Desmoid

In clinical practice, along with the term "desmoid", the term "aggressive fibromatosis" is equally used. The following synonyms are used less often: desmoid tumor, juvenile fibromatosis, deep fibromatosis, desmoid fibroma, invasive fibroma, muscular-aponeurotic fibromatosis.

Desmoid (aggressive fibromatosis) is a connective tissue tumor that develops from tendon and fascial-aponeurotic structures.

Formally, desmoid is not considered a malignant neoplasm. As is known, the clinical criteria for tumor malignancy are infiltrative growth and metastasis. Desmoid does not metastasize, but has the ability for local aggressive infiltrative growth with the destruction of basal membranes and fascial sheaths - this is its common property with malignant tumors. At the same time, the potential for invasive growth of desmoid significantly exceeds that of many truly malignant tumors. It is precisely the pronounced ability to invade surrounding tissues that predetermines the high frequency of local relapses of this tumor after radical operations. Such a complex of biological properties determines the position of desmoid on the border of benignity and malignancy and introduces this neoplasm into the sphere of interests of a pediatric oncologist.

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Epidemiology

Due to its rarity, the frequency of desmoid is not determined. This neoplasm can be found in patients from the neonatal period to old age. Among patients, males predominate.

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Histological structure and etiopathogenesis

The source of tumor growth in desmoid is fibrocyte. In its tumor transformation into a desmoid cell, excessive formation of the protein B-catenin plays a key role. Its increased content is noted in all patients. This protein is a regulator of fibrocyte proliferative activity. An increase in the amount of B-catenin may have two unrelated causes.

• One of them is a somatic mutation of the APC gene (adenomatous polyposis coli gene). One of the functions of this gene is the regulation of intracellular B-catenin content. Clinically, somatic mutation of the APC gene manifests itself as Gardner syndrome - familial polyposis of the colon, which has a frequency of 1:7000. Penetrance of the APC gene is 90%. Gardner syndrome is an obligatory precancer of the colon. In 15% of adults diagnosed with aggressive fibromatosis, somatic mutation of the APC gene, localized on 5q22-q23, is detected. In addition, patients with Gardner syndrome are typical of multiple osteomas of the facial bones (frontal, ethmoid, zygomatic, upper and lower jaws), as well as epidermoid cysts and fibromas of the skin.
• The trigger point of the alternative mechanism of tumor fibrocyte transformation is increased expression of the c-sic gene and the associated hyperproduction of PDGF (platelet-derived growth factor). It has been established that increased PDGF levels lead to an increase in B-catenin levels. The established decrease in expression of the RM antioncogene in tumor cells is also important for understanding the biology of desmoid. Of great interest is the indication of the presence of estrogen receptors in the cells of aggressive fibromatosis. Cases of desmoid manifestation during pregnancy and its regression against the background of menopause are described, as well as the development of neoplasms in experiments on mice at the sites of estrogen injections with its subsequent reverse development after the cessation of injections.

In some patients, desmoid develops at the sites of intramuscular injections, injuries, and surgical operations.

Desmoid Symptoms

Desmoid can develop in all areas of the body where connective tissue is present. When localized in the extremities, neoplasms arise exclusively on the flexor surfaces (anterior surfaces of the shoulder and forearm, posterior surfaces of the shin, thigh, gluteal region). The source of tumor growth is always tissue located deep relative to the superficial fascia. This important feature of desmoid also serves as a differential diagnostic sign that allows one to distinguish this neoplasm from other diseases, such as palmar fibromatosis (Dupuytren's contracture). The tumor growth rate is usually slow, while the relapse of desmoid usually reaches the size of the removed neoplasm or exceeds it within several months. Cases of multifocal tumor growth have been noted. In this case, isolated tumor foci are usually detected within the same limb or anatomical region. The frequency of multifocal neoplasms reaches 10%. Desmoid of the gluteal region and thigh may be accompanied by a similar tumor in the pelvic cavity.

Clinically, desmoid appears as a dense, non-replaceable or slightly displaceable tumor located in the thickness of muscles or intimately associated with the muscle mass. In the clinical picture, the determining factors are the presence of a neoplasm mass, pain and symptoms associated with the localization of the tumor. Given the ability of aggressive fibromatosis to local invasion, local symptoms can be associated not only with compression of the organs of a given anatomical region, but also with the growth of a neoplasm into them. The distinction in the clinic between the concepts of "abdominal desmoid" (accounts for 5% of cases) and "extra-abdominal desmoid" has no morphological basis. Such a distinction is caused mainly by the peculiarities of the clinical picture of this tumor with its abdominal location (development of intestinal obstruction), the complexity of surgical treatment in case of neoplasm invasion into the abdominal organs, as well as worse outcomes.

Diagnosis of desmoid

Diagnostics of aggressive fibromatosis is aimed at assessing the local status of the neoplasm, determining the hormonal background and recording the effect of the treatment. Determining the tumor boundaries and its relationship with the vessels is an important task for planning the subsequent operation and is difficult due to aggressive local infiltrative growth. For this purpose, ultrasound, Doppler duplex angioscanning, and magnetic resonance imaging (MRI) should be used. If a single formation is detected, it is necessary to exclude the presence of additional neoplasms in the same anatomical area or limb. In case of desmoid of soft tissues of the thigh and buttock, it is necessary to perform ultrasound of the pelvis in order to exclude tumor growth through the greater sciatic foramen and the presence of a neoplasm component in the pelvis. Radiography of the affected area allows to identify secondary bone changes due to bone compression by the tumor.

MRI can be used to determine the desmoid boundaries most reliably (in 70-80% of cases). The high information content of MRI also allows detecting additional isolated tumor foci in the anatomical area under study in case of multicentric aggressive fibromatosis (the diagnostic capabilities of ultrasound and CT are much weaker in this regard). Performing MRI after surgery allows evaluating its results in comparison with the preoperative MRI picture. However, it should be taken into account that in the early postoperative periods, MRI can make it difficult to differentiate a relapse of a neoplasm from a postoperative cicatricial process.

The possibility of a desmoid connection with the colon cancer gene makes it necessary to conduct colonoscopy and gastroesophageal tract denoscopy in all patients over 10 years of age with desmoid in order to exclude polyps of the gastrointestinal tract. Hormonal background is assessed using a study of the dynamics of the serum estradiol and sex-related globulin (SHBG).

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Mandatory diagnostic tests

• Complete physical examination with assessment of local status
• Clinical blood test
• Clinical urine analysis
• Blood biochemistry (electrolytes, total protein, liver function tests, creatinine, urea, lactate hydrogenase, alkaline phosphatase, phosphorus-calcium metabolism)
• Coulogram
• Ultrasound of the retroperitoneal space
• X-ray of the affected area
• MRI of the affected area
• Ultrasound color duplex scanning of the affected area
• Serum estradiol
• SHBQ (sex-related globulin) blood serum
• FEGDS and OZH in patients over 10 years old
• ECG
• Angiography
• X-ray of the bones in the affected area
• When localized in the area of the anterior abdominal wall and pelvis:
  • excretory urography;
  • cystography

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Desmoid treatment

Treatment of desmoid by surgical method alone proved to be ineffective: 75% of operated patients had multiple local relapses of the neoplasm. The risk of relapse does not depend on gender, localization and number of previous surgical interventions and is associated with aggressive infiltrative growth of desmoid. At the present stage, limiting desmoid treatment by surgical operation alone is considered a mistake.

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Conservative treatment

In adult patients, encouraging results have been obtained when conducting radiotherapy for desmoid (distance y-therapy at a dose of 60 Gy or more), and it is possible to achieve stabilization and even regression of the neoplasm. Attempts to conduct radiotherapy in children have proven unsuccessful due to the risk of skeletal deformation due to premature closure of bone growth zones in the irradiated areas.

Currently, the most promising method of treating desmoid in children is considered to be a combination of radical surgery with long-term (up to 1.5-2 years or more) therapy with cytostatics (low doses of methotrexate and vinblastine) and anti-estrogen drugs (tamoxifen). Drug treatment is carried out before and after surgery.

• The goal of preoperative treatment is to isolate the neoplasm from the surrounding tissues, compact it and reduce its size or stabilize it.
• The goal of postoperative therapy is to prevent recurrent growth of desmoid from microscopic remnants in the bed of the removed tumor.

When diagnosing a relapse of desmoid in patients who have not previously undergone conservative therapy, even if the tumor appears resectable, treatment should begin with chemohormonal therapy.

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Surgical treatment

A necessary requirement for surgical treatment of desmoid is the radical nature of the operation. When desmoid is localized in the soft tissues of the extremities, organ-removing operations (amputations and disarticulations) almost exclude the possibility of local relapse. However, in clinical practice, organ-removing operations are performed only in the absence of strict contraindications to organ-preserving operations (ingrowth of main vessels and nerves, ingrowth into a joint, giant demoid, circularly affecting the limb). Organ-preserving surgical treatment consists in excision of all nodes of the neoplasm within healthy tissues. When desmoid is localized in the soft tissues of the thigh and gluteal region, a serious problem is the sciatic nerve, which can be partially or completely involved in the desmoid; removal of the neoplasm is associated with the risk of postoperative monoparesis of the limb and possible non-radicality due to the impossibility of completely freeing the sciatic nerve from the tumor without cutting it. Similar problems with nerve trunks occur with desmoid in the upper limb.

As a rule, due to the significant volume of tumor nodes, the presence of a pronounced cicatricial process and the lack of intact local tissues after numerous repeated operations, often performed on patients with desmoids due to repeated relapses, a significant problem is the plastic surgery of defects formed after excision of the neoplasm. This problem is especially difficult when the desmoid is localized in the chest and abdomen. In the latter cases, the use of synthetic plastic materials (for example, polypropylene mesh) can be recommended for closing the defects.

What is the prognosis for desmoid?

When conducting combined treatment, including long-term chemo-hormonal therapy and radical surgery, a relapse-free course is observed in 85-90% of patients. Tumors localized in the tissues of the foot and the back of the leg are subject to more frequent relapse. The highest frequency of relapses is noted within 3 years after radical surgery. Due to the lack of ability of desmoid to metastasize, the death of some patients occurs with neoplasms resistant to conservative therapy, in the case of their progression with compression or invasion of vital organs - mainly with localizations in the head and neck, chest and with abdominal location of the tumor.