This document discusses sex cord-stromal tumors of the ovary, including granulosa cell tumors, thecoma, and fibroma. It provides details on the histological features, immunoprofile, and genetics of these tumor types. Granulosa cell tumors are further broken down into adult and juvenile subtypes. Adult granulosa cell tumors commonly present in the childbearing age and can cause estrogen excess. Juvenile granulosa cell tumors are more aggressive and often present with precocious puberty. Thecoma typically affects postmenopausal women and presents with estrogen excess. Fibromas are the most common sex cord-stromal tumor and usually present as a unilateral ovarian mass in women after puberty.

1. Granulosa stromal cell tumours
Sertoli stromal cell tumours
Sex cord stromal tumours of mixed or
unclassified cell types.
Steroid cell tumours
SEX CORD STROMAL TUMOURS

2. Granulosa stromal cell tumours
(SEX CORD STROMAL TUMOURS)
 Granulosa cell
tumour group
a) Adult granulosa cell tumour.
b) Juvenile granulosa cell
tumour.
 Thecoma fibroma
group
a) Thecoma (typical or
lutenised)
b) Fibroma
c) Cellular fibroma
d) Fibrosarcoma
e) Sclerosing stromal
tumours
f) Signet ring stromal tumour
g) Stromal tumour with minor
sex cord elements
h) Unclassified

3. Granulosa Cell Tumor group
(sex cord stromal tumor)
Differentiation towards follicular granulosa cells that can
occur in adults (adult granulosa cell tumor) and in younger
patients (juvenile granulosa cell tumor).
Two distinct types:
* adult
* juvenile

4. Adult Granulosa Cell Tumor
 Usually childbearing age.
 - 75% have hyperestrinism, which may result in:
+isosexual precocious puberty
+proliferative breast disease, endometrial hyperplasia
and endometrial caecinoma.
 Elevated serum inhibin and follicle regulatory proteins.

5. AGCT
The tumors are usually large
(>10 cm) and unilateral.
The cut surface is soft and
yellow-tan with cysts and
hemorrhage.
Cut surface:
-predominantly solid
May be:
cystic:
 -filled with straw-colored
or mucoid fluid
-sometimes so prominent
as to simulate appearance
of a cystadenoma
Granulosa cell tumor with solid cut
surface.

6. AGCT
Different histologic patterns
occur, including microfollicular,
macrofollicular, nested, cords,
gyriform, and diffuse.
However, all are composed of
round to oval granulosa cells
that have little cytoplasm and
round to angular nuclei with
longitudinal nuclear grooves
(coffee bean appearance)
There is minimal cytologic
atypia. Mitotic rate is low.

7. Coffee-bean nuclei

8. Insular pattern

9. The microfollicular
and diffuse
variants often
contain
characteristic
Call–Exner
bodies consisting
of a very small
collection of
eosinophilic
material lined by
well-differentiated
granulosa cells.

10. Cells may be luteinized (plump with ample cytoplasm),
particularly during pregnancy; may have theca cell component.
Positive stains: Inhibin alpha, vimentin, calretinin, CD99, smooth
muscle actin, desmoplakin, S100 (50%), keratin (dot-like in 30-50%).
- Silver stains demonstrate reticulin surrounding cluster of cells.
Negative stains: EMA

11. Inhibin

12. Juvenile Granulosa Cell Tumor
 More aggressive than adult GCT
 More likely to produce distant metastases
 ≈80% during first two decades of life
* Usually presents with isosexual precocity
* Occasionally associated with:
- enchondromatosis (Ollier's disease)
- Maffucci's syndrome

13. Juvenile Granulosa Cell
Tumor
-Diffuse or macrofollicular patterns
of growth
- eosinophilic mucin-positive
intrafollicular secretion.
- larger tumor cells with
extensive luteinization
- paucity of nuclear grooves
- nuclear atypia
- variable but often high mitotic
activity.
The follicle-like spaces seen on low-power
examination are a common feature of this
neoplasm.

14. On high power the tumor cells lack the coffee-bean nuclei seen in
the adult type

17. Special Stains and Immunohistochemistry granulosa cell
tumors
Adult Granulosa Cell Tumor


* Immunohistochemically:
- steroid production:
+ by both theca and granulosa cells
with predominance of:
# estradiol in granulosa cell
# progesterone in luteinized theca
cells
- vimentin
- desmoplakin (desmosomal plaque
protein)
 - inhibin (also JGCT)
 follicle regulatory proteins
- CD99
keratin:
+ 33–50% of cases
+ typical dot-like distribution
+ mainly CK8 and CK18 types25,26
smooth muscle actin:
+ nearly all cases
S-100- 50% cases
Strong immunoreactivity for inhibin in
granulosa cell tumor.

19. Thecoma
Postmenopausal women.
Symptoms of hyperestrogenism.
Most are unilateral and can measure up to 10 cm in
diameter.

20. Thecoma
Usually unilateral
Well-defined capsule
Firm consistency
Cut surface: White to
yellow color
* largely or entirely
solid
* may be cystic
Cut surface of thecoma showing a predominance of
yellow areas alternating with whitish foci

22. THECOMA
Fascicles of spindle cells with:
centrally placed nuclei
moderate amount of pale
cytoplasm.
 Only mild atypia and rare mitoses
Intervening tissue may show
considerable collagen
deposition with focal hyaline
plaque formation.
Degree of cellularity varies
considerably
Some thecomas in young
women are heavily calcified

25. Special Stains and Immunohistochemistry
Oil red O: (require fresh tissue)
- abundant intracytoplasmic neutral fat
 Positive for inhibin expression
Reticulin stain: Demonstrates reticulin fibers
surrounding individual cells (note: reticulin surrounds
clusters of cells in granulosa cell tumors)
Estradiol usually limited to a small number of tumor cell

26. FIBROMA
The most common type of sex-cord stromal tumor developing
from specialized ovarian stroma.
Usually unilateral
Almost invariably after puberty
Fibromas are not hormonally functional
average of 5 cm in diameter
Sometimes in young women with basal cell nevus (Gorlin's)
syndrome.
Benign
May be ascites:
 especially if large
 sometimes with right-sided pleural effusion (Meigs' syndrome)
(disappears on removal of tumor).

27. Gross Pathology
Cut surface: Solid, firm,
white, lobulated
Outer aspect of ovarian
fibroma

29. FIBROMA
Spindle stromal cells:
- closely packed
- arranged in 'feather-stitched'
or storiform pattern
- no atypia and few mitoses
May be:
- hyaline bands
- edema
If in basal cell nevus (Gorlin's)
syndrome:
- calcified
- usually bilateral
- often multinodular
Cellular fibroma. The tumor is
hypercellular, but
pleomorphism and mitotic
activity are minimal

30. Immunohistochemistry
-WT1, FOXL2, vimentin, CD56, SF1 positive
-SMA, CD34, desmin, ER, PR may be positive
Inhibin and calretinin rarely focally positive
-CD10 typically negative
Genetic Testing
-No FOXL2 mutations
-Trisomy &/or tetrasomy 12
-Trisomy 8 (fibrosarcoma)