Granulosa cell tumour

Granulosa cell tumour
Other names	Granulosa-theca cell tumours or Folliculoma
Micrograph of a juvenile granulosa cell tumour with hyaline globules. H&E stain.
Specialty	Gynecologic oncology, obstetrics and gynaecology, oncology, endocrinology

Granulosa cell tumours are

Juvenile granulosa cell tumour is a similar but histologically distinct rare tumour. It too occurs in both the ovary and testis. In the testis it is extremely rare, and has not been reported to be malignant.[5] Although this tumour usually occurs in children (hence its name), it has been reported in adults.^[6]

Presentation

Estrogens are produced by functioning tumours, and the clinical presentation depends on the patient's age and sex.^{[citation needed]}

• Female
  • If the patient is
    postmenopausal, she usually presents with abnormal uterine bleeding
    , and in some cases hemoperitoneum.
  • If the patient is of
    reproductive age, she would present with menometrorrhagia
    . However, in some cases she may stop ovulating altogether.
  • If the patient has not undergone puberty, early onset of puberty may be seen.
  • these tumours tend to have late recurrences (even after 30 years)

Genetics

Adult granulosa cell tumours

Using next generation DNA sequencing, 97% of adult granulosa cell tumours were found to contain an identical mutation in the FOXL2 gene [1]. This is a somatic mutation, meaning it is not usually transmitted to descendants. Mutation c.402C>G in the sequence of FOXL2 leads to the amino acid substitution p. C134W. It is believed that this mutation may be the cause of granulosa cell tumours.^{[citation needed]}

Juvenile granulosa cell tumours

Two recent studies show that the enzyme AKT1 is involved in juvenile granulosa cell tumours. In-frame duplications in the pleckstrin-homology domain of the protein were found in more than 60% of juvenile granulosa cell tumours occurring in girls under 15 years of age. The tumours without duplications carried point mutations affecting highly conserved residues. The mutated proteins carrying the duplications displayed a non-wild-type subcellular distribution, with a marked enrichment at the plasma membrane, leading to a strong activation of AKT1.^[8] Analysis by RNA-Seq pinpointed a series of differentially expressed genes that are involved in cytokine and hormone signaling and cell division-related processes. Further analyses pointed to a possible dedifferentiation process, and suggested that most of the transcriptomic dysregulations might be mediated by a limited set of transcription factors perturbed by AKT1 activation. These results incriminate somatic mutations of AKT1 as probable driver events in the pathogenesis of juvenile granulosa cell tumours.^[9]

Diagnosis

Gross appearance

Tumours vary in size, from tiny spots to large masses, with an average of 10 cm in diameter. Tumours are oval and soft in consistency. On cut-section, histology reveals reticular, trabecular areas with interstitial haemorrhage and

Inhibin, a hormone, has been used as biomarker for granulosa cell tumours.^[10]

Histology

Juvenile granulosa cell tumors can be distinguished from adult granulosa cell tumors on histology by their abundant, eosinophilic cytoplasm; primitive, highly mitotic nuclei in polygonal cells; and disorganized follicles.^[12][13]

In animals

In the ovaries of aging

• Inhibin, alpha

References