Invasive breast carcinoma - IARC

mal origin without crystals of Reinke
{ 1 1 6 4 } .
Clinical features
Most occur in postmenopausal women
and are associated with estro g e n i c
e ffects, but occasional patients have
a n d rogenic manifestations {477}.
M a c r o s c o p y
These are usually unilateral tumours and
are generally small. They are typically
well circumscribed and on sectioning are
usually grey-white or yellow.
H i s t o p a t h o l o g y
These neoplasms are well circ u m-
scribed, are located in the ovarian stroma
and are composed of a nodule of
luteinized stromal cells that may be
arranged diffusely or, less commonly, in
nests and cords. The cytoplasm is pale
or eosinophilic, the nuclei are bland,
and mitoses are rare. Most cases are
associated with stromal hypert h e c o s i s
in the same and/or contralateral ovary.
In such cases it is arbitrary when a nodule
of luteinized cells in stromal hyperthecosis
is re g a rded as a stromal luteoma,
but generally a cut-off of 1.0 cm
in diameter is used. Degenerative
changes may occur in stromal luteomas
resulting in the formation of spaces that
can simulate vessels or glandular formation.
Reinke crystals are not pre s e n t .
S t romal luteomas usually exhibit positive
immunohistochemical staining for
a l p h a - i n h i b i n .
Prognosis and predictive factors
All of the re p o rted cases have behaved
in a benign fashion.
Leydig cell tumours
D e f i n i t i o n
R a re ovarian steroid cell neoplasms
composed entirely or predominantly of
Leydig cells that contain crystals of
Reinke. In the case of larger tumours it
may not be possible to determ i n e
whether the tumour arose in the ovarian
p a renchyma or in the hilus, and these
a re re f e r red to as Leydig cell tumours
not otherwise specified. Other tumours
in this group include hilar cell tumours
and Leydig cell tumour of non-hilar
t y p e .
Clinical features
These neoplasms typically occur in
postmenopausal women {2171,2472}
(average age 58 years) but may occur
in young women, pregnant women
{2165} or children. They are usually
associated with androgenic manifestations,
but occasionally produce estrogenic
effects and are associated with
endometrial carcinoma {1278,2455}. In
single re p o rts ovarian Leydig cell
tumours have been associated with multiple
endocrine neoplasia syndro m e
{2630} and congenital adrenal hyperplasia
{1718}.
I m m u n o p ro f i l e
Leydig cell tumours of all types are
intensely positive for alpha-inhibin and
vimentin. There may be focal re a c t i v i t y
for keratins (CAM 5.2, AE1/AE3) with
positivity for actin, CD68, desmin,
epithelial membrane antigen and S-100
p rotein re p o rted {2620}.
Prognosis and predictive factors
The clinical behaviour of all neoplasms
in the pure Leydig cell category is
benign, and neither clinical re c u r re n c e
nor metastasis has been documented.
Hilus cell tumour
D e f i n i t i o n
A Leydig cell tumour arising in the ovarian
hilus separated from the medullary
s t ro m a .
M a c r o s c o p y
Hilus cell tumours are usually small, well
c i rcumscribed lesions located at the
ovarian hilus and typically have a re d
b rown to yellow appearance on sectioning.
Rare l y, they are bilateral {739,1718}.
When they are larger, the hilar location
may no longer be appare n t .
H i s t o p a t h o l o g y
On histological examination the lesion is
well circumscribed and comprised of
cells with abundant cytoplasm that usually
is eosinophilic but which may be
clear with abundant intracytoplasmic
lipid. Lipofuscin pigment is often seen,
and characteristic Reinke crystals were
p resent in 57% of cases in the largest
series {2171}. These are eosinophilic,
rod-shaped inclusions. Occasionally,
they are numerous, but they are often
identified only after extensive searc h i n g .
P TAH histological staining or electro n
m i c roscopy may facilitate their identification.
Often the nuclei in Leydig cell
tumours cluster with nuclear-rich are a s
separated by nuclear- f ree zones. The
nuclear features are usually bland, but
occasionally focal nuclear atypia may
be found, an observation of no clinical
significance. Mitotic figures are rare .
Often, there is a background of hyperplasia
of the adjacent non-neoplastic
hilar cells in association with non-myelinated
nerve fibres.
Although the definitive diagnosis of a
hilar cell tumour re q u i res the identification
of Reinke crystals, a pre s u m p t i v e
diagnosis can be made without cry s t a l s
if the typical histological features are
p resent in a neoplasm with a hilar location,
especially if it is associated with
hilus cell hyperplasia or nerve fibre s
{ 2 1 7 1 } .
Leydig cell tumour, non-hilar type
D e f i n i t i o n
A Leydig cell tumour that orginates fro m
the ovarian stroma and containing cry s-
tals of Reinke.
E p i d e m i o l o g y
Leydig cell tumours of non-hilar type
have been re p o rted much less often
than hilus cell tumours, but their true re l-
ative frequency is unknown.
M a c r o s c o p y
These tumours are macroscopically well
c i rcumscribed and centered in the
m e d u l l a ry region {2472}.
H i s t o p a t h o l o g y
They are histologically composed of
s t e roid cells without discernible lipid
and surrounded by ovarian stroma that
often shows stromal hypert h e c o s i s .
Leydig cells containing demonstrable
c rystals of Reinke must be identified histologically
in order to make the diagnosis,
and lipofuscin pigment is often
p re s e n t .
H i s t o g e n e s i s
These tumours originate from the ovarian
stroma, an origin supported by the
r a re non-neoplastic transformation of
ovarian stromal cells to Leydig cells
{ 2 7 8 9 } .
Sex cord-stromal tumours 161