Invasive breast carcinoma - IARC

Fig. 1.27 Medullary carcinoma. The tumour is composed of a syncytial sheet of large pleomorphic cells. There
is no glandular differentiation. The adjacent stroma contains numerous plasma cells and mature lymphocytes.
been reported {1386,3170}. MC typically
lack estrogen receptors (ER) expression
{1244,1340,2204,2272}, and have a low
incidence of ERBB2 overe x p re s s i o n
{2439,2746,2750}.
The cytokeratin profile is similar in typical
and atypical MC, and does not differ significantly
from that of common ductal
tumours {610,1340,2943}. The cell cohesiveness
of MC, contrasting with the
poorly diff e rentiated pattern and high
mitotic index, has been characterized by
the expression of the intercellular adhesion
molecule-1 {156} and of E-cadherin
{444}. This feature might account for the
good limitation of the tumour and the late
axillary lymph node extension.
Immunophenotyping of the lymphoid
infiltrate of MC has shown that most cells
correspond to mature T lymphocytes, a
profile similar to that observed in common
ductal carcinomas {214}. Evidence
Fig. 1.28 Medullary carcinoma. Note multinucleated
malignant cells with atypical mitoses.
of polyclonality of the B-cell infiltrate has
been obtained {1510}. Plasma cells
w e re found to express IgG {1310} or
IgA {1254}. The recent finding of an
i n c reased number of activated cytotoxic
lymphocytes in MC may correspond to
an active host versus tumour response
{3169}. Expression of HLA class I and
class II molecules by carcinoma cells,
as a cause or a consequence of the
immune response, was reported to characterize
MC {840}. Although EBV-associated
lymphoepithelioma shares some
morphological features with MC, only a
few cases were found associated with
EBV, in contrast with the 31-51% rate of
EBV-positive common ductal carcinomas
{310,857}.
Genetics
A high frequency of MC has been reported
in patients with BRCA1 germ line
mutation, whereas this observation was
less common among patients with
BRCA2 mutation or with no known germ
line mutation. Typical MC were observed
in 7.8% {1767} to 13% {8} of BRCA1-
associated carcinomas, versus 2% in
control populations. However, the presence
of medullary features was found in
35% {1767} to 60% {121} of tumours arising
in BRCA1 carriers. Reciprocally, in a
population of MC, germ line mutations of
BRCA1 was observed in 11% of the
cases {764}. There is thus a large overlap
between medullary features and the phenotype
of BRCA1 germline associated
tumours, but not all BRCA1 mutations
lead to medullary phenotype.
MC are also characterized by a high rate
of TP53 alterations. Somatic mutations
were found in 39% {1766} to 100% {643}
of MC, together with protein accumulation
in 61-87% of the cases {643,
711,1345}. This contrasts with the 25-
30% rate of TP53 alterations found in
common ductal carcinomas {643,711,
1345}. No specific TP53 mutation was
found to characterize MC {643} but TP53
overstaining may be considered as a
biological marker of MC. Both TP53 and
BRCA1 are involved in the process of
DNA repair and the alteration of these
genes, together with a high proliferation
rate, may account for the high sensitivity
of MC to radio- and/or chemotherapy.
Prognosis and predictive factors
MC has been re p o rted to have a better
p rognosis than the common IDC {1339,
1 7 4 0 , 1 9 0 8 , 2 2 0 4 , 2 3 3 4 , 2 3 5 2 , 2 3 6 7 , 2 3 7 0 ,
3064} but this has been questioned by
others {285,771,876}. The overall 10-yearsurvival
re p o rted for MC varies between
about 50% {285,771,1740} to more than
90% {1339,2334,3064}. Diff e rences in
diagnostic criteria may account for this
disparity and several re p o rts underline
that stringency in diagnostic criteria is
re q u i red to preserve the anatomo-clinical
identity of MC {876,2334,2370,3064}
which is justified by the characteristic
p rognosis of this tumour. The outcome of
MC associated with more than thre e
metastatic axillary lymph nodes has been
re p o rted to be poor {285,1740,2202} or
no diff e rent from that of common ductal
tumours {876,2352}. However, less than
10% of MC {876,1339,2334,2352,2370}
p resent with node metastases, and this
might account in part for the re l a t i v e l y
favourable overall prognosis of MC.
Table 1.06
Histological criteria required for a diagnosis of MC.
> Syncytial growth pattern (> 75%)
> Absence of glandular structures
> Diffuse lymphoplasmacytic infiltrate,
moderate to marked
> Nuclear pleomorphism, moderate to marked
> Complete histological circumscription
Invasive breast cancer
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