Fibromatosis

Fibromatosis is a condition where fibrous overgrowths of dermal and subcutaneous connective tissue develop tumours called fibromas. These fibromas are usually benign (non-cancerous).

1. 4/15/2015 1

2. Fibromatosis Dr. Muhammad Umar Nisar

3. What is fibromatosis? Fibromatosis is a condition where fibrous overgrowths of dermal and subcutaneous connective tissue develop tumours called fibromas. These fibromas are usually benign (non-cancerous).

4. classification of fibromatosis There appears to be many different ways to classify fibromatosis. One classification system used is based on age (i.e.: juvenile vs adult fibromatoses) and localisation (i.e.: superficial vs deep fibromatoses).

5. features of fibromatosis

6. Whilst most fibromatoses are benign tumours and do not metastasise (spread to other parts of the body), the desmoid tumours although they do not metastasise like malignant cancers can be locally aggressive . They can grow quickly into large tumours that can obstruct vital structures such as major blood vessels, nerves and organs.

7. Causes The cause of fibromatosis remains unclear In some types of fibromatosis such as desmoid tumours it is thought that the condition may be related to: Trauma Hormonal factors Estrogens Genetic association: Trisomy 8 Deletion of 5q

8. Causes cont... Superficial fibromatoses such as palmar, plantar and penile fibromatosis have sometimes been linked to certain diseases such as Diabetes Liver disease Hypertension

9. Staging of soft tissue tumors The usual tumor-node-metastases (TNM) classification scheme is modified into a grade-tumor-node-metastases (GTNM) scheme for staging soft tissue tumors In the GTNM system, possible values for tumor grade (G) are defined as follows: G1 - Well differentiated G2 - Moderately differentiated G3 - Poorly differentiated

10. Possible values for primary tumor (T) are defined as follows: T1 - Tumor less than 5 cm in greatest diameter T2 - Tumor more than 5 cm in greatest diameter

11. Possible values for regional lymph node involvement (N) are defined as follows: N0 - No known metastasis to lymph nodes N1 - Verified metastasis to lymph nodes

12. Possible values for distant metastasis are defined as follows: M0 - No known distant metastasis M1 - Known distant metastasis

13. GTNM Classification and Stage Grouping of Soft Tissue Tumors Stage Groupings Tumor Grade Primary Tumor Regional Lymph Node Involvement Distant Metastasis Stage IA G1 T1 N0 M0 Stage IB G1 T2 N0 M0 Stage II A G2 T1 N0 M0 Stage IIB G2 T2 N0 M0 Stage IIIA G3 T1 N0 M0 Stage IIIB G3 T2 N0 M0 Stage IVA Any G Any T N1 M0 Stage IVB Any G Any T Any N M1

14. Deep (musculoaponeurotic) fibromatoses Desmoid Tumor

15. Background Desmoid tumors are tumors that arise from cells called fibroblasts. Fibroblasts are found throughout our body and their main function is to provide structural support and protection to the vital organs They also play a critical role in wound healing. When fibroblast cells undergo mutations they can become cancerous and become desmoid tumors  The term desmoid, coined by Muller in 1838, is derived from the Greek word  desmos ,  which means tendonlike.

16. Epidemiology Frequency International Overall, desmoid tumors are reported to account for 0.03% of all neoplasms.When present in patients with familial polyposis of the colon, the prevalence of desmoid tumors is as high as 13%. Mortality/Morbidity Despite their benign histologic appearance and negligible metastatic potential, the tendency of desmoid tumors to cause local infiltration is significant in terms of (1) deformity, morbidity, and mortality resulting from pressure effects (2) potential obstruction of vital structures and organs. Sex Twice as common in females than in males Age more common in persons aged 10-40 years

17. Pathophysiology most commonly arise from the rectus abdominis muscle in postpartum women and in scars due to abdominal surgery, they may arise in any skeletal muscle. Desmoid tumors tend to infiltrate adjacent muscle bundles, frequently entrapping them and causing their degeneration. The myofibroblast is the cell considered to be responsible for the development of desmoid tumors May be familial (associated with Gardner's syndrome/FAP syndrome , or familial desmoid syndrome, or related to trauma.

18. Clinical Presentation History Lump that can arise in any skeletal muscle, they most commonly develop in the anterior abdominal wall and shoulder girdle. A history of trauma (often surgical) to the site of the desmoid tumor is elicited in 1 in 4 cases. Implant-associated breast desmoid tumors may occur Clusters of cases in families without evidence of any associated syndromes have also been reported.

19. Physical Examination: Peripheral desmoid tumors Peripheral desmoid tumors are firm, smooth, and mobile . They often adhere to surrounding structures. The overlying skin is usually unaffected. Intra-abdominal and extra-abdominal desmoid tumors Intra-abdominal desmoid tumors remain asymptomatic until their growth and infiltration cause visceral compression. Symptoms of intestinal, vascular, ureteric, or neural involvement may be the initial manifestations. Breast desmoid tumors Desmoid tumors account for 0.2% of primary breast tumors, developing from muscular fasciae and aponeuroses. Desmoid tumors may mimic breast cancer.

20. Skeletal distribution of extra-abdominal desmoid tumours.

21. Differential diagnosis Fibrosarcoma : atypia or mitotic figures present GIST : strong CD117+, CD34+ Idiopathic retroperitoneal fibrosis  inflammatory, strangles the ureters Leiomyoma : bright pink cytoplasm of smooth muscle, desmin+ Low grade fibromyxoid sarcoma : heavily collagenized stroma with abrupt transition to myxoid areas, often epithelioid areas or poorly formed but large collagen rosettes; beta catenin negative Neurofibroma : no myofibroblasts, S100+ Schwannoma : palisading Schwann cells, usually minimal collagen, S100+ Sclerosing omentitis :  grows like panniculitis, beta catenin negative

22. Work up Laboratory Studies Immunostaining with vimentin, alpha smooth muscle actin, muscle actin, and desmin are helpful in distinguishing the tumors in the differential diagnosis of desmoid tumors

23. Imaging Studies CT and MRI are used for the diagnosis and follow-up of desmoid tumors. They can help determine the extent of the tumor and its relationship to nearby structures, especially prior to surgical removal

24. Biopsy of the tumor: A fine-needle aspiration biopsy specimen may be considered. Fine-needle aspirates of desmoid tumors showing coherent clusters of uniform spindle cells with abundant cytoplasm and oval-to-elongated nuclei with evenly distributed chromatin

25. Electron microscopy: Fibroblastic and myofibroblastic features, including intrareticular collagen fibers, thin filament bundles, cytoplasmic dense bodies

26. Colonoscopy : indicated to investigate for the presence of Gardner syndrome Multiple large intestinal polyp in a patient with gardner syndrome

27. Treatment & Management Surgery Aggressive, wide surgical resection with complete excision is the treatment of choice. In selected patients, radical resection with intraoperative margin evaluation by frozen sections followed by immediate reconstruction of the defect may be a safe and effective procedure providing definitive cure yet minimizing functional limitations . Resection of Tumor

28. In those patients who refuse surgery or are not surgical candidates, the following options may be considered. Treatment Options for Nonsurgical Patients

29. Radiation therapy may be used as a treatment for recurrent disease or as primary therapy to avoid mutilating surgical resection. It may be used postoperatively, preoperatively, or as the sole treatment. Pharmacologic therapy with antiestrogens and prostaglandin inhibitors may also be used. chemotherapeutic regimen: Recurrent extra-abdominal: doxorubicin, dacarbazine, and carboplatin may be effective Intra abdominal : May respond to systemic doxorubicin, and ifosfamide 

30. Follow up Further Outpatient Care After surgery, MRI may be useful for monitoring desmoid tumor recurrence  follow-up visits are every three months for two years, and then in 6 to 12 month intervals.

31. Prognosis Local desmoid tumor recurrence rates are reported to be as high as 70%. A positive surgical margin is a significant risk factor for recurrence Five-year survival rates of such patients with stage I, II, III, and IV intra-abdominal desmoid tumors were found to be 95%, 100%, 89%, and 76%, respectively. The 5-year survival rate of stage IV patients with severe pain/narcotic dependency, tumor size larger than 10 cm, and need for total parenteral nutrition was only 53%.

32. Take home message There should be proper follow up of the patients to reduce the misery of the patients as well as the cost of treatment. There should be a multidisciplinary approach in the management of agressive fibromatosis. Whenever there is a doubt histopathologist himself/herself should proceed for immunohistochemistry instead of waiting for surgeon’s advice..

33. References Book: Textbook of Dermatology. Ed Rook A, Wilkinson DS, Ebling FJB, Champion RH, Burton JL. Fourth edition. Blackwell Scientific Publications. Wu C, Amini-Nik S, Nadesan P, Stanford WL, Alman BA. Aggressive fibromatosis (desmoid tumor) is derived from mesenchymal progenitor cells.  Cancer Res . Oct 1 2010;70(19):7690-8.  [Medline] . Brueckl WM, Ballhausen WG, Fortsch T, et al. Genetic testing for germline mutations of the APC gene in patients with apparently sporadic desmoid tumors but a family history of colorectal carcinoma.  Dis Colon Rectum . Jun 2005;48(6):1275-81.  [Medline] . Sturt NJ, Gallagher MC, Bassett P, et al. Evidence for genetic predisposition to desmoid tumours in familial adenomatous polyposis independent of the germline APC mutation.  Gut . Dec 2004;53(12):1832-6. [Medline] . Caspari R, Olschwang S, Friedl W, et al. Familial adenomatous polyposis: desmoid tumours and lack of ophthalmic lesions (CHRPE) associated with APC mutations beyond codon 1444.  Hum Mol Genet . Mar 1995;4(3):337-40.  [Medline] . Wang WL, Nero C, Pappo A, Dina Lev DL, Lazar AJ, Lopez-Terrada DH. CTNNB1 Genotyping and APC Screening in Pediatric Desmoid Tumors: A Proposed Alogrithm.  Pediatr Dev Pathol . Feb 28 2012; [Medline] . Mullen JT, Delaney TF, Rosenberg AE, Le L, Iafrate AJ, Kobayashi W, et al. ß-Catenin Mutation Status and Outcomes in Sporadic Desmoid Tumors.  Oncologist . Aug 19 2013; [Medline] . Shields CJ, Winter DC, Kirwan WO, Redmond HP. Desmoid tumours.  Eur J Surg Oncol . Dec 2001;27(8):701-6.  [Medline] . Klemmer S, Pascoe L, DeCosse J. Occurrence of desmoids in patients with familial adenomatous polyposis of the colon.  Am J Med Genet . Oct 1987;28(2):385-92.  [Medline] . Lee JC, Thomas JM, Phillips S, Fisher C, Moskovic E. Aggressive fibromatosis: MRI features with pathologic correlation.  AJR Am J Roentgenol . Jan 2006;186(1):247-54.  [Medline] . Raynham WH, Louw JH. Desmoid tumours in familial polyposis of the colon.  S Afr J Surg . Jul-Sep 1971;9(3):133-40.  [Medline] . Gaches C, Burke J. Desmoid tumour (fibroma of the abdominal wall) occurring in siblings.  Br J Surg . Jul 1971;58(7):495-8.  [Medline] . Lopez R, Kemalyan N, Moseley HS, Dennis D, Vetto RM. Problems in diagnosis and management of desmoid tumors.  Am J Surg . May 1990;159(5):450-3.  [Medline] . Jeong WS, Oh TS, Sim HB, Eom JS. Desmoid tumor following augmentation mammoplasty with silicone implants.  Arch Plast Surg . Jul 2013;40(4):470-2.  [Medline] .  [Full Text] .