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The management of soft tissue tumours of the abdominal wall
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ScienceDirect EJSO xx (2017) 1e9
www.ejso.com
Review
The management of soft tissue tumours of the abdominal wall H.G. Smith a, D. Tzanis b, C. Messiou a, C. Benson a, J.A. van der Hage c, M. Fiore d, S. Bonvalot b, A.J. Hayes a,* a
b
The Sarcoma Unit, The Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom Sarcoma Unit, Department of Surgery, Institut Curie, PSL Research University, 26 rue d’Ulm, Paris, France c Division of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands d Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy Accepted 24 April 2017 Available online - - -
Abstract Background: Soft tissue tumours of the abdominal wall account for approximately 10% of all soft tissue tumours. Tumours at this site comprise a heterogeneous group of pathologies with distinct clinical behaviours and responses to treatment. The management of these tumours has largely been extrapolated from studies of soft tissue tumours at other sites. This review aims to summarise the existing data relating to abdominal wall tumours and suggest principles for managing soft tissue tumours at this site. Methods: Relevant articles were retrieved from a comprehensive literature search using the PubMed database. Key words included abdominal wall, soft tissue tumours, surgery, radiotherapy and chemotherapy. No restrictions on publication date were used. Results: The most common pathologies presenting in the abdominal wall are desmoid tumours, soft-tissue sarcoma and dermatofibrosarcoma protuberans (DFSP). Desmoid tumours should be managed with an initial period of observation, with surgery reserved for progressive lesions. Surgery should be the primary treatment for soft-tissue sarcomas and DFSP, with radiotherapy reserved for large-high grade tumours and preferentially given pre-operatively. Conclusions: Abdominal wall tumours are rare and should be managed in centres with experience in the management of soft tissue tumours. Management should be tailored to the biological behaviour of specific pathologies. Ó 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.
Keywords: Abdominal wall; Desmoid tumours; Soft tissue sarcoma; Dermatofibrosarcoma protuberans
Introduction Soft tissue tumours arising in the abdominal wall comprise a range of different pathologies, with distinct clinical behaviours and patterns of relapse. Tumours of the abdominal wall are rare, accounting for less than 10% of all soft tissue tumours.1 As soft tissue tumours most commonly affect the extremities, the principles of management of abdominal wall tumours are in part extrapolated from randomised trials in extremity sarcoma, coupled with cohort studies that include abdominal wall tumours * Corresponding author. E-mail address: [email protected] (A.J. Hayes).
alongside soft tissue tumours at other anatomical sites. There are a relatively small number of retrospective studies of abdominal tumours studied in isolation. This review article will summarise the data that exists relating to abdominal wall tumours and suggest management principles for patients with soft tissue tumours arising at this site. Epidemiology The most commonly occurring tumours of the abdominal wall are desmoid tumours and soft tissue sarcomas, accounting for 45% and 40% of all abdominal wall tumours respectively, with dermatofibrosarcoma protuberans (DFSP) accounting for the remaining cases.2e4
http://dx.doi.org/10.1016/j.ejso.2017.04.009 0748-7983/Ó 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. Please cite this article in press as: Smith HG, et al., The management of soft tissue tumours of the abdominal wall, Eur J Surg Oncol (2017), http:// dx.doi.org/10.1016/j.ejso.2017.04.009
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Desmoid tumours, also known as aggressive fibromatosis, are monoclonal fibroblastic proliferations that are characterised by an unpredictable potential for progression or spontaneous regression. The estimated incidence of desmoid tumours is 5/1,000,000 per year, with evidence that their incidence has increased over the past two decades.5 Desmoid tumours lack the ability to metastasise but local progression may cause significant morbidity or even death, particularly when located within the abdominal cavity. Desmoids demonstrate an infiltrative growth pattern and are associated with high rates of local recurrence. These tumours typically occur in younger patients, with a peak incidence in the fourth decade.5e7 Sporadic mutations in the bcatenin gene, CTNNB1, account for the majority of desmoid tumours, with approximately 10% of cases arising in association with an APC mutation in the context of the familial adenomatous polyposis (FAP) syndrome.8e11 Although desmoid tumours may occur virtually anywhere within the body, the extremities and the abdominal wall are the most commonly affected sites.12 Desmoid tumours occur more commonly in females, who account for over two-thirds of desmoids at any site.5,7,12 Abdominal wall desmoid tumours show a particular predilection for women of childbearing age, who account for over 90% of patients presenting with desmoids at this site.13,14 Current hypotheses for the increased incidence of abdominal wall desmoids in these patients include physical trauma secondary to pregnancy or, as these tumours may often express oestrogen or progesterone receptors, a hormonal component to their aetiology.15,16 Intra-abdominal disease is most commonly seen with FAP-associated desmoids and it is important to exclude this syndrome in such patients, as the management of intra-abdominal desmoids is very different between patients with FAP and those without.12,17,18 Surgical management of intra-abdominal desmoids in the context of FAP is associated with high peri-operative morbidity and mortality as well as high rates of local recurrence.17,19 In contrast, surgery for sporadic intra-abdominal desmoids is associated with fewer complication or recurrences.18 As such, in FAPassociated intra-abdominal desmoids, there is a high threshold for surgical intervention, which is generally reserved for patients who have failed medical management. Soft tissue sarcomas represent a diverse group of cancers of mesenchymal origin with an estimated incidence of 4e5/ 100,000 per year in Europe.20 The propensity for distant metastasis varies between distinct histological subtypes, although all subtypes have the potential for local recurrence.21 Soft tissue sarcomas can arise at almost any anatomical site but most commonly present in the extremities or the abdominal cavity/retroperitoneum. Primary abdominal wall sarcomas account for less than 5% of cases.1,3 The most common subtypes manifesting in the abdominal wall are undifferentiated pleomorphic sarcomas (previously known as malignant fibrous histiocytomas), fibrosarcomas and synovial sarcomas.2e4 In contrast to desmoid tumours, soft tissue sarcomas do not display a
preference for gender and occur later in life, with a median age at presentation of approximately 50 years.3,22 DFSP is a locally aggressive tumour with low metastatic potential.23e25 Rather than representing a true abdominal wall tumour, DFSP originates from the cutaneous tissues and is typically limited to superficial structures. DFSPs have an infiltrative growth pattern, particularly in the cutaneous plane, and a propensity for local recurrence. Progression to a fibrosarcoma may occur in around 15% of patients with DFSPs, conferring a more aggressive biological behaviour, with a greater risk of involvement of deeper structures and increased metastatic potential.25 Almost all DFSPs contain a fusion gene, COL1A1-PDFGB, leading to activation of the platelet-derived growth factor b (PDGFb) signalling pathway.26,27 As such, tyrosine kinase inhibitors targeting the PDGFb pathway, such as imatinib, may be of therapeutic benefit in both localised and disseminated disease. Diagnosis, staging and imaging The principles of investigation for abdominal wall tumours are broadly similar to those of soft tissue sarcomas of other anatomical sites.28 Due to the rarity of these lesions, patients with suspected soft tissue tumours of the abdominal wall should be referred to specialist centres benefitting from multidisciplinary teams experienced in the management of soft tissue tumours. Patients with desmoid tumours and soft-tissue sarcomas may have similar clinical presentations. The majority of patients with either pathology will present with a mass that is typically painless. Size is a poor discriminator between these pathologies, although soft-tissue sarcomas may present with slightly larger dimensions with a median size of 6e15 cm compared with 6e8 cm for desmoid tumours.3,4 Fixation to underlying structures is suggestive of a soft-tissue sarcoma, whereas a lesion occurring in a young female, particularly with a recent history of pregnancy, is more suggestive of a desmoid tumour. In contrast to the other pathologies, DFSPs tend to present as an indurated superficial lesion with characteristic purple or blue discolouration. In the presence of a small (<5 cm) and superficial lesion, ultrasound may be used to identify clearly benign lesions. Larger or deep lesions or those with equivocal or suspicious ultrasound features should be further assessed with crosssectional imaging. Magnetic resonance imaging (MRI) is probably the modality of choice for imaging abdominal wall tumours, as the improved soft tissue contrast provides better delineation of tumour margins than computed tomography (CT).29 However, CT is still a good investigation for surgical planning for soft tissue lesions of the trunk or abdominal wall, with the advantage that staging of the lungs and assessment of intra-abdominal viscera can be performed at the same time as imaging the primary tumour, and is less prone to movement artefact that MRI. MRI is reasonably accurate in differentiating benign and malignant lesions (though not accurate enough to circumvent the need for a diagnostic core
Please cite this article in press as: Smith HG, et al., The management of soft tissue tumours of the abdominal wall, Eur J Surg Oncol (2017), http:// dx.doi.org/10.1016/j.ejso.2017.04.009
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biopsy), but its ability to reliably determine histological subtype or grade is limited.30,31 Variations in the appearance of desmoid tumours, in terms of signal intensity and contrast enhancement, may occur not only between patients but also within distinct lesions in the same patient. However, this variation in imaging appearances has not been shown to be predictive of tumour behaviour.32 Further detail regarding the specific imaging appearances of different abdominal wall tumours may be found in a review by Bashir et al.33 A histological diagnosis should be confirmed with a percutaneous core needle biopsy. A range of different pathologies, both benign and malignant, may present as a mass in the abdominal wall, with a list of differential diagnoses shown in Table 1. When used appropriately, and with expert histo-pathological analysis, percutaneous core biopsy has an accuracy rate of 97.6% (sensitivity 96.3%, specificity 99.4%) in distinguishing benign from malignant soft tissue lesions and will determine the correct tumour grade and histological subtype in over 80% of cases.34,35 Pre-operative histological diagnosis by this method should only be forgone if the lesion is superficial and too small for biopsy to be technically feasible (i.e. <2 cm) or when preoperative imaging is pathognomic (e.g. for atypical lipomatous tumour). Biopsies should be performed at an anatomical site that allows the biopsy tract to be included in any subsequent excision and hence the biopsy should be performed with knowledge of the planned surgical resection. Patients with soft tissue sarcomas and DFSP should be staged at diagnosis to exclude distant metastatic disease.28 In patients where pre-operative imaging or biopsy are suggestive of well-differentiated liposarcomas or other low grade sarcomas, staging with a chest x-ray may suffice. In the remaining patients, CT of the chest should be considered. In patients with histological subtypes prone to extrapulmonary dissemination, such as myxoid liposarcomas, cross sectional imaging of the abdomen and pelvis should also be performed at staging.36 Management Desmoid tumours Historically, desmoid tumours were managed in a similar fashion to soft tissue sarcomas, with the aim of Table 1 Differential diagnoses of abdominal wall masses. Pseudo-tumours
Myositis Nodular fasciitis Haematoma
Tumours
Lipoma Desmoid tumour Soft-tissue sarcoma Endometriosis Carcinoma Lymphoma Metastasis
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achieving negative margins with wide surgical excisions. However, in contrast to soft tissue sarcoma, several large series have demonstrated that margin status is not prognostic for local recurrence in desmoid tumours.7,37,38 Furthermore, desmoid tumours demonstrate the potential for prolonged periods of stable growth and spontaneous regression.7 With an increased understanding of the natural history of these rare tumours, a more conservative approach to management is now advocated.39 However, an important distinction must be made between the management of desmoid tumours of the abdominal wall and those of the most common other site e the extremities. Surgery in the extremities is often followed by local recurrence, with repeated surgical intervention increasing the risk of cumulative functional impairment. As such, systemic therapies are preferred, with surgery reserved for unresponsive, symptomatic cases. In contrast, as discussed below, surgery often secures local disease control in the abdominal wall and, as such, still plays a prominent role in the management of desmoids at this site. Observation Although desmoid tumours appear to have an increased frequency in relation to pregnancy and certain mutations in the CTNNB1 gene are associated with greater risks of recurrence, there are no known reliable prognostic factors of progression or regression of these tumours at presentation.16,40,41 As such, it is recommended that all patients be initially managed with a period of close observation. Serial imaging and clinical examination may be performed at intervals of 3e6 months over a period of at least 2 years if symptoms permit. When managed in such a fashion, progression-free survival is approximately 50% at 5 years and further intervention may be avoided altogether in up to two-thirds of patients.13,42,43 Surgical management In rapidly progressive or symptomatic disease, surgical excision should be considered. In contrast to desmoid tumours of the extremities, where surgery may result in significant functional morbidity, excision of abdominal wall desmoids is associated with minimal complications.3,14 Abdominal wall reconstruction is necessary in between 60 and 90% of cases.3,13,14 However, the incidence of incisional hernias is low at less than 5% and, importantly given the propensity for these tumours to occur in women of childbearing age, abdominal wall reconstruction is not associated with an increase in perinatal complications.4,14 Furthermore, with recurrence rates of less than 10%, surgery is a more definitive management in the abdominal wall than in the extremities, where recurrence occurs in more than 60% of patients.6,7,13,14,43,44 Systemic therapies Hormonal therapies, such as tamoxifen, are an alternative to surgery in patients with symptomatic lesions and
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may be used in conjunction with non-steroidal anti-inflammatory drugs. Although the response rates with such agents are low, ranging from 30 to 50% in small case series, and an objective response may take several months to develop, hormonal therapies are generally well tolerated and rarely lead to significant toxicities.45 However, as responses are often delayed, hormonal therapies may not be suitable for patients with rapidly progressive disease. In such patients and in those unresponsive to hormonal therapies or in whom surgery is unfeasible or declined, systemic chemotherapy may be considered. Treatment typically needs to be continued for 6e12 months for durable results and patients should be counselled appropriately. Pegylated liposomal doxorubicin is the treatment of choice in many centres, benefitting from quicker responses and a more acceptable toxicity profile than other regimes such as methotrexate with or without vinblastine.46,47 There is also some evidence that tyrosine kinase inhibitors, such as imatinib, sorafenib and pazopanib, may be effective in this pathology, and although the use of these agents remains investigational, they provide an alternative option in patients unresponsive to hormonal therapy or traditional chemotherapies.48e50 The progression through systemic therapies and the timing of surgery may vary between institutions but is also dependent on patient preference. A proposed algorithm from a collaboration between the French and Italian Sarcoma Groups provides a starting point on which to base these discussions with patients.51 Radiotherapy and other local therapies Although radiotherapy may be considered in the management of inoperable desmoid tumours of the extremities, it is not felt to have a role in the management of abdominal wall disease due to concerns about both the short term treatment toxicity and the risk of radiation induced malignancies in this young cohort of patients.39 The use of ablative therapies in desmoid tumours has also been reported.52e54 Though patients may require repeated treatments, ablative techniques appear to be well tolerated. With evidence limited to small case series, the role of ablative therapies in desmoid tumours remains to be defined. However, they may offer an additional option for patients with progressive disease that is unresponsive to other modalities. Surveillance and pregnancy With an increasing number of patients with desmoid tumours undergoing conservative management involving prolonged clinical observation, issues relating to the frequency of and appropriate modality used for surveillance will be encountered in the future. Short-interval imaging every 3e4 months with contrast-enhanced MRI has been suggested for the first 2 years of surveillance. In the case of stable disease or regression, longer time intervals may be adopted and MRI replaced with ultrasound surveillance.55 Females of childbearing age require special consideration. The complex and incompletely understood relationship
between desmoid tumours, hormones and pregnancy warrants a comprehensive discussion to assist and educate patients with family planning. Available data do not suggest any medical advice to avoid or interrupt pregnancy in patients with a history of desmoids, although oestrogen and/ or progesterone containing contraceptives are discouraged. On the contrary, desmoid tumours may be safely managed in the event of progression during or after pregnancy, with obstetric complications rarely encountered despite the presence of these abdominal wall tumours.56 Soft tissue sarcomas As with other anatomical sites, surgery forms the mainstay of management of soft tissue sarcomas of the abdominal wall. The aim should be to achieve negative margins with a wide surgical excision. The excision of superficial tumours should be extended to include the anterior rectus sheath as a deep margin, with excision of the posterior sheath or peritoneum indicated in the case of deep tumours. As such, abdominal wall mesh reconstruction is required in the majority of patients.3,4 Tumours may be adherent to underlying viscera or bony structures, necessitating extended resections in approximately 25% of cases.3,4 The role of radiotherapy in the management of abdominal wall sarcoma may be extrapolated from randomised trials in extremity sarcoma, where radiotherapy whether given pre- or post-operatively has been shown to reduce the risk of local recurrence.57,58 There have been no large series investigating prognostic factors of local recurrence exclusively in abdominal wall sarcomas. In those studies including abdominal wall sarcomas alongside other anatomical sites, tumour depth, tumour size, histological subtype, margin status and grade have been shown to be independently associated with local recurrence.59e61 It is recommended that radiotherapy should be given to those patients with deep, large (i.e. >5 cm), high-grade tumours, carrying the greatest risk of recurrence. Neoadjuvant radiotherapy allows the delivery of a lower dose of radiation, which may be of particular benefit in abdominal wall sarcomas due to the proximity of radiosensitive viscera.57 Adjuvant chemotherapy has not been shown to be of benefit in unselected soft tissue sarcomas and its use should be limited to specific chemosensitive subtypes, such as Ewing’s sarcomas, rhabdomyosarcomas or synovial sarcomas.62 DFSP should be managed in a similar fashion to abdominal wall sarcomas, with wide surgical excision. However, as margin status is the only independent prognostic factor for local recurrence in DFSP, a 2e3 cm margin has been advocated for the excision of these lesions,63,64 in contrast to the greater than 1 mm margin on a fixed specimen recommended for soft tissue sarcomas.65,66 Mohs surgery has been shown to achieve low local recurrence rates in small retrospective series of DFSP, although the role of this technique in the management of this pathology is
Please cite this article in press as: Smith HG, et al., The management of soft tissue tumours of the abdominal wall, Eur J Surg Oncol (2017), http:// dx.doi.org/10.1016/j.ejso.2017.04.009
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unclear, particularly given the relative ease of reconstructing soft-tissue defects on the abdominal wall.67,68 Although the majority of DFSPs tend to be less than 5 cm in maximal diameter, due to these wider margins plastic reconstruction of the resultant tissue defect is necessary in approximately 15e20% of patients.2,3 Despite the majority of these lesions appearing to be limited to the superficial tissues, it is not unusual to obtain unexpectedly positive margins at the deep margin, due to their infiltrative nature. For this reason, inclusion of the deep fascia en bloc with the soft tissue is recommended and may necessitate a mesh repair of the abdominal wall even if major reconstruction is not required. As mutations in the PDGFb pathway are present in almost all patients with DFSP, tyrosine kinase inhibitors targeting this pathway, such as imatinib, may play a role in the management of patients with inoperable local or metastatic disease. In a pooled analysis of two phase II trials in this setting, the response rates to imatinib were approximately 45%.69 Imatinib may also develop a neoadjuvant role prior to surgery, with a response rate of 50% and a local recurrence rate of less than 10% following excision in a further phase II trial.70 Although the role of these agents should ideally be clarified with further randomised studies, targeted therapies may be considered in patients with inoperable disease or in those in whom surgery would be technically challenging. Radiotherapy may also be of use in patients unsuitable for primary surgical management. Whether used in isolation or in combination with a conservative surgical resection, radiotherapy can achieve durable local disease control in DFSP.71e73 As such, radiotherapy may be considered in inoperable or challenging cases of abdominal wall DFSP, but should be given preferentially
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given in the neoadjuvant setting due to the proximity of radiosensitive viscera. Follow-up On-going surveillance for patients with abdominal wall tumours should mirror that employed with soft tissue sarcomas of other sites.28 All abdominal wall tumours have the potential for local recurrence, and clinical examination of the primary site should be conducted every 6 months for the first 5 years and annually for a further 5 years thereafter. Those patients with high-grade lesions may benefit from more regular review during the first 2e3 years following surgery, when the majority of relapses occur. Suspicious findings should be further investigated with crosssectional imaging. Patients with sarcomas or DFSP should undergo imaging of the chest at each follow-up, with either CT or plain radiographs, to detect metastatic spread. Such imaging surveillance of the thorax is not indicated in desmoid tumours due to their lack of metastatic potential, although serial MRI may be used to monitor treatment responses as described above. Abdominal wall reconstruction following resection If surgery is indicated in the management of an abdominal wall tumour, the preferred method of reconstruction is influenced by the structures involved by the lesion. When only the skin and subcutaneous tissues are involved, as is often the case in DFSP, the integrity of the musculofascial component of the abdominal wall is rarely compromised. In such cases, only soft-tissue coverage is required. If the defect is too large for primary closure, soft-tissue coverage
Figure 1. A desmoid tumour confined to the rectus abdominis muscle as demonstrated on MRI (A). The rectus sheath and muscle were resected (B, D, E), with an underlay mesh reconstruction sutured to the remnant abdominal wall (C, F). Please cite this article in press as: Smith HG, et al., The management of soft tissue tumours of the abdominal wall, Eur J Surg Oncol (2017), http:// dx.doi.org/10.1016/j.ejso.2017.04.009
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Figure 2. An extensive soft-tissue sarcoma infiltrating the inguinal ligament as demonstrated on MRI (A) and clinical examination (C). Following resection, mesh reconstruction was performed with microplates securing the mesh to the pelvic margin (B, D).
may be achieved with split-thickness skin grafts, local advancement flaps or regional rotational flaps, dependent on local expertise and preference. If the musculofascial component of the abdominal wall is included in a resection, reconstruction of the abdominal wall
with either a synthetic or biological mesh is mandatory. For those tumours in which only the muscle is involved, an underlay mesh repair should be performed, with the mesh sutured onto the posterior surface of the remnant abdominal wall (Fig. 1). In the case of more extensive musculofascial
Figure 3. A soft-tissue sarcoma infiltrating the full-thickness of the abdominal wall as demonstrated on MRI (A). Resection included all components of the abdominal wall (B, C) followed by mesh reconstruction and a free flap from the ipsilateral thigh (D). Please cite this article in press as: Smith HG, et al., The management of soft tissue tumours of the abdominal wall, Eur J Surg Oncol (2017), http:// dx.doi.org/10.1016/j.ejso.2017.04.009
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resections, there may little or no remnant abdominal wall on which to base a mesh reconstruction. A commonly encountered example is where of infiltration of the inguinal ligament necessitates its resection. In such cases, microplates may be used to fix the mesh to the pelvic and/or costal margins (Fig. 2). In these cases, where there is little or no involvement of the skin and subcutaneous tissues, primary closure following mesh reconstruction may be achievable. However, in the presence of extensive involvement of skin, subcutaneous tissue and muscle, resection of the full thickness of the abdominal wall is necessary and reconstruction may require the additional use of a free flap, most commonly taken from the thigh (Fig. 3). Conclusion Abdominal wall tumours are rare entities and should be managed in centres with experience in the management of soft tissue tumours. Management should be tailored to the biological behaviour of specific pathologies. Patients with desmoid tumours should be offered a period of observation to determine which patients require and may benefit from further intervention. Roughly, 2/3 of patients may be spared from surgery. Surgery should be the primary treatment option for progressive abdominal wall desmoids, with hormonal or medical therapies reserved for those declining or unsuitable for operative intervention. Soft tissue sarcomas of the abdominal wall should be managed primarily with surgical resection, with radiotherapy reserved for large, highgrade tumours and preferentially given pre-operatively. A wider margin of resection (2e3 cm) should be employed for DFSPs to minimise the risk of local recurrence. Conflict of interest statement The authors have no conflicts of interest to disclose.
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COL1A1 in dermatofibrosarcoma protuberans and giant-cell fibroblastoma. Nat Genet 1997;15:95–8. Group ESESNW. Soft tissue and visceral sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2014;25(Suppl. 3):iii102–12. Fisher SM, Joodi R, Madhuranthakam AJ, Oz OK, Sharma R, Chhabra A. Current utilities of imaging in grading musculoskeletal soft tissue sarcomas. Eur J Radiol 2016;85:1336–44. Vanhoenacker FM, Van Looveren K, Trap K, et al. Grading and characterization of soft tissue tumors on magnetic resonance imaging: the value of an expert second opinion report. Insights Imaging 2012;3: 131–8. Gielen JL, De Schepper AM, Vanhoenacker F, et al. Accuracy of MRI in characterization of soft tissue tumors and tumor-like lesions. A prospective study in 548 patients. Eur Radiol 2004;14:2320–30. Castellazzi G, Vanel D, Le Cesne A, et al. Can the MRI signal of aggressive fibromatosis be used to predict its behavior? Eur J Radiol 2009;69:222–9. Bashir U, Moskovic E, Strauss D, et al. Soft-tissue masses in the abdominal wall. Clin Radiol 2014;69:e422–31. Heslin MJ, Lewis JJ, Woodruff JM, Brennan MF. Core needle biopsy for diagnosis of extremity soft tissue sarcoma. Ann Surg Oncol 1997; 4:425–31. Strauss DC, Qureshi YA, Hayes AJ, Thway K, Fisher C, Thomas JM. The role of core needle biopsy in the diagnosis of suspected soft tissue tumours. J Surg Oncol 2010;102:523–9. Moreau LC, Turcotte R, Ferguson P, et al. Canadian Orthopaedic Oncology Society. Myxoid/round cell liposarcoma (MRCLS) revisited: an analysis of 418 primarily managed cases. Ann Surg Oncol 2012;19:1081–8. Gronchi A, Casali PG, Mariani L, et al. Quality of surgery and outcome in extra-abdominal aggressive fibromatosis: a series of patients surgically treated at a single institution. J Clin Oncol 2003;21:1390–7. Lewis JJ, Boland PJ, Leung DH, Woodruff JM, Brennan MF. The enigma of desmoid tumors. Ann Surg 1999;229:866–72. [Discussion 72e3]. Kasper B, Baumgarten C, Bonvalot S, et al. Management of sporadic desmoid-type fibromatosis: a European consensus approach based on patients’ and professionals’ expertise e a sarcoma patients EuroNet and European Organisation for Research and Treatment of Cancer/ Soft Tissue and Bone Sarcoma Group initiative. Eur J Cancer 2015;51:127–36. Domont J, Salas S, Lacroix L, et al. High frequency of beta-catenin heterozygous mutations in extra-abdominal fibromatosis: a potential molecular tool for disease management. Br J Cancer 2010;102: 1032–6. Lazar AJ, Tuvin D, Hajibashi S, et al. Specific mutations in the betacatenin gene (CTNNB1) correlate with local recurrence in sporadic desmoid tumors. Am J Pathol 2008;173:1518–27. Fiore M, Rimareix F, Mariani L, et al. Desmoid-type fibromatosis: a front-line conservative approach to select patients for surgical treatment. Ann Surg Oncol 2009;16:2587–93. Burtenshaw SM, Cannell AJ, McAlister ED, et al. Toward observation as first-line management in abdominal desmoid tumors. Ann Surg Oncol 2016;23:2212–9. van Broekhoven DL, Verhoef C, Elias SG, et al. Local recurrence after surgery for primary extra-abdominal desmoid-type fibromatosis. Br J Surg 2013;100:1214–9. Janinis J, Patriki M, Vini L, Aravantinos G, Whelan JS. The pharmacological treatment of aggressive fibromatosis: a systematic review. Ann Oncol 2003;14:181–90. Constantinidou A, Jones RL, Scurr M, Al-Muderis O, Judson I. Pegylated liposomal doxorubicin, an effective, well-tolerated treatment for refractory aggressive fibromatosis. Eur J Cancer 2009;45:2930–4. Garbay D, Le Cesne A, Penel N, et al. Chemotherapy in patients with desmoid tumors: a study from the French Sarcoma Group (FSG). Ann Oncol 2012;23:182–6.
48. Penel N, Le Cesne A, Bui BN, et al. Imatinib for progressive and recurrent aggressive fibromatosis (desmoid tumors): an FNCLCC/ French Sarcoma Group phase II trial with a long-term follow-up. Ann Oncol 2011;22:452–7. 49. Gounder MM, Lefkowitz RA, Keohan ML, et al. Activity of Sorafenib against desmoid tumor/deep fibromatosis. Clin Cancer Res 2011; 17:4082–90. 50. Martin-Liberal J, Benson C, McCarty H, Thway K, Messiou C, Judson I. Pazopanib is an active treatment in desmoid tumour/aggressive fibromatosis. Clin Sarcoma Res 2013;3:13. 51. Gronchi A, Colombo C, Le Pechoux C, et al. Sporadic desmoid-type fibromatosis: a stepwise approach to a non-metastasising neoplasm e a position paper from the Italian and the French Sarcoma Group. Ann Oncol 2014;25:578–83. 52. Wang Y, Wang W, Tang J. Ultrasound-guided high intensity focused ultrasound treatment for extra-abdominal desmoid tumours: preliminary results. Int J Hyperthermia 2011;27:648–53. 53. Schmitz JJ, Schmit GD, Atwell TD, et al. Percutaneous cryoablation of extraabdominal desmoid tumors: a 10-year experience. Am J Roentgenol 2016;207:190–5. 54. Ilaslan H, Schils J, Joyce M, Marks K, Sundaram M. Radiofrequency ablation: another treatment option for local control of desmoid tumors. Skelet Radiol 2010;39:169–73. 55. Fiore M, MacNeill A, Gronchi A, Colombo C. Desmoid-type fibromatosis: evolving treatment standards. Surg Oncol Clin N Am 2016;25:803–26. 56. Fiore M, Coppola S, Cannell AJ, et al. Desmoid-type fibromatosis and pregnancy: a multi-institutional analysis of recurrence and obstetric risk. Ann Surg 2014;259:973–8. 57. O’Sullivan B, Davis AM, Turcotte R, et al. Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial. Lancet 2002;359:2235–41. 58. Pisters PW, Harrison LB, Leung DH, Woodruff JM, Casper ES, Brennan MF. Long-term results of a prospective randomized trial of adjuvant brachytherapy in soft tissue sarcoma. J Clin Oncol 1996;14:859–68. 59. Coindre JM, Terrier P, Bui NB, et al. Prognostic factors in adult patients with locally controlled soft tissue sarcoma. A study of 546 patients from the French Federation of Cancer Centers Sarcoma Group. J Clin Oncol 1996;14:869–77. 60. Italiano A, Le Cesne A, Mendiboure J, et al. Prognostic factors and impact of adjuvant treatments on local and metastatic relapse of softtissue sarcoma patients in the competing risks setting. Cancer 2014; 120:3361–9. 61. Zagars GK, Ballo MT, Pisters PW, et al. Prognostic factors for patients with localized soft-tissue sarcoma treated with conservation surgery and radiation therapy: an analysis of 1225 patients. Cancer 2003;97:2530–43. 62. Woll PJ, Reichardt P, Le Cesne A, et al. Adjuvant chemotherapy with doxorubicin, ifosfamide, and lenograstim for resected soft-tissue sarcoma (EORTC 62931): a multicentre randomised controlled trial. Lancet Oncol 2012;13:1045–54. 63. Farma JM, Ammori JB, Zager JS, et al. Dermatofibrosarcoma protuberans: how wide should we resect? Ann Surg Oncol 2010;17: 2112–8. 64. Fields RC, Hameed M, Qin LX, et al. Dermatofibrosarcoma protuberans (DFSP): predictors of recurrence and the use of systemic therapy. Ann Surg Oncol 2011;18:328–36. 65. Bonvalot S, Levy A, Terrier P, et al. Primary extremity soft tissue sarcomas: does local control impact survival? Ann Surg Oncol 2017 Jan; 24(1):194–201. 66. Gronchi A, Lo Vullo S, Colombo C, et al. Extremity soft tissue sarcoma in a series of patients treated at a single institution: local control directly impacts survival. Ann Surg 2010;251:506–11. 67. Galimberti G, Montano AP, Kowalczuk A, Ferrario D, Galimberti R. Outcomes in 11 patients with dermatofibrosarcoma protuberans treated with Mohs micrographic surgery. Int J Dermatol 2012;51:89–93.
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H.G. Smith et al. / EJSO xx (2017) 1e9 68. Meguerditchian AN, Wang J, Lema B, Kraybill WG, Zeitouni NC, Kane 3rd JM. Wide excision or Mohs micrographic surgery for the treatment of primary dermatofibrosarcoma protuberans. Am J Clin Oncol 2010;33:300–3. 69. Rutkowski P, Van Glabbeke M, Rankin CJ, et al. Imatinib mesylate in advanced dermatofibrosarcoma protuberans: pooled analysis of two phase II clinical trials. J Clin Oncol 2010;28:1772–9. 70. Ugurel S, Mentzel T, Utikal J, et al. Neoadjuvant imatinib in advanced primary or locally recurrent dermatofibrosarcoma protuberans: a multicenter phase II DeCOG trial with long-term follow-up. Clin Cancer Res 2014;20:499–510.
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71. Castle KO, Guadagnolo BA, Tsai CJ, Feig BW, Zagars GK. Dermatofibrosarcoma protuberans: long-term outcomes of 53 patients treated with conservative surgery and radiation therapy. Int J Radiat Oncol Biol Phys 2013;86:585–90. 72. Haas RL, Keus RB, Loftus BM, Rutgers EJ, van Coevorden F, Bartelink H. The role of radiotherapy in the local management of dermatofibrosarcoma protuberans. Soft Tissue Tumours Working Group. Eur J Cancer 1997;33:1055–60. 73. Suit H, Spiro I, Mankin HJ, Efird J, Rosenberg AE. Radiation in management of patients with dermatofibrosarcoma protuberans. J Clin Oncol 1996;14:2365–9.
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Review
The management of soft tissue tumours of the abdominal wall H.G. Smith a, D. Tzanis b, C. Messiou a, C. Benson a, J.A. van der Hage c, M. Fiore d, S. Bonvalot b, A.J. Hayes a,* a
b
The Sarcoma Unit, The Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom Sarcoma Unit, Department of Surgery, Institut Curie, PSL Research University, 26 rue d’Ulm, Paris, France c Division of Surgical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands d Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy Accepted 24 April 2017 Available online - - -
Abstract Background: Soft tissue tumours of the abdominal wall account for approximately 10% of all soft tissue tumours. Tumours at this site comprise a heterogeneous group of pathologies with distinct clinical behaviours and responses to treatment. The management of these tumours has largely been extrapolated from studies of soft tissue tumours at other sites. This review aims to summarise the existing data relating to abdominal wall tumours and suggest principles for managing soft tissue tumours at this site. Methods: Relevant articles were retrieved from a comprehensive literature search using the PubMed database. Key words included abdominal wall, soft tissue tumours, surgery, radiotherapy and chemotherapy. No restrictions on publication date were used. Results: The most common pathologies presenting in the abdominal wall are desmoid tumours, soft-tissue sarcoma and dermatofibrosarcoma protuberans (DFSP). Desmoid tumours should be managed with an initial period of observation, with surgery reserved for progressive lesions. Surgery should be the primary treatment for soft-tissue sarcomas and DFSP, with radiotherapy reserved for large-high grade tumours and preferentially given pre-operatively. Conclusions: Abdominal wall tumours are rare and should be managed in centres with experience in the management of soft tissue tumours. Management should be tailored to the biological behaviour of specific pathologies. Ó 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.
Keywords: Abdominal wall; Desmoid tumours; Soft tissue sarcoma; Dermatofibrosarcoma protuberans
Introduction Soft tissue tumours arising in the abdominal wall comprise a range of different pathologies, with distinct clinical behaviours and patterns of relapse. Tumours of the abdominal wall are rare, accounting for less than 10% of all soft tissue tumours.1 As soft tissue tumours most commonly affect the extremities, the principles of management of abdominal wall tumours are in part extrapolated from randomised trials in extremity sarcoma, coupled with cohort studies that include abdominal wall tumours * Corresponding author. E-mail address: [email protected] (A.J. Hayes).
alongside soft tissue tumours at other anatomical sites. There are a relatively small number of retrospective studies of abdominal tumours studied in isolation. This review article will summarise the data that exists relating to abdominal wall tumours and suggest management principles for patients with soft tissue tumours arising at this site. Epidemiology The most commonly occurring tumours of the abdominal wall are desmoid tumours and soft tissue sarcomas, accounting for 45% and 40% of all abdominal wall tumours respectively, with dermatofibrosarcoma protuberans (DFSP) accounting for the remaining cases.2e4
http://dx.doi.org/10.1016/j.ejso.2017.04.009 0748-7983/Ó 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. Please cite this article in press as: Smith HG, et al., The management of soft tissue tumours of the abdominal wall, Eur J Surg Oncol (2017), http:// dx.doi.org/10.1016/j.ejso.2017.04.009
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Desmoid tumours, also known as aggressive fibromatosis, are monoclonal fibroblastic proliferations that are characterised by an unpredictable potential for progression or spontaneous regression. The estimated incidence of desmoid tumours is 5/1,000,000 per year, with evidence that their incidence has increased over the past two decades.5 Desmoid tumours lack the ability to metastasise but local progression may cause significant morbidity or even death, particularly when located within the abdominal cavity. Desmoids demonstrate an infiltrative growth pattern and are associated with high rates of local recurrence. These tumours typically occur in younger patients, with a peak incidence in the fourth decade.5e7 Sporadic mutations in the bcatenin gene, CTNNB1, account for the majority of desmoid tumours, with approximately 10% of cases arising in association with an APC mutation in the context of the familial adenomatous polyposis (FAP) syndrome.8e11 Although desmoid tumours may occur virtually anywhere within the body, the extremities and the abdominal wall are the most commonly affected sites.12 Desmoid tumours occur more commonly in females, who account for over two-thirds of desmoids at any site.5,7,12 Abdominal wall desmoid tumours show a particular predilection for women of childbearing age, who account for over 90% of patients presenting with desmoids at this site.13,14 Current hypotheses for the increased incidence of abdominal wall desmoids in these patients include physical trauma secondary to pregnancy or, as these tumours may often express oestrogen or progesterone receptors, a hormonal component to their aetiology.15,16 Intra-abdominal disease is most commonly seen with FAP-associated desmoids and it is important to exclude this syndrome in such patients, as the management of intra-abdominal desmoids is very different between patients with FAP and those without.12,17,18 Surgical management of intra-abdominal desmoids in the context of FAP is associated with high peri-operative morbidity and mortality as well as high rates of local recurrence.17,19 In contrast, surgery for sporadic intra-abdominal desmoids is associated with fewer complication or recurrences.18 As such, in FAPassociated intra-abdominal desmoids, there is a high threshold for surgical intervention, which is generally reserved for patients who have failed medical management. Soft tissue sarcomas represent a diverse group of cancers of mesenchymal origin with an estimated incidence of 4e5/ 100,000 per year in Europe.20 The propensity for distant metastasis varies between distinct histological subtypes, although all subtypes have the potential for local recurrence.21 Soft tissue sarcomas can arise at almost any anatomical site but most commonly present in the extremities or the abdominal cavity/retroperitoneum. Primary abdominal wall sarcomas account for less than 5% of cases.1,3 The most common subtypes manifesting in the abdominal wall are undifferentiated pleomorphic sarcomas (previously known as malignant fibrous histiocytomas), fibrosarcomas and synovial sarcomas.2e4 In contrast to desmoid tumours, soft tissue sarcomas do not display a
preference for gender and occur later in life, with a median age at presentation of approximately 50 years.3,22 DFSP is a locally aggressive tumour with low metastatic potential.23e25 Rather than representing a true abdominal wall tumour, DFSP originates from the cutaneous tissues and is typically limited to superficial structures. DFSPs have an infiltrative growth pattern, particularly in the cutaneous plane, and a propensity for local recurrence. Progression to a fibrosarcoma may occur in around 15% of patients with DFSPs, conferring a more aggressive biological behaviour, with a greater risk of involvement of deeper structures and increased metastatic potential.25 Almost all DFSPs contain a fusion gene, COL1A1-PDFGB, leading to activation of the platelet-derived growth factor b (PDGFb) signalling pathway.26,27 As such, tyrosine kinase inhibitors targeting the PDGFb pathway, such as imatinib, may be of therapeutic benefit in both localised and disseminated disease. Diagnosis, staging and imaging The principles of investigation for abdominal wall tumours are broadly similar to those of soft tissue sarcomas of other anatomical sites.28 Due to the rarity of these lesions, patients with suspected soft tissue tumours of the abdominal wall should be referred to specialist centres benefitting from multidisciplinary teams experienced in the management of soft tissue tumours. Patients with desmoid tumours and soft-tissue sarcomas may have similar clinical presentations. The majority of patients with either pathology will present with a mass that is typically painless. Size is a poor discriminator between these pathologies, although soft-tissue sarcomas may present with slightly larger dimensions with a median size of 6e15 cm compared with 6e8 cm for desmoid tumours.3,4 Fixation to underlying structures is suggestive of a soft-tissue sarcoma, whereas a lesion occurring in a young female, particularly with a recent history of pregnancy, is more suggestive of a desmoid tumour. In contrast to the other pathologies, DFSPs tend to present as an indurated superficial lesion with characteristic purple or blue discolouration. In the presence of a small (<5 cm) and superficial lesion, ultrasound may be used to identify clearly benign lesions. Larger or deep lesions or those with equivocal or suspicious ultrasound features should be further assessed with crosssectional imaging. Magnetic resonance imaging (MRI) is probably the modality of choice for imaging abdominal wall tumours, as the improved soft tissue contrast provides better delineation of tumour margins than computed tomography (CT).29 However, CT is still a good investigation for surgical planning for soft tissue lesions of the trunk or abdominal wall, with the advantage that staging of the lungs and assessment of intra-abdominal viscera can be performed at the same time as imaging the primary tumour, and is less prone to movement artefact that MRI. MRI is reasonably accurate in differentiating benign and malignant lesions (though not accurate enough to circumvent the need for a diagnostic core
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biopsy), but its ability to reliably determine histological subtype or grade is limited.30,31 Variations in the appearance of desmoid tumours, in terms of signal intensity and contrast enhancement, may occur not only between patients but also within distinct lesions in the same patient. However, this variation in imaging appearances has not been shown to be predictive of tumour behaviour.32 Further detail regarding the specific imaging appearances of different abdominal wall tumours may be found in a review by Bashir et al.33 A histological diagnosis should be confirmed with a percutaneous core needle biopsy. A range of different pathologies, both benign and malignant, may present as a mass in the abdominal wall, with a list of differential diagnoses shown in Table 1. When used appropriately, and with expert histo-pathological analysis, percutaneous core biopsy has an accuracy rate of 97.6% (sensitivity 96.3%, specificity 99.4%) in distinguishing benign from malignant soft tissue lesions and will determine the correct tumour grade and histological subtype in over 80% of cases.34,35 Pre-operative histological diagnosis by this method should only be forgone if the lesion is superficial and too small for biopsy to be technically feasible (i.e. <2 cm) or when preoperative imaging is pathognomic (e.g. for atypical lipomatous tumour). Biopsies should be performed at an anatomical site that allows the biopsy tract to be included in any subsequent excision and hence the biopsy should be performed with knowledge of the planned surgical resection. Patients with soft tissue sarcomas and DFSP should be staged at diagnosis to exclude distant metastatic disease.28 In patients where pre-operative imaging or biopsy are suggestive of well-differentiated liposarcomas or other low grade sarcomas, staging with a chest x-ray may suffice. In the remaining patients, CT of the chest should be considered. In patients with histological subtypes prone to extrapulmonary dissemination, such as myxoid liposarcomas, cross sectional imaging of the abdomen and pelvis should also be performed at staging.36 Management Desmoid tumours Historically, desmoid tumours were managed in a similar fashion to soft tissue sarcomas, with the aim of Table 1 Differential diagnoses of abdominal wall masses. Pseudo-tumours
Myositis Nodular fasciitis Haematoma
Tumours
Lipoma Desmoid tumour Soft-tissue sarcoma Endometriosis Carcinoma Lymphoma Metastasis
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achieving negative margins with wide surgical excisions. However, in contrast to soft tissue sarcoma, several large series have demonstrated that margin status is not prognostic for local recurrence in desmoid tumours.7,37,38 Furthermore, desmoid tumours demonstrate the potential for prolonged periods of stable growth and spontaneous regression.7 With an increased understanding of the natural history of these rare tumours, a more conservative approach to management is now advocated.39 However, an important distinction must be made between the management of desmoid tumours of the abdominal wall and those of the most common other site e the extremities. Surgery in the extremities is often followed by local recurrence, with repeated surgical intervention increasing the risk of cumulative functional impairment. As such, systemic therapies are preferred, with surgery reserved for unresponsive, symptomatic cases. In contrast, as discussed below, surgery often secures local disease control in the abdominal wall and, as such, still plays a prominent role in the management of desmoids at this site. Observation Although desmoid tumours appear to have an increased frequency in relation to pregnancy and certain mutations in the CTNNB1 gene are associated with greater risks of recurrence, there are no known reliable prognostic factors of progression or regression of these tumours at presentation.16,40,41 As such, it is recommended that all patients be initially managed with a period of close observation. Serial imaging and clinical examination may be performed at intervals of 3e6 months over a period of at least 2 years if symptoms permit. When managed in such a fashion, progression-free survival is approximately 50% at 5 years and further intervention may be avoided altogether in up to two-thirds of patients.13,42,43 Surgical management In rapidly progressive or symptomatic disease, surgical excision should be considered. In contrast to desmoid tumours of the extremities, where surgery may result in significant functional morbidity, excision of abdominal wall desmoids is associated with minimal complications.3,14 Abdominal wall reconstruction is necessary in between 60 and 90% of cases.3,13,14 However, the incidence of incisional hernias is low at less than 5% and, importantly given the propensity for these tumours to occur in women of childbearing age, abdominal wall reconstruction is not associated with an increase in perinatal complications.4,14 Furthermore, with recurrence rates of less than 10%, surgery is a more definitive management in the abdominal wall than in the extremities, where recurrence occurs in more than 60% of patients.6,7,13,14,43,44 Systemic therapies Hormonal therapies, such as tamoxifen, are an alternative to surgery in patients with symptomatic lesions and
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may be used in conjunction with non-steroidal anti-inflammatory drugs. Although the response rates with such agents are low, ranging from 30 to 50% in small case series, and an objective response may take several months to develop, hormonal therapies are generally well tolerated and rarely lead to significant toxicities.45 However, as responses are often delayed, hormonal therapies may not be suitable for patients with rapidly progressive disease. In such patients and in those unresponsive to hormonal therapies or in whom surgery is unfeasible or declined, systemic chemotherapy may be considered. Treatment typically needs to be continued for 6e12 months for durable results and patients should be counselled appropriately. Pegylated liposomal doxorubicin is the treatment of choice in many centres, benefitting from quicker responses and a more acceptable toxicity profile than other regimes such as methotrexate with or without vinblastine.46,47 There is also some evidence that tyrosine kinase inhibitors, such as imatinib, sorafenib and pazopanib, may be effective in this pathology, and although the use of these agents remains investigational, they provide an alternative option in patients unresponsive to hormonal therapy or traditional chemotherapies.48e50 The progression through systemic therapies and the timing of surgery may vary between institutions but is also dependent on patient preference. A proposed algorithm from a collaboration between the French and Italian Sarcoma Groups provides a starting point on which to base these discussions with patients.51 Radiotherapy and other local therapies Although radiotherapy may be considered in the management of inoperable desmoid tumours of the extremities, it is not felt to have a role in the management of abdominal wall disease due to concerns about both the short term treatment toxicity and the risk of radiation induced malignancies in this young cohort of patients.39 The use of ablative therapies in desmoid tumours has also been reported.52e54 Though patients may require repeated treatments, ablative techniques appear to be well tolerated. With evidence limited to small case series, the role of ablative therapies in desmoid tumours remains to be defined. However, they may offer an additional option for patients with progressive disease that is unresponsive to other modalities. Surveillance and pregnancy With an increasing number of patients with desmoid tumours undergoing conservative management involving prolonged clinical observation, issues relating to the frequency of and appropriate modality used for surveillance will be encountered in the future. Short-interval imaging every 3e4 months with contrast-enhanced MRI has been suggested for the first 2 years of surveillance. In the case of stable disease or regression, longer time intervals may be adopted and MRI replaced with ultrasound surveillance.55 Females of childbearing age require special consideration. The complex and incompletely understood relationship
between desmoid tumours, hormones and pregnancy warrants a comprehensive discussion to assist and educate patients with family planning. Available data do not suggest any medical advice to avoid or interrupt pregnancy in patients with a history of desmoids, although oestrogen and/ or progesterone containing contraceptives are discouraged. On the contrary, desmoid tumours may be safely managed in the event of progression during or after pregnancy, with obstetric complications rarely encountered despite the presence of these abdominal wall tumours.56 Soft tissue sarcomas As with other anatomical sites, surgery forms the mainstay of management of soft tissue sarcomas of the abdominal wall. The aim should be to achieve negative margins with a wide surgical excision. The excision of superficial tumours should be extended to include the anterior rectus sheath as a deep margin, with excision of the posterior sheath or peritoneum indicated in the case of deep tumours. As such, abdominal wall mesh reconstruction is required in the majority of patients.3,4 Tumours may be adherent to underlying viscera or bony structures, necessitating extended resections in approximately 25% of cases.3,4 The role of radiotherapy in the management of abdominal wall sarcoma may be extrapolated from randomised trials in extremity sarcoma, where radiotherapy whether given pre- or post-operatively has been shown to reduce the risk of local recurrence.57,58 There have been no large series investigating prognostic factors of local recurrence exclusively in abdominal wall sarcomas. In those studies including abdominal wall sarcomas alongside other anatomical sites, tumour depth, tumour size, histological subtype, margin status and grade have been shown to be independently associated with local recurrence.59e61 It is recommended that radiotherapy should be given to those patients with deep, large (i.e. >5 cm), high-grade tumours, carrying the greatest risk of recurrence. Neoadjuvant radiotherapy allows the delivery of a lower dose of radiation, which may be of particular benefit in abdominal wall sarcomas due to the proximity of radiosensitive viscera.57 Adjuvant chemotherapy has not been shown to be of benefit in unselected soft tissue sarcomas and its use should be limited to specific chemosensitive subtypes, such as Ewing’s sarcomas, rhabdomyosarcomas or synovial sarcomas.62 DFSP should be managed in a similar fashion to abdominal wall sarcomas, with wide surgical excision. However, as margin status is the only independent prognostic factor for local recurrence in DFSP, a 2e3 cm margin has been advocated for the excision of these lesions,63,64 in contrast to the greater than 1 mm margin on a fixed specimen recommended for soft tissue sarcomas.65,66 Mohs surgery has been shown to achieve low local recurrence rates in small retrospective series of DFSP, although the role of this technique in the management of this pathology is
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unclear, particularly given the relative ease of reconstructing soft-tissue defects on the abdominal wall.67,68 Although the majority of DFSPs tend to be less than 5 cm in maximal diameter, due to these wider margins plastic reconstruction of the resultant tissue defect is necessary in approximately 15e20% of patients.2,3 Despite the majority of these lesions appearing to be limited to the superficial tissues, it is not unusual to obtain unexpectedly positive margins at the deep margin, due to their infiltrative nature. For this reason, inclusion of the deep fascia en bloc with the soft tissue is recommended and may necessitate a mesh repair of the abdominal wall even if major reconstruction is not required. As mutations in the PDGFb pathway are present in almost all patients with DFSP, tyrosine kinase inhibitors targeting this pathway, such as imatinib, may play a role in the management of patients with inoperable local or metastatic disease. In a pooled analysis of two phase II trials in this setting, the response rates to imatinib were approximately 45%.69 Imatinib may also develop a neoadjuvant role prior to surgery, with a response rate of 50% and a local recurrence rate of less than 10% following excision in a further phase II trial.70 Although the role of these agents should ideally be clarified with further randomised studies, targeted therapies may be considered in patients with inoperable disease or in those in whom surgery would be technically challenging. Radiotherapy may also be of use in patients unsuitable for primary surgical management. Whether used in isolation or in combination with a conservative surgical resection, radiotherapy can achieve durable local disease control in DFSP.71e73 As such, radiotherapy may be considered in inoperable or challenging cases of abdominal wall DFSP, but should be given preferentially
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given in the neoadjuvant setting due to the proximity of radiosensitive viscera. Follow-up On-going surveillance for patients with abdominal wall tumours should mirror that employed with soft tissue sarcomas of other sites.28 All abdominal wall tumours have the potential for local recurrence, and clinical examination of the primary site should be conducted every 6 months for the first 5 years and annually for a further 5 years thereafter. Those patients with high-grade lesions may benefit from more regular review during the first 2e3 years following surgery, when the majority of relapses occur. Suspicious findings should be further investigated with crosssectional imaging. Patients with sarcomas or DFSP should undergo imaging of the chest at each follow-up, with either CT or plain radiographs, to detect metastatic spread. Such imaging surveillance of the thorax is not indicated in desmoid tumours due to their lack of metastatic potential, although serial MRI may be used to monitor treatment responses as described above. Abdominal wall reconstruction following resection If surgery is indicated in the management of an abdominal wall tumour, the preferred method of reconstruction is influenced by the structures involved by the lesion. When only the skin and subcutaneous tissues are involved, as is often the case in DFSP, the integrity of the musculofascial component of the abdominal wall is rarely compromised. In such cases, only soft-tissue coverage is required. If the defect is too large for primary closure, soft-tissue coverage
Figure 1. A desmoid tumour confined to the rectus abdominis muscle as demonstrated on MRI (A). The rectus sheath and muscle were resected (B, D, E), with an underlay mesh reconstruction sutured to the remnant abdominal wall (C, F). Please cite this article in press as: Smith HG, et al., The management of soft tissue tumours of the abdominal wall, Eur J Surg Oncol (2017), http:// dx.doi.org/10.1016/j.ejso.2017.04.009
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Figure 2. An extensive soft-tissue sarcoma infiltrating the inguinal ligament as demonstrated on MRI (A) and clinical examination (C). Following resection, mesh reconstruction was performed with microplates securing the mesh to the pelvic margin (B, D).
may be achieved with split-thickness skin grafts, local advancement flaps or regional rotational flaps, dependent on local expertise and preference. If the musculofascial component of the abdominal wall is included in a resection, reconstruction of the abdominal wall
with either a synthetic or biological mesh is mandatory. For those tumours in which only the muscle is involved, an underlay mesh repair should be performed, with the mesh sutured onto the posterior surface of the remnant abdominal wall (Fig. 1). In the case of more extensive musculofascial
Figure 3. A soft-tissue sarcoma infiltrating the full-thickness of the abdominal wall as demonstrated on MRI (A). Resection included all components of the abdominal wall (B, C) followed by mesh reconstruction and a free flap from the ipsilateral thigh (D). Please cite this article in press as: Smith HG, et al., The management of soft tissue tumours of the abdominal wall, Eur J Surg Oncol (2017), http:// dx.doi.org/10.1016/j.ejso.2017.04.009
H.G. Smith et al. / EJSO xx (2017) 1e9
resections, there may little or no remnant abdominal wall on which to base a mesh reconstruction. A commonly encountered example is where of infiltration of the inguinal ligament necessitates its resection. In such cases, microplates may be used to fix the mesh to the pelvic and/or costal margins (Fig. 2). In these cases, where there is little or no involvement of the skin and subcutaneous tissues, primary closure following mesh reconstruction may be achievable. However, in the presence of extensive involvement of skin, subcutaneous tissue and muscle, resection of the full thickness of the abdominal wall is necessary and reconstruction may require the additional use of a free flap, most commonly taken from the thigh (Fig. 3). Conclusion Abdominal wall tumours are rare entities and should be managed in centres with experience in the management of soft tissue tumours. Management should be tailored to the biological behaviour of specific pathologies. Patients with desmoid tumours should be offered a period of observation to determine which patients require and may benefit from further intervention. Roughly, 2/3 of patients may be spared from surgery. Surgery should be the primary treatment option for progressive abdominal wall desmoids, with hormonal or medical therapies reserved for those declining or unsuitable for operative intervention. Soft tissue sarcomas of the abdominal wall should be managed primarily with surgical resection, with radiotherapy reserved for large, highgrade tumours and preferentially given pre-operatively. A wider margin of resection (2e3 cm) should be employed for DFSPs to minimise the risk of local recurrence. Conflict of interest statement The authors have no conflicts of interest to disclose.
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