2.4 Malignant tumours of soft tissues

Three major categories of vascular tumours have been identified: benign lesions such as haemangiomas; tumours of intermediate malignancy (haemangioendothelioma); and highly malignant tumours (angiosarcoma). They are all very rare tumours accounting for less than 1% of soft tissue sarcomas.

The majority of haemangioendotheliomas are solitary lesions but may occur in association with other cutaneous vascular abnormalities such as those found in Klippel–Trenaunay or Mafucci’s syndrome. The mass is usually painless.

The majority of angiosarcomas arise in skin. Associations exist with lymphoedema, trauma, and previously irradiated tissues. Lesions are often diffuse and can present late with ulceration and a nodular character.

Plain radiographs may demonstrate punctate calcification within the tumour, which can be encountered in any vascular lesion. Magnetic resonance imaging (MRI) may show high-flow signals of vascular structures. Angiography is useful as it may help to identify feeding vessels for preoperative embolization.

The vessel in which endotheliomas arise usually remains intact with the tumour developing within the lumen of the vessel.

Cutaneous angiosarcomas are usually well- or moderately-differentiated tumours that tend to form vascular-like structures infiltrating or dissecting irregularly into the dermis (unlike haemangiomas).

Surgery with or without adjuvant radiotherapy is the mainstay of treatment. Angiosarcomas are generally more difficult to control locally because of their infiltrative nature.

The prognosis of haemangioendothelioma is comparatively good with more than 80% 5-year survival (lung and local lymph nodes being the commonest sites of dissemination).

Angiosarcomas are aggressive tumours with less than 20% 5-year survival. They commonly metastasize to the lung, liver, and spleen.

Synovial sarcoma is a rare and aggressive soft-tissue tumour, which accounts for 8–10% of all human malignant sarcomas diagnosed annually. Its peak incidence is in adults in their third to fifth decades of life, but it can also occur in children.

The most common mode of presentation is a deep-seated, painless mass. Periarticular regions in the extremities are especially affected. It is more common in the lower limb and appears to have a close association with tendon sheaths, bursae, joint capsules and in less than 10% of cases involves the articular surface. Invasion of adjacent bone is seen in 10–20% of cases, which is not as common as in other soft-tissue sarcomas. Other sites of involvement include the head and neck, trunk, lung, intestine, and retroperitoneum.

Plain radiography of synovial sarcomas reveals calcifications within the lesion in 30% of cases. Computed tomography (CT) scanning demonstrates heterogeneous lobulated masses with mixed cystic and solid appearances, which can be secondary to necrosis and/or haemorrhage. Thoracic CT scans are obtained to detect pulmonary metastases, and are an important part of the staging process.

MRI is the imaging modality of choice for diagnosing synovial sarcoma. The clear contrast between the lesion and normal tissues enables accurate assessment of tumour local invasion. It also is very valuable in revealing involvement of the neurovascular bundle and lymphatics. MRI is also excellent for surveillance and monitoring of the development of local recurrence after surgical resection, or sarcomatous changes secondary to radiation treatment.

Tumours appear sharply marginated, largely cystic or multiloculated with internal septations. Because of the cystic appearance and the well-defined margins, synovial sarcomas can be misdiagnosed on MRI.

Technectium-99m (^99mTc) bone scans and positron emission tomography (PET) scans are obtained to screen for bony metastases. These can be either lytic or mixed in nature.

Histologically, synovial sarcomas are divided into three subtypes: biphasic, monophasic, and poorly differentiated. The biphasic type contains epithelial and spindle cell elements (Figure 2.4.1A). The monophasic contains only spindle cells (Figure 2.4.1B). The poorly differentiated type has areas of mono-biphasic morphology surrounded by poorly differentiated areas with high cellularity, pleomorphism, round cells, mitoses, and necrosis.

Ninety to 95% of synovial sarcoma cells are characterized by the presence of a translocation t(X:18). This seems specific to the disease, as it is not seen in other soft-tissue sarcomas, and this can be used as a good diagnostic tool.

Complete surgical excision is the mainstay of treatment. The extent of resection has a significant bearing on the outcome. Local recurrence and metastases are common with contaminated surgical margins. Many authors have reported the use of radiotherapy as an aid to surgery to achieve local disease control, especially in cases with positive resection margins. However, its role after achieving complete excision has not been fully evaluated.

The use of chemotherapy remains a controversial issue, and its influence on survival is debatable. Some authors recommend its use for systemic disease control, especially in children, but other believe the use of multiple chemotherapy agents does not affect survival.

Overall survival for completely resected lesions ranges from 50–80% at 5 years, compared to 25–30% when there are distant metastases at the time of presentation.

These are a rare variety of soft-tissue sarcomas of ectomesenchymal origin. The World Health Organization (WHO) recommends the use of the term MPNST as a replacement for the terms malignant schwannoma, malignant neurilemmoma, and new ribbon sarcoma. They are commonly misdiagnosed because of their cellular origin and the histopathological similarities with other spindle cell sarcomas (leiomyosarcoma, rhabdomyosarcoma).

MPNST represent 10% of all soft-tissue sarcomas, affecting adults in their second to fifth decades of life. Patients with type 1 neurofibromatosis are, however, affected at an earlier age. The most common sites of occurrence include the sciatic nerve, brachial plexus, and sacral plexus. Other sites include the pelvis, retroperitoneum, and infratemporal fossa. They usually present as painful mass with a biologically aggressive behaviour.

MRI of these tumours reveals inhomogeneous lesions with necrosis and haemorrhage. It is the imaging modality of choice as in all soft-tissue sarcomas, as it can reveal the nerve of origin and the relationship to adjacent structures.

Histological examination in most cases shows spindled cells with many nuclei, similar to Schwann cells. These are arranged in sweeping fascicles alternating with myxoid areas. Mitotic figures are frequent. Heterotopic islands of cartilage and bone can also be seen. Four subtypes are recognized in the literature and include: cartilagenous, epitheliod, glandular, and rhabdoid. Tumour cells in all four subtypes show positive staining for S100.

Radical surgical resection is the treatment of choice. In extremity lesions, amputations should be considered when there is extensive involvement of surrounding structures, especially the neurovascular bundle, making excisions not feasible. These tumours are resistant to radiation and chemotherapy, but radiotherapy is still sometimes used in cases with contaminated surgical margins.

Local recurrence occurs in approximately 40% of MPNST cases, this being the highest local recurrence rate of any soft-tissue sarcoma. Survival at 5 years is 40–45%. Metastases occur in the lungs, bone, pleura, and retroperitoneum.

Represents the most common soft-tissue sarcoma in children, accounting for 5–8% of all childhood cancers.

These are fast growing and highly malignant neoplasms, arising from rhabdomyoblasts. Lesions can arise in any part of the body except bone. The most commonly affected sites include the head and neck, extremities, genitourinary (GU) tract, trunk, orbit, and retroperitoneum. Approximately 90% of patients are younger than 18, with two age peaks (2–6 years—head and neck tumours; 14–18 years—extremities).

Plain radiographs usually reveal calcifications in lesions. CT scans are obtained to diagnose pulmonary and liver metastases. MRI is the main diagnostic tool and it reveals a clear definition of the mass and its invasion of adjacent structures. It is also very valuable in detecting local recurrence, and bone marrow metastases. The latter cases are usually associated with normal ^99mTc and PET scans, which are insensitive to bone marrow infiltration when the bone cortex is intact.

Histologically, rhabdomyosarcomas are divided into four different subtypes according to the cells encountered in the tumour (Figure 2.4.2). These are embryonal, alveolar, spindle cell, and undifferentiated (anaplastic, pleomorphic).

The embryonal is the most common and affects children under the age of 15, occurring mainly in the head and neck. In the botryoid subtype of embryonal rhabdomyosarcoma, the cambium layer is characteristic, and contains a condensation of loose tumour cells below an epithelial surface. This usually affects the vagina and GU tract. The alveolar type is characterized by cells lining up along membranes resembling lung alveoli. This is more aggressive and affects the trunk and extremities. The spindle cell type has a fascicular, spindled, and leiomyomatous growth pattern and can demonstrate notable rhabdomyoblastic differentiation. In the undifferentiated type, no evidence of myogenesis differentiation is present.

Treatment involves a combination of surgery, radiotherapy, and chemotherapy. Obtaining a 2-cm clear margin is recommended, and all cases are routinely given radiotherapy postoperatively. Chemotherapy is used in certain cases to shrink the tumour to aid later surgical resection. Common agents used include cyclophosphamide, adriamycin, and ifosfamide.

Patients with non-metastatic rhabdomyosarcoma have a survival rate of 70% at 5 years after combined modality therapy. In 14% of patients, metastases are present at the time of diagnosis, decreasing the survival rate to 20% at 5 years. The most common sites of distant lesions include the lungs and bone marrow.

Leiomyosarcoma is an aggressive soft-tissue sarcoma derived from smooth muscle cells. These malignant tumours arise from mesenchymal cell lines.

Of all soft-tissue sarcomas, approximately 5–10% are leiomyosarcomas. The aetiology of this tumour is unknown. Leiomyosarcoma of soft tissue is thought to arise from the smooth muscle cells lining small blood vessels. Leiomyosarcoma can also arise directly from the viscera, including the gastrointestinal tract and uterus.

There are no specific clinical features diagnostic of leiomyosarcoma of soft tissue that distinguish these tumours from other soft tissue sarcomas. Women are affected more than men (2:1), with the disease typically occurring in the fifth and sixth decades of life. This gender distribution may reflect the proliferation of smooth muscle in response to oestrogen. It is a tumour of adulthood but it does account for about 6–7% of all childhood malignancies.

The most common site of involvement of leiomyosarcoma is the retroperitoneum, accounting for approximately 50% of occurrences. Presenting signs and symptoms for retroperitoneal tumours can include: an abdominal mass, pain, swelling, weight loss, nausea, or vomiting.

Leiomyosarcoma of somatic soft tissues, like other soft tissue sarcomas, often present as an enlarging, painless mass. However, when leiomyosarcoma arises from a major blood vessel, symptoms of vascular compromise or leg oedema may be present, as well as neurologic symptoms.

Approximately 15–30% of patients have metastatic disease at presentation. The most common metastatic site is the lung. Other common sites for metastases are the skin, bone, liver, and lymph nodes.

Initial imaging should include plain radiographs of the affected area, an MRI of the lesion, and a chest CT scan (to evaluate for the presence of metastatic disease).

MRI is the study of choice for the evaluation of the anatomic extent of the tumour, especially to adjacent structures. CT imaging is useful in evaluating the extent of retroperitoneal tumours.

While histologically similar, soft tissue leiomyosarcoma has classically been subdivided into three groups for prognostic and treatment purposes: leiomyosarcoma of somatic soft tissue; cutaneous leiomyosarcoma; and leiomyosarcoma of vascular origin.

There is little histological difference between leiomyosarcoma arising from deep, subcutaneous, or dermal sites or in association with vessels.

Leiomyosarcomas are typified by spindle cells with a centrally placed blunt-ended cigar-shaped nucleus and abundant cytoplasm, arranged in intersecting bundles (Figure 2.4.3). Greater nuclear eccentricity, hyperchromatism, atypia, and size accompany more poorly differentiated cells.

Leiomyosarcomas are aggressive tumours that are often difficult to treat. The prognosis is poor, with survival rates among the lowest of all soft tissue sarcomas.

Surgical resection remains the only potentially curative treatment option. Five-year survival rates of 80% and 67%, respectively, in stages I and II, and of 12–50% in the more advanced stages. Tumours of the extremity have a better prognosis with greater than 60% survival at 5 years.

Adjuvant radiotherapy is indicated if the tumour is larger than 10cm or situated adjacent to neurovascular structures, which, if spared, necessitate a marginal resection. Chemotherapy comes into play as the primary treatment with inoperable tumours and may be a first line of treatment of choice in the case of lung disease. The two drugs most frequently used are doxorubicin and ifosfamide.

The prognoses of infants and young children tend to be better than those of adolescents and adults with similar diagnoses.

The term ‘epithelioid sarcoma’ was first coined by Enzinger in 1970. He described a group of hand sarcomas often confused with a chronic inflammatory process, a necrotizing granuloma, or a squamous cell carcinoma.

These represent the most common soft tissue sarcomas occurring in the hand in young adults. They mainly arise from the subcutaneous tissue, fascia, tendon sheaths, or joint capsule. The upper extremity is more commonly affected than the lower extremity. In many cases, patients present with a small, painless, ulcerating nodule on the extensor surface of the hand or forearm.

MRI is the imaging modality of choice to reveal the extent of local invasion and association with surrounding structures.

The histological features of epithelioid sarcoma include the presence of malignant cells which are epithelioid, spindled, or mixed in appearance. An abundance of chronic inflammatory cells is commonly encountered along the margins of tumour nodules, which can obscure the diagnosis in some cases.

Radical resection and/or amputation are the treatments of choice. The role of radiotherapy and chemotherapy as adjuvant treatments is not very clear and has not yet been fully determined. Five-year survival in the literature ranges between 50–70%. Local recurrence and metastases, especially pulmonary, are common features of the disease. Routes of spread include the tendon sheaths, the fascia, and the lymphatic system.

Clear cell sarcoma of tendons and aponeuroses is a rare and aggressive cancer, accounting for less than 1% of all soft tissue sarcomas. They are easily mistaken for malignant melanomas because of their histochemical and structural similarities. Many authors use the term ‘malignant melanoma of the soft parts’ to refer to these tumours.

They represent a distinct entity with a predilection for occurring in the tendons and aponeuroses of young adults. Eighty to 90% of lesions develop in the lower limb, with the ankle and foot being the commonest sites. Other sites include the knee, thigh, elbow, hand, head and neck, and trunk. They all exhibit an aggressive behaviour with a high incidence of local recurrence and metastases.

The commonest presentation is a painless, deep-seated mass, which is bound to adjacent tendons or aponeuroses.

Intralesional calcifications are rarely seen on plain radiography or CT scanning. MRI commonly reveals areas of necrosis and/or haemorrhage within the lesion.

Clear cell sarcomas are mainly made up of round or fusiform cells arranged in nests separated by fibrosclerotic bands or septa. Giant cells with more than 10–12 nuclei may also be encountered within the tumour mass. Tumour cells are mostly uniform and have vesicular nuclei containing prominent nucleoli and clear or pale staining cytoplasm. These tumours and malignant melanomas share similar histological characteristics and features, and both are positive for the protein S100, suggesting a close relationship between both entities. The site of occurrence is, however, different. The majority of cases are associated with a chromosomal translocation t(12:22)(q13: q12).

The recommended treatment is a wide/radical excision or amputation if necessary, both with local lymph node clearance. The roles of adjuvant radiotherapy and chemotherapy are debatable, but used in many centres.

The prognosis is generally poor, with a 5-year survival rate of 60–70% after radical excision ± adjuvant treatments. This falls to 30% at 10 years. Local recurrence and metastases are common features, especially with a positive surgical margin. Metastases are usually to lymph nodes and the lungs. Less common sites include the skin, bone, and liver. Overall, 70% of patients develop metastases at some stage of the disease.

Malignant fibrous histiocytoma (MFH), described by O‘Brien and Stout in 1964, is the most common soft tissue sarcoma of late adult life accounting for 20–24% of soft tissue sarcomas.

It is a heterogeneous tumour with respect to histology and prognosis with malignant cells of histiocytic origin. Early osseous invasion and metastases to regional lymph nodes is common. The term MFH is still in use, but is gradually being replaced by the term pleomorphic sarcoma.

MFH occurs more commonly in Caucasian patients. The male to female ratio is approximately 2:1. Peak incidence is in the fifth and sixth decades. Although rare in children, the angiomatoid subtype is the most frequently occurring variety in patients younger than 20 years.

MFH occurs most commonly in the extremities (70–75%, with lower extremities accounting for 59% of cases), followed by the retroperitoneum. Tumours typically arise in deep fascia or skeletal muscle.

MFH has been associated with hematopoietic diseases such as non-Hodgkin lymphoma, Hodgkin lymphoma, multiple myeloma, and malignant histiocytosis.

The most common clinical presentation is an enlarging painless soft tissue mass in the thigh, typically 5–10cm in diameter. Two-thirds are intramuscular. Retroperitoneal MFH usually presents with constitutional symptoms, including fever, malaise, and weight loss. This can be confused with infection or abscess presentation. MFH also occurs secondary to radiation exposure and may occasionally be seen adjacent to metallic devices, including total joint prostheses.

Plain radiographs are always indicated, reflecting the invasive nature of tumour. Bony lesions will show destructive changes with cortical erosion and a poorly defined, permeative margin. Other changes such as matrix mineralization are less common. CT typically reveals a non-specific, large, lobulated, soft tissue mass of predominantly muscle density, with nodular and peripheral enhancement of solid portions.

One should keep in mind that the diagnosis of MFH is made using histopathology, not by imaging; however, MRI remains invaluable for delineating tumour extent.

Uncertain histogenesis and numerous subtypes make MFH a rather controversial entity.

The tumour contains both fibroblast-like and histiocyte-like cells in varying proportions, with spindled and rounded cells exhibiting a storiform arrangement.

Five histologic subtypes have been described:

Early and complete surgical removal is indicated because of the aggressive nature of the tumour. Surgical excision with irradiation to residual local disease is the treatment modality of choice. The sensitivity of MFH to radiotherapy and chemotherapy is poor, and evidence is lacking for adjuvant treatment.

Patients with low-grade, intermediate-grade, and high-grade tumours have 10-year survival rates of 90%, 60%, and 20%, respectively. Patients with tumours smaller than 5cm at presentation have survival rates of 79–82%. Patients with tumours larger than 10cm have survival rates of 41–51%.

The rate of metastasis varies with the histologic subtype from 23% (myxoid) to 50% (giant cell). Distant metastasis most commonly occurs to the lung (90%) and bone (8%) Resection with negative microscopic margins decreases the incidence of local recurrence.

The overall survival rate of patients with MFH ranges from 36–58% at 5 years; however, patients with retroperitoneal tumours have an overall 5-year survival rate of 15–20%.

Chordoma is a relatively rare malignant midline tumour strictly arising in the midline of the axial skeleton, primarily at its cranial and caudal ends. Chordomas are tumours derived from remnants of the primitive notochord. They often metastasize late and despite surgical resection, and adjuvant radiotherapy, recurrence is common.

Chordomas are tumours arising from remnants of the primitive notochord and are epithelial in origin. They are relatively rare (make up only 1–4% of primary malignant soft tissue tumours) slow growing, malignant neoplasms. Peak distribution is in patients aged 55–65 years. Males are affected twice as frequently as are females, with a preponderance of cases in the sacrococcygeal location.

Chordomas have a predilection for the ends of the spinal column. Approximately 50% of spinal chordomas originate in the sacrococcygeal area. Approximately 35% occur at the base of the skull near the spheno-occipital area, and 15% are found in the vertebral column. These lesions present clinically as destructive bony masses with extensive soft tissue involvement. They erode and impinge upon adjacent structures, giving rise to variable presentation.

In the cranial region, they can cause cranial nerve palsies, hydrocephalus, headaches, and torticollis.

Sacral chordomas are often missed at the initial presentation, with patients being symptomatic for several months or even years prior to being correctly diagnosed. Most patients have pain that is difficult to distinguish from mechanical back pain. Symptoms may include altered bowel habits, or a feeling of fullness in the rectal area. Physical examination must include a rectal examination to exclude a potential presacral mass.

Chordomas are locally aggressive but metastasis is relatively uncommon.

Plain radiographs do not provide sufficient information concerning the diagnosis or the planning of the surgical procedure and can often be obscured by bowel gas. Chordoma lesions are seen as midline lobular lesions, with areas of osteolysis, occasionally with expansion and osteosclerotic rimming. MRI scans are essential to map out the true extent of the tumour especially sagittal views of the whole of the sacrum (Figure 2.4.4).

Based on light microscopic morphology, chordomas have been divided into three subtypes: conventional, chondroid, and dedifferentiated. Grossly, conventional chordomas have a soft, tan, myxoid appearance with areas of haemorrhage. Immunochemistry is extremely useful for distinguishing chordoma from other tumours, especially chondrosarcoma.

Dedifferentiation or sarcomatous transformation occurs in 2–8% of chordomas and is associated with a poor prognosis.

Definitive resection should always wait until a final pathological diagnosis is made. The mainstay of treatment is en bloc resection of the tumour with a wide margin, leaving a cuff of normal tissue.

Aggressive initial therapy improves overall outcome. Tumours detected and diagnosed early have a favourable prognosis if treated with a complete or en bloc excision. A complete excision may involve a combined anterior-posterior operation, vertebrectomy if the spine is involved, and subsequent stabilization. A permanent colostomy may be required and the patient may need intermittent self catheterization in the long term.

The importance of a complete excision is demonstrated by the longer disease-free period compared to that following an incomplete excision. In aiming to achieve a clear resection margin, sacrificing sacral nerve roots and excision of the rectum may be required.

Surgical resection margins are reportedly the most important predictor of survival and local recurrence with sacral chordomas. The findings suggest that obtaining wide surgical margins posteriorly, by excising parts of the piriformis, gluteus maximus, and sacroiliac joints, may result in better local disease control in patients with sacral chordoma.

Adjuvant radiotherapy must be given in the case of incomplete excision. Radiation therapy may also salvage some patients with local recurrence.

The 5-year and 10-year survival rates for conventional chordoma are approximately 50% and 25–30%, respectively. Survival rates appear to be influenced more by local tumour progression than by metastasis.

All three types of chordomas can metastasize, usually later in the course of the disease (except dedifferentiated chordomas, which can metastasize early). Vertebral body chordomas have a higher incidence of metastasis than do those arising in the clivus or sacrum.