Invasive breast carcinoma - IARC

is yellow to tan with a variable admixture
of cystic and solid areas {906,2058}.
Haemorrhage is seen in larger tumours;
n e c rosis is focal and uncommon. A small
p e rcentage is totally cystic, either uniloculated
or multiloculated {2058,2716}. A
solid or cystic tumour with a combination
of yellow tissue and haemorrhage is highly
suggestive of a granulosa cell tumour.
Histopathology
Histologically, there is a proliferation of
granulosa cells often with a stromal component
of fibroblasts, theca or luteinized
cells. The granulosa cells have scant cytoplasm
and a round to ovoid nucleus
with a longitudinal groove. The mitotic
activity rarely exceeds 1-2 per 10 high
power fields. When luteinized, the cells
develop abundant eosinophilic or vacuolated
cytoplasm, and the nuclei become
round and lose their characteristic
groove. The rare presence of bizarre nuclei
does not have an adverse effect on
the prognosis {2890,3210}. The tumour
cells grow in a variety of patterns. The
best known of these is the microfollicular
pattern characterized by the presence of
Call-Exner bodies. Others include the mac
ro f o l l i c u l a r, characterized by large spaces
lined by layers of granulosa cells,
insular, trabecular, diffuse (sarcomatoid)
and the moiré silk (watered silk) patterns.
A fibrothecomatous stroma often surrounds
the granulosa cells.
Immunoprofile
Granulosa cell tumours are immunoreactive
for CD99, alpha-inhibin, vimentin,
cytokeratin (punctate), calretinin, S-100
protein and smooth muscle actin. The
tumour cells are negative for cytokeratin
7 and epithelial membrane antigen {482,
563,889,1815,2124,2379}.
Differential diagnosis
Although endometrioid carcinomas may
display an abundant rosette-like arrangement
of nuclei mimicking Call-Exner bodies,
they often show squamous metaplasia
and lack nuclear grooves. Undiff e-
rentiated carcinomas and poorly diff e re n-
tiated adenocarcinomas may re s e m b l e
the diffuse (sarcomatoid) pattern of granulosa
cell tumours. These carc i n o m a s
have abundant mitotic figures and frequently
have already extended beyond
the ovary at presentation.
The insular and trabecular patterns of granulosa
cell tumour may be mistaken for a
Fig. 2.57 Adult granulosa cell tumour, trabecular pattern.
The granulosa cells form cords and trabeculae
in a background of cellular fibrous stroma.
Fig. 2.59 Adult granulosa cell tumour, gyriform pattern.
Immunostain for alpha-inhibin is moderately
positive. The cords have a zigzag arrangement.
c a rcinoid and vice versa. Carcinoids have
u n i f o rm round nuclei with coarse chromatin,
lack nuclear grooves and show
c h romogranin positivity. Furt h e rm o re, prim
a ry carcinoids of the ovary are usually
associated with other teratomatous elements,
whereas the metastatic ones are
generally multi-nodular and bilateral.
The diffuse pattern of granulosa cell
tumours may be confused with a benign
thecoma, particularly when there is
luteinization. A reticulin stain is helpful
since granulosa cells typically grow in
sheets or aggregates bound by reticulin
f i b res, whereas thecomas contain an
abundance of intercellular fibrils surrounding
individual cells. The distinction
A
Fig. 2.58 Adult granulosa cell tumour. Reticulin surrounds
the cords rather than investing individual
cells (reticulin stain).
Fig. 2.60 Adult granulosa cell tumour. Immunostain
for alpha-inhibin shows a diffuse, intensely positive
reaction.
is important since granulosa cell tumours
have an aggressive potential, whereas
thecomas are with rare exceptions
benign. Similarly, the presence of nuclear
grooves and the absence of the characteristic
vascular pattern of endometrioid
stromal sarcoma distinguish AGCT from
the former.
Somatic genetics
In contrast to older studies {1635,2862},
recent karyotypic and fluorescence in situ
hybridization analyses have shown that
trisomy and tetrasomy 12 are rarely pre s-
ent in granulosa cell tumours {1635,
1653,2221,2635,2862}. The few available
studies have shown trisomy 14 {1043}
Fig. 2.61 Adult granulosa cell tumour, diffuse pattern. A Mitotic figures are more readily identifiable in the
diffuse variant. B Note the presence of several nuclear grooves.
B
Sex cord-stromal tumours 147