Invasive breast carcinoma - IARC

Fig. 2.62 Juvenile granulosa cell tumour. Neoplas -
tic cell aggregates form multiple round to oval follicles
containing basophilic fluid.
and structural changes in chromosome 6
with loss of 6q material {3021}.
Prognosis and predictive factors
All granulosa cell tumours have a potential
for aggressive behaviour. From 10-
50% of patients develop re c u r re n c e s .
Some re c u r rences of AGCT develop as
late as 20-30 years following the initial
diagnosis {906,2058,2786}, and long term
follow-up is re q u i red.
The most important prognostic factor is
the stage of the tumour {1815}. Nearly
90% of patients with granulosa cell
tumour have stage I disease, however,
and the prediction of tumour behaviour is
most difficult in this group. Factors re l a t e d
to a relatively poor prognosis include age
over 40 years at the time of diagnosis,
large tumour size (>5cm), bilaterality,
mitotic activity and atypia {906,1871,
2786}. There is, however, disagre e m e n t
on the precise significance of some of
these factors. Among adults, survival is
adversely affected by tumour rupture .
Juvenile granulosa cell tumour
Epidemiology
Accounting for nearly 5% of all granulosa
cell tumours, juvenile granulosa cell tumour
(JGCT) is encountered pre d o m i n a n t-
ly during the first 3 decades of life {3195}.
Clinical features
In prepubertal girls, approximately 80%
are associated with isosexual pseudoprecocity
{277,3195,3242}.
bilateral, and only 2% have extraovarian
s p re a d .
Histopathology
JGCT is characterized by a nodular or diffuse
cellular growth punctuated by macrofollicles
of varying sizes and shapes.
Their lumens contain eosinophilic or
basophilic fluid. A fibrothecomatous stroma
with variable luteinization and/or oedema
is often evident. The typically ro u n d e d
neoplastic granulosa cells have abundant
eosinophilic and/or vacuolated cytoplasm;
and almost all nuclei lack gro o v e s .
Mitotic figures are abundant. Cytomegaly
with macronuclei, multinucleation and
b i z a r re multilobulated nuclei is occasionally
observed {2890,3210}.
Differential diagnosis
Only the entity of small cell carcinoma
associated with hypercalcaemia, which
A
also occurs in children and young
women, poses a significant diagnostic
p roblem. The clinical presentation of
JGCT with estrogenic manifestations and
that of small cell carcinoma with hypercalcaemia
are important clues to the precise
diagnosis.
Dissemination beyond the ovary is evident
in 20% of these small cell carcinomas
at presentation, a feature that is
most unusual for a JGCT. The presence
of necrosis and more eccentric nuclei in
the carcinomas are additional features
that can help. The presence of mucinous
epithelium in 10% of cases and clusters
of larger cells in most small cell carcinomas
provide further support. Finally,
immunostains for alpha-inhibin are positive
in granulosa cell tumours but completely
negative in the carcinomas. Both
tumours may be negative with a variety of
epithelial markers.
Macroscopy
The macroscopic appearance of JGCT is
not distinctive and is similar in its spectrum
of appearances to the adult variant.
Tumour spread and staging
JGCT presents almost always as stage I
disease; less than 5% of tumours are
B
Fig. 2.63 Juvenile granulosa cell tumour. A Solid nests of primitive granulosa cells alternate with macrofollicles
lined by the same cell population. B Moderate to severe atypia is sometimes evident in both the solid
and the cystic areas.
148 Tumours of the ovary and peritoneum