Invasive breast carcinoma - IARC

Fig. 1.15 Invasive carcinomas with stromal osteoclastic
giant cells often have vascular stromal tissue
with haemosiderin pigment accumulation giving
them a brown macroscopic appearance.
vascular stroma, with extravasated re d
blood cells, lymphocytes, monocytes
along with mononucleated and binucleated
histiocytes some containing
haemosiderin. The giant cells are variable
in size and appear to embrace the
epithelial component or are found within
lumena formed by the cancer cells. The
giant cells contain a variable number of
nuclei. The giant cells and hypervascular
reactive stroma can be observed in
lymph node metastases and in re c u r-
rences {2952}.
The carcinomatous part of the lesion is
most frequently a well to moderately diff
e rentiated infiltrating ductal carc i n o m a
but all the other histological types have
been observed particularly invasive
c r i b r i f o rm carcinoma {2003,2241}, and
also tubular, mucinous, papillary {3062},
lobular {1274,2837}, squamous and
other metaplastic patterns {1200,2044,
3 0 6 2 } .
About one-third of the re p o rted cases
had lymph nodes metastasis. The five
year survival rate is around 70%, similar
to, or better than, patients with ord i n a ry
infiltrating carcinomas {3062}. Pro g n o s i s
is related to the characteristics of the
associated carcinoma and does not
appear to be influenced by the pre s-
ence of stromal giant cells.
The giant cells show uniform expre s s i o n
of CD68 (as demonsrated by KP1 antibody
on paraffin sections) {1200} and
a re negative for S100 protein, actin, and
negative for cytokeratin, EMA, estro g e n
and pro g e s t e rone receptors {2869}.
The giant cells are strongly positive
for acid phosphatase, non-specific
esterase and lysosyme, but negative
for alkaline phosphatase indicative of
morphological similarity to histiocytic
cells and osteoclasts {2423,2869,2952,
3 0 2 5 } .
A number of ultrastructural and immunohistochemical
studies have confirm e d
the histiocytic nature of the osteoclastic
cells present in these unusual carc i n o-
mas {2632,2869,2952,3025}. In vitro
studies have recently shown that o s t e o-
clasts may form directly from a precursor
cell population of monocytes
and macrophages. Tumour associated
m a c rophages (TAMs) are capable of diff
e rentiating into multinucleated cells,
which can affect bone resorption in
metastases {2313}. Osteoclastic giant
cells in carcinoma are probably also
related to TAMs. Angiogenesis and
chemotactic agents produced by the
c a rcinoma may be responsible for the
migration of histiocytes to the are a
involved by cancer and their ultimate
t r a n s f o rmation to osteoclastic giant cells
{ 2 6 3 8 , 2 8 6 9 } .
Carcinoma with
choriocarcinomatous features
Patients with ductal NOS carcinoma may
have elevated levels of serum human
β −chorionic gonadotrophin (β- H C G )
{2649} and as many as 60% of ductal
NOS carcinoma have been found to contain
β-HCG positive cells {1243}.
Histological evidence of choriocarcinomatous
diff e rentiation, however, is
exceptionally rare with only a few cases
re p o rted {993,1061,2508}. All were in
women between 50 and 70 years old.
Carcinoma with melanotic features
A few case re p o rts have described
exceptional tumours of the mammary
parenchyma that appear to represent
combinations of ductal carcinoma and
malignant melanoma {2031,2146,2485}
and in some of these cases, there
appeared to be a transition from one cell
type to the other. A recent genetic analysis
of one such case showed loss of heterozygosity
at the same chromosomal
loci in all the components of the tumour,
suggesting an origin from the same neoplastic
clone {2031}.
The mere presence of melanin in bre a s t
cancer cells should not be construed as
evidence of melanocytic diff e re n t i a t i o n ,
since melanin pigmentation of carc i n o m a
cells can occur when breast cancers
invade the skin and involve the derm o -
e p i d e rmal junction {150}. In addition,
c a re must be taken to distinguish tumours
showing melanocytic diff e rentiation fro m
b reast carcinomas with prominent cytoplasmic
lipofuscin deposition {2663}.
A
B
Fig. 1.16 A Invasive ductal carcinoma with stromal osteoclastic giant cells and haemosiderin-laden macrophages. B The invasive ductal carcinoma is low grade.
Multinucleated giant cells are evident in the stroma.
22 Tumours of the breast