Ovarian carcinoid is a tumor of the female gonads, prone to the production of hormones and hormone–like substances. It is their synthesis that causes various syndromes (more often carcinoid), which are often the only external manifestations of the disease. The diagnosis is established on the basis of anamnesis data, the results of radiation imaging methods, laboratory studies (morphological, immunohistochemical, blood and urine tests for markers). The main method of treatment of carcinoid is surgical. Depending on the type of neoplasm, its hormonal activity, pharmacotherapy can be used.
Ovarian carcinoid is a benign or malignant ovarian neoplasia related to neuroendocrine tumors (HET). The disease is registered in patients aged 14-80 years, most often occurs at the age of peri- and postmenopause. Primary ovarian carcinoid is a rare, usually unilateral formation that makes up to 1.7% in the structure of endocrine tumors. Among all gonadal neoplasms, the proportion of carcinoid is less than 0.1%. Ovarian localization is most common among HET female genitalia.
The etiology of ovarian carcinoid has not yet been clarified. In most patients, it is not possible to identify common causes leading to the development of neoplasia. The connection of individual cases of carcinoid with genetic factors – mutations inherited or arising for the first time has been established. Risk factors include:
- Multiple endocrine neoplasia (MEN). Ovarian carcinoid occurs in MEN-1 syndrome (the first type) associated with a mutation of the suppressor gene MEN1. The syndrome is characterized by the appearance of HET parathyroid glands, digestive tract, adenohypophysis. The risk group includes women with established MEN-1, their daughters, mothers, and sisters.
- Isolated ovarian carcinoid in female relatives. According to a number of authors, there is a vague connection between the occurrence of ovarian carcinoid and the presence of a similar neoplasm in the closest blood relatives. The mutation responsible for tumor growth is unknown, as is the sign of its inheritance.
Ovarian NEOS are neoplasms from various tissues of the ovarian teratoma (dermoid cyst). Their sizes range from microscopic to 15-20 cm. The mechanism of development of carcinoids is unknown. The common feature that unites these tumors is the ability to synthesize biologically active compounds, the excess of which in the blood leads to the development of certain symptoms from various organs and systems.
Currently, there are more than 30 compounds produced by different types of NEO (among them serotonin, tachykinins, histamine). The functional activity (production of hormones, hormone-like substances) of neoplasia may differ significantly in each case. The clinical picture of the disease, the prognosis of treatment, and the outcome depend on the origin of the carcinoid.
According to the degree of malignancy, there are 3 classes of carcinoid: I, II class – relatively benign highly differentiated tumors, III – malignant, with low differentiation. According to the microscopic structure, the following types of ovarian carcinoid are distinguished by the peculiarities of secretion:
- Insular. The most common type of carcinoid. Neoplasia develops from the epithelium of the respiratory organs, the digestive tract as part of mature ovarian teratomas. It has a favorable prognosis, in a third of cases it is accompanied by carcinoid syndrome (with tumors larger than 7 cm, it is noted in 66% of patients).
- Trabecular. Highly differentiated ovarian HET, rarely accompanied by carcinoid syndrome. The course of the disease, as a rule, is benign in nature with a favorable prognosis (metastasis is very rare).
- Strumal (ovarian struma, ovarian goiter). Neoplasia contains inclusions of thyroid tissue, has specific symptoms due to increased synthesis of thyroid hormones. It has a relatively favorable prognosis (especially in the early stages), it is malignized in 10-20% of cases.
- Mucinous. A rare type of ovarian carcinoid (1.5% in the HET structure of the female reproductive sphere). Its cells contain mucin and neuroendocrine granules. This tumor is more aggressive than those listed above, and is prone to lymphogenic, hematogenous metastasis.
- Mixed type. Mixed carcinoids consist of two or more components (usually adenocarcinoma and squamous cell carcinoma). These include small cell carcinoma of the pulmonary type, non-small cell neuroendocrine carcinoma. They are distinguished by a high degree of malignancy, aggressiveness, poor prognosis (often regardless of the stage of the disease).
Ovarian carcinoid has no specific symptoms, it can exist asymptomatically for 10-15 years, its external manifestations are most often similar to the symptoms of other diseases. Often, the disease debuts long before the tumor is detected by a number of signs of various tumor-associated syndromes (endocrine, rheumatological, general paraneoplastic symptoms). The impetus for manifestation is often the menopause.
Most often, a carcinoid syndrome is registered. Its manifestations are diarrhea, “hot flashes” (episodes of intense redness of the face, upper body with a feeling of heat, weakness), the occurrence of telangiectasia in the face, cyanosis of the extremities. Sometimes Meigs syndrome is observed (abdominal enlargement due to ascites, hydrothorax, accompanied by shortness of breath, difficulty breathing). An actively functioning ovarian goiter leads to thyrotoxicosis syndrome.
For malignant forms, the general manifestations of paraneoplastic syndrome are first characteristic – an increase in body temperature, night sweating, weight loss. Sometimes there are symptoms of rheumatological pathologies (scleroderma, lupus erythematosus, dermatomyositis). As the tumor grows of any degree of malignancy, menstrual disorders develop (dysmenorrhea, menometrorrhagia), epigastric discomfort, indefinite pelvic pain.
Any carcinoid can be complicated by a twist of the tumor leg or ovary. The culmination of carcinoid syndrome, thyrotoxicosis can be a carcinoid or thyrotoxic crisis. The listed conditions are life-threatening. Malignized ovarian struma often causes pathological fractures as a result of multiple bone metastases. Metastatic lesions of bones, liver, lymph nodes are often accompanied by mixed carcinoid cancer.
Diagnosis of ovarian carcinoid is difficult due to a long asymptomatic course, the absence of pathognomonic symptoms, a variety of signs “masquerading” as diseases that have no obvious connection with gonad pathology. In modern oncogynecology, the following mandatory methods are used:
- Clinical examination. Carcinoid can be suspected on the basis of complaints, information about the presence of the disease in the next of kin. A general examination reveals the symptoms of thyrotoxicosis, ascites. Gynecological examination reveals the presence of a voluminous formation.
- Instrumental research. By means of ultrasound of the ovaries, even small neoplasms of the female gonads can be determined, their nature can be assumed. CT and MRI of the pelvic organs are used to clarify the diagnosis.
- Urine and blood tests. It is prescribed for the purpose of biochemical identification of the tumor. A study of the level of markers in serum or plasma (chromogranin A, neuron-specific enolase, somatostatin) is performed, the concentration of serotonin, metanephrine in the daily urine is determined.
- Puncture of the Douglas space. Culdocentesis with sampling of the contents of the rectum-uterine recess, cytological examination of the biopsy is the only method of verifying the diagnosis at the preoperative stage. Its main value is the ability to distinguish benign neoplasia from malignated.
The final diagnosis is made after surgery, based on the results of histological and immunohistochemical examination of the neoplasm. Ovarian carcinoid is differentiated with:
- metastatic tumor (thyroid cancer, gastrointestinal carcinoid);
- other neoplasia of the ovary (mucinous cyst, leidigoma, Brenner’s tumor);
- diseases of the thyroid gland.
Treatment of ovarian NEO is carried out under the guidance of an oncogynecologist with the involvement, if necessary, of an endocrinologist, endocrine surgeon, radiologist. The main method is surgery, in some cases, chemotherapy is performed before or after surgery. If necessary, pharmacotherapy of syndromes is prescribed.
Ovarian carcinoid is a rare tumor, it has been diagnosed relatively recently, so unified treatment protocols have not yet been developed. Conservative therapy is aimed at eliminating the remnants of tumor tissue, metastases, relieving the general condition of patients and includes:
- Polychemotherapy. Adjuvant chemotherapy (etoposide in combination with platinum preparations, antitumor antibiotics, cyclophosphamide) is indicated for patients with malignant ovarian HET. If there is an effusion into the abdominal and pleural cavities, chemotherapy is performed before surgery.
- Radio adulation. This is a method of radiation (radionuclide) therapy, indicated for malignant ovarian stroma. The preparation of radioactive iodine is taken orally. The use of radioiodotherapy allows you to preserve an unaffected ovary, but requires a preliminary thyroidectomy.
- Symptomatic treatment. It is prescribed to improve the quality of life, prevent complications in syndromes associated with different types of HET. Synthetic analogues of somatostatin are used in the treatment of carcinoid syndrome. Thyrostatic drugs are used to temporarily eliminate the symptoms of thyrotoxicosis.
Different types of ovarian carcinoid differ significantly in morphological structure, course, and degree of malignancy. The volume and type of surgery is selected individually and depends on the characteristics of the tumor, the age of the patient. The main types of surgical operations for ovarian HET include:
- Organ-preserving. The intervention includes removal of the affected ovary and resection of the large omentum. It is recommended for unilateral ovarian carcinoids with a benign course in young patients who want to preserve menstrual and reproductive function. To exclude carcinoma during surgery, an urgent histological examination of the tumor is performed.
- Complete cytoreductive. During the operation, the uterus, both ovaries, and the large omentum are removed. Treatment is prescribed to peri- and postmenopausal patients with carcinoids of any class of malignancy, to women of reproductive age – with carcinoid ovarian cancer. In small- and large-cell carcinoma, total pelvic lymphadenectomy is additionally performed.
Prognosis and prevention
The five-year survival rate of patients with all forms of ovarian carcinoid is on average 67-82%. At the time of tumor diagnosis, 13% of patients have metastases. The outcome depends on the histological type, the degree of prevalence and differentiation of the neoplasm. There is no primary prevention of the disease. For early detection of a tumor, patients at risk need a comprehensive examination every 3-5 years.