- Email: [email protected]
Desmoid-type fibromatosis
Clinical Radiology 70 (2015) 1038e1045
Contents lists available at ScienceDirect
Clinical Radiology journal homepage: www.clinicalradiologyonline.net
Pictorial Review
Desmoid-type fibromatosis S. Otero*, E.C. Moskovic, D.C. Strauss, C. Benson, A.B. Miah, K. Thway, C. Messiou Department of Radiology and Soft Tissue Sarcoma Unit, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK
article in formation Article history: Received 1 October 2014 Received in revised form 23 April 2015 Accepted 27 April 2015
Desmoid-type fibromatosis is a rare, locally infiltrative, mesenchymal neoplasm that is associated with high rates of local recurrence but lacks the potential to metastasise. The disease affects younger individuals, with a peak age of 30 years, and is the most common cause of an anterior abdominal wall mass in young women of childbearing age. It may, however, involve nearly every body part, including the extremities, head and neck, trunk, and abdominal cavity; as such, desmoid-type fibromatosis may present to a range of general and subspecialty radiologists. These rare tumours have a widely variable clinical presentation and unpredictable natural history, hence input from a soft-tissue tumour centre is recommended, although much of the imaging may be performed at the patient’s local hospital. The consensus for treatment has changed over the past decade, with most centres moving away from primary radical surgery towards a front-line ‘watch-and-wait’ policy. Therefore, imaging has an increasingly important role to play in both the diagnosis and follow-up of these patients. This review will discuss the typical imaging characteristics of these lesions and suggest diagnostic and followup magnetic resonance imaging protocols, with details of suitable sequences and scanning intervals. Ó 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction Desmoid-type fibromatosis (DF) is a rare, locally infiltrative, mesenchymal neoplasm. Although nonmetastasising, morbidity results from local complications, and rates of local recurrence following resection can be high. It can occur in many locations, often involving the extremities, the trunk, including the pelvic and shoulder girdles, and the abdominal cavity. DF accounts for 0.03% of all neoplasms and 3% of softtissue tumours,1 with a reported incidence of 2e4 individuals per million per year.2 It is mostly sporadic,
* Guarantor and correspondent: S. Otero, Department of Radiology and Soft Tissue Sarcoma Unit, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK. Tel.: þ44 020 7602 3993, þ44 07919 563725 (mobile). E-mail address: oterosofi[email protected] (S. Otero).
however, there is an association with familial adenomatous polyposis (FAP) in approximately 7.5% of patients, conferring an 800-fold risk when compared to the general population.3 DF affects a wide age range, but is most common between 10 and 40 years of age. In the paediatric population, there is an equal sex ratio, with tumours being predominantly extra-abdominal. Between puberty and 40 years of age tumours are most prevalent in females, with a predilection for the abdominal wall. Later in adulthood, there is a more equal distribution between abdominal and extra-abdominal tumours and the sex ratio tends towards parity.4 Extra-abdominal fibromatosis has a peak incidence between 25 and 30 years of age, with a predilection for the upper torso, most commonly the upper arm (approximately 30%). When encountered in the head and neck (Fig 1), lesions can behave more aggressively than at other sites and involvement of the axillary vessels, brachial plexus, or
http://dx.doi.org/10.1016/j.crad.2015.04.015 0009-9260/Ó 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
S. Otero et al. / Clinical Radiology 70 (2015) 1038e1045
1039
Figure 1 Fibromatosis of the left posterior neck. (a) Coronal (lesion depicted by arrows) and (b) axial STIR MRI shows an infiltrative lesion in the region of the left brachial plexus. The axial image shows tumour infiltration into the C7 neural exit foramen (arrow).
airway can limit surgical resectability.5 Although most often solitary, synchronous tumours can occur.6 Abdominal wall fibromatosis tends to occur in women of childbearing age, and is more frequent during and within the first year following pregnancy, and with oral contraceptive use.7,8 It is the most common soft-tissue neoplasm of the abdominal wall,9 and is generally solitary and slow growing. Approximately 87% of affected individuals are females and 95% have had at least one child. Twenty per cent of cases occur following a surgical procedure.7 Lesions tend to be smaller at presentation than other types of DF, perhaps because they are easily palpable and thus present earlier, and are usually solitary. Intra-abdominal fibromatosis occurs in the pelvis, mesentery and retroperitoneum, most often within the small bowel mesentery,10 where it is the most common primary tumour.7 Neoplasms here are frequently large (10 cm) before presentation.4 Pathogenesis is multifactorial with postulated endocrine, physical and genetic elements. Several factors indicate a role for oestrogens in the development and evolution of the disease, including a higher incidence in women during or shortly after pregnancy, and spontaneous regression or disease stabilisation with oestrogen blockade (Fig 2). Several studies have demonstrated oestrogen receptor (ERb) positivity in up to 90% of neoplasms.11,12 DF is also reported to occur at sites of previous surgery or blunt trauma.13 Sporadic cases show mutations in the b-catenin gene on 3p21, such that it is overexpressed in nuclei.14 bcatenin has an important role in regulating the size of cutaneous wounds and is required to mediate the effect of TGF-b,15 which is known to promote wound hyperplasia via fibroblast proliferation. It can therefore be postulated that DF represents, in part, uncontrolled wound healing.
Histopathology Histologically, DF is usually infiltrative and composed of sweeping fascicles of uniform myofibroblasts within
densely collagenous stroma (Fig 3). Approximately 80% of neoplasms show granular nuclear expression of b-catenin.16e18 The histological differential diagnosis is wide, and encompasses an extensive range of spindle cell lesions ranging from scarring to abdominal gastrointestinal stromal tumour and liposarcoma with “low-grade” dedifferentiation; however, a confident diagnosis may be made by virtue that most neoplasms resembling fibromatosis have specific histological diagnostic features and lack nuclear b-catenin immunoreactivity.14
Imaging characteristics Although often the first-line imaging investigation for a palpable lump, ultrasound features are non-specific. In one study of 44 lesions, the number displaying welldefined versus ill-defined borders was approximately equal.19 Neoplasms appear solid with variable, but predominantly low, echogenicity, 75% demonstrate posterior acoustic enhancement (Fig 4), and vascularity is variable on colour Doppler imaging; features that could lead to these solid lesions being misinterpreted as cystic.20 Although of limited diagnostic value, ultrasound provides a useful diagnostic adjunct when used to guide core biopsy. The computed tomography (CT) attenuation values of intra-abdominal or pelvic DF are variable, but lesions are most frequently isodense to skeletal muscle. Foci of higher attenuation are thought to correspond to areas of higher collagen content. Areas of low attenuation are less commonly seen and may indicate myxoid components, a pattern that is more frequent in chest wall disease. Contrast enhancement is variable and can be prominent, probably a sequelae of the abundant capillary network seen in these neoplasms.5 Intra-abdominal DF is usually seen as a soft-tissue mass in the mesentery with radiating strands projecting into the adjacent mesenteric fat (Fig 5).7 CT is often the technique of choice for follow-up
1040
S. Otero et al. / Clinical Radiology 70 (2015) 1038e1045
Figure 2 Fibromatosis of the right anterior abdominal wall. (a) Axial STIR MRI of the abdomen showing a hyperintense lesion, which developed in a woman during pregnancy (arrow). (b) Axial STIR MRI of the abdomen in the same female patient after a delay following childbirth, showing spontaneous regression once oestrogen stimulation has been withdrawn. The lesion, marked with a cod liver oil capsule on the skin, is no longer visible (arrow).
of intra-abdominal fibromatosis, as the mesenteric fat allows accurate delineation of the tumour and there is less bowel-motion artefact than with magnetic resonance imaging (MRI). MRI is the mainstay of imaging in DF and can be used for primary diagnosis, local surgical staging and follow-up. Its superior soft-tissue contrast allows accurate evaluation of tumour borders and their relationship to adjacent structures including muscles, nerves, blood vessels, and bones. DF usually displays heterogeneous signal intensity on T2weighted (T2W) images, which reflects the variable quantities and distribution of myofibroblasts, extracellular collagen and myxoid matrix; it is these appearances that raise suspicion for the diagnosis of DF (Fig 6).21 In approximately 90% of cases, the key diagnostic feature of hypointense bands is identifiable on T2W images, which correspond to the dense assemblies of collagen bundles seen at histological analysis.22 As with ultrasound, approximately half of lesions appear well-defined on MRI, and half have
Figure 3 Abdominal wall fibromatosis. Low-power haematoxylineeosin stain of this rectus sheath lesion shows sweeping fascicles of myofibroblasts within a densely collagenous stroma. Typically there are two populations of vessels: small, rounded thick-walled vessels (long arrow), and larger, thin-walled slit-like vessels (short arrows).
irregular infiltrative margins.21 On T1-weighted (T1W) sequences, lesions are often of intermediate signal intensity, isointense to muscle. At an early stage, lesions are more cellular and consequently appear predominantly hyperintense on T2W images. A statistically significant association has been shown between lesion growth on follow-up scanning and high T2W signal intensity.23 Over time an increase in collagen deposition, and consequent decrease in extracellular space, results in a decrease in T2W signal intensity.7,24 This pattern is also observed in lesions as they respond to treatment; as they undergo progressive collagen deposition, there is a corresponding reduction in tumour signal intensity.25 Lesions display moderate-marked enhancement with gadolinium contrast agents, other than the hypo-intense collagen bundles, which do not enhance. Lesions are most often centred in an intermuscular location and may be surrounded by a thin rim of fat, the “split-fat” sign (Fig 7).26 Infiltration along the fascia, also described as
Figure 4 Fibromatosis of the right anterior abdominal wall. Transverse ultrasound shows a well-defined hypo-echoic mass with posterior acoustic enhancement.
S. Otero et al. / Clinical Radiology 70 (2015) 1038e1045
1041
Figure 5 Two examples of intra-abdominal fibromatosis. (a) Contrast-enhanced axial CT of the abdomen shows an ill-defined soft-tissue mass within the mesentery. Intra-abdominal fat allows visualisation of the strands radiating into the adjacent mesenteric fat (arrows). (b) Contrastenhanced axial CT of the abdomen shows a large, well-defined, homogeneous mass, isodense to skeletal muscle, within the left side of the mesentery. There is associated displacement of the bowel (arrow) and mesenteric vessels (arrowhead).
a “fascial tail” (Fig 8), is observed in approximately 80% of cases.8 Although MRI features can be highly suggestive of DF, the differential diagnosis includes other infiltrative lesions such as malignant fibrous histiocytoma, fibrosarcoma, lymphoma, and densely calcified masses.
Guidelines for imaging, biopsy and specialist referral The following clinical features of any soft-tissue mass, which raise suspicion for a sarcoma, should prompt referral
Figure 6 Extra-abdominal fibromatosis of the right deltoid muscle. (a) Axial T2W MRI shows the classical appearance of fibromatosis: a heterogeneous, predominantly hyperintense (cellular) mass with hypo-intense (collagenous) bands. Lesions are most accurately measured on T2W images, as these confer the highest spatial resolution. (bec) Axial and coronal STIR MRI. Cellular lesions are often better demonstrated on this sequence, as the cellular components are markedly hyperintense (black arrows). Collagenous bands are hypo-intense on this sequence (asterisks). Measurements should not be performed on STIR, however, due to the inherent lower resolution and tendency to overestimate size. (dee) Axial and coronal T1W MRI provide an anatomical overview (mass outlined by arrows).
1042
S. Otero et al. / Clinical Radiology 70 (2015) 1038e1045
Figure 7 Fibromatosis of the left anterior abdominal wall. Axial T1W MRI of the abdomen showing a lesion that is isointense to skeletal muscle in an intermuscular location, with a thin rim of fat separating the lesion from muscle (arrows): the “split-fat” sign.
to a soft-tissue diagnostic centre: size >5 cm; mass deep to the deep fascia; mass increasing in size; and pain or recurrence at the site of previous excision. Lesions that do not fulfil these criteria should be assessed with ultrasound and clearly benign lesions managed accordingly. As ultrasound features of fibromatosis are non-specific (Fig 4), MRI of suspected superficial or limb lesions is usually indicated. For diagnosis, a combination of T2W, T1W, T1W fatsaturated contrast-enhanced, and short tau inversion recovery (STIR) sequences can be used for characterisation and delineation of the mass. T2W sequences demonstrate the features that are most specific for fibromatosis (Fig 6).21 The utility of diffusion-weighted MRI in DF is poorly described. For intra-abdominal and pelvic masses the broad
differential diagnosis often makes contrast-enhanced CT the most sensible first-line investigation. Any degree of suspicion for a soft-tissue sarcoma should trigger referral to a specialist soft-tissue sarcoma centre, along with imaging for review in the multidisciplinary meeting. Hand-held clinical or image-guided core biopsy is preferably performed at specialist centres to obtain benefit from on-site histopathology expertise, and to allow resection of the needle tract if a malignant soft-tissue sarcoma is confirmed. Excision biopsy is always contraindicated as this spoils soft-tissue planes if soft-tissue sarcoma is diagnosed. Once a diagnosis of fibromatosis is confirmed, surveillance can be performed with a shortened MRI protocol, often tailored to the anatomical site but excluding contrast medium: generally, a combination of T2W and STIR in two planes and T1W in a single plane (Fig 6). Changes in T2W signal are most useful for assessing changes in activity (Fig 9),24 whereas T1W and STIR serve as a useful overview. Changes in signal over time can be subtle and, therefore, consistent patient positioning and a choice of reproducible planes is essential. Furthermore, when reporting such studies, comparison over multiple time-points may be necessary for detection of slow change. There is no definitive guidance on frequency of follow-up imaging; however, the recently published European consensus approach suggests the following protocol: the first radiological re-evaluation should be performed at 4e8 weeks to avoid missing rapidly progressing disease, especially for lesions that are not easily palpable or that are located at critical sites; if MRI is stable, follow up is 3-monthly for the first year, 6-monthly up to the 5th year, and yearly thereafter27; for patients on medical treatment, imaging is generally performed at 3e6 month intervals, depending on symptoms and site of disease. (FDG) Combined 2-[18F]-fluoro-2-deoxy-D-glucose positron-emission tomography (PET) and computed tomography (CT) is not routinely used to assess or monitor DF; however, it has been proposed as a potential prognostic marker in discriminating responders from non-responders in patients undergoing treatment with tyrosine kinase inhibitors.28
Management Due to the unpredictable natural history of the disease, establishing a therapeutic regimen for DF is challenging. Historically, surgery with or without radiation therapy was the principle treatment. More recently, several series have reported spontaneous regression or prolonged indolent disease without treatment, with many institutions, including the authors’, proposing a “watch and wait” policy (Fig 9).29e32 This strategy enables identification of those patients who will remain asymptomatic with stable disease or undergo spontaneous regression, thus sparing this cohort from treatment.33,34 Figure 8 Extra-abdominal fibromatosis. Axial STIR MRI of the abdomen showing a predominantly hyperintense, wellcircumscribed mass within the left erector spinae muscle, with linear extension along the posterior fascia (arrow): the “fascial tail” sign.
Surgical management of fibromatosis There is ongoing debate as to the value of surgery for DF.30 Several studies have shown tumour location to be a
S. Otero et al. / Clinical Radiology 70 (2015) 1038e1045
1043
Figure 9 Fibromatosis of the right anterior abdominal wall. (a) Axial STIR MRI of the abdomen shows a well-circumscribed, markedly hyperintense mass, indicating a highly cellular neoplasm (arrows). (b) Axial STIR MRI of the abdomen showing the same lesion after a 2-year interval with no treatment. The lesion now has a large hypo-intense component indicating collagen deposition (arrow), consistent with spontaneous regression. There is a rim of residual cellular tissue posteriorly (arrowhead). Note the stability in size; it is critical to interrogate the signal changes.
prognostic factor, and propose that it may be beneficial to develop individualised therapeutic strategies for different prognostic subgroups. Abdominal wall and sporadic intraabdominal tumours have a limited risk of recurrence (8% and 13%, respectively),33,35 whereas surgical series for extremity and limb girdle fibromatosis report much higher recurrence rates of 39e79%.36
Abdominal wall fibromatosis In patients who progress to symptomatic abdominal wall disease, surgical resection remains the treatment of choice due to the achievability of excellent local control and low recurrence rates at this anatomical site. Complete resection with mesh reconstruction of the abdominal wall defect is safe, reliable, and delivers an excellent functional outcome.
Intra-abdominal sporadic fibromatosis
Patients with biopsy-proven intra-abdominal fibromatosis should be endoscopically screened for FAP and, if confirmed, these individuals should be treated in specialist units.36 Intra-abdominal fibromatosis can be complicated by small bowel fistulation, abscess formation, gastrointestinal tract bleeding, and bowel obstruction. Given the risk of complications and low recurrence rates following surgical resection in non-FAP-associated intra-abdominal fibromatosis, there should be a low threshold for surgery, provided that it can be offered with low morbidity, complete tumour resection, and without excessive organ resection or mutilating long-term effects. Systemic therapy may be used to treat non-resectable disease.
Limb fibromatosis Surgical resection with negative margins was previously considered to be the best treatment for limb, limb girdle, and truncal fibromatosis; however, due to the locally aggressive growth pattern, margin-negative resection is
often associated with significant functional and cosmetic consequences. Furthermore, surgical resection alone for extremity fibromatosis has a local recurrence rate of approximately 50% despite negative resection margins.29,36 Therefore, the past decade has seen a move away from primary radical surgery towards a first-line “watch and wait” policy that distinguishes indolent from aggressive forms and reserves medical treatment for progressive disease. Results have been encouraging, with prolonged progression-free survival being seen in a large proportion of patients.32,37 In patients with symptomatic or progressive disease during surveillance, medical treatment should be considered next. Surgery should only be employed when medical treatment fails to achieve radiological stabilisation or clinical improvement, and if surgery is possible without significant functional impairment. If surgery will lead to substantial disability, chemotherapy or radiotherapy may be a preferred option.29 When a decision for surgery is made, the goal should be to preserve function with negative resection margins.
Systemic management of fibromatosis The aim of systemic treatment is to slow or stop growth of fibromatosis as well as improve disease-related symptoms such as pain. Due to disease rarity, the evidence base for many systemic treatments is scanty and characterised by small, retrospective case studies. First-line therapy comprises the combination of anti-oestrogen treatment and non-steroidal anti-inflammatory drugs (NSAIDs) (Fig 10). Tamoxifen is the most widely used hormonal therapy.38,39 Systemic chemotherapy may be indicated following failure of first-line tamoxifen and NSAID treatment. Anthracyclines are associated with the highest response rates, and data from the authors’ institution support the use of
1044
S. Otero et al. / Clinical Radiology 70 (2015) 1038e1045
Figure 10 Fibromatosis of the left anterior abdominal wall. (a) Axial T2W MRI of the abdomen shows a predominantly hyperintense (cellular) mass within the left anterior abdominal wall (arrow). (b) Axial T2W MRI of the abdomen shows the same lesion following treatment with tamoxifen and naproxen. The mass is now markedly hypo-intense (arrow), consistent with collagen deposition and disease response.
pegylated liposomal doxorubicin (Caelyx) with an overall response rate of 36%. Notably, 86% of patients treated with Caelyx experienced decreased pain.40 Other options include methotrexate and vinblastine in combination, tyrosine kinase inhibitors, and pazopanib.25,41e43
Radiotherapy Radiotherapy can be an effective treatment for active fibromatosis.44e46 The lack of metastatic potential, excellent survival outcomes, and age of the patient (often young), must be taken into consideration when planning treatment with radiotherapy due to the risk of radiation-induced morbidity and secondary malignancies. Therefore, radiotherapy is usually recommended only in cases where medical and surgical options have been exhausted, and where disease is at risk of causing life-threatening problems or severely disabling outcomes. Clear guidance from a specialist soft-tissue radiologist can be invaluable in calculating the gross tumour volume and clinical target volume for treatment, which is done with STIR or T1W fat-saturated contrast-enhanced MRI sequences fused with a radiotherapy-planning CT. Response assessment following radiation is best performed at least 3 months after radiotherapy, with further evaluation at 6 months. Alternative methods of achieving local control, including cryoablation and radiofrequency ablation, remain in the early stages of evaluation with evidence resulting from small case series or reports. Cryoablation was shown to be effective in small and moderately sized extra-abdominal tumours in a very small series, but is of doubtful benefit in larger tumours or lesions at critical sites.47,48
Conclusion An awareness of the distribution and typical imaging characteristics of DF enables the radiologist to narrow the differential diagnosis; for example, DF is the commonest cause of an anterior abdominal wall mass in females of childbearing age. Core biopsy is mandatory for proof of diagnosis, and referral to a specialist soft-tissue diagnostic
centre is advisable. With many centres now adopting a firstline “watch and wait” policy, interval imaging every 3e6 months with MRI is becoming the norm. It is, therefore, essential to understand the imaging characteristics of these lesions over time, with progressive collagen deposition being indicated by decreasing T2W signal intensity, which often predates a reduction in size. The converse indicates disease progression and possible requirement for secondline systemic therapies, with surgery being reserved for refractory disease and for intra-abdominal fibromatosis, which carries a high risk of complications.
Acknowledgements We acknowledge support from NHS funding to the NIHR Biomedical Research Centre at Royal Marsden Hospital.
References 1. Desmoid-type fibromatoses. In: Fletcher JA, Bridge JA, Hogendoorn PCW, et al., editors. WHO Classification of Tumours of Soft Tissue and Bone. 4th ed. Lyon: IARC Press; 2013. p. 72e3. €yry P, Nykyri E, et al. The desmoid tumor. I. Incidence, sex-, 2. Reitamo JJ, Ha age- and anatomical distribution in the Finnish population. Am J Clin Pathol 1982;77:665e73. 3. Nieuwenhuis MH, Casparie M, Mathus-Vliegen LMH, et al. A nationwide study comparing sporadic and familial adenomatous polyposisrelated desmoid-type fibromatoses. Int J Cancer 2011;129:256e61. 4. Desmoid-type fibromatoses. In: Fletcher CDM, Unni KK, Mertens F, editors. Pathology and Genetics of Tumours of Soft Tissue and Bone. World Health Organization Classification of Tumours. Lyon: IARC Press; 2002. p. 83. 5. Murphey MD, Ruble CM, Tyszko SM, et al. From the archives of the AFIP. musculoskeletal fibromatoses: radiologicepathologic correlation. RadioGraphics 2009;29:2143e73. 6. Sundaram M, Duffrin H, McGuire MH, et al. Synchronous multicentric desmoid tumors (aggressive fibromatosis) of the extremities. Skeletal Radiol 1988;17:16e9. 7. Walker EA, Petscavage JM, Brian PL, et al. Imaging features of superficial and deep fibromatoses in the adult population. Sarcoma 2012;2012:215810. 8. Dinauer PA, Brixey CJ, Moncur JT, et al. Pathologic and MR imaging features of benign fibrous soft-tissue tumors in adults. RadioGraphics 2007;27:173e87. 9. Bashir U, Moskovic E, Strauss D, et al. Soft-tissue masses in the abdominal wall. Clin Radiol 2014;69:e422e31.
S. Otero et al. / Clinical Radiology 70 (2015) 1038e1045 10. Levy A, Rimola J, Mehrotra A, et al. From the archives of the AFIP. Benign fibrous tumors and tumorlike lesions of the mesentery: radiologicpathologic correlation. RadioGraphics 2006;26:245e65. 11. Santos GAC, Cunha IW, Rocha RM, et al. Evaluation of estrogen receptor alpha, estrogen receptor beta, progesterone receptor, and cKIT expression in desmoids tumors and their role in determining treatment options 2010;4:25e30. 12. Deyrup AT, Tretiakova M, Montag AG. Estrogen receptor-beta expression in extraabdominal fibromatoses: an analysis of 40 cases. Cancer 2006;106:208e13. 13. Reitamo JJ, Scheinin TM, H€ ayry P. The desmoid syndrome. New aspects in the cause, pathogenesis and treatment of the desmoid tumor. Am J Surg 1986;151:230e7. 14. Fisher C, Thway K. Aggressive fibromatosis. Pathology 2014;46:135e40. 15. Cheon SS, Wei Q, Gurung A, et al. Beta-catenin regulates wound size and mediates the effect of TGF-beta in cutaneous healing. FASEB J 2006;20:692e701. 16. Montgomery E, Torbenson MS, Kaushal M, et al. Beta-catenin immunohistochemistry separates mesenteric fibromatosis from gastrointestinal stromal tumor and sclerosing mesenteritis. Am J Surg Pathol 2002;26:1296e301. 17. Bhattacharya B, Dilworth HP, Iacobuzio-Donahue C, et al. Nuclear betacatenin expression distinguishes deep fibromatosis from other benign and malignant fibroblastic and myofibroblastic lesions. Am J Surg Pathol 2005;29:653e9. 18. Thway K, Gibson S, Ramsay A, et al. Beta-catenin expression in pediatric fibroblastic and myofibroblastic lesions: a study of 100 cases. Pediatr Dev Pathol 2009;12:292e6. 19. Wang Y, Tang J, Luo Y. Sonographic diagnosis of fibromatosis. J Clin Ultrasound 2008;36:330e4. 20. Lou L, Teng J, Qi H, et al. Sonographic appearances of desmoid tumors. J Ultrasound Med 2014;33:1519e25. 21. Lee JC, Thomas JM, Phillips S, et al. Aggressive fibromatosis: MRI features with pathologic correlation. AJR Am J Roentgenol 2006;186:247e54. 22. Hartman TE, Berquist TH, Fetsch JF. MR imaging of extraabdominal desmoids: differentiation from other neoplasms. AJR Am J Roentgenol 1992;158:581e5. 23. Healy JC, Reznek RH, Clark SK, et al. MR appearances of desmoid tumors in familial adenomatous polyposis. AJR Am J Roentgenol 1997;169:465e72. 24. Sundaram M, McGuire MH, Schajowicz F. Soft-tissue masses: histologic basis for decreased signal (short T2) on T2-weighted MR images. AJR Am J Roentgenol 1987;148:1247e50. 25. Gounder MM, Lefkowitz RA, Keohan ML, et al. Activity of sorafenib against desmoid tumor/deep fibromatosis. Clin Cancer Res 2011;17:4082e90. 26. Rhim JH, Kim J-H, Moon KC, et al. Desmoid-type fibromatosis in the head and neck: CT and MR imaging characteristics. Neuroradiology 2013;55:351e9. 27. Kasper B, Baumgarten C, Bonvalot S, et al. Management of sporadic desmoid-type fibromatosis: a European consensus approach based on patients’ and professionals’ expertiseda sarcoma patients EuroNet and European Organisation for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group. Eur J Cancer 2015;51:127e36. 28. Kasper B, Dimitrakopoulou-Strauss A, Pilz LR, et al. Positron emission tomography as a surrogate marker for evaluation of treatment response in patients with desmoid tumors under therapy with imatinib. Biomed Res Int 2013;2013:389672. choux C, et al. Sporadic desmoid-type 29. Gronchi A, Colombo C, Le Pe fibromatosis: a stepwise approach to a non-metastasising neoplasm-a
30.
31.
32.
33.
34.
35.
36. 37.
38.
39.
40.
41.
42.
43.
44.
45.
46.
47.
48.
1045
position paper from the Italian and the French Sarcoma Group. Ann Oncol 2014;25:578e83. Gronchi A, Raut CP. Optimal approach to sporadic desmoid tumors: from radical surgery to observation. Time for a consensus? Ann Surg Oncol 2012;19:3995e7. Salas S, Dufresne A, Bui B, et al. Prognostic factors influencing progression-free survival determined from a series of sporadic desmoid tumors: a wait-and-see policy according to tumor presentation. J Clin Oncol 2011;29:3553e8. Fiore M, Rimareix F, Mariani L, et al. Desmoid-type fibromatosis: a frontline conservative approach to select patients for surgical treatment. Ann Surg Oncol 2009;16:2587e93. Wilkinson MJ, Chan KE, Hayes AJ, et al. Surgical outcomes following resection for sporadic abdominal wall fibromatosis. Ann Surg Oncol 2014;21:2144e9. s N, Fiore M, et al. Spontaneous regression of primary Bonvalot S, Terne abdominal wall desmoid tumors: more common than previously thought. Ann Surg Oncol 2013;20:4096e102. Wilkinson MJ, Fitzgerald JEF, Thomas JM, et al. Surgical resection for non-familial adenomatous polyposis-related intra-abdominal fibromatosis. Br J Surg 2012;99:706e13. Berri RN, Baumann DP, Madewell JE, et al. Desmoid tumor: current multidisciplinary approaches. Ann Plast Surg 2011;67:551e64. Bonvalot S, Eldweny H, Haddad V, et al. Extra-abdominal primary fibromatosis: aggressive management could be avoided in a subgroup of patients. Eur J Surg Oncol 2008;34:462e8. Hansmann A, Adolph C, Vogel T, et al. High-dose tamoxifen and sulindac as first-line treatment for desmoid tumors. Cancer 2004;100:612e20. Skapek SX, Anderson JR, Hill DA, et al. Safety and efficacy of high-dose tamoxifen and sulindac for desmoid tumor in children: results of a Children’s Oncology Group (COG) Phase II Study. Pediatr Blood Cancer 2013;60:1108e12. Constantinidou A, Jones RL, Scurr M, et al. Pegylated liposomal doxorubicin, an effective, well-tolerated treatment for refractory aggressive fibromatosis. Eur J Cancer 2009;45:2930e4. Chugh R, Wathen JK, Patel SR, et al. Efficacy of imatinib in aggressive fibromatosis: results of a phase II multicenter Sarcoma Alliance for Research through Collaboration (SARC) trial. Clin Cancer Res 2010;16:4884e91. Jo JC, Hong YS, Kim KP, et al. A prospective multicenter phase II study of sunitinib in patients with advanced aggressive fibromatosis. Invest New Drugs 2014;32:369e76. Martin-Liberal J, Benson C, McCarty H, et al. Pazopanib is an active treatment in desmoid tumour/aggressive fibromatosis. Clin Sarcoma Res 2013;3:13. Ballo MT, Zagars GK, Pollack A, et al. Desmoid tumor: prognostic factors and outcome after surgery, radiation therapy, or combined surgery and radiation therapy. J Clin Oncol 1999;17:158e67. Guadagnolo BA, Zagars GK, Ballo MT. Long-term outcomes for desmoid tumors treated with radiation therapy. Int J Radiat Oncol Biol Phys 2008;71:441e7. Nuyttens JJ, Rust PF, Thomas CR, et al. Surgery versus radiation therapy for patients with aggressive fibromatosis or desmoid tumors: a comparative review of 22 articles. Cancer 2000;88:1517e23. Kujak JL, Liu PT, Johnson GB, et al. Early experience with percutaneous cryoablation of extra-abdominal desmoid tumors. Skeletal Radiol 2010;39:175e82. Walczak BE, Rose PS. Desmoid: the role of local therapy in an era of systemic options. Curr Treat Options Oncol 2013;14:465e73.
Contents lists available at ScienceDirect
Clinical Radiology journal homepage: www.clinicalradiologyonline.net
Pictorial Review
Desmoid-type fibromatosis S. Otero*, E.C. Moskovic, D.C. Strauss, C. Benson, A.B. Miah, K. Thway, C. Messiou Department of Radiology and Soft Tissue Sarcoma Unit, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK
article in formation Article history: Received 1 October 2014 Received in revised form 23 April 2015 Accepted 27 April 2015
Desmoid-type fibromatosis is a rare, locally infiltrative, mesenchymal neoplasm that is associated with high rates of local recurrence but lacks the potential to metastasise. The disease affects younger individuals, with a peak age of 30 years, and is the most common cause of an anterior abdominal wall mass in young women of childbearing age. It may, however, involve nearly every body part, including the extremities, head and neck, trunk, and abdominal cavity; as such, desmoid-type fibromatosis may present to a range of general and subspecialty radiologists. These rare tumours have a widely variable clinical presentation and unpredictable natural history, hence input from a soft-tissue tumour centre is recommended, although much of the imaging may be performed at the patient’s local hospital. The consensus for treatment has changed over the past decade, with most centres moving away from primary radical surgery towards a front-line ‘watch-and-wait’ policy. Therefore, imaging has an increasingly important role to play in both the diagnosis and follow-up of these patients. This review will discuss the typical imaging characteristics of these lesions and suggest diagnostic and followup magnetic resonance imaging protocols, with details of suitable sequences and scanning intervals. Ó 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction Desmoid-type fibromatosis (DF) is a rare, locally infiltrative, mesenchymal neoplasm. Although nonmetastasising, morbidity results from local complications, and rates of local recurrence following resection can be high. It can occur in many locations, often involving the extremities, the trunk, including the pelvic and shoulder girdles, and the abdominal cavity. DF accounts for 0.03% of all neoplasms and 3% of softtissue tumours,1 with a reported incidence of 2e4 individuals per million per year.2 It is mostly sporadic,
* Guarantor and correspondent: S. Otero, Department of Radiology and Soft Tissue Sarcoma Unit, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK. Tel.: þ44 020 7602 3993, þ44 07919 563725 (mobile). E-mail address: oterosofi[email protected] (S. Otero).
however, there is an association with familial adenomatous polyposis (FAP) in approximately 7.5% of patients, conferring an 800-fold risk when compared to the general population.3 DF affects a wide age range, but is most common between 10 and 40 years of age. In the paediatric population, there is an equal sex ratio, with tumours being predominantly extra-abdominal. Between puberty and 40 years of age tumours are most prevalent in females, with a predilection for the abdominal wall. Later in adulthood, there is a more equal distribution between abdominal and extra-abdominal tumours and the sex ratio tends towards parity.4 Extra-abdominal fibromatosis has a peak incidence between 25 and 30 years of age, with a predilection for the upper torso, most commonly the upper arm (approximately 30%). When encountered in the head and neck (Fig 1), lesions can behave more aggressively than at other sites and involvement of the axillary vessels, brachial plexus, or
http://dx.doi.org/10.1016/j.crad.2015.04.015 0009-9260/Ó 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
S. Otero et al. / Clinical Radiology 70 (2015) 1038e1045
1039
Figure 1 Fibromatosis of the left posterior neck. (a) Coronal (lesion depicted by arrows) and (b) axial STIR MRI shows an infiltrative lesion in the region of the left brachial plexus. The axial image shows tumour infiltration into the C7 neural exit foramen (arrow).
airway can limit surgical resectability.5 Although most often solitary, synchronous tumours can occur.6 Abdominal wall fibromatosis tends to occur in women of childbearing age, and is more frequent during and within the first year following pregnancy, and with oral contraceptive use.7,8 It is the most common soft-tissue neoplasm of the abdominal wall,9 and is generally solitary and slow growing. Approximately 87% of affected individuals are females and 95% have had at least one child. Twenty per cent of cases occur following a surgical procedure.7 Lesions tend to be smaller at presentation than other types of DF, perhaps because they are easily palpable and thus present earlier, and are usually solitary. Intra-abdominal fibromatosis occurs in the pelvis, mesentery and retroperitoneum, most often within the small bowel mesentery,10 where it is the most common primary tumour.7 Neoplasms here are frequently large (10 cm) before presentation.4 Pathogenesis is multifactorial with postulated endocrine, physical and genetic elements. Several factors indicate a role for oestrogens in the development and evolution of the disease, including a higher incidence in women during or shortly after pregnancy, and spontaneous regression or disease stabilisation with oestrogen blockade (Fig 2). Several studies have demonstrated oestrogen receptor (ERb) positivity in up to 90% of neoplasms.11,12 DF is also reported to occur at sites of previous surgery or blunt trauma.13 Sporadic cases show mutations in the b-catenin gene on 3p21, such that it is overexpressed in nuclei.14 bcatenin has an important role in regulating the size of cutaneous wounds and is required to mediate the effect of TGF-b,15 which is known to promote wound hyperplasia via fibroblast proliferation. It can therefore be postulated that DF represents, in part, uncontrolled wound healing.
Histopathology Histologically, DF is usually infiltrative and composed of sweeping fascicles of uniform myofibroblasts within
densely collagenous stroma (Fig 3). Approximately 80% of neoplasms show granular nuclear expression of b-catenin.16e18 The histological differential diagnosis is wide, and encompasses an extensive range of spindle cell lesions ranging from scarring to abdominal gastrointestinal stromal tumour and liposarcoma with “low-grade” dedifferentiation; however, a confident diagnosis may be made by virtue that most neoplasms resembling fibromatosis have specific histological diagnostic features and lack nuclear b-catenin immunoreactivity.14
Imaging characteristics Although often the first-line imaging investigation for a palpable lump, ultrasound features are non-specific. In one study of 44 lesions, the number displaying welldefined versus ill-defined borders was approximately equal.19 Neoplasms appear solid with variable, but predominantly low, echogenicity, 75% demonstrate posterior acoustic enhancement (Fig 4), and vascularity is variable on colour Doppler imaging; features that could lead to these solid lesions being misinterpreted as cystic.20 Although of limited diagnostic value, ultrasound provides a useful diagnostic adjunct when used to guide core biopsy. The computed tomography (CT) attenuation values of intra-abdominal or pelvic DF are variable, but lesions are most frequently isodense to skeletal muscle. Foci of higher attenuation are thought to correspond to areas of higher collagen content. Areas of low attenuation are less commonly seen and may indicate myxoid components, a pattern that is more frequent in chest wall disease. Contrast enhancement is variable and can be prominent, probably a sequelae of the abundant capillary network seen in these neoplasms.5 Intra-abdominal DF is usually seen as a soft-tissue mass in the mesentery with radiating strands projecting into the adjacent mesenteric fat (Fig 5).7 CT is often the technique of choice for follow-up
1040
S. Otero et al. / Clinical Radiology 70 (2015) 1038e1045
Figure 2 Fibromatosis of the right anterior abdominal wall. (a) Axial STIR MRI of the abdomen showing a hyperintense lesion, which developed in a woman during pregnancy (arrow). (b) Axial STIR MRI of the abdomen in the same female patient after a delay following childbirth, showing spontaneous regression once oestrogen stimulation has been withdrawn. The lesion, marked with a cod liver oil capsule on the skin, is no longer visible (arrow).
of intra-abdominal fibromatosis, as the mesenteric fat allows accurate delineation of the tumour and there is less bowel-motion artefact than with magnetic resonance imaging (MRI). MRI is the mainstay of imaging in DF and can be used for primary diagnosis, local surgical staging and follow-up. Its superior soft-tissue contrast allows accurate evaluation of tumour borders and their relationship to adjacent structures including muscles, nerves, blood vessels, and bones. DF usually displays heterogeneous signal intensity on T2weighted (T2W) images, which reflects the variable quantities and distribution of myofibroblasts, extracellular collagen and myxoid matrix; it is these appearances that raise suspicion for the diagnosis of DF (Fig 6).21 In approximately 90% of cases, the key diagnostic feature of hypointense bands is identifiable on T2W images, which correspond to the dense assemblies of collagen bundles seen at histological analysis.22 As with ultrasound, approximately half of lesions appear well-defined on MRI, and half have
Figure 3 Abdominal wall fibromatosis. Low-power haematoxylineeosin stain of this rectus sheath lesion shows sweeping fascicles of myofibroblasts within a densely collagenous stroma. Typically there are two populations of vessels: small, rounded thick-walled vessels (long arrow), and larger, thin-walled slit-like vessels (short arrows).
irregular infiltrative margins.21 On T1-weighted (T1W) sequences, lesions are often of intermediate signal intensity, isointense to muscle. At an early stage, lesions are more cellular and consequently appear predominantly hyperintense on T2W images. A statistically significant association has been shown between lesion growth on follow-up scanning and high T2W signal intensity.23 Over time an increase in collagen deposition, and consequent decrease in extracellular space, results in a decrease in T2W signal intensity.7,24 This pattern is also observed in lesions as they respond to treatment; as they undergo progressive collagen deposition, there is a corresponding reduction in tumour signal intensity.25 Lesions display moderate-marked enhancement with gadolinium contrast agents, other than the hypo-intense collagen bundles, which do not enhance. Lesions are most often centred in an intermuscular location and may be surrounded by a thin rim of fat, the “split-fat” sign (Fig 7).26 Infiltration along the fascia, also described as
Figure 4 Fibromatosis of the right anterior abdominal wall. Transverse ultrasound shows a well-defined hypo-echoic mass with posterior acoustic enhancement.
S. Otero et al. / Clinical Radiology 70 (2015) 1038e1045
1041
Figure 5 Two examples of intra-abdominal fibromatosis. (a) Contrast-enhanced axial CT of the abdomen shows an ill-defined soft-tissue mass within the mesentery. Intra-abdominal fat allows visualisation of the strands radiating into the adjacent mesenteric fat (arrows). (b) Contrastenhanced axial CT of the abdomen shows a large, well-defined, homogeneous mass, isodense to skeletal muscle, within the left side of the mesentery. There is associated displacement of the bowel (arrow) and mesenteric vessels (arrowhead).
a “fascial tail” (Fig 8), is observed in approximately 80% of cases.8 Although MRI features can be highly suggestive of DF, the differential diagnosis includes other infiltrative lesions such as malignant fibrous histiocytoma, fibrosarcoma, lymphoma, and densely calcified masses.
Guidelines for imaging, biopsy and specialist referral The following clinical features of any soft-tissue mass, which raise suspicion for a sarcoma, should prompt referral
Figure 6 Extra-abdominal fibromatosis of the right deltoid muscle. (a) Axial T2W MRI shows the classical appearance of fibromatosis: a heterogeneous, predominantly hyperintense (cellular) mass with hypo-intense (collagenous) bands. Lesions are most accurately measured on T2W images, as these confer the highest spatial resolution. (bec) Axial and coronal STIR MRI. Cellular lesions are often better demonstrated on this sequence, as the cellular components are markedly hyperintense (black arrows). Collagenous bands are hypo-intense on this sequence (asterisks). Measurements should not be performed on STIR, however, due to the inherent lower resolution and tendency to overestimate size. (dee) Axial and coronal T1W MRI provide an anatomical overview (mass outlined by arrows).
1042
S. Otero et al. / Clinical Radiology 70 (2015) 1038e1045
Figure 7 Fibromatosis of the left anterior abdominal wall. Axial T1W MRI of the abdomen showing a lesion that is isointense to skeletal muscle in an intermuscular location, with a thin rim of fat separating the lesion from muscle (arrows): the “split-fat” sign.
to a soft-tissue diagnostic centre: size >5 cm; mass deep to the deep fascia; mass increasing in size; and pain or recurrence at the site of previous excision. Lesions that do not fulfil these criteria should be assessed with ultrasound and clearly benign lesions managed accordingly. As ultrasound features of fibromatosis are non-specific (Fig 4), MRI of suspected superficial or limb lesions is usually indicated. For diagnosis, a combination of T2W, T1W, T1W fatsaturated contrast-enhanced, and short tau inversion recovery (STIR) sequences can be used for characterisation and delineation of the mass. T2W sequences demonstrate the features that are most specific for fibromatosis (Fig 6).21 The utility of diffusion-weighted MRI in DF is poorly described. For intra-abdominal and pelvic masses the broad
differential diagnosis often makes contrast-enhanced CT the most sensible first-line investigation. Any degree of suspicion for a soft-tissue sarcoma should trigger referral to a specialist soft-tissue sarcoma centre, along with imaging for review in the multidisciplinary meeting. Hand-held clinical or image-guided core biopsy is preferably performed at specialist centres to obtain benefit from on-site histopathology expertise, and to allow resection of the needle tract if a malignant soft-tissue sarcoma is confirmed. Excision biopsy is always contraindicated as this spoils soft-tissue planes if soft-tissue sarcoma is diagnosed. Once a diagnosis of fibromatosis is confirmed, surveillance can be performed with a shortened MRI protocol, often tailored to the anatomical site but excluding contrast medium: generally, a combination of T2W and STIR in two planes and T1W in a single plane (Fig 6). Changes in T2W signal are most useful for assessing changes in activity (Fig 9),24 whereas T1W and STIR serve as a useful overview. Changes in signal over time can be subtle and, therefore, consistent patient positioning and a choice of reproducible planes is essential. Furthermore, when reporting such studies, comparison over multiple time-points may be necessary for detection of slow change. There is no definitive guidance on frequency of follow-up imaging; however, the recently published European consensus approach suggests the following protocol: the first radiological re-evaluation should be performed at 4e8 weeks to avoid missing rapidly progressing disease, especially for lesions that are not easily palpable or that are located at critical sites; if MRI is stable, follow up is 3-monthly for the first year, 6-monthly up to the 5th year, and yearly thereafter27; for patients on medical treatment, imaging is generally performed at 3e6 month intervals, depending on symptoms and site of disease. (FDG) Combined 2-[18F]-fluoro-2-deoxy-D-glucose positron-emission tomography (PET) and computed tomography (CT) is not routinely used to assess or monitor DF; however, it has been proposed as a potential prognostic marker in discriminating responders from non-responders in patients undergoing treatment with tyrosine kinase inhibitors.28
Management Due to the unpredictable natural history of the disease, establishing a therapeutic regimen for DF is challenging. Historically, surgery with or without radiation therapy was the principle treatment. More recently, several series have reported spontaneous regression or prolonged indolent disease without treatment, with many institutions, including the authors’, proposing a “watch and wait” policy (Fig 9).29e32 This strategy enables identification of those patients who will remain asymptomatic with stable disease or undergo spontaneous regression, thus sparing this cohort from treatment.33,34 Figure 8 Extra-abdominal fibromatosis. Axial STIR MRI of the abdomen showing a predominantly hyperintense, wellcircumscribed mass within the left erector spinae muscle, with linear extension along the posterior fascia (arrow): the “fascial tail” sign.
Surgical management of fibromatosis There is ongoing debate as to the value of surgery for DF.30 Several studies have shown tumour location to be a
S. Otero et al. / Clinical Radiology 70 (2015) 1038e1045
1043
Figure 9 Fibromatosis of the right anterior abdominal wall. (a) Axial STIR MRI of the abdomen shows a well-circumscribed, markedly hyperintense mass, indicating a highly cellular neoplasm (arrows). (b) Axial STIR MRI of the abdomen showing the same lesion after a 2-year interval with no treatment. The lesion now has a large hypo-intense component indicating collagen deposition (arrow), consistent with spontaneous regression. There is a rim of residual cellular tissue posteriorly (arrowhead). Note the stability in size; it is critical to interrogate the signal changes.
prognostic factor, and propose that it may be beneficial to develop individualised therapeutic strategies for different prognostic subgroups. Abdominal wall and sporadic intraabdominal tumours have a limited risk of recurrence (8% and 13%, respectively),33,35 whereas surgical series for extremity and limb girdle fibromatosis report much higher recurrence rates of 39e79%.36
Abdominal wall fibromatosis In patients who progress to symptomatic abdominal wall disease, surgical resection remains the treatment of choice due to the achievability of excellent local control and low recurrence rates at this anatomical site. Complete resection with mesh reconstruction of the abdominal wall defect is safe, reliable, and delivers an excellent functional outcome.
Intra-abdominal sporadic fibromatosis
Patients with biopsy-proven intra-abdominal fibromatosis should be endoscopically screened for FAP and, if confirmed, these individuals should be treated in specialist units.36 Intra-abdominal fibromatosis can be complicated by small bowel fistulation, abscess formation, gastrointestinal tract bleeding, and bowel obstruction. Given the risk of complications and low recurrence rates following surgical resection in non-FAP-associated intra-abdominal fibromatosis, there should be a low threshold for surgery, provided that it can be offered with low morbidity, complete tumour resection, and without excessive organ resection or mutilating long-term effects. Systemic therapy may be used to treat non-resectable disease.
Limb fibromatosis Surgical resection with negative margins was previously considered to be the best treatment for limb, limb girdle, and truncal fibromatosis; however, due to the locally aggressive growth pattern, margin-negative resection is
often associated with significant functional and cosmetic consequences. Furthermore, surgical resection alone for extremity fibromatosis has a local recurrence rate of approximately 50% despite negative resection margins.29,36 Therefore, the past decade has seen a move away from primary radical surgery towards a first-line “watch and wait” policy that distinguishes indolent from aggressive forms and reserves medical treatment for progressive disease. Results have been encouraging, with prolonged progression-free survival being seen in a large proportion of patients.32,37 In patients with symptomatic or progressive disease during surveillance, medical treatment should be considered next. Surgery should only be employed when medical treatment fails to achieve radiological stabilisation or clinical improvement, and if surgery is possible without significant functional impairment. If surgery will lead to substantial disability, chemotherapy or radiotherapy may be a preferred option.29 When a decision for surgery is made, the goal should be to preserve function with negative resection margins.
Systemic management of fibromatosis The aim of systemic treatment is to slow or stop growth of fibromatosis as well as improve disease-related symptoms such as pain. Due to disease rarity, the evidence base for many systemic treatments is scanty and characterised by small, retrospective case studies. First-line therapy comprises the combination of anti-oestrogen treatment and non-steroidal anti-inflammatory drugs (NSAIDs) (Fig 10). Tamoxifen is the most widely used hormonal therapy.38,39 Systemic chemotherapy may be indicated following failure of first-line tamoxifen and NSAID treatment. Anthracyclines are associated with the highest response rates, and data from the authors’ institution support the use of
1044
S. Otero et al. / Clinical Radiology 70 (2015) 1038e1045
Figure 10 Fibromatosis of the left anterior abdominal wall. (a) Axial T2W MRI of the abdomen shows a predominantly hyperintense (cellular) mass within the left anterior abdominal wall (arrow). (b) Axial T2W MRI of the abdomen shows the same lesion following treatment with tamoxifen and naproxen. The mass is now markedly hypo-intense (arrow), consistent with collagen deposition and disease response.
pegylated liposomal doxorubicin (Caelyx) with an overall response rate of 36%. Notably, 86% of patients treated with Caelyx experienced decreased pain.40 Other options include methotrexate and vinblastine in combination, tyrosine kinase inhibitors, and pazopanib.25,41e43
Radiotherapy Radiotherapy can be an effective treatment for active fibromatosis.44e46 The lack of metastatic potential, excellent survival outcomes, and age of the patient (often young), must be taken into consideration when planning treatment with radiotherapy due to the risk of radiation-induced morbidity and secondary malignancies. Therefore, radiotherapy is usually recommended only in cases where medical and surgical options have been exhausted, and where disease is at risk of causing life-threatening problems or severely disabling outcomes. Clear guidance from a specialist soft-tissue radiologist can be invaluable in calculating the gross tumour volume and clinical target volume for treatment, which is done with STIR or T1W fat-saturated contrast-enhanced MRI sequences fused with a radiotherapy-planning CT. Response assessment following radiation is best performed at least 3 months after radiotherapy, with further evaluation at 6 months. Alternative methods of achieving local control, including cryoablation and radiofrequency ablation, remain in the early stages of evaluation with evidence resulting from small case series or reports. Cryoablation was shown to be effective in small and moderately sized extra-abdominal tumours in a very small series, but is of doubtful benefit in larger tumours or lesions at critical sites.47,48
Conclusion An awareness of the distribution and typical imaging characteristics of DF enables the radiologist to narrow the differential diagnosis; for example, DF is the commonest cause of an anterior abdominal wall mass in females of childbearing age. Core biopsy is mandatory for proof of diagnosis, and referral to a specialist soft-tissue diagnostic
centre is advisable. With many centres now adopting a firstline “watch and wait” policy, interval imaging every 3e6 months with MRI is becoming the norm. It is, therefore, essential to understand the imaging characteristics of these lesions over time, with progressive collagen deposition being indicated by decreasing T2W signal intensity, which often predates a reduction in size. The converse indicates disease progression and possible requirement for secondline systemic therapies, with surgery being reserved for refractory disease and for intra-abdominal fibromatosis, which carries a high risk of complications.
Acknowledgements We acknowledge support from NHS funding to the NIHR Biomedical Research Centre at Royal Marsden Hospital.
References 1. Desmoid-type fibromatoses. In: Fletcher JA, Bridge JA, Hogendoorn PCW, et al., editors. WHO Classification of Tumours of Soft Tissue and Bone. 4th ed. Lyon: IARC Press; 2013. p. 72e3. €yry P, Nykyri E, et al. The desmoid tumor. I. Incidence, sex-, 2. Reitamo JJ, Ha age- and anatomical distribution in the Finnish population. Am J Clin Pathol 1982;77:665e73. 3. Nieuwenhuis MH, Casparie M, Mathus-Vliegen LMH, et al. A nationwide study comparing sporadic and familial adenomatous polyposisrelated desmoid-type fibromatoses. Int J Cancer 2011;129:256e61. 4. Desmoid-type fibromatoses. In: Fletcher CDM, Unni KK, Mertens F, editors. Pathology and Genetics of Tumours of Soft Tissue and Bone. World Health Organization Classification of Tumours. Lyon: IARC Press; 2002. p. 83. 5. Murphey MD, Ruble CM, Tyszko SM, et al. From the archives of the AFIP. musculoskeletal fibromatoses: radiologicepathologic correlation. RadioGraphics 2009;29:2143e73. 6. Sundaram M, Duffrin H, McGuire MH, et al. Synchronous multicentric desmoid tumors (aggressive fibromatosis) of the extremities. Skeletal Radiol 1988;17:16e9. 7. Walker EA, Petscavage JM, Brian PL, et al. Imaging features of superficial and deep fibromatoses in the adult population. Sarcoma 2012;2012:215810. 8. Dinauer PA, Brixey CJ, Moncur JT, et al. Pathologic and MR imaging features of benign fibrous soft-tissue tumors in adults. RadioGraphics 2007;27:173e87. 9. Bashir U, Moskovic E, Strauss D, et al. Soft-tissue masses in the abdominal wall. Clin Radiol 2014;69:e422e31.
S. Otero et al. / Clinical Radiology 70 (2015) 1038e1045 10. Levy A, Rimola J, Mehrotra A, et al. From the archives of the AFIP. Benign fibrous tumors and tumorlike lesions of the mesentery: radiologicpathologic correlation. RadioGraphics 2006;26:245e65. 11. Santos GAC, Cunha IW, Rocha RM, et al. Evaluation of estrogen receptor alpha, estrogen receptor beta, progesterone receptor, and cKIT expression in desmoids tumors and their role in determining treatment options 2010;4:25e30. 12. Deyrup AT, Tretiakova M, Montag AG. Estrogen receptor-beta expression in extraabdominal fibromatoses: an analysis of 40 cases. Cancer 2006;106:208e13. 13. Reitamo JJ, Scheinin TM, H€ ayry P. The desmoid syndrome. New aspects in the cause, pathogenesis and treatment of the desmoid tumor. Am J Surg 1986;151:230e7. 14. Fisher C, Thway K. Aggressive fibromatosis. Pathology 2014;46:135e40. 15. Cheon SS, Wei Q, Gurung A, et al. Beta-catenin regulates wound size and mediates the effect of TGF-beta in cutaneous healing. FASEB J 2006;20:692e701. 16. Montgomery E, Torbenson MS, Kaushal M, et al. Beta-catenin immunohistochemistry separates mesenteric fibromatosis from gastrointestinal stromal tumor and sclerosing mesenteritis. Am J Surg Pathol 2002;26:1296e301. 17. Bhattacharya B, Dilworth HP, Iacobuzio-Donahue C, et al. Nuclear betacatenin expression distinguishes deep fibromatosis from other benign and malignant fibroblastic and myofibroblastic lesions. Am J Surg Pathol 2005;29:653e9. 18. Thway K, Gibson S, Ramsay A, et al. Beta-catenin expression in pediatric fibroblastic and myofibroblastic lesions: a study of 100 cases. Pediatr Dev Pathol 2009;12:292e6. 19. Wang Y, Tang J, Luo Y. Sonographic diagnosis of fibromatosis. J Clin Ultrasound 2008;36:330e4. 20. Lou L, Teng J, Qi H, et al. Sonographic appearances of desmoid tumors. J Ultrasound Med 2014;33:1519e25. 21. Lee JC, Thomas JM, Phillips S, et al. Aggressive fibromatosis: MRI features with pathologic correlation. AJR Am J Roentgenol 2006;186:247e54. 22. Hartman TE, Berquist TH, Fetsch JF. MR imaging of extraabdominal desmoids: differentiation from other neoplasms. AJR Am J Roentgenol 1992;158:581e5. 23. Healy JC, Reznek RH, Clark SK, et al. MR appearances of desmoid tumors in familial adenomatous polyposis. AJR Am J Roentgenol 1997;169:465e72. 24. Sundaram M, McGuire MH, Schajowicz F. Soft-tissue masses: histologic basis for decreased signal (short T2) on T2-weighted MR images. AJR Am J Roentgenol 1987;148:1247e50. 25. Gounder MM, Lefkowitz RA, Keohan ML, et al. Activity of sorafenib against desmoid tumor/deep fibromatosis. Clin Cancer Res 2011;17:4082e90. 26. Rhim JH, Kim J-H, Moon KC, et al. Desmoid-type fibromatosis in the head and neck: CT and MR imaging characteristics. Neuroradiology 2013;55:351e9. 27. Kasper B, Baumgarten C, Bonvalot S, et al. Management of sporadic desmoid-type fibromatosis: a European consensus approach based on patients’ and professionals’ expertiseda sarcoma patients EuroNet and European Organisation for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group. Eur J Cancer 2015;51:127e36. 28. Kasper B, Dimitrakopoulou-Strauss A, Pilz LR, et al. Positron emission tomography as a surrogate marker for evaluation of treatment response in patients with desmoid tumors under therapy with imatinib. Biomed Res Int 2013;2013:389672. choux C, et al. Sporadic desmoid-type 29. Gronchi A, Colombo C, Le Pe fibromatosis: a stepwise approach to a non-metastasising neoplasm-a
30.
31.
32.
33.
34.
35.
36. 37.
38.
39.
40.
41.
42.
43.
44.
45.
46.
47.
48.
1045
position paper from the Italian and the French Sarcoma Group. Ann Oncol 2014;25:578e83. Gronchi A, Raut CP. Optimal approach to sporadic desmoid tumors: from radical surgery to observation. Time for a consensus? Ann Surg Oncol 2012;19:3995e7. Salas S, Dufresne A, Bui B, et al. Prognostic factors influencing progression-free survival determined from a series of sporadic desmoid tumors: a wait-and-see policy according to tumor presentation. J Clin Oncol 2011;29:3553e8. Fiore M, Rimareix F, Mariani L, et al. Desmoid-type fibromatosis: a frontline conservative approach to select patients for surgical treatment. Ann Surg Oncol 2009;16:2587e93. Wilkinson MJ, Chan KE, Hayes AJ, et al. Surgical outcomes following resection for sporadic abdominal wall fibromatosis. Ann Surg Oncol 2014;21:2144e9. s N, Fiore M, et al. Spontaneous regression of primary Bonvalot S, Terne abdominal wall desmoid tumors: more common than previously thought. Ann Surg Oncol 2013;20:4096e102. Wilkinson MJ, Fitzgerald JEF, Thomas JM, et al. Surgical resection for non-familial adenomatous polyposis-related intra-abdominal fibromatosis. Br J Surg 2012;99:706e13. Berri RN, Baumann DP, Madewell JE, et al. Desmoid tumor: current multidisciplinary approaches. Ann Plast Surg 2011;67:551e64. Bonvalot S, Eldweny H, Haddad V, et al. Extra-abdominal primary fibromatosis: aggressive management could be avoided in a subgroup of patients. Eur J Surg Oncol 2008;34:462e8. Hansmann A, Adolph C, Vogel T, et al. High-dose tamoxifen and sulindac as first-line treatment for desmoid tumors. Cancer 2004;100:612e20. Skapek SX, Anderson JR, Hill DA, et al. Safety and efficacy of high-dose tamoxifen and sulindac for desmoid tumor in children: results of a Children’s Oncology Group (COG) Phase II Study. Pediatr Blood Cancer 2013;60:1108e12. Constantinidou A, Jones RL, Scurr M, et al. Pegylated liposomal doxorubicin, an effective, well-tolerated treatment for refractory aggressive fibromatosis. Eur J Cancer 2009;45:2930e4. Chugh R, Wathen JK, Patel SR, et al. Efficacy of imatinib in aggressive fibromatosis: results of a phase II multicenter Sarcoma Alliance for Research through Collaboration (SARC) trial. Clin Cancer Res 2010;16:4884e91. Jo JC, Hong YS, Kim KP, et al. A prospective multicenter phase II study of sunitinib in patients with advanced aggressive fibromatosis. Invest New Drugs 2014;32:369e76. Martin-Liberal J, Benson C, McCarty H, et al. Pazopanib is an active treatment in desmoid tumour/aggressive fibromatosis. Clin Sarcoma Res 2013;3:13. Ballo MT, Zagars GK, Pollack A, et al. Desmoid tumor: prognostic factors and outcome after surgery, radiation therapy, or combined surgery and radiation therapy. J Clin Oncol 1999;17:158e67. Guadagnolo BA, Zagars GK, Ballo MT. Long-term outcomes for desmoid tumors treated with radiation therapy. Int J Radiat Oncol Biol Phys 2008;71:441e7. Nuyttens JJ, Rust PF, Thomas CR, et al. Surgery versus radiation therapy for patients with aggressive fibromatosis or desmoid tumors: a comparative review of 22 articles. Cancer 2000;88:1517e23. Kujak JL, Liu PT, Johnson GB, et al. Early experience with percutaneous cryoablation of extra-abdominal desmoid tumors. Skeletal Radiol 2010;39:175e82. Walczak BE, Rose PS. Desmoid: the role of local therapy in an era of systemic options. Curr Treat Options Oncol 2013;14:465e73.