A granulosa prison cell tumor (GCT) is a sexual practice-cord stromal tumor of the ovary. It is past far the near common tumor of the equine ovary. When the tumor is composed primarily of granulosa cells, the term GCT is used; when both granulosa and theca cells are present, the term granulosa-theca cell tumor (GTCT) is used.
Epidemiology
Species, Age, Sexual practice
Intact equine females of any age. The mean historic period is 10.vi years with a range of 2 to 20 years. Juvenile cases have also been reported.
Associated Conditions and Disorders
Behavioral problems, infertility
Clinical Presentation
Disease Forms, Subtypes
History, Chief Complaint
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Behavioral abnormalities
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Prolonged anestrus
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Aggressive or stallion-like behavior
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Persistent estrus
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Infertility
Physical Exam Findings
The affected ovary is enlarged and firm, and the ovulation fossa is unremarkably non palpable. The contralateral ovary is almost ever pocket-sized and inactive. Rarely, bilateral tumors accept been reported.
Etiology and Pathophysiology
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GCT is a neoplasm of the sexual activity cord stroma.
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Information technology is the simply ovarian abnormality in mares associated with inactivity of the contralateral ovary.
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Inactivity of the contralateral ovary is presumed to occur by suppression of pituitary follicle-stimulating hormone equally a event of inhibin secretion from the neoplastic ovary.
NOEL WEIDNER , ... MICHAEL PETERSON , in Modernistic Surgical Pathology (2d Edition), 2009
IMMUNOHISTOCHEMISTRY AND DIFFERENTIAL DIAGNOSIS
Granulosa cell tumors are alpha-inhibin and calretinin positive, with the latter marker existence more sensitive but less specific.185,324-326 Other immunostains that are typically positive in granulosa prison cell tumors include vimentin, smooth muscle actin, and CD99 (MIC2).184,327 Approximately half of granulosa cell tumors limited Due south-100 poly peptide.328 Meaning negative markers include desmin, CK7, and EMA, although approximately one-half of juvenile granulosa cell tumors are EMA positive.328,329
Granulosa cell tumors, specially the adult form, may be distinguished from cellular thecomas and fibromas with reticulin stains. Reticulin is abundant around individual cells in the latter tumors, whereas granulosa cell tumors contain scant reticulin surrounding groups or nests of cells. Poorly differentiated, predominantly solid surface epithelial-stromal tumors, especially endometrioid and clear cell adenocarcinomas, may be hard to distinguish from granulosa cell tumors. These carcinomas typically take more pleomorphic nuclei and frequent mitotic figures. Other clinicopathologic features and immunohistochemistry may be useful in problematic cases, as previously discussed. In contrast to ovarian carcinomas, granulosa cell tumors may exhibit dotlike paranuclear staining rather than lengthened immunoreactivity for cytokeratin,330 are negative for EMA,328 and are usually positive for inhibin.185,324,325 The differential diagnosis of granulosa cell tumors, particularly the juvenile type, also includes malignant germ cell tumor, carcinoid tumor, and small-scale jail cell carcinoma of the hypercalcemic type (discussed later).
Edmund South. Cibas , in Cytology (Third Edition), 2009
Juvenile Granulosa Cell Tumor
Juvenile granulosa cell tumors (JGCTs) occur predominantly in babyhood and adolescence. Like AGCT, JGCTs secrete estrogens and thus are oftentimes associated with sexual pseudoprecocity. JGCTs are unremarkably solid and cystic, unilateral, and restricted to the ovary. Patients may present with an astute abdomen after rupture of the tumor capsule. The tumor forms follicles lined past granulosa cells and luteinized theca cells. In dissimilarity to AGCT, almost all nuclei lack grooves. Despite the presence of pleomorphism and frequent mitoses, merely 10% comport aggressively. The cells of JGCT are positive for cytokeratin, inhibin, and vimentin,52 and lack reactivity for CEA, human chorionic gonadotropin, and AFP.
On FNA, tumor cells are seen in loose clusters and single cells.50 Nuclei are round, with fine chromatin and modest to prominent nucleoli. At that place may be nuclear protrusions, but nuclear grooves are absent. Some mitoses are seen. There is a moderate amount of granular cytoplasm, and the oil-red-O stain demonstrates intracytoplasmic lipid. Call-Exner bodies are usually not found.
JGCTs should be distinguished from the small jail cell carcinoma, hypercalcemic blazon, which occurs in the same age range. The clinical clan of JGCT with estrogenic manifestations, and pocket-size cell carcinoma with hypercalcemia are helpful clues. Immunostaining for inhibin (positive in JGCT, negative in pocket-sized prison cell carcinoma) can provide confirmation.
Juvenile granulosa cell tumor is a stromal tumor bearing a lite microscopic resemblance to ovarian juvenile granulosa cell tumor. Granulosa cell tumors occur near exclusively in the first year of life, most in the first 6 months. Of 22 newborn tumors in the Prepubertal Testis Tumor Registry,20 six were juvenile granulosa jail cell tumors, 6 were yolk sac tumors, and 6 were unspecified stromal tumors. Structural abnormalities of the Y chromosome and mosaicism are mutual in boys with juvenile granulosa prison cell tumor.30 Several cases have been described in association with ambiguous genitalia.34 These tumors are hormonally inactive and benign. Although these children should undergo chromosomal assay, no handling or metastatic evaluation is required across orchiectomy or tumor enucleation.35
Diane DeFriend , in Clinical Ultrasound (3rd Edition), 2011
Granulosa cell tumours
Granulosa prison cell tumours are rare, bookkeeping for iii% of all ovarian malignancies, simply are the most common malignant sex cord stromal tumour. They include adult granulosa cell and juvenile granulosa jail cell tumours, with only the former discussed here. Developed granulosa cell tumours occur predominantly in perimenopausal or postmenopausal women, are unilateral in 95% cases and are generally of depression-class malignancy. They are the most mutual oestrogen-producing tumour, and manifest clinically as irregular haemorrhage in premenopausal women or equally postmenopausal bleeding.72 Approximately i-third of women with granulosa cell tumours will accept endometrial hyperplasia73 and up to 25% of patients will have endometrial carcinoma.72 Granulosa prison cell tumours tin can occasionally exist androgenic and present with virilisation.54 They vary in size at presentation, with hormonally active tumours tending to present with a smaller size.72 In contrast to epithelial tumours, more xc% of granulosa jail cell tumours are confined to the ovary at presentation and hence take a better prognosis.72
Ultrasonically the appearances are non-specific and granulosa cell tumours may present as large multilocular cystic masses with solid components or as solid tumours72,73 (Fig. 35.42). A more than recent study suggests two typical patterns: (i) a solid mass with heterogeneous echogenicity of the solid tissue or (ii) a multilocular-solid mass with large solid areas just but rarely papillary projections.74 It is reported that the virilising blazon are more commonly cystic.72 Granulosa cell tumours have a propensity to rupture and up to fifteen% may present with haemoperitoneum.54
MRI may testify more specific features, with high indicate on T1-weighted imaging reflecting their propensity for haemorrhage and T2-weighted imaging showing a characteristic sponge-like appearance.54,72
Jaime Prat , ... Emanuela D'Angelo , in Encyclopedia of Cancer (Third Edition), 2019
Granulosa prison cell tumor
Granulosa cell tumors business relationship for 12% of all sex string-stromal tumors. About granulosa cell tumors (95%) occur afterwards the menopause (adult form) and are unusual earlier puberty. A juvenile form that develop in children and young women has distinct clinical and pathologic features (hyperestrinism and precocious puberty). Development of granulosa cell tumors is linked to loss of oocytes. Oocytes appear to regulate granulosa cells, and tumorigenesis occurs when follicles are disorganized or atretic. Adult-type granulosa cell tumors, are clinically palpable and, like about ovarian tumors, focally cystic and solid. The cut surface shows yellow areas, owing to lipid-rich luteinized granulosa cells, white zones of stroma, and focal hemorrhages (Fig. 23). Granulosa cell tumors show various growth patterns: (1) lengthened (sarcomatoid), (2) insular (islands of cells) or (3) trabecular (anastomotic bands of granulosa cells). Random nuclear arrangement almost a central degenerative space (Call-Exner bodies) gives a feature follicular pattern (Fig. 24). Tumor cells are typically spindle shaped and have a cleaved, elongated nucleus (java bean appearance). They secrete inhibin, a poly peptide that suppresses pituitary release of follicle-stimulating hormone (FSH). These tumors tin can also limited calretinin, a primarily neuronal protein, which suggests possible neural differentiation or derivation for these neoplasms. Three fourths of granulosa cell tumors secrete estrogens; thus, endometrial hyperplasia is a common presenting sign. Endometrial hyperplasia or low-grade endometrioid carcinoma may develop if a functioning granulosa cell tumor remains undetected. At diagnosis, 90% of granulosa jail cell tumors are within the ovary (stage I). Over 90% of these patients survive 10 years. Tumors that accept extended into the pelvis and lower belly have a poorer prognosis. Late recurrence, 5–10 years after surgical removal, is not uncommon and is usually fatal. The most common chromosomal abnormalities are trisomy 12, trisomy xiv, monosomy sixteen, deletion of 16q, and monosomy 22. Missense somatic point mutations in the FOXL2 gene (402 C to G) are constitute in over ninety% of adult granulosa cell tumors.
Fig. 23. Adult granulosa cell tumor. Cystic and solid tumor. The solid component is yellow and the cysts contain clotted blood.
R.J. Rodgers , H.F. Irving-Rodgers , in Encyclopedia of Hormones, 2003
III.H Call-Exner Bodies
Telephone call-Exner bodies of ovarian follicles have been described as "a ring of granulosa cells disposed radially around a central cavity filled with fluid and showing histochemical reactions similar to the liquor folliculi [follicular fluid]." They are present in follicles of many species and in ovarian tumors. The part, if whatever, of Phone call-Exner bodies is non known. The fundamental extracellular region is lined past a basal lamina-like structure, which can be highly folded or unassembled. Bovine Phone call-Exner bodies of preantral follicles contain basal lamina components, including the α1 to α5 chains of type IV collagen, the α1, β2, and γ1 bondage of laminin, perlecan, and nidogen, reflecting the composition of the follicular basal lamina at that phase of follicular development. On farther follicular development, the basal lamina material of Phone call-Exner bodies changes in the apparent ratio of type IV collagen to laminin, similar to what occurs in the follicular basal lamina. In addition, laminin α2, which is believed to be derived from the thecal layer and non from granulosa cells, is non nowadays in the Call-Exner bodies.
Irregularities of the Estrous Bicycle and Ovulation in Mares (Including Seasonal Transition)
KATRIN HINRICHS , in Current Therapy in Big Animal Theriogenology (2nd Edition), 2007
Granulosa Prison cell or Other Functional Tumor
Granulosa cell tumors (GCTs) are by far the most mutual ovarian tumors in mares. These neoplasms of the sexual activity-cord stroma may too contain thecal cells (granulosa cell–theca cell tumors). They may be found in mares of any historic period, and are almost invariably beneficial.
Behavioral changes associated with GCTs include aggressive or stallion-like behavior, constant or erratic estrus, or anestrus, with near equal frequency. These changes are attributed to steroid production by the neoplasm. Theoretically, production of testosterone or loftier concentrations of estrogen may exist associated with aggressive or stallion-like behavior; estrogen with constant estrus; and progesterone with constant diestrous-like beliefs; however, progesterone is typically depression in cases of GCT. Anestrous beliefs (including erratic signs of rut) may be associated with neoplasms that exercise not produce steroids. The contralateral ovary is typically inactive and minor. This is attributed to loftier concentrations of inhibin or steroids from the tumor, causing suppression of follicle-stimulating hormone (FSH) release. In rare cases, apparently no pituitary suppression is present and mares with GCT bicycle normally, ovulating from the contralateral ovary.
Diagnosis of GCT is based largely on the history (abnormal beliefs or cyclicity) and findings on palpation and ultrasonography per rectum. The affected ovary is typically large, polish walled, and spherical. The ovulation fossa is usually not present. The contralateral ovary is usually small and inactive, resembling an anestrous ovary. Ultrasonography is useful for differentiating normal follicular activity from pathologic changes in the ovarian stroma and for confirming the lack of activity of the contralateral ovary. In that location is no 1 typical appearance of GCT on ultrasonography, however. The almost mutual ultrasonographic appearance is that of multiple cystic structures ("honeycomb" appearance); all the same, GCT may also appear every bit unilocular cysts or may exist solid throughout.vi The honeycomb appearance of a GCT may exist confused with that of a clotting hematoma (run into following give-and-take). A hematoma may be differentiated from a GCT by several features: with a hematoma, the activity of the contralateral ovary is normal and the mare has normal cycles; the ovulation fossa is present on the ovary, as the hematoma causes enlargement of simply one pole; and the hematoma appears abruptly and regresses over time (commonly inside 30 days). Serum testosterone concentrations are elevated in l% to 90% of GCT, and inhibin concentrations are elevated in over 85% of mares with GCT; tests for these hormones may be used as a diagnostic assistance.vii Management is past surgical removal of the afflicted ovary; approximately 75% of mares resume normal cyclicity from the remaining ovary inside 2 years of removal of a GCT.
Teratomas are relatively rare in comparing with GCTs; they may be difficult to diagnose as the ovarian enlargement may non be pronounced, and ultrasonographic findings may be unremarkable. Although non usually considered to be functional tumors, teratomas may be associated with disruption of cyclicity. Serous cystadenomas of mare ovaries accept also been reported; these are associated with multiple large cystic structures resembling normal follicles on palpation and ultrasonography. Serous cystadenomas may be associated with elevated serum testosterone concentrations, but do not appear to affect cyclicity.
JoAnne Southward. Richards , in Vitamins and Hormones, 2018
five.2 Granulosa Prison cell Tumors
GCTs are quite rare and are divided into juvenile and adult types (Jamieson & Fuller, 2012). Mutant mouse models in which GCTs develop include activating mutations in β-catenin (Ctnnb1) combined with either the loss of Pten or the expression of active KrasG12D (Boerboom et al., 2005; Richards et al., 2011). GCTs too develop in mice post-obit granulosa jail cell-specific disruption of Foxo1/Foxo3 (Liu, Ren, et al., 2015), depletion of Smad1/five (Middlebrook, Eldin, Li, Shivasankaran, & Pangas, 2009) and depletion of Inha. GCTs in the Foxo1/3, Smad1/5, and Inha (Matzuk, Finegold, Su, Hsueh, & Bradley, 1992) mutant mice showroom persistent phosphorylation of SMAD2/3 that can exist explained, in office, by the apparent unopposed proliferative actions of activin with sustained expression of FOXL2, GATA4, and WNT4 (Liu, Ren, et al., 2015).
Sarah C. Baumgarten , Carlos Stocco , in Encyclopedia of Reproduction (2nd Edition), 2018
Tumors
Granulosa cell tumors (GCT) are the about common type of ovarian sex activity string tumors, which represent approximately 8% of ovarian cancers. GCTs are classified into juvenile GCT or adult GCT, each having unique histology and genetic mutations. Juvenile GCTs are rare and brand up only 5% of all GCTs. Approximately 30% of these tumors have activating mutations in the Gsp oncogene, which encodes the α subunit of Gs. Also, roughly 60% of GCT tumors contain activating mutations of AKT. In contrast, more than 97% of adult GCTs comprise a unmarried missense mutation in the FOXL2 factor, FOXL2 C134W. Interestingly, although the biological action of FOXL2 in many aspects of ovarian physiology is well understood, the mechanisms past which FOXL2 C134W results in tumorigenesis have not been established.
Both juvenile and adult GCTs produce high levels of estrogens that can become symptomatic. Hyperestrogenism can cause precocious puberty in children and irregular bleeding in reproductive-historic period or postmenopausal women. These symptoms often atomic number 82 to the GCT diagnosis. The loftier levels of estrogen tin also result in endometrial hyperplasia or carcinoma. Granulosa prison cell markers, such every bit AMH and inhibin, are used in diagnosis and monitoring of GCTs. Overall, the majority of GCTs are diagnosed at an early on stage and accept a skillful prognosis after surgical intervention.
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