Desmoid

In clinical practice, along with the term "desmoid", the term "aggressive fibromatosis" is equally used. Less commonly used are the following synonyms: desmoid tumor, juvenile fibromatosis, deep fibromatosis, desmoid fibroids, invasive fibroid, muscular aponeurotic fibromatosis.

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

Formally, the desmoid is not considered a malignant neoplasm. As is known, infiltrative growth and metastasis serve as clinical criteria for tumor malignancy. Desmoid does not metastasize, however, it has the ability to local aggressive infiltrative growth with destruction of basal membranes and fascial cases - this is its common property with malignant tumors. At the same time, the potential of invasive desmoid growth significantly exceeds that of many truly malignant tumors. It is the pronounced ability to invade surrounding tissues that determines the high incidence of local recurrences of this tumor after radical operations. Such a complex of biological properties determines the position of the desmoid at the border of good quality and malignancy and introduces this neoplasm into the sphere of interests of the children's oncologist.

[1], [2], [3]

Epidemiology

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

[4], [5], [6], [7], [8]

Histological structure and etiopathogenesis

The source of tumor growth with desmoid is fibrocyte. In its tumor transformation, the excessive formation of the B-catenin protein plays a key role in the desmoid cell. Its elevated level is noted in all patients. This protein is a regulator of proliferative activity of fibroblasts. An increase in the amount of 6-catenin can have two unrelated causes.

• One of them is the somatic mutation of the APC gene (adenomatous polyposis gene of the large intestine). One of the functions of this gene is the regulation of intracellular content of B-catenin. Clinically, the somatic mutation of the APC gene is manifested by Gardner's syndrome - the family polyposis of the large intestine, which has a frequency of 1: 7000. Penetration of the APC gene is 90%. Gardner's syndrome is thawed with the obligate premalignant of the large intestine. In 15% of adults with diagnosed aggressive fibromatosis, a somatic mutation of the APC gene localized to 5q22-q23 is detected. In addition, multiple osteomas of the facial bones (frontal, latticed, zygomatic, upper and lower jaws), as well as epidermoid cysts and fibroids of the skin are typical for patients with Gardner's syndrome.
• The starting point of the alternative mechanism of tumor cell transfection is the increased expression of the c-sic gene and the associated hyperproduction of PDGF (platelet-derived growth factor). It was found that an increased content of PDGF leads to an increase in the content of B-catenin. Important for understanding the biology of the desmoid is also the established reduction in the expression of the RM antiochigen in tumor cells. Of great interest is the indication of the presence in the cells of aggressive fibromatosis receptors for estrogens. Describes cases of manifestation of desmoid during pregnancy and its regression against the background of menopause, as well as the development of new formation in experiments on mice at the sites of injection of estrogens with its subsequent reverse development after the termination of injections.

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

Symptoms of desmoid

Desmoid can develop in all areas of the body, where the connective tissue is represented. With localization in the limbs, neoplasms occur exclusively on the flexural surfaces (the forelegs of the shoulder and forearms, the posterior surfaces of the shin, hips, gluteal region). The source of tumor growth is always tissues located deep in relation to the superficial fascia. This important feature of the desmoid serves simultaneously as a differential diagnostic feature that distinguishes this neoplasm from other diseases, for example, from palmar fibromatosis (Dupuytren's contracture). The growth rate of the tumor is usually slow, with the desmoid relapse usually reaching the size of the removed lesion or exceeding them within a few months. There have been cases of multifocal tumor growth. However, isolated isolated tumor lesions are usually detected within the same limb or anatomical region. The frequency of multifocal neoplasms reaches 10%. The desmoid of the gluteal region and thigh may be accompanied by a similar tumor in the pelvic cavity.

Clinically, the desmoid appears as a dense, non-replaceable or small-displacement tumor located in the muscle mass or intimately associated with the muscle mass. In the clinical picture, the determining factors are the presence of a mass of neoplasm, 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 the compression of organs of this anatomical region, but also with the germination in them of the neoplasm. The distinction in the clinic of the concepts "abdominal desmoid" (is 5% of cases) and "extra-abdominal desmoid" does not have a morphological base. This distinction is caused. Mainly, the peculiarities of the clinical picture of this tumor with its abdominal location (the development of intestinal obstruction), the complexity of surgical treatment for invasion of the neoplasm into the abdominal cavity organs, and also by the worst outcomes.

Diagnosis of desmoid

Diagnosis of aggressive fibromatosis is aimed at assessing the local status of the tumor, determining the hormonal background and recording the effect of the treatment. Determining the boundaries of the tumor and its relationship with the vessels is important for the planning of subsequent surgery and a difficult task, which is associated with aggressive local infiltrative growth. To this end, you should use ultrasound. Doppler duplex angioscanning. Magnetic resonance imaging (MRI). When a single formation is detected, it is necessary to exclude the presence of additional neoplasms in the same anatomical zone or limb. With desmoid soft tissues of the hip and buttock, it is necessary to perform ultrasound of the small pelvis in order to exclude the germination of the tumor through the large sciatic foramen and the presence of the tumor component in the small pelvis. Radiography of the affected area allows us to identify secondary bone changes due to compression of the bones with a tumor.

With the help of MRI, the desmoid border can be established most reliably (in 70-80% of cases). High information content of MRI also allows to identify additional isolated tumor lesions in the anatomical region under investigation with multicentric aggressive fibromatosis (the diagnostic capabilities of ultrasound and RCT in this respect are much weaker). Performing MRI after the operation allows you to evaluate its result in comparison with the picture of preoperative MRI. However, it should be borne in mind that at early postoperative periods with MRI it is difficult to differentiate relapse of the neoplasm from the postoperative cicatricial process.

The possibility of communication of the desmoid with the colon cancer gene makes it necessary for all patients older than 10 years with desmoid colonoscopy and gasgro-esophagoduodenoscopy to exclude polyps of the gastrointestinal tract. Estimation of the hormonal background is carried out with the help of a study in the dynamics of serum levels of estradiol and sex-linked globulin (SHBG).

[9], [10], [11], [12], [13], [14], [15]

Compulsory diagnostic tests

• Complete physical examination with assessment of local status
• Clinical blood test
• Clinical analysis of urine
• Biochemical blood test (electrolytes, total protein, liver tests, creatinine, urea, lactatehydrogenase, alkaline phosphatase, phosphoric calcium metabolism)
• Coalgram
• Ultrasound of the retroperitoneal space
• Radiography of the affected area
• MRI of the affected area
• Ultrasound color duplex scanning of the affected area
• Serum oestradiol
• SHBQ (sex-linked globulin) blood serum
• FEGDS and OZS in patients older than 10 years
• ECG
• Angiography
• Radiography of the bones of the affected area
• When localized in the area of the anterior abdominal wall and small pelvis:
  • excretory urography;
  • cystography

[16], [17], [18], [19], [20], [21], [22], [23],

Desmoid treatment

The treatment of desmoid only by a surgical method proved to be ineffective: in 75% of operated patients there were multiple local recurrences of the neoplasm. The risk of relapse does not depend on sex, location and number of previous surgical interventions and is associated with aggressive infiltrative growth of the desmoid. At the present stage, limiting the treatment of desmoid by surgery alone is considered a mistake.

[24], [25], [26], [27], [28]

Conservative treatment

In adult patients, encouraging results were obtained in the treatment of radiation therapy with desmoid (remote gamma therapy at a dose of 60 Gy and more), while stabilization and even regression of the tumor can be achieved. Attempts to conduct radiation therapy in children proved untenable because of the risk of deformation of the skeleton due to premature closure of bone growth zones in irradiated areas.

At present, the most promising method for treating desmoid in children is the combination of a radical operation with long-term (up to 1.5-2 years or more) cytostatic therapy (low doses of methotrexate and vinblastine) and anti-estrogen drugs (tamoxifen). Medicinal treatment is performed before and after the operation.

• The purpose of preoperative treatment is the delimitation of the neoplasm from surrounding tissues, its densification and reduction in size or their stabilization.
• The goal of postoperative therapy is the prevention of recurrent desmoid growth from microscopic remains in the bed of a distant tumor.

In the diagnosis of desmoid relapse in patients who have not previously had conservative therapy, even with apparent resectability of the neoplasm, treatment should begin with chemo-hormonal therapy.

[29], [30], [31], [32], [33], [34], [35],

Surgery

A necessary requirement for surgical treatment of the desmoid is the radical nature of the operation. When the desmoid is localized in the soft tissues of the extremities, organo-carrying out operations (amputations and exarticulations) almost exclude the possibility of local recurrence. However, in clinical practice, organ-carrying operations are performed only in the absence of strict contraindications to organ-preserving operations (germination of the main vessels and nerves, ingrowth into the joint, a giant demoid, circularly affecting the limb). Organ-preserving surgical treatment consists in excision of all nodes of the tumor in the limits of healthy tissues. When the desmoid is localized in the soft tissues of the thigh and the gluteal region, a sciatic nerve is a serious problem, which may be partially or completely involved in the desmoid; removal of the neoplasm involves a risk of postoperative limb monopaper and possible non-radicality due to the inability to completely free the sciatic nerve from the tumor without its crossing. Similar problems with nerve trunks arise 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 in patients with desmoids for repeated relapses, a significant problem is the plastic of defects formed after excision of the tumor. This problem is particularly complex in the localization of the desmoid in the region of the chest and abdomen. In the latter cases, the use of synthetic plastic materials (for example, polypropylene mesh) can be recommended to cover defects.

What is the prognosis of a desmoid?

When carrying out combined treatment, including prolonged chemo-hormonal therapy and radical surgery, a relapse-free current is observed in 85-90% of patients. Tumors located in the tissues of the foot and the posterior surface of the tibia are more likely to recur. The highest frequency of recurrence was observed within 3 years after radical surgery. In connection with the lack of the ability of the desmoid to metastasize, the death of some patients occurs in neoplasms resistant to conservative therapy, in case of their progression with compression or germination of vital organs - mainly in the localization of the head and neck, chest and abdominal location of the tumor.