Aggressive fibromatosis

You can help expand this article with text translated from the corresponding article in Polish. (August 2023) Click [show] for important translation instructions. View a machine-translated version of the Polish article. Machine translation, like DeepL or Google Translate, is a useful starting point for translations, but translators must revise errors as necessary and confirm that the translation is accurate, rather than simply copy-pasting machine-translated text into the English Wikipedia. Do not translate text that appears unreliable or low-quality. If possible, verify the text with references provided in the foreign-language article. You must provide copyright attribution in the edit summary accompanying your translation by providing an interlanguage link to the source of your translation. A model attribution edit summary is Content in this edit is translated from the existing Polish Wikipedia article at [[:pl:Guz desmoidalny]]; see its history for attribution. You may also add the template {{Translated|pl|Guz desmoidalny}} to the talk page. For more guidance, see Wikipedia:Translation.

Aggressive fibromatosis or desmoid tumor is a

The World Health Organization reclassified desmoid tumors (termed desmoid-type fibromatosis) as a specific type of tumor in the category of intermediate (locally aggressive) fibroblastic and myofibroblastic tumors.^[4]

Histologically they resemble very low-grade fibrosarcomas,^[5] but they are very locally aggressive and tend to recur even after complete resection. The condition is "characterized by a variable and often unpredictable clinical course."^[2] There is a tendency for recurrence in the setting of prior surgery; in one study, two-thirds of patients with desmoid tumors had a history of prior abdominal surgery.^[6] The condition can be chronic and may be debilitating.^[7]

History and etymology

The condition was first described in 1832 by

The majority of cases are sporadic, most of which – 85% – involve a CTNNB1 mutation.[14] Of these, "the three distinct mutations identified are 41A, 45F, and 45. Mutation 45F is associated with a high risk of recurrence."^[1] APC mutations affect FAP patients and make up a smaller percentage, 10–15%, of sporadic cases.^[14]

The disease has a tendency to occur during and after pregnancy and in exposure to higher

Risk factors for desmoid disease amongst FAP patients include female sex, a 3' APC mutation, a positive family history, and a history of previous abdominal surgery.[17]

Occurrence

The incidence of desmoid tumors is 5–6 per million per year;^[2] they constitute 0.03% of tumors and less than 3% of soft-tissue tumors. The primary age range is 15–60, with a peak between 30 and 40 years old; it is 2–3 times more common in females than males.^[1][8][18] A 2012 retrospective multi-institutional analysis of 211 patients found a median age of 36 and a 68% female prevalence.^[19] Children do not have the same sex disparity and are most commonly affected around 15 or 16 years old.^[20]

Diagnosis

Diagnosis

A biopsy is always indicated as the definitive method to determine the nature of the tumor.^[1] Diagnosis may be difficult in part due to the use of core needle biopsy over open biopsy.^[21]

Similarities among bland spindle-cell lesions lead to a large number of possibilities in diagnosis, including fibroblastic sarcomas,

Desmoid tumors can occur almost anywhere in the body.

One analysis has shown a median tumor size of 7.5 cm (3.0 in).[19] Though metastasis cannot occur, the tumors may in some cases be multifocal, with several located in the same body part.^[28]

A 3' APC mutation is the most significant risk factor for intra-abdominal desmoid development amongst FAP patients.^[29] FAP patients presenting with an abdominal wall desmoid pre-operatively are at an increased risk of developing an intra-abdominal desmoid post-operatively.^[30]

Desmoid tumors of the breast are rare, constituting 4% of extra-abdominal cases and 0.2% of breast tumors.

Desmoid tumors may occur in the head and neck, more commonly among children, and tend to be more aggressive than in other extra-abdominal locations. These tumors constitute up to 23% of extra-abdominal cases.[16]

Staging

There is no standard staging system; desmoid tumors do not fall under cancer staging systems as they do not metastasize.^[31]

Disease course, treatment, and impacts

Disease course

The condition is "characterized by a variable and often unpredictable clinical course",^[2] often considered chronic,^[13] and with the potential to be debilitating.^[7] Death, however, is uncommon.^[20][18] Tumors may grow, regress, or remain stable:^[24]

• Resolution without treatment (10–28%)
• Progression and resolution (30%)
• Stable (50%)
• Rapid progression (10%)

Management of these lesions is complex, the main problem being the high rates of recurrence particularly in FAP-associated disease. Recurrence rates in general vary from 19 to 77 percent.^[16] Conversely, for intra-abdominal fibromatosis without evidence of FAP, although extensive surgery may still be required for local symptoms, the risk of recurrence appears to be lower.^[33]

Treatment, trials, and management

Patients with desmoid tumors should be evaluated by a multi-disciplinary team of surgeons, medical oncologists, radiation oncologists, and geneticists. They should be treated by desmoid tumor experts, typically soft-tissue sarcoma specialists.^[34][35][36] The 2020 global consensus paper on desmoid treatment notes, "Clearly, patients need to be referred to centers with experience in [desmoid tumors (DT)] to minimize the risk of active surveillance and avoid unnecessarily debilitating or mutilating surgery when possibly needed. Surgery by surgeons without significant experience in the management of DT is strongly discouraged."^[37]

Nirogacestat, a selective gamma secretase inhibitor, was approved for medical use in the United States in November 2023.^[38] It is the first medication approved by the US Food and Drug Administration (FDA) for the treatment of desmoid tumors.^[38][39]

A Phase 2/3 trial on AL102, another selective gamma secretase inhibitor, is also ongoing as of 2023^[update], having begun in 2021.^[40] The drug was granted orphan drug status in 2023.^[41]

Surgery was the standard treatment for desmoid tumors up to the early 2000s.^[2][42] Due to the condition's unpredictability, more conservative management such as watchful waiting has since become common due to the potential impacts of surgical interventions. As of the 2010s, there is a "clear consensus"^[2] from medical groups, including the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group and the European Society for Medical Oncology: immediate surgical resection is no longer the first-line treatment, particularly in asymptomatic patients.^[13][26][2] Complete removal is not always possible due to the tumors' infiltrative nature and tendril-like growth.^[15]

In more advanced, recurring, or rapidly progressing cases, treatment may consist of complete surgical removal, radiation therapy, antiestrogens (e.g. tamoxifen), nonsteroidal anti-inflammatory drugs (NSAIDs), chemotherapy, or ablation (cold, heat, ultrasound). Treatment with oral tyrosine kinase inhibitor drugs (e.g. imatinib, sorafenib, pazopanib) shows promising success rates.^[43][28][44] Radiation therapy after surgery may improve outcomes.^[15] Despite the condition's hormonal link, anti-hormonal therapies only appear to work in a small subset of patients.^[15]

Intestinal transplant is a treatment option for those patients with complicated desmoid tumor, such as those involving the mesenteric root, or those with intestinal failure resulting from the tumor or prior interventions.^[45]

One review summarizes the disease's impact on patients stating, "the burden of [desmoid tumors] is disproportionately borne by women of childbearing and working age, and because it is associated with low mortality and a relatively young patient population, it typically continues for decades."[18]

Symptoms vary significantly as they are dependent on the tumor's location and effects on the surrounding structures.^[18] Though desmoid tumors do not metastasize, their invasiveness may lead to pain and loss of function or restricted movement. Chronic pain is an issue for as many as 63% of patients and may be debilitating and lead to reliance on pain medication.^[24][18] Pressure on vital organs or deformity may occur.^[24][15] Rarely, amputation may be necessary due to injury caused by the tumor or its treatments.^[18]

Tumors may be misdiagnosed (30–40%)^[24] due to their rarity and a lack of knowledge; patients may initially be given inappropriate treatment or poor prognoses due to misdiagnosis with conditions such as malignant sarcoma.^[47][48] Patients may need to visit multiple healthcare providers to receive a diagnosis, causing delay in care. Patients may experience issues including anxiety, fatigue, or trouble sleeping; despite the increased survival rate, their level of emotional distress has been compared to that of cancer patients, including "patients with sarcoma, also a malignant connective tissue disorder".^[24][48][18] A lack of knowledge by healthcare providers and of information available to patients and others have also been cited as issues.^[47]

The economic burden of treatment may be significant, with surgery costs estimated at $50,000 in 2022 US dollars.^[42]

Specific instruments to determine health-related quality of life impacts for desmoid patients, the Gounder/Desmoid Tumor Research Foundation (DTRF) Desmoid Symptom/Impact Scale (GODDESS) and the Desmoid-type fibromatosis Quality of Life Questionnaire (DTF-QOL) have been developed and validated.^[24]

ICD-10-CM diagnosis codes

Few rare diseases have a specific code in the International Classification of Diseases.^[49] As of October 2023, specific codes for desmoid tumors will be included in the ICD-10-CM, the United States' diagnosis code system, after a request from the Desmoid Tumor Research Foundation.^[50] A subcategory of D48.1, Neoplasm of uncertain behavior of connective and other soft tissue, has been created with more specific codes:^[49]

• D48.11: Desmoid tumor
  • D48.110: Desmoid tumor of head and neck
  • D48.111: Desmoid tumor of chest wall
  • D48.112: Desmoid tumor, intrathoracic
  • D48.113: Desmoid tumor of abdominal wall
  • D48.114: Desmoid tumor, intraabdominal
    • Desmoid tumor of pelvic cavity
    • Desmoid tumor, peritoneal, retroperitoneal
  • D48.115: Desmoid tumor of upper extremity and shoulder girdle
  • D48.116: Desmoid tumor of lower extremity and pelvic girdle
    • Desmoid tumor of buttock
  • D48.117: Desmoid tumor of back
  • D48.118: Desmoid tumor of other site
  • D48.119: Desmoid tumor of unspecified site

Notable patients

• Dave Dravecky, American baseball pitcher and motivational speaker^[51][52]
• Kevin Reilly, American football player^[53]

In animals

Desmoid tumors occur in dogs, primarily on the head, and more infrequently in horses and cats.^[54] A case has also been observed in a goat.^[55]

References