Brenner tumor is a fibroepithelial neoplasm of the ovary, characterized by a rocky density and a tendency to hormonal activity, often accompanied by polyserositis. The disease does not have an acute onset and a clear picture. As neoplasia grows, there may be signs of epigastric discomfort, pelvic pain, constipation, abdominal enlargement, difficulty breathing, weakness and decreased ability to work. Hormone–producing tumors have a feminizing, less often – masculinizing effect. The diagnosis is established on the basis of the results of a clinical examination, visualizing research methods. Surgical or complex treatment depends on the nature of the pathology.
ICD 10
D27 C56
General information
Brenner tumor (mucoid fibroepithelioma) is a transitional cell ovarian neoplasia, rarely registered in practical gynecology, consisting of elements of stroma and epithelium. The disease is named after the German pathologist Brenner, who first described it in 1907 as a “follicular oophoroma”. Neoplasm can develop at any age, starting from early childhood, but it is more common in women over fifty years of age. The proportion of mucoid fibroepithelioma is 0.5-2% in the structure of all ovarian neoplasms, in 95-98% of cases the tumor is benign in nature. In 93-95% of patients, one ovary is affected, in 30% of cases it is combined with other epithelial ovarian neoplasms, including those located contralterally.
Causes
The etiology of Brenner tumor, like the vast majority of other neoplasms, remains unknown. The most significant cause is considered to be a prolonged state of absolute or relative hyperestrogenism, which arose due to various (natural, associated with disorders of neuroendocrine and immune regulation) circumstances. Risk factors are similar to those for other (excluding hereditary ovarian cancer) ovarian neoplasia:
- The specifics of the anamnesis of childbearing function. The probability of developing ovarian fibroepithelioma increases the absence of childbirth, a long (over 35 years) reproductive period, too early (up to 19 years) or late (after 35) term of the first birth, short-term (less than six months) lactation, abortions.
- Diseases and injuries of the genitals. Chronic inflammation or multiple acute reinfections of the uterine appendages create a premorbid background for tumor cell transformation. The adhesive process, the operations performed on the pelvic organs worsen the nutrition of the ovarian tissues, which can also contribute to the appearance of neoplasms.
- Endocrine and metabolic pathologies. Disorders of reproductive and energy homeostasis (especially in combination) significantly increase the risk of neoplasia of organs and tissues rich in hormone receptors. In the development of ovarian tumors, the role of female infertility of endocrine genesis is especially great. The incidence is increased in women suffering from diabetes mellitus, metabolic syndrome, dysfunction of the ovaries, pituitary gland, thyroid gland and adrenal glands.
- Taking medications. The formation of an ovarian neoplasm can provoke the use of high-dose combined oral contraceptives, as well as estrogens as part of replacement therapy in peri- and postmenopausal.
Predisposing conditions for the development of a tumor create severe prolonged infections, intoxication, excessive consumption of saturated fatty acids and prolonged stress. In young girls, fibroepithelioma can be a consequence of frequent colds, the use of talc containing asbestos particles for the toilet of the perineum in infancy.
Pathogenesis
The pathogenesis of the neoplasm is still unclear. It is assumed that the source of neoplasia is the integumentary coelomic epithelium of the ovary or clusters of cells that resemble the urothelium (Waldhard’s nest). The progression of the tumor to invasive (malignant) occurs gradually in the process of malignancy of benign formation. Exposure to adverse factors leads to mutation of the PIK3CA gene, triggers a metaplastic process, as a result of which the coelomic epithelium and Waldhard nodules are transformed into transitional cellular (phenotypically resembling the urothelium – the mucous lining of the bladder) and glandular epithelium. Malignant Brenner tumors belong to ovarian carcinomas of the first type (according to the dualistic theory of the pathogenesis of ovarian cancer) – long-term, having a low malignant potential.
The neoplasm is represented by a solid, cystic or cystic-solid node of increased density, the cysts are filled with mucous contents. In benign neoplasias, the fibrous component usually prevails, in malignant neoplasias, the epithelial component. The diameter varies from small (up to 5 cm), characteristic of benign formations, to large (10-20 cm), observed in malignant tumors. Sometimes fibroepitheliomas reach gigantic sizes (up to 30 cm). The development of Meigs syndrome is typical. Estrogen-producing forms are almost always combined with hyperplastic processes of the endometrium and mammary glands.
Classification
The most important prognostic value is the histological characteristics of the neoplasm: the presence or absence of invasive growth, the level of atypia of cells, a decrease in their differentiation. Taking into account these criteria, there are three forms of Brenner tumor that require a different therapeutic approach (WHO publication, fourth edition of the classification of tumors of the female reproductive system):
- Benign. Characterized by proliferation without atypia of cells. Macroscopically, a clear separation from neighboring tissues, a smooth or lobular surface, and calcification of the stroma are revealed.
- Borderline. They have a small malignant potential, are prone to proliferative growth and cellular atypia, but without germination into neighboring structures. Formed by single-chamber or multi-chamber cysts with solid papillary inclusions. Borderline fibroepitheliomas, unlike serous and mucinous atypical proliferating neoplasms, are not prone to metastasis.
- Malignant. They are characterized by a decrease in cellular differentiation, uncontrolled growth with germination and destruction of neighboring structures. Malignant fibroepitheliomas can be both cystic and solid formations with pronounced stroma fibrosis.
In addition, borderline and malignant neoplasia are usually distinguished by stages (FIGO classification) and degree of prevalence (international classification TNM). The first stage (TNM – T1N0M0 compliance) is characterized by damage to the ovaries only; the second (T2N0M0) – spread to the peritoneum and pelvic organs; the third (T3N0M0 or T1-3N1M0) – damage to regional lymph nodes, liver capsules and spleen; the fourth (T1-3N0-1M1) – involvement of distant organs, peripheral lymph nodes.
Symptoms
Small neoplasms are more often asymptomatic, are detected accidentally during instrumental examination or surgical intervention for another disease. There may be pain in the lower abdomen – dull, pulling, unilateral (from the side of the lesion). If the tumor has estrogenic activity, menorrhagia and metrorrhagia may occur in patients of reproductive age, in girls – premature puberty of the isosexual type (early appearance of secondary sexual characteristics, menstruation). In postmenopausal women, there is a resumption of menstrual-like bloody discharge from the genital tract, a youthful appearance, an increase in libido.
Androgen–producing tumors are characterized by amenorrhea, oligorrhea, infertility, virilization – hairiness in the chin, cheeks, chest, limbs and midline of the abdomen, diamond-shaped pubic hair, coarsening of the voice, atrophy or underdevelopment (in youth) of the mammary glands, hypertrophy of the clitoris. Girls have delayed puberty. Polyserositis (Meigs triad) can develop against the background of microscopic neoplasia and is manifested by weakness, fatigue, difficulty breathing, palpitations.
Sometimes, even with severe ascites or large tumors, the patient may complain only of an increase in the abdomen, but large neoplasms are often accompanied by symptoms of compression of the gastrointestinal tract – pain in the navel, epigastric region, a feeling of overflow, abdominal distension after eating, bloating, belching, nausea, vomiting, constipation. Compression of the urinary tract leads to pollakiuria, difficulty urinating.
Complications
Fibroepitheliomas, like other ovarian neoplasms, can be complicated by leg twisting with subsequent ischemia and tissue necrosis – a condition requiring emergency surgery. With large neoplasias and Meigs syndrome, violations of the activity of vital organs are observed, leading to severe cardiovascular and respiratory insufficiency. The most formidable complication of Brenner tumor is associated with its malignancy. Malignant forms in 50% of cases are accompanied by metastases to the lymph nodes, peritoneum and distant organs – liver, lungs, bones and brain. Although benign ovarian neoplasia itself is rarely malignized, its hormonal activity in 20% of patients provokes the development of carcinoma of the uterine body, less often of the mammary gland.
Diagnostics
Diagnosis of mucoid fibroepithelioma is difficult due to its low availability, the absence of pathognomonic symptoms, the specifics of the microscopic structure – stroma fibrosis, complicating the detection of microinvasive cancer. The pathology is differentiated with metastatic carcinoma originating from the bladder, uterine fibroids, other ovarian neoplasms (primarily with more aggressive non-Brenner transitional cell carcinoma), inflammatory diseases of the appendages and appendicitis. The examination is conducted under the guidance of a gynecologist or oncogynecologist. The diagnostic program includes:
- Physical examination. Analysis of the patient’s complaints, general and gynecological examination make it possible to suspect a tumor based on subjective and objective signs of Meigs syndrome, hyperestrogenism or hyperandrogenism. A sufficiently large neoplasia can be detected and differentiated from ascites by palpation.
- Introscopic methods. The main method of instrumental diagnostics is ultrasound of the pelvic organs, which allows detecting even small formations and suggesting the presence of a Brenner tumor by characteristic echographic signs. To clarify the diagnosis, CT and MRI of the pelvis can also be prescribed.
The diagnosis is verified during surgery based on the results of an urgent histological examination of the drug of a remote neoplasm. Prior to surgery, a biopsy is not performed in order to avoid dissemination of the process in the case of a borderline or malignant nature of the tumor.
Treatment of Brenner tumor
Since neoplasia is rare and little has been studied, there is no single tactic for the treatment of pathology. The main method is surgery, the volume of which depends on the histological type and prevalence of the neoplasm. For benign tumors, ovarian resection or unilateral adnexectomy is sufficient. With borderline and microinvasive malignant neoplasia in young patients who want to preserve fertility, unilateral adnexectomy can be performed with the condition of subsequent careful observation, however, extirpation of the uterus with appendages, supplemented by omentectomy, is a more reliable method.
Benign and borderline tumors are treated only promptly. In the case of the spread of the malignant process to the peritoneum, lymph nodes and distant organs, radiation and chemotherapy can additionally be prescribed, but there are no uniform protocols, and the expediency and effectiveness of the use of these techniques in one case or another remains a subject of debate to date.
Prognosis and prevention
The prognosis of benign and borderline Brenner tumors is favorable, the five-year survival rate is approaching 100%, however, borderline neoplasia often recurs, and the recurrent neoplasm may be malignant. In the case of a malignant lesion limited to the ovaries, 88% of patients live for five or more years after treatment, the spread of the tumor process leads to a worsening of the prognosis.
The main measures of primary prevention are timely treatment of diseases of the female genital organs, correction of hormonal disorders, the fight against obesity, a balanced diet, where the bulk of fats should come from products rich in polyunsaturated fatty acids (fatty varieties of marine fish, nuts, vegetable oils). Secondary prevention consists in dispensary gynecological observation of women suffering from infertility and metabolic and endocrine pathologies, with the aim of early detection of the tumor and lifelong observation by an oncogynecologist of patients treated for borderline and malignant neoplasia.
