Invasive breast carcinoma - IARC

Mean ages of 21 and 38 years and
median ages of 33 and 50 years have
been re p o rted in the two largest series
{2882,3215}.
Clinical features
The tumours are functional in 40-60% of
cases, most often estrogenic, but occasionally
androgenic or rarely both.
R a re l y, the tumour produces pro g e s t i n s .
Clinical manifestations include isosexual
pseudopre c o c i t y, menometro r r h a g i a ,
amenorrhea, hirsutism, breast atro p h y,
clitoral hypert rophy and hoarseness.
Cases with menstrual disturbances or
postmenopausal bleeding may show
hyperplasia or adenocarcinoma of the
endometrium. A peritoneal decidual
reaction may be seen. Patients with
S e rtoli cell tumour may have elevated
levels of serum estrogen, pro g e s t e ro n e
and luteinizing hormone. Rare l y, the
tumour may cause hypertension due to
renin pro d u c t i o n .
M a c r o s c o p y
These are unilateral neoplasms, and the
ovaries are involved with equal fre q u e n-
c y. They range in size from 1-28 cm with
an average of 7-9 cm. They are well circumscribed,
solid neoplasms with a
smooth or lobulated external surface, a
fleshy consistency and a yellow-tan sectioned
surface. Areas of haemorrhage
and/or cystic degeneration may be seen
in larger tumours. Rare examples are
totally cystic or are solid with fibro s i s
and ossification.
H i s t o p a t h o l o g y
A variety of tubular arrangements characterize
Sertoli cell tumours. The tubular
p a t t e rn is either open or closed (with
p a i red cell arrangements) and simple or
complex. Simple tubules are surro u n d-
ed by a basement membrane and may
contain a central hyaline body. Complex
tubules form multiple lumens often filled
with hyaline bodies and surrounded by
a thick basement membrane that may
coalesce to form hyalinized are a s .
D i ffuse and pseudopapillary pattern s
may be seen. In some tumours, cells
distended by intracytoplasmic lipid are
dominant in a pattern known as "folliculome
lipidique". The Sertoli cell tumours
that occur in women with the Peutz-
Jeghers syndrome may have abundant
eosinophilic cytoplasm, termed the
oxyphilic variant {852}. The nucleus is
Fig. 2.81 Sex cord tumour with annular tubules in a case not associated with the Peutz-Jeghers syndrome. A
complex annular tubular pattern consists of pale cells arranged around multiple hyaline bodies.
typically oval or spherical with a small
nucleolus. The cytoplasm is clear or
lightly vacuolated, stains for lipid are
positive, and glycogen may be demonstrated.
Mitotic figures are usually
scanty (9 mitotic figures per 10 high power
fields may be seen in tumours fro m
younger women. The neoplasm may
contain rare Leydig cells, but lacks the
primitive gonadal stroma characteristic
of Sertoli-Leydig cell tumours.
I m m u n o p ro f i l e
S e rtoli cell tumours are variably positive
for keratins, vimentin and alpha-inhibin.
CD99 and calretinin are positive in
about 50% of cases. The tumours are
negative for epithelial membrane antigen.
E l e c t ron micro s c o p y
A diagnostic feature of Sertoli cell
tumour is the presence of Charc o t -
Böttcher (CB) filaments and Spangaro
bodies. These bodies re p resent aggregates
of intracytoplasmic micro f i l a m e n t s
of varying sizeand are not present in
e v e ry cell or every tumour. CB filaments
have been found most frequently in the
complex tubular variant, the so-called
sex cord tumour with annular tubules
( S C TAT ) .
D i ff e rential diagnosis
S e rtoli cell tumours must be distinguished
from struma ovarii, carc i n o i d
and endometrioid carcinoma (see section
on endometrioid carc i n o m a ) .
Phenotypic females with the andro g e n
insensitivity syndrome (AIS) may be
i n c o r rectly diagnosed as having a
S e rtoli cell tumour of the ovary if the synd
rome has not been diagnosed pre o p-
eratively {2498}. On the other hand,
S e rtoli cell tumours can occur in the
testes of patients with AIS. While most
a re benign, rare malignant Sertoli cell
tumours have been re p o rted in this setting
{3165}.
Somatic genetics
T h e re is little information on chro m o s o-
mal abnormalities in these tumours. An
extra isochromosome 1q was seen in
one tumour {2208}.
Genetic susceptibility
A variety of Sertoli cell phenotypes
including SCTAT {2599}, oxyphilic {852}
and lipid rich (folliculome lipidique) variants
have been described in patients
with the Peutz-Jeghers syndrome (PJS),
an autosomal dominant disease with a
p ropensity for breast, intestinal and
gynaecological neoplasia.
Prognosis and predictive factors
These tumours are typically benign. In
the rare forms that behave clinically in
an aggressive fashion, infiltration of the
ovarian stroma, extension beyond the
o v a ry and intravascular extension may
be seen. Cytological atypia and a high
Sex cord-stromal tumours 157