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AUTHOR AND EDITOR INFORMATION

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Author: Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Medicine, Professor of Pediatrics, Professor of Pathology, Professor of Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School

Robert A Schwartz is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi

Coauthor(s): Matthew J Trovato, MD, Staff Physician, Department of Dermatology, UMDNJ-New Jersey Medical School; Peter C Lambert, MD, Resident, Department of Dermatology, New Jersey Medical School

Editors: Neil Shear, MD, Professor and Chief of Dermatology, Professor of Medicine, Pediatrics and Pharmacology, University of Toronto Faculty of Medicine; Head of Dermatology, Sunnybrook Women's College Health Sciences Center and Women's College Hospital, Canada; David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Director, Division of Dermatology, Scott and White Clinic; Director Dermatology Residency Training Program, Scott and White Clinic; Jeffrey Meffert, MD, Assistant Clinical Professor of Dermatology, University of Texas Health Science Center-San Antonio; Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University; William D James, MD, Paul R Gross Professor of Dermatology, University of Pennsylvania School of Medicine; Vice-Chair, Program Director, Department of Dermatology, University of Pennsylvania Health System

Author and Editor Disclosure

Synonyms and related keywords: musculoaponeurotic fibromatosis, aggressive fibromatosis, deep fibromatosis, nonmetastasizing fibrosarcoma, grade I fibrosarcoma

INTRODUCTION

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Background

Desmoid tumors are histologically benign fibrous neoplasms originating from the musculoaponeurotic structures throughout the body. The term desmoid, coined by Muller in 1838, is derived from the Greek word desmos, which means tendonlike.

Desmoid tumors often appear as infiltrative, usually well-differentiated, firm overgrowths of fibrous tissue, and they are locally aggressive. The synonym aggressive fibromatosis describes the marked cellularity and aggressive local behavior. This course and the tendency for recurrence make the treatment of these relatively rare fibrous tumors challenging.

The Medscape CME course Stay Connected: Update on the Management of Sarcoma (Slides With Transcript) may be of interest.

Pathophysiology

Although desmoid tumors 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. The tumors tend to infiltrate adjacent muscle bundles, frequently entrapping them and causing their degeneration. Although fixation to musculoaponeurotic structures is apparent, the overlying skin is normal. The myofibroblast is the cell considered to be responsible for the development of desmoid tumors (see Procedures).

Gardner syndrome or familial adenomatous polyposis (FAP) is characterized by colorectal adenomatous polyps and soft and hard tissue neoplasms. The former may number in the hundreds to thousands. Gardner syndrome was regarded as a separate disease until the identification of the APC (adenomatous polyposis coli) gene, at which point mutations in the APC gene were recognized as the underlying cause of both Gardner syndrome and FAP. Some authors regard Gardner syndrome as a subset of FAP, and some have even suggested that the term Gardner syndrome be replaced by FAP. Additionally, evidence also exists for a genetic predisposition to desmoid tumors in FAP, independent of the APC mutation.

Desmoid tumors occur at a rate of 10-15% in patients with FAP, an autosomal inherited disease caused by germline mutations in the APC gene. Sporadic forms have no hereditary background.1 Desmoid tumors show biallelic APC mutation, with one change usually occurring distal to the second beta-catenin binding/degradation repeat of the gene (3' to codon 1399).2, 3 The relationship between extracolonic manifestations and the site of the APC mutation suggests a specific role of the APC protein in different tissues. However, unknown genetic factors independent of APC may be important in the susceptibility to desmoid tumors in patients with FAP.

In desmoid tumors, 1 of the 2 mutations usually occurs distal to the second beta-catenin binding/degradation repeat of the gene (3' to codon 1399). Catenin and catenin-binding genes have been found to be associated with neoplastic processes in a number of ways. Independent predictors of increased desmoid risk in one study were said to be (1) germline mutation distal to codon 1399, (2) any family history of gastrointestinal disease, and (3) a strong family history of desmoid tumors.

The relationship between certain extracolonic manifestations and sites of the APC mutation suggests specific roles of the APC protein in different tissues. These different roles may correspond to specific sites of missense mutations in the APC gene. For example, dental manifestations of Gardner syndrome have been suggested to be associated with mutations at or near codon 1556. However, the influence of unknown genetic factors independent of APC in susceptibility to desmoid tumors in FAP needs to be explored.

FAP results from a germline mutation in the APC gene. Desmoid tumors are associated with a biallelic APC mutation in the affected tissue. This usually results from a spontaneous somatic mutation in the unaffected APC gene of a single cell in a patient with the FAP syndrome. This process is an example of the Knudsen "two hit" hypothesis, in which a tumor suppressor gene, such as APC, must be biallelically mutated in order for a specific type of tumor to occur.

In genetically normal individuals, with normal germline genes, this necessitates a rare combination of events, such that at least 2 somatic mutations must occur in both alleles of a single tumor suppressor gene, in this case the APC gene. In FAP syndrome patients, one APC germline gene is already mutated in every cell in the body (barring a rare reverse somatic mutation in some cells), and, therefore, only one new somatic mutation is required in the opposite APC gene for the tumor to develop.

FAP may be associated with mutations in the APC gene, but mutations in several other genes, particularly mismatch DNA repair genes, which are primarily responsible for ensuring integrity of polymerases responsible for DNA replication, may also result in familial colonic polyposis. These patients with familial colonic polyposis typically do not show other manifestations of Gardner syndrome. Conversely, extracolonic manifestations characteristic of Gardner syndrome may occur independent of intestinal polyps or a mutation in the APC gene.

Frequency

International

Overall, desmoid tumors are reported to account for 0.03% of all neoplasms.4 When present in patients with familial polyposis of the colon, the prevalence of desmoid tumors is as high as 13%.5

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 and (2) potential obstruction of vital structures and organs.

Sex

Desmoid tumors most commonly occur in women after childbirth. Desmoid tumors are twice as common in females than in males; however, 60 patients were described,6 and the female-to-male ratio was 1.2:1. In children, the sex incidence is equal.

Age

Although desmoid tumors are more common in persons aged 10-40 years than in others, they do occur in young children and older adults. Sixty patients were described by Lee et al6 in 2006, with an average age at diagnosis of 41.3 years.


CLINICAL

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History

  • Although desmoid tumors can arise in any skeletal muscle, they most commonly develop in the anterior abdominal wall and shoulder girdle.
  • Retroperitoneal neoplasms are more common in familial polyposis coli and Gardner syndrome after abdominal surgery than in other conditions.7
  • Clusters of cases in families without evidence of any associated syndromes have also been reported.8
  • A history of trauma (often surgical) to the site of the tumor is elicited in 1 in 4 cases.9

Physical

  • Peripheral desmoid tumors
    • Peripheral desmoid tumors are firm, smooth, and mobile.
    • They often adhere to surrounding structures.
    • The overlying skin is usually unaffected.
    • The presence of such a soft tissue growth should alert the clinician to delve more deeply into the family history for evidence of familial polyposis coli and Gardner syndrome.
    • Extra-abdominal desmoid tumors are rare and may be first evident as gradually increasing leg swelling.10
  • Intra-abdominal desmoid tumors may be seen. Extra-abdominal desmoid tumors may also be seen (rarely) in the urological system, including in the bladder and scrotum.11
    • 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.
    • Ethmoidal desmoid tumor has been described in a pediatric patient.12

Causes

The cause of desmoid tumors is uncertain and may be related to trauma or hormonal factors, or they may have a genetic association.

  • The familial polyposis gene on chromosome 5 has been extensively studied.3, 13
  • An endocrine etiology is suggested.
    • Desmoid tumors most commonly appear in young women during or after pregnancy.
    • The tumors regress during menopause14 and after tamoxifen treatment.15
    • Desmoid tumors may regress after exposure to oral contraceptives.16
  • The proliferative response of fibroblasts to estrogen has been established.17


DIFFERENTIALS

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Gardner Syndrome

Other Problems to be Considered

Fibrosarcoma
Familial polyposis of the colon


WORKUP

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Lab 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.
  • APC germline mutations in apparently sporadic desmoid tumor patients who have no clinical or familial signs of FAP but have a family history of colorectal carcinoma in at least one family member were evaluated by Brueckl et al1 in 2005. They reported that patients with sporadic desmoid tumors and no clinical or laboratory signs of FAP may not need to be routinely tested for germline mutations of the APC gene. However, performing an APC mutational analysis instead of other tests (eg, esophagogastroduodenoscopy, complete colonoscopy) may be a more time- and cost-effective plan.

Imaging Studies

  • CT scan 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.
    • MRI is superior to CT scan in defining the pattern and the extent of involvement as well as in determining if recurrence has occurred after surgery.

Procedures

  • The diagnostic test is biopsy of the tumor.
  • Electron microscopy may be performed.
    • On electron microscopic examination, the spindle cells of desmoid tumors appear to be myofibroblasts.
    • This finding is thought to represent an abnormal proliferation of myofibroblasts, which normally disappear gradually during the later stages of wound healing.
  • Colonoscopy and fundal examination are indicated to investigate for the presence of Gardner syndrome.

Histologic Findings

The tumors are composed of abundant collagen surrounding poorly circumscribed bundles of spindle cells. The dense bundles of eosinophilic spindle cells contain regular nuclei and pale cytoplasm with neither mitoses nor giant cells. Macrophages, giant cells, and lymphocytes are present peripherally.

The aforementioned features are in contrast to those in a fibrosarcoma, which has greater mitotic activity, an increased nuclear-to-cytoplasm ratio, greater vascularity, less collagen production, and a paucity of immune cells.4


TREATMENT

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Medical Care

  • Primary surgery with negative surgical margins is the most successful primary treatment modality. Positive margins after surgery reflect a high risk for recurrence.18
  • In those patients who refuse surgery or are not surgical candidates the following options may be considered:
    • Radiation therapy may be used as a treatment of recurrent disease or as primary therapy to avoid mutilating surgical resection.
    • Pharmacologic therapy with antiestrogens and prostaglandin inhibitors may also be used.
    • In cases of recurrent extra-abdominal desmoid tumors in which surgery is contraindicated or in cases of recurrence, a chemotherapeutic regimen of doxorubicin, dacarbazine, and carboplatin may be effective. Intra-abdominal desmoid tumors as a part of Gardener syndrome may respond to systemic doxorubicin, and ifosfamide can be useful for patients with complications from the tumor.19

Surgical Care

  • Aggressive, wide surgical resection is the treatment of choice.
  • Complete surgical excision of desmoid tumors is the only effective method of cure.


MEDICATION

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The goals of pharmacotherapy are to induce remission, to prevent complications, and to reduce morbidity.20 Local recurrences are frequent after surgery, particularly if margins are positive. Radiotherapy alone for gross disease or after a microscopically incomplete resection yields local control rates of approximately 75-80%.

Drug Category: Antineoplastic agents

These agents inhibit cell growth and proliferation. Pharmacologic agents result in objective response rates of approximately 40-50%; the duration of response is variable.20

Drug NameDoxorubicin (Adriamycin, Rubex)
DescriptionInhibits topoisomerase II and produces free radicals, which may cause the destruction of DNA. The combination of these 2 events can, in turn, inhibit the growth of neoplastic cells.
Adult Dose60-90 mg/m2 IV per protocol for 7 cycles
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; severe heart failure; cardiomyopathy; impaired cardiac function; preexisting myelosuppression
InteractionsMay decrease phenytoin and digoxin plasma levels; phenobarbital may decrease plasma levels; cyclosporine may induce coma or seizures; mercaptopurine increases toxicity; cyclophosphamide increases cardiac toxicity
PregnancyD - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
PrecautionsIrreversible cardiac toxicity and myelosuppression may occur; extravasation may result in severe local tissue necrosis; reduce dose in patients with impaired hepatic function

Drug NameDacarbazine (DTIC-Dome)
DescriptionInhibits DNA, RNA, and protein synthesis. Inhibits cell replication throughout all phases of the cell cycle.
Adult Dose1000 mg/m2 IV per protocol for 7 cycles
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity
InteractionsNone reported
PregnancyC - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
PrecautionsCaution in patients with bone marrow suppression or renal and/or hepatic impairment; avoid extravasation

Drug NameCarboplatin (Paraplatin)
DescriptionAnalog of cisplatin. Has same efficacy as cisplatin but with better toxicity profile.
Adult Dose400 mg/m2 IV per protocol for 7 cycles
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity; bone marrow suppression
InteractionsNephrotoxicity increases with aminoglycosides and other nephrotoxic drugs
PregnancyD - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
PrecautionsMonitor bone marrow function


FOLLOW-UP

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Further Outpatient Care

After surgery, MRI may be useful for monitoring recurrence.

Prognosis

Local recurrence rates are reported to be as high as 70%.


MULTIMEDIA

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Media file 1:  Bland fibrocytic cells of a desmoid tumor growing in a haphazard-to-storiform manner and producing collagen (hematoxylin-eosin, original magnification X100).
Click to see larger pictureClick to see detailView Full Size Image
Media type:  Photo

Media file 2:  Desmoid tumor spindle cells invading skeletal muscle (hematoxylin-eosin, original magnification X100).
Click to see larger pictureClick to see detailView Full Size Image
Media type:  Photo

Media file 3:  Dermoid tumor spindle cells surrounding and destroying skeletal muscle cells (hematoxylin-eosin, original magnification X100)
Click to see larger pictureClick to see detailView Full Size Image
Media type:  Photo


REFERENCES

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  1. Brueckl WM, Ballhausen WG, Förtsch T, Günther K, Fiedler W, Gentner B, 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].
  2. Sturt NJ, Gallagher MC, Bassett P, Philp CR, Neale KF, Tomlinson IP, 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].
  3. Caspari R, Olschwang S, Friedl W, Mandl M, Boisson C, Böker T, 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].
  4. Shields CJ, Winter DC, Kirwan WO, Redmond HP. Desmoid tumours. Eur J Surg Oncol. Dec 2001;27(8):701-6. [Medline].
  5. 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].
  6. 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].
  7. Raynham WH, Louw JH. Desmoid tumours in familial polyposis of the colon. S Afr J Surg. Jul-Sep 1971;9(3):133-40. [Medline].
  8. Gaches C, Burke J. Desmoid tumour (fibroma of the abdominal wall) occurring in siblings. Br J Surg. Jul 1971;58(7):495-8. [Medline].
  9. 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].
  10. Agrawal PS, Jagtap SM, Mitra SR. Extra-abdominal desmoid tumour of the leg. Singapore Med J. Jan 2008;49(1):e6-7. [Medline].
  11. Shi B, Zhu Y, Xu Z, Liu Y, Zheng B, Qi T. Aggressive fibromatosis in the urological system. Report of two adult patients and review of the literature. Urol Int. 2007;78(1):93-6. [Medline].
  12. Neri HA, Villagra EJ, Alvarez AC, Valencia P, Jiménez E, de la Torre C, et al. Ethmoidal desmoid tumor in a pediatric patient. Otolaryngol Head Neck Surg. Jan 2007;136(1):137-8. [Medline].
  13. Gurbuz AK, Giardiello FM, Petersen GM, Krush AJ, Offerhaus GJ, Booker SV, et al. Desmoid tumours in familial adenomatous polyposis. Gut. Mar 1994;35(3):377-81. [Medline].
  14. Lotfi AM, Dozois RR, Gordon H, Hruska LS, Weiland LH, Carryer PW, et al. Mesenteric fibromatosis complicating familial adenomatous polyposis: predisposing factors and results of treatment. Int J Colorectal Dis. 1989;4(1):30-6. [Medline].
  15. Wilcken N, Tattersall MH. Endocrine therapy for desmoid tumors. Cancer. Sep 15 1991;68(6):1384-8. [Medline].
  16. Waddell WR. Treatment of intra-abdominal and abdominal wall desmoid tumors with drugs that affect the metabolism of cyclic 3',5'-adenosine monophosphate. Ann Surg. Mar 1975;181(3):299-302. [Medline].
  17. Dhingra K. Antiestrogens--tamoxifen, SERMs and beyond. Invest New Drugs. 1999;17(3):285-311. [Medline].
  18. Buitendijk S, van de Ven CP, Dumans TG, den Hollander JC, Nowak PJ, Tissing WJ, et al. Pediatric aggressive fibromatosis: a retrospective analysis of 13 patients and review of literature. Cancer. Sep 1 2005;104(5):1090-9. [Medline].
  19. Bhama PK, Chugh R, Baker LH, Doherty GM. Gardner's syndrome in a 40-year-old woman: successful treatment of locally aggressive desmoid tumors with cytotoxic chemotherapy. World J Surg Oncol. Dec 17 2006;4:96. [Medline].
  20. Mendenhall WM, Zlotecki RA, Morris CG, Hochwald SN, Scarborough MT. Aggressive fibromatosis. Am J Clin Oncol. Apr 2005;28(2):211-5. [Medline].
  21. Abdelkader M, Riad M, Williams A. Aggressive fibromatosis of the head and neck (desmoid tumours). J Laryngol Otol. Oct 2001;115(10):772-6. [Medline].
  22. Anna L, Viviana L, Massimo B, Chiara Z. Desmoid tumor of the breast: radiologic appearance with a focus on its magnetic resonance features. Breast J. Jan-Feb 2008;14(1):106-7. [Medline].
  23. Cohen S, Ad-El D, Benjaminov O, Gutman H. Post-traumatic soft tissue tumors: case report and review of the literature a propos a post-traumatic paraspinal desmoid tumor. World J Surg Oncol. Feb 29 2008;6:28. [Medline].
  24. Covotta L, Tesoriere A, Ferrazza P, Di Paola M, Regolo L, Diomedi Camassei F, et al. [Desmoids associated with multiple familial polyposis: description of a clinical case]. G Chir. May 1998;19(5):223-6. [Medline].
  25. Dormans JP, Spiegel D, Meyer J, Asada N, Alman BA, Pill SG, et al. Fibromatoses in childhood: the desmoid/fibromatosis complex. Med Pediatr Oncol. Aug 2001;37(2):126-31. [Medline].
  26. Erguvan-Dogan B, Dempsey PJ, Ayyar G, Gilcrease MZ. Primary desmoid tumor (extraabdominal fibromatosis) of the breast. AJR Am J Roentgenol. Aug 2005;185(2):488-9. [Medline].
  27. Gonatas NK. Extra-abdominal desmoid tumors. Report of six cases. Arch Pathol. Feb 1961;71:214-21. [Medline].
  28. Hamilton L, Blackstein M, Berk T, McLeod RS, Gallinger S, Madlensky L, et al. Chemotherapy for desmoid tumours in association with familial adenomatous polyposis: a report of three cases. Can J Surg. Jun 1996;39(3):247-52. [Medline].
  29. Moon JI, Selvaggi G, Nishida S, Levi DM, Kato T, Ruiz P, et al. Intestinal transplantation for the treatment of neoplastic disease. J Surg Oncol. Dec 15 2005;92(4):284-91. [Medline].
  30. Mungas JE, Platz CE, Block GE. Desmoid tumors of the abdominal wall. Surg Clin North Am. Feb 1976;56(1):207-18. [Medline].
  31. Rai AT, Nguyen TP, Hogg JP, Gabriele FJ. Aggressive fibromatosis of the neck in a patient with Gardner's syndrome. Neuroradiology. Aug 2001;43(8):650-2. [Medline].
  32. Rajesh A, Sandrasegaran K. Mesenteric desmoid mimicking recurrent testicular cancer. Abdom Imaging. Nov-Dec 2005;30(6):777-9. [Medline].
  33. Schwartz RA, Trovato MJ, Lambert PC. The desmoid tumor -- a locally aggressive neoplasm. Cesko-Slovenska Dermatologie. 2007;82:34-8.
  34. Senol M, Ozcan A, Sasmaz S, Ozen S, Ciralik H. Giant vascular eccrine spiradenoma. Int J Dermatol. Mar 1998;37(3):221-3. [Medline].
  35. Taylor LJ. Musculoaponeurotic fibromatosis. A report of 28 cases and review of the literature. Clin Orthop. Nov 1987;(224):294-302. [Medline].
  36. Thuret R, Renaudin K, Leclere J, Battisti S, Bouchot O, Theodore C. Uncommon malignancies: case 3. Paratesticular desmoplastic small round-cell tumor. J Clin Oncol. Sep 1 2005;23(25):6253-5. [Medline].

Desmoid Tumor excerpt

Article Last Updated: May 13, 2008