Desmoid tumors (DT) are mesenchymal neoplasms that are considered locally invasive but non-metastasizing.  They are also known as aggressive fibromatosis, deep fibromatosis and musculoaponeurotic fibromatosis. Even though they do not metastasize, they are locally invasive and cause significant morbidity and mortality. The management of DT is challenging and requires a discussion at a multidisciplinary tumor board (MTB). DT is primarily treated with surgery with or without radiation therapy (RT). Despite surgical resection, DT have a high rate of local recurrence, and hence, they have been labeled as intermediate locally aggressive tumors by World Health Organization (WHO). According to the WHO, DT is a “clonal fibroblastic proliferation that arises in the deep soft tissues and is characterized by infiltrative growth and a tendency toward local recurrence but an inability to metastasize,” even though it may be multifocal in the same limb or body part. Systemic chemotherapy is used in patients where surgery and RT are either not feasible or will not achieve a cure.
The etiology of DT is unknown. Most DT occurs sporadically, and 85% have a mutation in the CTNNB1 encoding beta-catenin pathway. The three distinct mutations identified are 41A, 45F, and 45. Mutation 45F is associated with a high risk of recurrence. The 5-year recurrence-free survival was 23% for 45F, 57% for 41A, and 68% for no mutation. Desmoid tumor is seen at increased frequency in familial adenomatous polyposis (FAP), mostly abdominal FAP caused by a mutation in the APC gene. DT arising in FAP has a predilection for the prior surgical site, and previous surgery is a risk factor. In patients who are treated with prophylactic colectomy, DT is the more important cause of morbidity and mortality than colon cancer. The DT occurs with increased frequency in the female during or after pregnancy, and anecdotal evidence suggests abdominal wall trauma and high estrogen states are the possible reason. Pregnancy-associated DT have overall better outcomes.
DT is a rare tumor, with a reported incidence of 2–4 per million population and accounts for 0.03% of all neoplasms. The peak age of occurrence is 30-40 years. It occurs more commonly in women compared to men and between the ages of 15-60 years. DT may occur at abdominal, intra-abdominal, and extra-abdominal locations. Approximately 5 to 10% arise in the context of familial adenomatous polyposis (FAP).
The diagnosis of DT must be reviewed by an expert soft-tissue pathologist. Histologically, DT is characterized by the proliferation of uniform spindle cells resembling myofibroblasts, in the background of abundant collagenous stroma and vascular network. Other features like hyperchromasia and cellular atypia are not present usually. The tumor cells are similar to the myofibroblasts, as seen during the proliferative stage of wound healing. Cells may have nuclei containing euchromatin of heterochromatin. Large amounts of the myxoid stroma may be seen in some tumors, especially those that develop in the mesentery. On microscopy, the tumor may appear like a low-grade fibrosarcoma, but the cells lack the nuclear atypia and typical cytoplasmic features of malignancy.
On immunohistochemistry, DT stains positive for nuclear beta-catenin, vimentin, cyclooxygenase-2, tyrosine kinase PDGFRb, androgen receptor, and estrogen receptor beta. DT stains negative for desmin, S-100, h-caldesmon, CD34, and c-KIT. Nuclear beta-catenin positivity supports the diagnosis of DT. However, a negative stain does not exclude DT. Next-generation sequencing must be done to evaluate for CTNNB1 mutations. The CTNNB1 and APC mutations are mutually exclusive. Hence, the detection of one can virtually exclude the other. In patients that are CTNNB1 wild type, especially for intra-abdominal DT, extensive clinical workup should be pursued to rule out FAP syndrome.
DT has a varied pattern of clinical presentation, characterized by a slow-growing tumor, that can stabilize and can even undergo spontaneous remission. DT commonly occurs in the rectus abdomins muscle, head and neck region, pelvis, and in the extremities. DT is also known to occur in association with pregnancy and with the use of oral contraceptive pills; and it is known to regress with menopause, indicating a potential influence of the female sex hormonal environment. Breast desmoid can be associated with surgery or implants. One in four cases has a history of trauma or surgery at the site of desmoid. DT also has a propensity to recur in the same area causing a lot of local destruction; however, it has no capacity to metastasize. Patients with FAP are at a much higher risk of developing DT (Up to 25% higher than the general population). In patients with DT, FAP can be diagnosed in up to 5% of patients. The peak incidence is in the late second decade of life, although, it can occur at any age.
The physical exam is usually benign unless the tumor causes pressure symptoms. They can certainly mimic cancer of the respective organ (for example; a DT occurring in the breast can mimic breast cancer), hence a biopsy is mandatory to accurately diagnose a DT.
Imaging studies like CT scan and MRI can be done during diagnosis and follow up. Imaging can determine the extent of the tumor, which organs are infiltrated, and a surgical resection plan. MRI seems to be more useful than CT scan in helping to establish the extent of tumor and relationship to nearby organs. On T1-weighted images, desmoids are hypo- or isointense to muscle, while on T2-weighted images they are hyperintense. With gadolinium contrast, DT shows moderate enhancement with hypo-intense bands because of collagen bundles.
DTs are primarily treated through surgery, however, RT and medical therapy have a role to play as well.
Surgical Treatment: The approach to DT is primarily surgical. The goal of surgery is to preserve the limb function and critical structures. Unlike other soft-tissue sarcomas where the goal of surgical resection is to achieve a microscopic negative margins (R0 resection), an R0 resection is only deemed 'desirable', but not a necessity in the surgery of a DT. The significance of a positive margin (R1 or R2 resection) is highly debated. Positive margins after surgery have been reported as an independent prognostic factor in determining the risk of recurrence, however, guidelines clearly prohibit a morbid surgery in an attempt to achieve an R0 resection. In combination with RT and medical therapy, the surgical treatment of DT has become more and more conservative.
Radiation therapy: RT is primarily used in the adjuvant setting when surgery leaves behind a positive margin, or when surgical resection is not possible. A dose of more than 56 Gy is associated with many complications and hence avoided. Non-randomized and retrospective data have shown a lower local recurrence rate with the addition of adjuvant RT in patients with a positive margin. The role of neoadjuvant RT is not established and currently not recommended.
Systemic Therapy: Systemic therapy is usually reserved for patients who experience rapid growth of DT or for those patients in whom the tumor is threatening a critical structure or the surgery would be extremely mutilating.
Desmoids may occasionally be encountered by the nurse practitioner, primary care provider or the internist. Because the diagnosis and treatment is complex, it is important to consult with an oncologist, pathologist, and a radiologist. The treatment of desmoid can be divided broadly into asymptomatic resectable, symptomatic resectable, unresectable, and recurrent desmoids. These lesions do not normally respond well to chemotherapy and radiation and surgery is the only treatment. However, recurrences are common. The prognosis for most patients is guarded. (Level V)
|||Childhood Soft Tissue Sarcoma Treatment (PDQ®): Health Professional Version 2002; [PubMed PMID: 26389361]|
|||Wang Z,Wu J,Lv A,Tian X,Hao C, En bloc resection for intra-abdominal/retroperitoneal desmoid-type fibromatosis with adjacent organ involvement: A case series and literature review. Bioscience trends. 2018; [PubMed PMID: 30674762]|
|||Cassidy MR,Lefkowitz RA,Long N,Qin LX,Kirane A,Sbaity E,Hameed M,Coit DG,Brennan MF,Singer S,Crago AM, Association of MRI T2 Signal Intensity With Desmoid Tumor Progression During Active Observation: A Retrospective Cohort Study. Annals of surgery. 2018 Nov 9; [PubMed PMID: 30418203]|
|||Ganeshan D,Amini B,Nikolaidis P,Assing M,Vikram R, Current Update on Desmoid Fibromatosis. Journal of computer assisted tomography. 2019 Jan/Feb; [PubMed PMID: 30211798]|
|||Timbergen MJM,van de Poll-Franse LV,Grünhagen DJ,van der Graaf WT,Sleijfer S,Verhoef C,Husson O, Identification and assessment of health-related quality of life issues in patients with sporadic desmoid-type fibromatosis: a literature review and focus group study. Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation. 2018 Dec; [PubMed PMID: 30014458]|
|||Couto Netto SD,Teixeira F,Menegozzo CAM,Leão-Filho HM,Albertini A,Ferreira FO,Akaishi EH,Utiyama EM, Sporadic Abdominal Wall Desmoid type Fibromatosis: treatment paradigm after thirty two years. BMC surgery. 2018 Jun 7; [PubMed PMID: 29879959]|
|||Nieuwenhuis MH,Casparie M,Mathus-Vliegen LM,Dekkers OM,Hogendoorn PC,Vasen HF, A nation-wide study comparing sporadic and familial adenomatous polyposis-related desmoid-type fibromatoses. International journal of cancer. 2011 Jul 1; [PubMed PMID: 20830713]|
|||de Camargo VP,Keohan ML,D'Adamo DR,Antonescu CR,Brennan MF,Singer S,Ahn LS,Maki RG, Clinical outcomes of systemic therapy for patients with deep fibromatosis (desmoid tumor). Cancer. 2010 May 1; [PubMed PMID: 20187095]|
|||Fiore M,MacNeill A,Gronchi A,Colombo C, Desmoid-Type Fibromatosis: Evolving Treatment Standards. Surgical oncology clinics of North America. 2016 Oct; [PubMed PMID: 27591500]|
|||The management of desmoid tumours: A joint global consensus-based guideline approach for adult and paediatric patients. European journal of cancer (Oxford, England : 1990). 2020 Mar; [PubMed PMID: 32004793]|
|||Muller E,Castagnaro M,Yandel DW,Wolfe HJ,Alman BA, Molecular genetic and immunohistochemical analysis of the tumor suppressor genes Rb and p53 in palmar and aggressive fibromatosis. Diagnostic molecular pathology : the American journal of surgical pathology, part B. 1996 Sep; [PubMed PMID: 8866233]|
|||Kotiligam D,Lazar AJ,Pollock RE,Lev D, Desmoid tumor: a disease opportune for molecular insights. Histology and histopathology. 2008 Jan; [PubMed PMID: 17952864]|
|||Guttadauro A,Maternini M,Frassani S,Guanziroli E,Lo Bianco G,Gabrielli F, Desmoid tumor of the abdominal wall A case report and literature review. Annali italiani di chirurgia. 2017 Nov 20; [PubMed PMID: 29424372]|
|||Asadoorian M,Matcuk GR Jr,Patel DB,Tomasian A,Wassef HR,White EA, Musculoskeletal Pitfalls on Fluorodeoxyglucose F 18 PET-Computed Tomography: Pictorial Review. PET clinics. 2018 Oct; [PubMed PMID: 30219190]|
|||Attanoos RL,Pugh MR, The Diagnosis of Pleural Tumors Other Than Mesothelioma. Archives of pathology [PubMed PMID: 30040453]|
|||Bishop AJ,Zarzour MA,Ratan R,Torres KE,Feig BW,Wang WL,Lazar AJ,Moon BS,Roland CL,Guadagnolo BA, Long-Term Outcomes for Patients With Desmoid Fibromatosis Treated With Radiation Therapy: A 10-Year Update and Re-evaluation of the Role of Radiation Therapy for Younger Patients. International journal of radiation oncology, biology, physics. 2018 Dec 12; [PubMed PMID: 30552963]|
|||Turner B,Alghamdi M,Henning JW,Kurien E,Morris D,Bouchard-Fortier A,Schiller D,Puloski S,Monument M,Itani D,Mack LA, Surgical excision versus observation as initial management of desmoid tumors: A population based study. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology. 2018 Oct 25; [PubMed PMID: 30420189]|