Borderline ovarian tumor are neoplasms of female gonads with low malignant potential, occupying an intermediate position between malignant and benign neoplasms. They do not have pathognomonic symptoms, most often patients complain of pelvic pain, decreased appetite, nausea and bloating. Diagnosis includes gynecological examination, ultrasound and determination of the titer level of tumor markers, the final diagnosis is established after surgery. The treatment is surgical. Depending on the age of the patient and the stage of the process, removal of a neoplasm or an affected ovary, bilateral adnexectomy, hysterovariectomy is performed.
Borderline ovarian tumor (atypical proliferating tumors) are epithelial neoplasms characterized by pronounced proliferation, cellular and nuclear atypia inherent in cancer, but without signs of destructive stroma invasion and solid growth. These tumor formations are characterized by recurrence, extraovarial spread, most often affecting the peritoneum, rarely (in 7-29% of cases) – lymph nodes, extremely rarely – distant organs. “Metastases” of borderline tumors are called implants. Implants can be invasive (with signs of malignancy) and non-invasive. Among borderline neoplasms, serous (50-55%) and mucinous (40-45%) neoplasms are most common. Borderline tumors account for 10-15% in the structure of all ovarian neoplasias and are most often found in women 30-50 years old.
Causes of borderline ovarian tumor
The etiology of borderline ovarian tumor is unknown. It is assumed that the main causes of the development of the disease are an increase in the number of ovulatory cycles during the life period, a violation of the secretion of gonadotropin hormones by the pituitary gland and sex – ovaries, disorders of immune regulation. In contrast to the causes, the risk factors of pathology have been sufficiently studied, including:
- Features of reproductive anamnesis. The probability of ovarian borderline neoplasia significantly increases infertility – this condition is present in 30-35% of women at the time of diagnosis of neoplasia. Other risk factors include unrealized reproductive function, shortening of lactation (less than six months), early (up to 11 years) menarche, later (after 55 years) onset of postmenopause, early (up to 19 years) or the late (after 35 years) age of the first pregnancy, abortions.
- Pathology of the genitals. The risk of atypical proliferating endometrioid tumor significantly increases ovarian endometriosis. Gynecological operations for uterine fibroids, ectopic pregnancy and purulent inflammation of the appendages can provoke the development of neoplasms due to ovarian trophic disorders.
- Endocrine disorders. The occurrence of ovarian tumors is caused by pathologies of the endocrine glands, metabolic disorders and nervous regulation, taking medications. Risk factors: hyperandrogenism of any genesis, pituitary adenoma, adrenal tumors, hypo- and hyperthyroidism, severe damage to the liver parenchyma, estrogen replacement therapy during menopause, taking contraceptives with a high content of estrogens.
- Infections. It is believed that the probability of tumor occurrence correlates with the number of transferred adnexitis, chronic inflammation, especially caused by specific (sexually transmitted) infectious agents. An important role is assigned to intracellular microorganisms – pathogenic types of mycoplasma and ureaplasma.
Predisposing conditions include diseases and conditions that weaken the immune response (diabetes mellitus, severe infections, poisoning), obesity (including those that occurred in childhood and adolescence), increased fat intake (especially at a young age). The appearance of tumors potentiates long-term psychoemotional stress.
The pathogenetic mechanisms of the disease have been poorly studied. Borderline neoplasms, like other tumors, begin to develop due to a violation of the regulation of the cell cycle. The effect of stimulating factors (gonadotropins, estrogens, pro-inflammatory cytokines) triggers the process of epithelial proliferation. Abnormally long period of stimulation and disturbances of the apoptosis process cause the development of hyperplasia. The probability of atypia of rapidly multiplying cells increases, the outcome is the appearance of a tumor. Why in some cases benign and borderline tumors are formed, which are not prone to malignancy for a long time, and in others – cancer, is still unknown.
The nature of the implants remains in question: some clinicians consider them to be metastases of borderline neoplasia, while others consider them to be independent tumor foci developed from multifocus rudiments. Most studies indicate their molecular and genetic similarity to ovarian tumors, but in some cases significant differences are revealed. An interesting fact is that with the maximum reduction of an ovarian tumor, peritoneal implants often undergo complete regression.
Taking into account the histological type , the following types of borderline neoplasia are distinguished: serous (atypical proliferating serous tumor, noninvasive highly differentiated serous carcinoma), mucinous, endometrioid, light cell, Brenner tumor, mixed. Serous tumors are more often observed in women of reproductive age, with a frequency of 35-45% they affect both ovaries, in 30% they spread to the peritoneum, in a quarter of cases invasive implants are found. With mucinous type of peritoneal lesion, the occurrence of implants is 10%. Other histotypes are characterized by localized unilateral lesion.
The classification of atypical hyperplasia by the degree of prevalence and stages of the tumor process is similar to the staging of invasive cancer, the current (2014 revision) version of FIGO is as follows:
Stage I (T1N0M0). The tumor process is limited to the ovaries.
- Stage IA (T1aN0M0). The primary focus is located within one ovary. There is no damage to its capsule, surface growths, malignant cells in flushes from the peritoneum.
- Stage IB (T1bN0M0). Both ovaries are involved in the process (the lesion criteria are similar to stage IA).
- Stage IC (T1cN0M0). It is characterized by a lesion of one or both ovaries with damage to their capsule, the presence of growths on the surface of the ovary or fallopian tube, tumor cells in flushes from the abdominal cavity.
Stage II (T2N0M0). The tumor spreads to the pelvic organs.
- Stage IIA (T2aN0M0). Metastasis to the uterus, fallopian tube (tubes).
- Stage IIB (T2bN0M0). Other pelvic structures are affected.
Stage III (T3N0M0 or T1-3N1M0). The tumor affects the peritoneum outside the pelvis or (and) regional lymph nodes (morphological confirmation is necessary).
- Stage IIIA (T1-3N0-1M0). It is characterized by the presence of microscopic implants in retroperitoneal lymph nodes and peritoneum.
- Stage IIIB (T3bN0M0 or T3bN1M0). Macrometastases in the peritoneal tissue < 2 cm in the largest size with the presence or absence of metastases in the lymph nodes.
- Stage IIIC (T3cN0M0 or T3cN1M0). Peritoneal implants >2 cm with (or without) lymph node involvement, as well as liver and spleen capsules without parenchyma involvement.
Stage IV (T1-3N0-1M1). There are metastases in distant organs.
- Stage IVA (T1-3N0-1M1a). Pleural effusion with tumor cells.
- Stage IVB (T1-3N0-1M1b). Implants that affect distant organs and peripheral lymph nodes.
The symptoms of the disease are diverse and variable. Most often, pain syndrome is registered – dull pulling pains in the lower abdomen and navel area, radiating into the hips, lower legs and lower back. Common symptoms include weakness, malaise, weight loss, fatigue, loss of performance, sleep disturbance and fever. On the part of the gastrointestinal tract, nausea, unpleasant sensations in the mouth, a feeling of overflow of the stomach when consuming even small amounts of food, belching, vomiting, constipation are observed. On the part of the urinary system, with the growth of the tumor, frequent urges, difficulty urinating are recorded. Up to 37% of borderline ovarian neoplasms occur without any subjective sensations.
The main formidable and most frequent complication of borderline neoplasia (mainly serous) is associated with desmoplasia – the ability of epithelial cells of implants to reproduce connective tissue. The result of this process are massive foci of fibrosis in the abdominal cavity, squeezing the intestines, which leads to irreversible violations of its function and intestinal obstruction, which often causes the death of the patient.
Another dangerous complication is malignancy of the tumor or implants. Relapses with malignant transformation are possible, characterized by all the properties of adenocarcinoma – aggressive local growth, high probability of metastasis to lymph nodes and distant organs. Malignant transformation occurs quite rarely, is the cause of death associated with the tumor and its treatment, only in 0.7% of cases.
Diagnostic tests are prescribed by a gynecologist or oncogynecologist. Histological verification of the diagnosis is performed intraoperatively, during therapeutic surgical intervention. An important role in the diagnosis belongs to the pathologist, since the establishment of a histological difference between invasive cancer and atypical hyperplasia often presents difficulties, requires high qualifications and professional experience. Preoperative diagnostic measures include:
- Ultrasonography. Abdominal and transvaginal examination is performed. Ultrasound of the pelvic and abdominal organs can reveal hidden (non-palpable) tumors of the ovary, disseminated peritoneum, diaphragm, liver and spleen, as well as suggest a borderline risk of malignancy of the formation.
- Immunochemical analysis. An increase in the level of cancer markers (CA 125, CA 19-9, NE-4, REA) indirectly indicates tumor growth. A significant increase in the titer of CA 125, NE-4 is characteristic of serous neoplasms, an increase in CA19-9 is characteristic of mucinous ones.
Additionally, radiography of the thoracic cavity, CT and MRI of the pelvis, abdominal cavity, colonoscopy, puncture biopsy of the Douglas space (to exclude cancer) can be prescribed. Differential diagnosis is carried out with primary and metastatic ovarian cancer, benign tumors, retention cysts of the ovaries, tumors of the uterus (more often with fibroids, sarcoma) and intestines, purulent inflammation of the appendages.
Treatment of borderline ovarian tumor
The only method of treatment is surgical. Since neoplasia is in many ways similar to malignant neoplasms, the operation should be performed by an oncogynecologist – this allows you to improve the prognosis, reduce the likelihood of relapse. The intervention is performed through laparotomy or laparoscopic access. Chemotherapy is not prescribed due to inefficiency (possibly due to the low proliferative activity of such neoplasms), according to some clinical studies, worsens the outcome of the disease.
The volume of surgery depends on the stage of neoplasia and the age of the patient, young women are treated, if possible, to preserve fertility. Patients of reproductive age at any stage can undergo resection of the ovary (ovaries), provided there is healthy tissue in it (them). With unilateral total organ damage, unilateral adnexectomy is performed, with bilateral – removal of both appendages of the uterus or hysterovariectomy. Women who have reached postmenopause, with tumors of stages I-IIIA with a lesion of one ovary, unilateral tubovariectomy is performed, with a bilateral lesion – bilateral (sometimes with removal of the uterus), with a greater prevalence of the process – extirpation of the uterus with appendages.
In case of peritoneal lesion, large visualized nodes are removed. The primary operation necessarily includes surgical staging to clarify the prevalence of the process and the histological characteristics of the implants. For this purpose, all patients undergo resection of the contralateral ovary and large omentum, peritoneal biopsy. According to the results of histological examination of samples, dynamic examination or repeated surgery is prescribed. When identifying areas with a decrease in histological differentiation – foci of invasive growth – invasive cancer treatment protocols are used, including chemotherapy and radiation therapy.
Prognosis and prevention
The prognosis of borderline ovarian tumor is favorable. In women with the first stage of the disease, the five–year survival rate is 99%, ten–year – 97%, with the second – 98% and 90%, respectively, with the third – 96% and 88%, with the fourth – 77% and 69%. Relapses most often occur two years after treatment, are observed in 35-50% of cases, after hysterovariectomy occur twice or three times less often than after organ-preserving operations. Relapses without malignant transformation do not worsen the prognosis. The presence of invasive implants reduces the ten-year survival rate by 25-30%.
The measures of primary prevention include rational contraception, the realization of reproductive function, timely treatment of hormonal disorders and inflammatory diseases of the genitals. Secondary prevention consists in lifelong observation of an oncogynecologist with sonographic and immunochemical control: for 5 years after surgery, ultrasound of the abdominal cavity and pelvic organs, analysis of tumor-associated markers is prescribed every 3-6 months, then these studies are performed once annually.