Definition: Ovarian sex cord stromal tumor showing differentiation towards follicular granulosa cells that can occur in adults (adult-type granulosa cell tumor) and in younger patients (juvenile granulosa cell tumor).
Clinical synopsis
Usually childbearing age
75% have hyperestrinism, which may result in:
- isosexual precocious puberty in children
- metrorrhagia in adults, including postmenopausal
Some cases clinically hormonally inactive
A few androgenic
Elevated serum inhibin and follicle regulatory proteins
Pathogenesis
Differentiation toward follicular granulosa cells
Debatable whether arises from:
- granulosa cells in preexisting follicles
- specialized ovarian stroma
See also
testicular tumors
ovarian tumors
-
ovarian granulosa cell tumor
ovarian granulosa-stromal cell tumors
- juvenile-type granulosa cell tumor
- fibroma-thecoma tumor groups
Macroscopy
Usually encapsulated
Usually smooth, lobulated outline
Cut surface:
- predominantly solid
- or cystic
- possible entirely cystic gross appearance.
- cysts filled with straw-colored or mucoid fluid
- sometimes so prominent as to simulate appearance of a cystadenoma
- a disproportionate number of androgenic tumors are large and cystic, either unilocular or multilocular
- admixture of solid and cystic areas
Color
- usually gray
- may be yellow in areas of luteinization
Microscopy
Extremely variable, even within same neoplasm
Patterns of growth:
- microfollicular (with Call–Exner bodies)
- macrofollicular
- trabecular
- insular
- watered-silk
- solid
- diffuse (sarcomatoid)
May be:
- a theca cell component
- focal luteinization of either granulosa or theca cell component:9
- particularly prominent if associated with pregnancy, together with edema and disorderly arrangement
- hepatocytic differentiation
Folds or grooves in nuclei (important diagnostic feature)
- result in ‘coffee-bean’ appearance
- coffee-bean nuclei in adult type of ovarian granulosa cell tumor
Occasionally:
- bizarre nuclei
- multinucleated giant cells (some ‘floret’ type)
- not a sign of malignancy
- degenerative nature
Ultrastructure
Neoplastic granulosa cells have:
abundant intermediate filaments
specialized cell junctions, some with appearance of typical desmosomes
Steroid production
by both theca and granulosa cells with predominance of:
- estradiol in granulosa cells
- progesterone in luteinized theca cells
Immunochemistry
vimentin
desmoplakin (desmosomal plaque protein)
inhibin
follicle regulatory proteins
CD99 (O13; MIC2)
A103 (melan-A)
cytokeratin
- 33–50% of cases
- typical dot-like distribution
- mainly CK8 and CK18 types
smooth muscle actin (SMA) (nearly all cases)
desmin (less common)
S-100 protein (≈50% of cases)
Negative for EMA
Differential diagnosis
Suspect granulosa cell origin of a metastatic tumor if a combination of microcystic and trabecular formations, especially if also Call–Exner bodies and grooved nuclei
thecoma
endometrial stromal tumors
endometrial carcinomas
sex cord tumor with annular tubules
gonadoblastoma
Links
References
see granulosa cell tumor