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what is the cause of granulosa cell tumor and what are the causes of granulosa cell tumor

what is the cause of granulosa cell tumor and what are the causes of granulosa cell tumor

Etiology of granulosa cell tumor

First, the cause of the disease

Up to now, the etiology of granulosa cell tumor is still unclear. However, the study found that 58% of them had genetic defects with wrong DNA replication.

Second, the pathogenesis

1. Granulosa cell tumor of ovary

(1) Adult granulosa cell tumor:

① Gross examination: Most tumors are unilateral, and bilateral accounts for 5% ~ 10%. The volume of tumors varies greatly. The small ones are only found under microscope, while the large ones can fill the abdominal cavity, and most of them are medium-sized with an average diameter of 12cm. Tumors are round, oval or lobulated, with smooth surface and complete capsule, but 10% ~ 15% of them may rupture spontaneously, and their texture is hard, tough or soft, which may be cystic, solid or both. The most typical appearance of tumor section is quite large polycystic and semi-solid mass, and the intracapsular fluid is mostly watery, bloody or jelly. The solid part of the section is white, brown, yellow or gray, and focal hemorrhage and necrosis can be seen. A few tumors consist of large single-locular, few-locular or multi-locular cysts containing aqueous clear fluid, similar to serous cystadenoma.

② Microscopic examination:

A. Characteristics of tumor cells: Tumor cells are small, round, oval, spindle-shaped and polygonal. Less cytoplasm, pale eosin or neutral, unclear cell boundary. The nucleus is oval or round, the chromatin is fine reticular, and there is a typical longitudinal sulcus in the center of the nucleus, which forms a coffee bean-like appearance. The nuclear sulcus is helpful for differential diagnosis and diagnosis. There is no reticular fiber around the tumor cells. Tumor cells have small atypia and few mitosis, generally less than 3/10 HPFs.

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, while others are mixed with several types.

Microfollicular type: The tumor cells are abundant and arranged in nests or irregular flakes. There is a layer of cubic epithelium arranged neatly around the nest, and chrysanthemum-shaped cluster-like structure can be seen in the nest. The center contains eosinophilic substances and nuclear fragments, which is a typical Call-Exner corpuscle, and the nuclear groove of tumor cells is obvious.

Giant follicle type: It is composed of several layers of granulosa cells arranged in a ring, which can form many cysts, similar to cystic follicles. There are a large number of Call-Exner corpuscles in granulosa cells that constitute the capsule wall.

Trabecular type: Tumor cells are arranged into one to several layers of cells, which are cords and flower bands. The cord width of tumor cells is different, and the roundabout distortion is distributed in connective tissue. In some tumor cells, the nuclear arrangement is perpendicular to the long axis of cell cord, showing antipodally arrangement. There may be edema or hyaline degeneration in connective tissue interstitium.

Ribbon type: The flower ribbon structure formed by tumor cells is narrow and arranged like wavy patterns, such as silk. There are few fibrous stroma around the tumor, which are sandwiched in the tumor tissue in filaments.

Diffuse type: Tumor cells are polygonal or spindle-shaped, diffuse and closely arranged. There is little fibrous connective tissue, which is often called sarcomatoid type.

③ Others: Some scholars have reported that small focal hepatocyte differentiation and AFP positive appeared in granulosa cell tumor. Balat et al. (2001) reported a case of granulosa cell tumor in the left ovary and a mature cystic teratoma in the right ovary. Robinson et al. (1999), Kim et al. (2001) reported granulosa cell tumors from pelvic wall and uterorectal fossa.

④ Immunohistochemical study:

Sex hormone: ER (estrogen receptor) expression was positive in cytoplasm of tumor cells.

Vimentin (vimentin): positive.

Cytokeratin: positive.

Epithelial cell membrane antigen (EMA): negative.

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

This method is helpful for the diagnosis and differential diagnosis of granulosa cell tumor.

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

① Gross examination: Most tumors are unilateral, and bilateral accounts for about 2%. The tumors were large in size, ranging from 3 cm to 32cm in diameter, with an average diameter of 12.5 cm. Most of them are solid or cystic and solid, and occasionally thin-walled single-locular or multi-locular cysts contain serous or jelly-like liquid or bloody liquid. The section of solid area is gray, milk yellow or yellow, and hemorrhage and necrosis can be seen in highly malignant cases.

② Microscopic examination:

A. Characteristics of tumor cells: The size and volume of tumor cells are uniform. The cytoplasm is rich, eosinophilic or vacuolar. The nucleus is deeply stained and lacks the longitudinal sulcus of adult granulosa cell tumor. Mitosis is more common, often exceeding 5/10 HPFs. Tumor cells can have a certain degree of atomorphism, and the severe atomorphism can reach 10% ~ 15%. The luteinization of cells was obvious.

B. Tumor cell tissue arrangement: Tumors can form atypical follicular morphology, nodules and diffuse solid areas with different sizes.

The typical form is solid flake tumor cells with round or irregular follicles with different sizes and shapes, clear boundaries. These follicles resemble normal developing follicles, covered with one or more layers of granulosa cells, containing eosinophilic or basophilic fluid in their cavities, and most of them are positive for mucus card red staining. Follicular structure is surrounded by follicular membrane cells.

The tumor cells in the solid area are diffuse or multi-nodular and arranged in small clusters, and there are vesicle cells in the surrounding stroma, and these two kinds of cells can also be mixed. Flavinization often occurs in follicular membrane cells.


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