Ovarian granulosa cell tumor

Introduction to ovarian granulosa cell tumor Ovarian granulosa cell tumor is a common tumor in ovarian cord stromal tumors, accounting for about 40% of stromal tumors. It is characterized by low grade malignancy and clinical advanced recurrence. According to its pathological morphology, it is divided into adult type granulosa cell tumor (adult type granulosa cell tumor) and juvenile type granulosa cell tumor (juvenile type granulosa cell tumor). Although 97% of juvenile granulosa cell tumors occur before the age of 30, the exact diagnosis is still the pathological tissue morphology of the tumor, not the age of onset. At present, in addition to the pathological diagnosis of juvenile granulosa cell tumors, the remaining granulosa cell tumors are collectively referred to as adult granulosa cell tumors. basic knowledge The proportion of illness: 0.001% Susceptible people: women Mode of infection: non-infectious Complications: abdominal pain

Ovarian granulosa cell tumor etiology

Cause of the disease (45%):

So far, the cause of granulosa cell tumors is unclear, but the study found that 58% of the genetic defects in DNA replication errors. Thus, the occurrence of this disease is related to heredity.

Pathogenesis (30%):

Ovarian granulosa cell tumor

(1) Adult granulosa cell tumor:

1 gross examination: most of the tumors are unilateral, bilateral 5% to 10%, the tumor volume is very different, the small one is only found under the microscope, the larger can be filled with abdominal cavity, most of them are medium size, the average diameter is 12cm, The tumor is round, oval or lobulated, with a smooth surface and intact capsule, but 10% to 15% may have spontaneous rupture, hard texture, tough or soft, and may be cystic, solid or both. The most typical appearance of the tumor section is a fairly large cystic, semi-solid mass. The fluid in the capsule is mostly watery, bloody or jelly liquid. The solid part of the cut surface is white, brown, yellow or gray. Hemorrhage and necrosis, a small number of tumors consist of large single-chamber, small or multi-atrial cysts, aqueous effluent, similar to serous cystadenoma.

2 inspection under the microscope:

A. Tumor cell characteristics: tumor cells are small, round, oval, fusiform, polygonal, cytoplasmic, eosinophilic or neutral, cell boundaries are unclear, nucleus oval or round, chromatin It has a fine mesh shape, and has a typical characteristic longitudinal groove, ie, a nuclear groove, which forms a coffee bean-like appearance. The nuclear groove helps differential diagnosis and diagnosis. There is no reticulated fiber around the tumor cells, and the tumor cells are small in shape. , nuclear division is less, generally less than 3/10HPFs.

B. Tumor cell tissue arrangement: tumor cells can be arranged in various forms, such as microfollicular type, giant follicular type, trabecular type, ribbon type, diffuse type, etc. Some tumors are mainly in one form, There are several types of hybrids.

Microfollicular type: The tumor cells are rich, arranged in a nest or irregular sheet, and there is a layer of cuboidal epithelium arranged neatly around the nest of cells. A chrysanthemum-like structure is visible in the nest, and the center contains eosinophils and nuclear fragments. For a typical Call-Exner body, the tumor cell nucleus is distinct.

Giant follicular type: It consists of several layers of ring-shaped granulosa cells, which can form a majority of cystic cavities. Similar to capsular follicles, it contains a large number of Call-Exner bodies in the granulosa cells that make up the wall of the capsule.

Trabecular type: The tumor cells are arranged in one to several layers of cells, which are in the shape of strips and flowers. The width of the tumor cells is narrow, and the twists are distributed in the connective tissue. Some of the tumor cells are arranged perpendicular to the long axis of the cell line. An antipodally arrangement, the connective tissue interstitial may have edema or glassy changes.

Ribbon type: The flower-like structure formed by tumor cells is narrow and arranged like a wavy pattern. For example, silk-like, the fibrous interstitial around the tumor is also rare, and it is pinched in the tumor tissue.

Diffuse type: The tumor cells are polygonal or fusiform, diffusely distributed, closely arranged, and less fibrous connective tissue, often referred to as sarcoma-like type.

3 Others: Some scholars have reported small focal hepatocyte differentiation in granulosa cell tumors, and AFP positive, Balat et al (2001) reported 1 patient with left ovarian granulosa cell tumor, right ovary for mature cystic teratoma, Robinson et al ( 1999), Kim et al (2001) reported granulosa cell tumors from the pelvic wall, the uterus rectal fossa.

4 immunohistochemical studies:

Sex hormones: ER (estrogen receptor) expression in the cytoplasm of tumor cells is positive.

Vimentin: positive.

Cytokeratin: positive.

Epithelial cell membrane antigen (EMA): negative.

Ovarian serous cystadenocarcinoma antigen (OM-1): negative.

This method contributes to the diagnosis and differential diagnosis of granulosa cell tumors.

(2) Juvenile granulosa cell tumor: first reported by Scully in 1979, has now been identified as a special subtype of granulosa cell tumor.

1 gross examination: most tumors are unilateral, bilateral accounts for about 2%, tumor volume is large, the diameter is 3 ~ 32cm, the average diameter is 12.5cm, most of them are solid or sac, and they coexist, occasionally thin Single- or multi-room cysts in the wall. The capsule contains serous or jelly-like liquid. It may also contain bloody fluid. The solid area has a gray cut surface, milk yellow or yellow. Hemorrhagic and necrotic lesions can be seen in highly malignant ones.

2 inspection under the microscope:

A. Tumor cell characteristics: tumor cell size, volume is uniform, cytoplasm is rich, eosinophilic or vacuolated, deep nuclear staining, lack of nuclear longitudinal groove of adult granulosa cell tumor, nuclear fission is more common, often more than 5 /10HPFs, tumor cells can have a certain degree of heteromorphism, of which severe heteromorphism can reach 10% to 15%, and cytochemicals are obvious.

B. Tumor cell tissue arrangement: tumors can form atypical follicular morphology of varying sizes, nodules and solid areas diffuse into pieces.

The typical morphology is solid flaky tumor cells, accompanied by follicles of different sizes and shapes, with clear boundaries, round or irregular shapes. These follicles are like normal developing follicles, covering one to several granule cells, and containing intrauterine cells. Eosin or basophilic liquid, most of the mucus card red staining is positive, and the follicular structure is surrounded by follicular cells.

The solid tumor cells are diffuse or multinodular, clustered in small clusters, and there are vesicular cells in the surrounding interstitial. These two cells can also be mixed, and the ovarian follicular cells often undergo flavinization.

Ovarian granulosa cell tumor prevention

Granulosa cell tumor is a low-grade ovarian malignant tumor, because it has the characteristics of "late recurrence", long-term follow-up is more necessary.

1. Adult granulosa cell tumors are followed up once every 3 months, and once every half year after 1 year, it is important to adhere to long-term follow-up, because adult granulosa cell tumors are 5 years, 10 years or even 20 years after operation. Recurrence has been reported, Lauszus et al (2001) reported that the 5-year survival rate of clinical stage I granulosa cell tumors is 94%, 82% in 10 years, and 62% in 20 years, so it is necessary to follow up for 5 to 10 years or even longer. time.

2. About 5% of juvenile granulosa cell tumors are malignant, and they are characterized by rapid recurrence. Generally, they can spread widely in the abdominal cavity within 2 years after the initial diagnosis, so the patients are closely followed up after surgery. More importantly, the follow-up time should be once every 3 months, and once every half year after 1 year.

Ovarian granulosa cell tumor complications Complications, abdominal pain

If the tumor grows fast, the capsule is ruptured or the tumor is reversed, there will often be symptoms of acute abdominal pain, and it is easy to relapse in the late stage. It has been reported that the primary tumor attachment resection and radiotherapy have recurrence after 15 years, and the original accessory resection is reported. After 15 years, multiple metastases and recurrences occurred in the lungs. In addition to the basin and intra-abdominal metastasis, vertebrae metastasis and liver parenchymal metastasis were reported.

Ovarian granulosa cell tumor symptoms Common symptoms Vaginal irregular bleeding, vaginal bleeding, ascites, bloating, pleural effusion, amenorrhea, premature menopause, menopausal, postmenopausal bleeding

About 3% of granulosa cell tumors have no obvious symptoms. They were found by accident. Most patients have clinical symptoms, mainly caused by endocrine disorders and abdominal masses.

Estrogen stimulating symptoms

Because tumor cells can secrete estrogen, if the tumor occurs in prepubertal children, most of them are precocious puberty. Such precocious puberty is caused by tumor stimulation, not true precocious puberty, also known as pseudo-prococious puberty. There may be breast enlargement, pubic development, pubic hair growth, internal and external genital abnormalities, and even anovulatory menstruation, and other height, bone age over-advanced development, and uncoordinated symptoms of mental and ideological development.

Tumors occur in women in the growth stage. Due to the estrogen secreted by the tumor, the endometrial proliferative pathological changes occur. The endometrium of the endometrium appears irregularly with the fluctuation of estrogen levels in the body. Therefore, about 2/3 of the patients in the clinic will have menstruation. Excessive, prolonged menstrual period and other abnormal vaginal bleeding symptoms, a small number of patients will also have persistent amenorrhea, or irregular bleeding, granulosa cell tumor patients with endometrial cancer, the chance of 10 times that of normal people, granulosa cell tumor Easy to combine uterine fibroids, more serious vaginal irregular bleeding symptoms, and about 6% of patients have the possibility of breast cancer.

When the tumor occurs in postmenopausal women, postmenopausal bleeding is a typical clinical symptom, and there will be breast swelling, breast enlargement, and scalp epithelial maturation index right shift in the vaginal smear. In this age group, the uterus Membranous proliferative diseases, precancerous lesions and cancer are higher than women in the childbearing age group, and patients with endometrial cancer are more than 50 years old.

2. masculine signs

Due to the occurrence of ovarian interstitial luteinization and luteinization of follicular endometrial cells, a small number of patients have menstrual thinning, amenorrhea, hairy, clitoris growth, facial acne, low dumb and other masculine phenomena, these symptoms often occur in cystic granules In patients with cell tumors, Casto et al reported in 2000 that a 13-year-old adult granulosa cell tumor patient has not yet undergone menstruation, and has clinical symptoms such as hairy, preoperative plasma testosterone, 17-hydroxyprogesterone, etc., after surgical removal of the tumor. Revert to the normal range.

3. Abdominal mass

The average diameter of ovarian granulosa cell tumor is about 12cm, which is generally medium size. It can be touched in gynecological pelvic examination, but it is not easy to touch in the abdomen. If the patient licks the lower abdomen mass and treats it as the main complaint, the tumor is often larger. .

If accompanied by ascites, there are often other symptoms such as bloating, fullness, and difficulty urinating.

Ovarian granulosa cell tumors can be accessed through abdominal examination and gynecological pelvic examination. They are usually medium-sized, smooth, and movable. Women of childbearing age can enlarge or merge with uterine fibroids, while menopausal women. Can be stimulated by tumor hormones, vaginal mucosa smooth, rosy, the uterus does not shrink, when the tumor or ascites, there may be obvious abdominal enlargement, abdominal distension, the patient occasionally combined with pleural effusion.

Examination of ovarian granulosa cell tumor

Determination of endocrine hormones: It can be used to detect estrogen, progesterone, testosterone, gonadotropin and urinary estrogen levels in patients with blood, to assist in clinical analysis and diagnosis. Postmenopausal women, vaginal cytology smear hormone level is simple and easy to check. OK, but it can be of great help to the diagnosis.

1. Imaging examination

MRI, CT, B-ultrasound and other examination methods can generally determine the location of the pelvic mass, the source, the relationship with the uterus and surrounding organs, the solid changes of the capsule, etc., but it is difficult to diagnose the histological category of the tumor. Estimate its good, malignant.

2. Diagnostic curettage

It can accurately understand the endometrial hyperplasia, precancerous or cancerous changes under tumor stimulation, and clear the tumor staging before surgery, which is conducive to formulating appropriate and appropriate treatment plan and obtaining satisfactory prognosis.

Diagnosis and diagnosis of ovarian granulosa cell tumor

Diagnostic criteria

Ovarian granulosa cell tumor is a tumor with obvious clinical features. The patient's attachment is found to have a mass, accompanied by obvious symptoms of endocrine disorders caused by estrogen stimulation. The diagnosis is not difficult. For patients with atypical clinical symptoms, it depends on their age and tumor. Comprehensive materials such as size, texture, and auxiliary examination are analyzed, and after diagnosis, a more accurate diagnosis is obtained. There are still a few patients who need to be diagnosed by intraoperative frozen pathological examination.

In recent years, in cytogenetics, granulosa cell tumors have also been meaningfully explored and studied. Some scholars have found that p53 tumor suppressor genes are often overexpressed in epithelial tumors, which are not common in granulosa cell tumors. Lack of G protein tumor gene (gip2), several cases of trisomy 13 (Trisomy12) have been reported in granulosa cell tumors. Shashi et al. further pointed out that although not all benign granulosa cell tumors have 12-trisomy, Most of the 12-trisomy granulosa cell tumors are clinically benign. Tanyi et al. have reported two cases of juvenile granulosa cell tumors with chromosome 12 trisomy combined with pregnancy.

Anti-Mulleria hormone is a tumor marker that has been reported to be helpful for diagnosis. In terms of tumor markers, Flemruing et al. have found that inhibin antibodies help identify granulosa cell tumors. With general soft tissue tumors, it can also be used as a tumor marker in serum, which can be detected before clinical symptoms appear, predicting tumor recurrence. Weidner et al reported that labeled MIC2 antibodies of Ewing sarcoma (primary peripheral neuroectodermal tumor) can be labeled normally. Ovarian granulosa cells and granulosa cell tumors have the significance of diagnosing granulosa cell tumors. Santala et al. (2001) reported a case of juvenile granulosa cell tumor with hyperprolactinemia.

These findings are all diagnostics for granulosa cell tumors. Monitoring provides meaningful insights. If clinical applications are introduced in the future, it will greatly help the diagnosis and differential diagnosis of granulosa cell tumors.

Differential diagnosis

1. Adult granulosa cell tumor and juvenile granulosa cell tumor.

2. Granulosa cell tumor and small cell carcinoma

Undifferentiated small cell carcinoma of the cancer, the differentiated tumor cells are poorly differentiated, and the cell morphology is sometimes similar to that of granulosa cell tumors, especially when the diffuse or similar follicular arrangement is arranged, the less experienced pathologist will make a mistake. The diagnosis is also an important reason for the malignant degree of granulosa cell tumors in the hospitals, and the prognosis is very different. The granulosa cell tumors and the latter two have obvious differences in clinical symptoms, signs and intraoperative exploration. For clinically questionable cases, it should be collaborated with pathologists. Specimens should be taken from multiple sources, and new techniques (electron microscopy, immunohistochemistry, etc.) can be used to identify them.

3. Granulosa cell tumor and other types of sex cord stromal tumors

The most common sex cord stromal tumors that are confused with the diagnosis of granulosa cell tumors are ring-shaped tubular tumors, supporting cell tumors, sclerosing stromal tumors, etc., and are unfamiliar with the characteristic morphological structures of these rare tumors. The main cause of misdiagnosis, in the past 10 years, domestic and foreign scholars have reported a large number of reports on the diagnosis, morphological characteristics, clinical prognosis of these rare tumors, and have significantly improved the understanding of these tumors, which are helpful for differential diagnosis. jobs.

4. Granulosa cell tumors and other ovarian tumor granulosa cell tumors that cause clinical endocrine disorders can cause endocrine disorders in patients, and a series of clinical symptoms appear, but this feature is not limited to granulosa cell tumors, and some epithelial tumors have interstitial luteinization (for example) Mucinous cystadenoma can also have symptoms of endocrine disorders, which will cause difficulties for clinicians to diagnose. Comprehensive analysis of clinical data should be performed to identify these two types of tumors, benign epithelial tumors and granulosa cell tumors abroad. There are obvious differences in the scope of surgery, postoperative treatment, and prognosis.

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