Invasive breast carcinoma - IARC

Fig. 2.43 Clear cell adenocarcinoma. Round
tubules lined by flattened to highly atypical hobnail
cells are present in a fibroedematous stroma (PAShematoxylin
stain).
fibrous tissue or abundant hyaline material.
The most common cell types are the
clear and hobnail cells. Clear cells tend
to be arranged in solid nests or masses
or lining cysts, tubules and papillae,
whereas hobnail cells line tubules and
cysts and cover papillary structures. The
clear cells tend to be rounded or polygonal
with eccentric nuclei, often containing
prominent nucleoli. The hobnail cells
have scant cytoplasm and contain bulbous
hyperc h romatic nuclei that protrude
into the lumens of the tubules.
Flattened or cuboidal cells are also
e n c o u n t e red. Occasionally, oxyphilic
cells with abundant eosinophilic cytoplasm,
which in a few instances make up
the majority of the neoplasm, are
observed. Signet-ring cells often contain
inspissated mucinous material in the
centre of a vacuole, creating what has
been referred to as a "targetoid" cell. The
clear cells contain abundant glycogen
and may also contain some lipid. Mucin
may be found, typically located in the
lumens of tubules and cysts and is abundant
within the cytoplasm of the signetring
cells.
Immmunoprofile
Clear cell adenocarcinomas stain strongly
and diffusely for keratins, epithelial
membrane antigen, Leu M1 and B72.3.
Stains for carcinoembryonic antigen are
positive in 38% of cases and for CA125
(OC-125) in 50%. There have been a few
reports of clear cell adenocarcinomas
containing AFP. In a patient with clear
cell adenocarcinoma who developed
h y p e rcalcaemia when the tumour
recurred, immunostains for parathyroid
h o rm o n e - related protein were stro n g l y
positive in the recurrent carcinoma but
negative in the primary carc i n o m a
{3209}.
Differential diagnosis
The differential diagnosis includes germ
cell tumours, particularly yolk sac
tumour, dysgerminoma and, rarely, struma
ovarii, endometrioid carcinoma with
s e c re t o ry change and steroid cell
tumours that contain prominent areas of
cells with clear cytoplasm. Metastatic
clear cell neoplasms from outside the
female genital system are very rare.
Clinical information can be particularly
helpful in the differential diagnosis as
g e rm cell tumours occur in young
women, and elevated serum alpha-fetoprotein
(AFP) levels are always found in
patients with yolk sac tumours. Histologically,
the papillary structures of clear
cell carcinoma are more complex than
those of yolk sac tumours and contain
hyalinized cores. In contrast, yolk sac
tumours display a variety of distinctive
features including a prominent reticular
p a t t e rn and Schiller-Duvall bodies.
Negative immunostains for AFP are useful
in excluding yolk sac tumours,
although rare examples of AFP-containing
clear cell carcinomas have been
reported. Positive staining for EMA and
diffuse strong positivity for cytokeratins
exclude dysgerminoma. Immunostains
for thyroglobulin are very useful in ruling
out struma ovarii.
Endometrioid carcinomas with secretory
change typically are composed of cells
that are columnar with subnuclear and
supranuclear vacuolization re s e m b l i n g
early secretory endometrium. In contrast,
the clear cell changes in clear cell carcinoma
are more diffuse, the cells are
polygonal, and they typically display the
other characteristic patterns of clear cell
c a rcinoma. A metaplastic squamous
component may be seen in endometrioid
carcinoma and is not observed in clear
cell carcinoma. In contrast to clear cell
carcinomas, steroid cell tumours of the
ovary that contain prominent clear cytoplasm
are smaller, well circumscribed,
have low grade nuclear features and
stain strongly for alpha-inhibin.
Grading
Nuclei in clear cell carcinomas range
from grade 1 to grade 3, but pure grade
A
B
Fig. 2.44 Borderline clear cell adenofibromatous tumour. A Though predominantly solid on the right, the tumour is composed of numerous small cysts on the left.
B Histologically, round glands, many of which are dilated and contain secretions, proliferate in a fibrous stroma.
138 Tumours of the ovary and peritoneum