Invasive breast carcinoma - IARC

A
Fig. 2.76 Poorly differentiated Sertoli-Leydig cell tumour. A Heterologous elements consisting of mucinous glands are intimately associated with primitive gonadal
stroma. B A nodule of primitive gonadal stroma is composed of poorly differentiated spindle-shaped cells with apoptotic bodies.
B
Clinical features
Signs and symptoms
O n e - t h i rd of patients are virilized, and
others may have estrogenic manifestations.
Androgenic manifestations
include amenorrhea, hirsutism, bre a s t
a t ro p h y, clitoral hypert rophy and
hoarseness, whereas estrogenic eff e c t s
include isosexual pseudoprecocity and
m e n o m e t rorrhagia. One-half of the
patients have no endocrine manifestations,
and the symptoms are non-specific.
Patients with poorly diff e re n t i a t e d
neoplasms are slightly more likely to
p resent with androgenic manifestations.
About 10% of cases have tumour rupt
u re or ovarian surface involvement, and
4% have ascites {3217}.
I m a g i n g
A solid, cystic or solid and cystic mass
may be identified on ultrasound, computed
tomography or magnetic re s o-
nance imaging.
M a c r o s c o p y
Over 97% of SLCTs are unilateral. They
may be solid, solid and cystic or, rare l y,
cystic. The size ranges from not
detectible to 35 cm (mean 12-14 cm).
Poorly diff e rentiated tumours are larger.
Solid areas are fleshy and pale yellow,
pink or gre y. Areas of haemorrhage and
n e c rosis are frequent, and torsion and
i n f a rction may be seen.
Tumour spread and staging
About 2-3% of tumours have spre a d
beyond the ovary at pre s e n t a t i o n
{ 3 2 1 7 } .
H i s t o p a t h o l o g y
In well diff e rentiated SLCTs, Sertoli cells
a re present in open or closed tubules
and lack significant nuclear atypia or
mitotic activity {3216}. There is a delicate
fibrous stroma in which Leydig
cells may be found in small clusters.
In tumours of intermediate differentiation,
cellular lobules composed of hyperchromatic
spindle-shaped gonadal stromal
cells with poorly defined cytoplasm are
separated by oedematous stroma. These
merge with cords and poorly developed
tubules of Sertoli cells, some with atypia.
With better differentiation of Sertoli cell
elements, the distinction between the
stromal and Sertoli cell components is
more easily made. Leydig cells are found
in clusters at the periphery of the cellular
lobules or admixed with other elements.
They may be vacuolated, contain lipofuscin
or rarely have Reinke crystals. Mitotic
figures average 5 per 10 high power
fields. Mitotic figures are rare among the
Leydig cells, which also lack cytological
atypia.
In poorly diff e rentiated tumours, a sarcomatoid
stroma resembling primitive
gonadal stroma is a dominant feature ,
and the lobulated arrangement of SLCT
of intermediate diff e rentiation is absent.
Occasional tumours contain bizarre
nuclei. The mitotic activity in the Sert o l i
and stromal elements is variable with a
mean of over 20 per 10 high power
f i e l d s .
I m m u n o p ro f i l e
Positivity is seen for vimentin, keratin
and alpha-inhibin with differing intensity
of expression between sex cord and
s t romal areas. Rare l y, positivity for
epithelial membrane antigen may be
seen. Positivity for estrogen and pro g e s-
t e rone receptors may also be seen in a
minority of cases.
G r a d i n g
S L C Ts are subdivided into well diff e re n-
tiated, intermediate and poorly diff e re n-
tiated forms based on the degree of
tubular diff e rentiation of the Sertoli cell
component (decreasing with incre a s i n g
grade) and the quantity of the primitive
gonadal stroma (increasing with
i n c reasing grade). Leydig cells also
d e c rease with increasing grade.
H e t e rologous elements and/or a re t i f o rm
p a t t e rn may be seen in all but the well
d i ff e rentiated variant.
Somatic genetics
Analysis of six SLCTs has shown limited,
if any, loss of heterozygosity with 10
polymorphic DNA markers that have
shown high rates of loss of hetero z y g o s-
ity in a variety of tumours. Three of these
w e re assessed for clonality by examining
the DNA methylation pattern at a
polymorphic site to the androgen re c e p-
tor gene. The Leydig cells in these thre e
cases were all polyclonal in contrast to
the cells from a pure Leydig cell tumour
that were monoclonal. These findings
suggest that the Leydig cells in SLCTs
a re reactive cells of ovarian stromal origin
and not a neoplastic component of
the tumour {1902}. Trisomy 8 was re p o rted
as the sole karyotypic abnormality in
a SLCT that metastasized {1756}.
154 Tumours of the ovary and peritoneum