Abstract
A soft tissue swelling is a common clinical presentation, and although the majority of causes are benign, an intermediate or malignant diagnoses must be ruled out. A thorough history and examination are key to highlight any red flags such as rapid growth, a large tumour size (>5 cm), a deep location, pain or recurrence. These flags should be investigated thoroughly, and if there is any diagnostic uncertainty patients should be discussed with a sarcoma multidisciplinary team (MDT) prior to treatment, and biopsy considered. The inadvertent resection of a malignant soft tissue sarcoma (termed a ‘whoops’ procedure) must be avoided at all costs. Ultrasound is a cheap and easily accessible first-line imaging modality that in specialist hands can identify or rule out aggressive features accurately. Magnetic resonance imaging is the gold standard cross-sectional imaging modality for soft tissue tumours, and allows a detailed anatomical assessment key for surgical planning. Most benign lesions can be managed conservatively or with active surveillance, although symptomatic patients may benefit from a surgical excision. Intermediate tumours should be managed in conjunction with a sarcoma MDT given their rarity and complexity, and will usually require an excision.
Introduction
Soft tissue swellings are common and present to professionals working in both primary and secondary care. The current UK National Institute for Health and Care Excellence (NICE) guidelines call for all adults with an enlarging, unexplained swelling to be referred for an urgent 2-week wait (2WW) ultrasound (US) for assessment. The same guidelines also recommend a specialist assessment via a 2WW suspected cancer pathway for all adults with a US suggestive of soft tissue sarcoma, an indeterminate US, or if any clinical concern persists. For children and young adults NICE recommends these scans and assessment are made within 48 hours.
Patient assessment
A detailed patient assessment is key to avoid the mismanagement of a soft tissue sarcoma (STS). An inadvertent resection in these cases (termed a ‘whoops’ procedure) can result in increased surgical morbidity from repeated surgeries and must be avoided.
History
A focused history can help differentiate many benign tumours from their malignant counterparts. Swelling duration, growth, associated pain and distal neurovascular symptoms should be determined. Slowly growing or static lesions suggest (but do not ensure) a benign diagnosis, whist rapid growth is more concerning for malignancy. The absence of pain should not provide false reassurance, as over 70% of newly diagnosed STS patients deny pain on presentation. Similarly, many benign soft tissue tumours including peripheral nerve sheath tumours (PNSTs), angioleiomyomas and glomus tumours may be extremely painful. Patients should be asked about recent trauma, which may precede haematoma formation or myositis, although is also reported in over 20% of new STS diagnoses. Any recent local surgery or infections should be noted (potentially resulting in regional lymphadenopathy) as well as regional neurological symptoms which may result from large sensory or motor nerve PNSTs. Constitutional symptoms such as pyrexia, malaise, weight loss or night-sweats should be noted, although the majority of patients with malignant tumours will deny these. Any systemic ramifications of infection should raise suspicion of an abscess. Past medical history should be elucidated, with particular attention paid to previous cancer, genetic conditions (neurofibromatosis types 1 and 2, Li Fraumeni syndrome), bleeding diathesis (associated with haematoma) and gout or rheumatoid arthritis (soft-tissue tophus or nodules). Family history should be noted considering that a cancer diagnosis is seen in a first-degree relative in 30% of STS patients. Current medications should be noted (with particular attention to anticoagulants).
Examination
The location, size, depth (mobility) and consistency of all swellings should be noted. Superficial, small (<5 cm) swellings are more likely to be benign (although one-third of STSs are superficial). Deep (immobile), firm characteristics are concerning although do not always correlate with malignancy. Overlying skin should be assessed for erythema and warmth (abscesses or malignant tumour neovascularization), scars (biopsy or previous resections) and bruising (haematoma). Fluctuance may be present in cystic lesions (including ganglions) or vascular malformations. Ganglion cysts may also trans-illuminate, and percussion may elucidate a positive Tinel’s sign in cases of PNST. Regional lymph node basins should be assessed for lymphadenopathy, and distal neurovascular status assessed and documented.
Bloods
Patients with concerning swellings should have a full blood count (FBC), inflammatory markers (C-reactive protein/erythrocyte sedimentation rate) and renal/clotting profile to both look for infection/inflammation, and to facilitate any subsequent contrast-enhanced cross-sectional imaging or a biopsy.
Imaging
Ultrasound
US imaging uses high-frequency sound waves emitted from a transducer to produce an image by recording the waves’ reflected echoes off tissues. US is usually the first investigation performed for soft tissue swellings as it is readily available, cost effective, non-invasive and very low risk. In secondary care it can also often be performed at the time of a patient’s initial assessment in a ‘one stop’ type clinic. Although US is very user dependent, it can characterize a swelling in many ways, providing detail on size, depth, vascularity (using Doppler) and heterogeneity. Importantly US also allows the most common soft tissue tumour (lipoma) to be diagnosed, and patients to be reassured.
Magnetic resonance imaging (MRI)
MRI is generally accepted as the gold standard cross-sectional imaging modality for the assessment of soft tissue tumours. All patients with tumours that are large, deep, or are indeterminate or aggressive appearing on US, should undergo MRI if not contraindicated. MRI provides the most detailed assessment of a soft tissue lesions’ characteristics including their size, depth, heterogeneity and relationship to other anatomical structures (a key factor when planning surgical intervention.) Like US, MRI is non-invasive and relatively low risk, although does have several contraindications including certain cardiac implants, and claustrophobia or severe obesity if an open scanner is unavailable. The modality is also of limited use for small lesions (<2 cm).
Plain radiographs
Radiographs have limited use in the assessment of soft tissue tumours. In some lesions maturation (in the form of calcification) over time can help diagnosis, e.g. myositis ossificans.
Biopsy
If a lesion remains indeterminate after appropriate imaging, or an intermediate or malignant diagnosis is suspected, discussions should be held with a sarcoma multidisciplinary team (MDT) who will likely recommend a biopsy. Most soft tissue lesions are biopsied using a core needle under US guidance, although image guidance may not be required for superficial lesions. An open incisional biopsy may be required if key nearby neurovascular structures preclude a safe image-guided percutaneous biopsy, or if insufficient tissue has been obtained for analysis using this approach. Excision biopsy may be suitable for small, superficial lesions away from any key neurovascular structures or joints after discussion with a sarcoma MDT. Fine needle aspiration (FNA) is generally not appropriate for the assessment of soft tissue tumours, as the cells provided are insufficient for the immunohistochemical and cytogenetic assays often required to diagnose soft tissue sarcoma subtypes and many other intermediate soft tissue tumours.
Soft tissue tumour classification
The World Health Organization (WHO) defines mesenchymal tumours as benign, intermediate (locally aggressive), intermediate (rarely metastasizing) or malignant. They also group tumours based on an integration of morphology with immunohistochemistry and molecular genetics (see Box 1 ). All intermediate and malignant mesenchymal tumours should be referred to and managed by a sarcoma MDT. The benign and intermediate soft tissue tumour subtypes that present most commonly to an orthopaedic specialist are discussed below.
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Adipocytic tumours
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Fibroblastic/myofibroblastic tumours
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Fibrohistiocytic tumours
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Vascular tumours
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Pericytic (perivascular) tumours
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Skeletal muscle tumours
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Smooth muscle tumours
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Chondro-osseous tumours
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Peripheral nerve sheath tumours
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Tumours of uncertain differentiation
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Undifferentiated small round cell sarcomas of bone and soft tissue
Adipocytic tumours
Benign: lipomas are the most common mesenchymal tumour which is histologically defined as lobules of mature adipocytes. They are usually slow growing, soft and painless. Most are small (2–5 cm), but they can grow to any size. They are often superficial, however can be deep (intra- or intermuscular). The majority of cases are sporadic but, in some cases, genetic links with conditions such as familial multiple lipomatosis are present. If symptomatic then a marginal surgical excision is the standard treatment.
Angiolipomas are a variant of the typical lipoma described above, and account for 5–17% of all benign lipomatous tumours. Clinically angiolipomas are often indiscernible from a standard lipoma, although on histological examination they contain clusters of capillary sized vessels with fibrin thrombi. Despite this, vascularity is only visible on US in <25% of cases, due to the small size of the capillary vessels present. Angiolipomas are more common in adults in the late second to third decades of life. Treatment follows the same principles as that for a standard lipoma.
Spindle cell/pleomorphic lipomas are a rare morphological spectrum of the same pathology, which together account for just 1.5% of all adipocytic tumours. Spindle cell lipomas are composed of mature adipocytes, bland spindle cells and hyalinized collagen fibres. In addition, pleomorphic lipomas also contain pleomorphic and multinucleated giant cells. Spindle-cell/pleomorphic lipomas are most common in middle aged males (<10% occurring in females) and the superficial tissues of the posterior neck, back and shoulders. Imaging will reveal a variable amount of non-adipose tissue, which can mimic more sinister pathologies necessitating biopsy. If symptomatic, then marginal surgical excision is the standard of treatment.
Hibernomas (fetal lipoma/lipoma of embryonic fat) are adipocytic soft tissue tumours that contain predominantly brown adipocytes. They account for 1% of lipomatous tumours and are most common in the third to fourth decade of life. Up to 10% of cases are intraosseous, where they present as sclerotic lesions. A myxoid or heterogeneous appearance may be seen on imaging, again often necessitating a biopsy. Symptomatic lesions may be excised marginally.
Intermediate: atypical lipomatous tumours (ALT) (previously known as well-differentiated liposarcomas) are composed of large, multilobulated, mature adipocytes. Importantly, ALTs show amplification of the MDM2 oncogene – a regulator of the p53 tumour suppressor. This can in very rare circumstances result in dedifferentiation of an ALT into a malignant soft tissue sarcoma (liposarcoma). Atypical lipomatous tumours may present in a very similar way to a lipoma, although are almost universally deep. They are also more likely to be located in the thigh, larger (>10 cm), and found in patients aged over 60 years. Radiological features suggestive of an ALT over a lipoma include thick septa (>2 mm), contrast enhancement and a deep location (see Figure 1 ). In cases of diagnostic uncertainty or any concerns regarding sarcoma dedifferentiation, referral to a sarcoma MDT and biopsy is essential. Marginal excision is the standard treatment for symptomatic ALTs (see Figure 2 ). Shared decision-making balancing the risks of surgery and the very low risk of malignant dedifferentiation is key in patients with asymptomatic ALTs. Cases managed non-operatively should be followed up closely, and any tumour growth or new pain explored with urgent, repeat MRI.
