually superficial and deep components without a well defined capsule. Treatment is undertaken for cosmetic or pressure effects, with wide excision being necessary if there is to be no recurrence.

Neurofibromas

Neurofibromas are of diverse lineage including Schwann cells, perineural cells and fibroblasts. They occur sporadically as cutaneous nodules, usually associated with hyperpigmentation of peripheral nerves as solitary lesions. Much more commonly they form a component of neurofibromatosis Type I, a common disorder with an incidence of 1 in 3000, characterised by a strong family history combined with autosomal dominant transmission. The clinical features are multiple neurofibromas throughout the body (including the eighth nerve, pigmented lesions (café au lait spots) and pigmented iris hamartomas (Lisch nodules). The neurofibromas may be plexiform in nature and may grow to an enormous size. Such lesions may undergo malignant transformation, often presenting with rapid growth or major internal haemorrhage. There is an association with other tumours, especially meningiomas, gliomas and phaeochromocytomas.

Desmoid tumours

Desmoid tumours are so named from the Greek term desmos, meaning band- or tendon-like appearance of the cut surface of the tumour. Desmoid tumours are locally malignant but do not form a capsule and do not metastasise. They may be multi-centric, but because of their infiltrative nature have a high rate of local recurrence following surgery. The pathogenesis of desmoid tumours has been linked to trauma, sex hormones, particularly oestrogen, and familial adenomatous polyposis (FAP) and Gardner's syndrome.

About 2% of desmoids are FAP associated and patients with FAP are at about 1000-fold-increased risk for developing desmoids compared to the general population. Furthermore, the desmoids seen in FAP are often in the root of the mesentry and here may be termed mesenteric fibromatosis. Mesenteric fibromatosis is now the second most common neoplastic cause of death after colorectal cancer in patients with FAP and is more common than death due to peri-ampullary carcinoma.

Sporadic or non-FAP-associated desmoids are more common in women of childbearing age and are thought to be related to oestrogen hormones. Desmoid tumours are a variety of fibromatosis which are a group of pathologies resulting from proliferation of welldifferentiated fibroblasts, which infiltrate and show repeated local recurrence, but are neither malignant nor inflammatory. They are locally malignant but do metastasise. Apart from desmoids, other fibromatoses include palmar fasciitis (Dupuytren's contracture), plantar fascitis, penile fibromatosis and keloids.

Kaposi's sarcoma

Kaposi's sarcoma is of unknown histogenesis, but is usually considered to be a form of angiosarcoma because of its structure: thin-walled, dilated vascular spaces with interstitial inflammatory cells with haemosiderin deposition. Four forms of the disease have been described.

First is the classical form described originally by Kaposi, in the form of pink to purple nodules in the skin of the lower extremities of adult patients of Eastern European origin. The tumours are locally aggressive, but rarely metastasise. The second form, African Kaposi's syndrome, is similar in appearance and behaviour but occurs in children and in young men in Africa. The third form occurs in transplant recipients, is more widespread and more aggressive, both locally and in terms of metastasis. This form of tumour usually regresses on cessation of immunosuppression. The fourth and now most common form of Kaposi's sarcoma is HIV associated and has a wide distribution, including visceral involvement. All four forms respond to cytotoxic chemotherapy with or without alpha-interferon, although HIV patients commonly die of intercurrent infection or develop further malignancies, usually in the form of lymphoma or leukaemia.

Investigation of soft tissue tumours

This will include radiology and biopsy.

Radiology

CT scanning and magnetic resonant imaging (MRI) are useful investigations to determine precisely the anatomical situation of a soft tissue sarcoma. In particular, the precise relationship to vessels and nerves will be well demonstrated by MRI. These studies are essential to the surgical planning of resection of the underlying tumour

In addition, some tumours (both benign and malignant) have characteristic radiological features. For example, a pure lipoma will have a characteristic CT scan appearance. However, it is important to appreciate that radiology can never determine the underlying histological nature of a soft tissue mass (CT scan of thigh, showing a large liposarcoma. There are some features to suggest lipoma; however, the heterogeneous nature of this lesion radiologically suggests the diagnosis of liposarcoma.).

CT scan of thigh, showing a large liposarcoma. There are some features to suggest lipoma; however, the heterogeneous nature of this lesion radiologically suggests the diagnosis of liposarcoma.

Ultrasound will confirm a soft tissue mass and often show the plane the mass is in; however, it is less helpful in determining precise anatomical relationships. It is of most use in obtaining ultrasound guided percutaneous core biopsies of soft tissue masses for histology.

The commonest site of distant metastases for soft tissue sarcomas is pulmonary and for this reason CT scanning of the thorax is essential to stage patients known to have a soft tissue sarcoma.

Biopsy

It is inappropriate to investigate all soft tissue tumours as if they were soft tissue sarcomas. It is estimated that for each soft tissue sarcoma diagnosed, 100 benign soft tissue lesions will be seen, and the majority of these will be lipomas. However, the differential diagnosis of soft tissue sarcoma versus lipoma must be considered in every case. Therefore, there needs to be a selective policy with regards to which tumours should be biopsied. In general, any tumour with clinical or radiological features of malignancy, a tumour which is growing, a tumour deep to the deep fascia or a tumour greater than 5 cm in size should be biopsied.

Biopsy is essential to obtain a specific diagnosis of the tumour, and for soft tissue sarcomas this will include the histological subtype and grade. This then enables a multidisciplinary planning of treatment and permits some prediction of prognosis.

Pre-operative percutaneous ultrasound guided core biopsies to provide histological diagnosis is becoming a more favoured technique, with the potential to facilitate one-stage surgery.

The principles of management of soft tissue sarcomas

The overall prognosis of soft tissue sarcomas is poor, with a mortality rate of 50% and a local recurrence rate of up to 25%. Nonetheless, with appropriate management many patients will be cured of their disease.

The goals of treatment are to achieve local tumour control, to prevent metastases and to preserve function.

The aim of the local treatment of soft tissue sarcomas is complete resection of the primary tumour with microscopically clear histological margins. Depending on the margin of resection, the recurrence rates vary. Local recurrence rates for amputation alone are 8% and for wide excision alone about 25%. However, when radiotherapy is added to this the local recurrence rates are reduced to rates approaching that following amputation. Therefore, there is no advantage in amputation as the local recurrence rate achieved is similar. When limb preservation function is preserved, a similar local recurrence rate is achieved and there is no difference in long-term survival. It is not currently believed that local recurrence influences overall survival in soft tissue sarcomas. Therefore, limb sparing treatment is usually possible in over 90% of patients with soft tissue sarcomas of the extremities.

Surgical margins following resection of soft tissue sarcomas are categorised as follows (Schematic diagram of surgical margins and compartments, based schematically on a transverse section of the thigh.). Intracapsular means that the lesion has been removed from within the pseudo-capsule and that gross tumour is seen at the wound margins. A marginal excision means that the tumour has been removed en bloc but that there is a significant possibility of tumour cells being left in the surrounding host tissue. A wide surgical margin means the lesion has been removed en bloc and that the plane of the resection has been sufficiently peripheral to the tumour to ensure clear histological margins. A radical resection means that the lesion and the entire compartment which it involves have been removed en bloc. The local recurrence rates following these resections are intracapsular 100%, marginal 90%, wide excision 25%, and radical excision 8%. These figures are reduced significantly by radiotherapy.

Schematic diagram of surgical margins and compartments, based schematically on a transverse section of the thigh.

Therefore, wide excision with at least a 2–3-cm margin, with preservation of vessels and nerves and at least one innervated muscle of the functional compartment to preserve as much function as possible, followed by adjuvant post-operative radiation therapy is the contemporary approach recommended for most extremity soft tissue sarcomas. Desmoid tumours should be treated by a similar wide local excision with a clear 2–3-cm margin to reduce the incidence of local recurrence.

If local recurrence of a soft tissue sarcoma occurs, further surgery is often possible. Distant recurrences in the lungs are on occasion treatable by surgical resection (metastasectomy). Chemotherapy for metastatic soft tissue sarcoma disease may provide symptomatic relief, but has no effect on overall survival.

Desmoid tumours again represent a special group and in addition to surgery there has been some benefit demonstrated by post-operative radiotherapy and the use of agents such as tamoxifen and sulindac.

Prognosis of soft tissue sarcomas

Overall there is a 50% mortality for patients with soft tissue sarcomas, and the vast majority of patients die from metastatic disease. Factors shown to be of importance in predicting survival on multivariate analysis include the grade of the tumour, the size of the tumour, the adequacy of resection, local recurrence and the depth of the tumour.

These factors are, in general, related more to the biology of the tumour itself. Local recurrence will occur in up to 25% of patients, and factors associated with this on multivariate analysis include the adequacy of surgery and the resection margins, previous local recurrence, grade of the tumour and whether or not radiotherapy has been administered.
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