Desmoid tumors are mesenchymal neoplasms which are considered locally invasive but non-metastasizing. They are also known as aggressive fibromatosis. Even though they do not metastasize, they are locally invasive and have a high rate of local resection even after complete resection. Management of Desmoid tumors requires a difficult decision for the patient, physician, and surgeon due to the extent of surgical resection needed, high local recurrence risk, and long natural history.
Most desmoid tumors occur sporadically, and 85% have a mutation in 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 APC gene. Desmoids arising in FAP have a prediction for the prior surgical site, and previous surgery is a risk factor. In patients who are treated with prophylactic colectomy, desmoid is the more important cause of morbidity and mortality than colon cancer. The desmoid tumor 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 desmoids have overall better outcomes.
These tumors are rare and account for less than 3% of all soft tissue sarcomas. The prevalence rises to as high as 13% in patients with familial adenomatosis of the colon. Women are more affected than men, especially after childbirth. In persons at risk, the desmoid tumor can arise after elective abdominal surgical procedures. No significant racial, ethnic, or geographical predilection has been linked to the desmoid tumor. It is more common in the 15 to 50 age group, but it can occur at any age group.
The exact molecular pathogenesis of desmoid tumor is not entirely understood. Evidence suggests that components of the WNT pathway, namely APC and beta-catenin, are involved in pathogenesis. While in FAP, APC inactivation leads to beta-catenin accumulation; in sporadic, desmoids arise from a mutation in the gene for beta-catenin, CTNNB1.
The characteristic feature of the desmoid tumor is small bundles of spindle cells in an abundant, fibrous stroma. These spindles are composed of proliferating monoclonal fibroblasts. The cellularity is low, and cells lack nuclear and cytoplasmic features of malignancy. Regarding immunohistochemistry, the spindle cells stain for vimentin, smooth muscle actin, and nuclear beta-catenin and are negative for desmin, cytokeratin’s, and S-100. Immunoreactivity to nuclear beta-catenin supports the diagnosis of a desmoid tumor. Next-generation sequencing can be very sensitive for the detection of CTNNB1 mutations in desmoid-type fibromatoses.
Most desmoids present as slow-growing, deep-seated, painless, or minimally painful masses. Common sites of the presentation include the abdominal wall, intraabdominal and trunk, or extremity; but it can occur anywhere. FAP patients with a predilection for intraabdominal desmoids predominate. A multifocal presentation is rare. 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.
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, desmoid tumor shows moderate enhancement with hypo-intense bands because of collagen bundles.
The treatment of desmoid can be divided broadly into asymptomatic resectable, symptomatic resectable, unresectable, and recurrent desmoids.
Asymptomatic Resectable: Retrospective evidence suggests that observation in the form of “wait and watch” approach may be a valid option for asymptomatic, small desmoids located in the region when growth would not lead to functional limitation or change the outcome of surgery. If the tumor progress, definitive therapy in the form of surgery or radiation therapy (RT) can be done.
Symptomatic Resectable: The main modality of treatment for symptomatic resectable desmoid is surgery. The risk of recurrence depends on following factors: (1) size, (2) location of the mass, (3) the age of the patient, and (4) margin status. Extra-abdominal tumors have a higher rate of recurrence than abdominal tumors. A controversy remains regarding the positive resection margins and risk of recurrence. Based on recent evidence, if physical therapy is followed carefully, there is no difference in outcomes between R0 and R1 resection. So, if achieving R0 resection would lead to excessive morbidity, then R1 resection is acceptable. One meta-analysis concluded that adjuvant radiotherapy appears to reduce the risk of recurrence after incomplete surgical resection, particularly in patients with recurrent tumors. Therefore, postoperative RT can be considered in high-risk patients.
Unresectable Desmoid: The options for unresectable tumor include systemic therapy, radiotherapy, and observation. Radical resection such as amputation should be avoided at all costs but is a reasonable option for the unresectable lesion. Response to RT is slow, and the continued response was seen even after 3 years. In a multicenter, phase 2 study at a median follow up of 4.8 years, the local control rate was 81.5%.
Systemic Therapy: Systemic therapy such as the use of nonsteroidal anti-inflammatory drugs like sulindac; celecoxib, hormonal agents like tamoxifen; biologics like l=interferomn; tyrosine kinase inhibitors like imatinib or sorafenib; and chemotherapy like liposomal doxorubicin, vinblastine, and methotrexate have shown promising results. In a phase 2 study for unresectable desmoid tumors, imatinib led to a one-year PFS of 66%. Long-term follow-up suggested that 2-year PFS and OS were 55% and 95% respectively. One study showed a good disease response rate with a combination of sulindac and tamoxifen, especially in FAP-associated desmoid. Doxorubicin-based chemotherapy has proven to be well tolerated and useful in advanced desmoid tumors.
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]|
|||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]|
|||Gounder MM,Thomas DM,Tap WD, Locally Aggressive Connective Tissue Tumors. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2018 Jan 10; [PubMed PMID: 29220303]|
|||Moding EJ,Million L,Avedian R,Ghanouni P,Kunder C,Ganjoo KN, Concurrent Imatinib and Radiation Therapy for Unresectable and Symptomatic Desmoid Tumors. Sarcoma. 2017; [PubMed PMID: 28761389]|
|||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]|
|||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]|