1.Tumour Molecular Genetics Group, Institute of Medical Genetics, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN, UK
2 theories account for the aetiology of sex cord-stromal tumours hypothesising that they develop either from:(1) mesenchyme of the developing genital ridge, or(2) precursors of the mesonephric and coelmic epithelium. No definite aetiologies have been established for granulosa cell tumours, although chromosomal abnormalities and abnormal autocrine and endocrine signalling have been suggested.
Adult and Juvenile Granulosa cell tumourAdult granulosa cell tumours contain granulosa cells in the presence or absence of theca cells. Granulosa theca cell tumours are composed of at least 25% theca cells in addition to the granulosa cells. Varying histologies have been reported in adult granulosa cell tumours, including well-differentiated histologies such as microfollicular, macrofollicular, trabecular and insular, and less well diffentiated subtypes including diffuse and watered-silk (gyriform). Call-Exner bodies are pathognomonic of granulosa cell tumour,and are found in the microfollicular pattern, the most common histological subtype. Call-Exner bodies consist of small rings of granulosa cells surrounding eosinophilic fluid and basement membrane material (http://www.emedicine.com/med/topic928.htm#target1). Macrofollicular granulosa cell tumours contain one or more large cysts lined with granulosa cells. Granulosa cells are organised into nests and bands in the trabecular and insular histologies, with an intervening fibrothecomatous stroma present in the trabecular type. The diffuse subtype contains sheets of cells arranged in no pattern (http://www.emedicine.com/med/topic928.htm#target2 ), and the watered-silk entity contains cells arranged in single file in lines (http://www.emedicine.com/med/topic928.htm#target4). Both the well-differentiated and the less well-differentiated adult granulosa cell tumours contain large, pale, ovoid or angular nuclei with nuclear grooves.Few mitotic figures, mild nuclear atypia and little cytoplasm are usually found, however luteinization can sometimes be evident.
The gross appearance of juvenile granulosa cell tumours is similar to the adult counterparts-both comprise a mixture of solid and cystic components with many haemorrhagic areas. However the similarity ceases at the gross level, as morphologically both types differ greatly. Juvenile granulosa cell tumours contain round hyperchromatic nuclei, nuclear grooves are usually absent, severe nuclear atypia, contain more mitotic figures, more cytoplasm (which is dense).
Gross image of granulosa cell tumour can be viewed at: http://www-medlib.med.utah.edu/WebPath/FEMHTML/FEM057.html
Microscopic images at varying magnification powers can be viewed at: http://www-medlib.med.utah.edu/WebPath/FEMHTML/FEM058.html http://www-medlib.med.utah.edu/WebPath/FEMHTML/FEM063.html http://pathweb.uchc.edu/eAtlas/GYN/1953.htm http://pathweb.uchc.edu/eAtlas/GYN/1954.htm http://pathweb.uchc.edu/eAtlas/GYN/1955.htm
Fibromas Fibromas are benign and are classified as such if they contain 4 mitoses per high-power field. Less than 5% of fibromas are malignant.
Gross appearance of an ovarian fibroma can be viewed at:http://www-medlib.med.utah.edu/WebPath/FEMHTML/FEM049.html http://pathweb.uchc.edu/eAtlas/GYN/469.htmhttp://pathweb.uchc.edu/eAtlas/GYN/470.htm http://pathweb.uchc.edu/eAtlas/GYN/471.htm
Histological images of fibromas can be viewed at: http://pathweb.uchc.edu/eAtlas/GYN/1956.htm http://pathweb.uchc.edu/eAtlas/GYN/1957.htm http://pathweb.uchc.edu/eAtlas/GYN/1958.htm
ThecomasThecomas or theca cell tumours contain exclusively theca cells. Thecomas are solid, tan or yellow-orange tumours. They are highly similar to fibromas, except that thecomas secrete excess oestrogen. Thecomas are usually benign, and are characterised by 3 mitoses per field. Microscopic analysis reveals round or ovoid cells with pale nuclei and a lipid-rich cytoplasm. Hyaline bands frequently intersperse cells (http://www.emedicine.com/med/topic928.htm#target5). Luteinized thecomas contain lipid rich cytoplasmic cells and a more fibromatous stroma (http://www.emedicine.com/med/topic928.htm#target6). Less than 5% of thecomas are malignant.http://pathy.med.nagoya-u.ac.jp/atlas/misc/thecoma.html
Sertoli cell tumoursSertoli cell tumours contain Sertoli cells in a tubular arrangement.
Sertoli-Leydig cell tumoursAs the name suggests, Sertoli-Leydig cells contain both Sertoli and Leydig cells. They are subclassified in accordance with the WHO as follows: 1. well-differentiation (predominant tubular pattern) 2. intermediate differentiation (sheets of immature Sertoli cells with some stroma) 3. poor differentiation (immature Sertoli cells with little or no stroma) 4. containing heterologous elements with retiform pattern.Less than 5% of Sertoli-Leydig tumours are malignant.
Leydig cell tumours Leydig cell tumours contain Leydig cells, and are usually benign. When located in the hilus they are described as hilus cell tumours. Leydig cell tumours contain Reinke crystals.
Lipid cell tumours Lipid cell tumours are characterised by round Leydig-like cells, luteinized stroma, adrenocortical cells and the absence of Reinke crystals. 30% of lipid cell tumours are malignant.
Gynandroblastoma These are rare ovarian tumours which contain granulosa stromal cells and Sertoli stromal cells. 100% of gynandroblastomas are malignant.
Sex cord tumour with annular tubules (SCTAT) Histologically SCTAT is intermediate between granulosa cell tumour and the Sertoli cell tumour. It is characterised by sex cord cells in the form of a ring with nuclei orientated around a central hyalonized body.
Trisomy 12 and 14, and monosomy 22 are the characteristic recurrent cytogenetic aberrations in granulosa cell tumours. There has been a single case of a Sertoli cell tumour in which cytogenetics was performed. Supernumerary i(1q) was present as the sole abnormality. Monosomy 22 was identified as the sole anomaly in a mixed germ cell-sex cord-stromal tumour in the ovary, by both karyotyping and CGH, which may suggest a common pathogenetic mechanism for both tumour types. Monosomy 22 was also identified as the sole abnormality in a fibrothecoma. Monosomy 22 and trisomy 14 may be early events in the pathogenesis of adult granulosa cell tumour, and particularly adult granulosa-thecoma cell tumours.
Other abnormalities found include:
Ovary: Sex cord-stromal tumors
Atlas Genet Cytogenet Oncol Haematol. 2003-11-01
Online version: http://atlasgeneticsoncology.org/solid-tumor/5223/ovary-sex-cord-stromal-tumors