Unusual Clinical Presentation of Carcinoma
923
FIG. 33.31.
Inflammatory carcinoma.
Spread to the chest
wall is evident.
In comparisons of samples from primary IBC before and
after neoadjuvant chemotherapy, two groups of investiga
tors found no significant difference in immunohistochemi
cal HER2 expression.
257,258
Overexpression of HER2 was also
maintained in metastatic carcinoma foci. Arens et al.
258
also
documented the absence of changes in HER2 expression in
pre- and posttreatment samples of the primary tumor by
fluorescence
in situ
hybridization (FISH) analysis. There
were no significant differences in the expression of ER and
PR and p53 between pre- and posttreatment samples from
primary carcinomas.
IBC exhibits prominent angiogenesis, as evidenced by
high microvessel density (MVD)
259
and a high endothelial
proliferation index.
260
It has been reported that a number of
angiogenesis-related genes are upregulated in IBC
261
and that
some angiogenic factors are overexpressed in these tumors.
262
Angiogenic factors are likely to be targeted as the treatment
of IBC evolves. Wedam et al.
263
described the antiangiogenic
effect of bevacizumab, a recombinant humanized monoclo
nal antibody to vascular endothelial growth factor (VEGF),
which was given prior to and during anthracycline and taxane
neoadjuvant treatment of 21 patients with inflammatory and
locally advanced breast carcinoma. After anti-VEGF treat
ment alone, expression of the phosphorylated tyrosine kinase
receptor VEGFR2 in tumor cells was reduced by a median
of 66.7%, and apoptosis in the tumor increased by a mean
of 128.9%, but there was no change in MVD or in VEGF-A
expression. Dynamic contrast-enhanced MRI yielded results
indicative of reduced angiogenesis. Antiangiogenic effects of
bevacizumab were also observed when the monoclonal anti
body was administered with combination chemotherapy.
Noninflammatory Cutaneous Involvement
by Breast Carcinoma
The histopathologic finding of tumor emboli in dermal lym
phatic channels without characteristic clinically evident cu
taneous manifestations does not qualify as IBC. Staging in
this group should be based on tumor size and axillary nodal
status. Guth et al.
264
reported that the prognosis of patients
with clinically evident noninflammatory cutaneous involve
ment by carcinoma was significantly less favorable than that
of patients with skin involvement that was not clinically
apparent. The 5-year distant DFS was 56.9% in the former
group and 82.0% in the latter.
Secondary Inflammatory Carcinoma
The term “secondary IBC” refers to metastatic foci with in
flammatory features in the skin of patients most of whom
did not have primary inflammatory carcinoma. It more of
ten develops on the chest wall at the site of prior mastectomy
than at sites of distant cutaneous metastases.
265
Clinically,
the inflammatory form of recurrent carcinoma is character
ized by discoloration, edema, and
peau d’orange
appearance
of the skin, similar to primary inflammatory carcinoma. Oc
casionally, secondary inflammatory carcinoma is limited to
the treated region in patients who received postoperative
radiotherapy, or it may occur only outside of an irradiated
field (Fig. 33.32). Palpable tumor infiltrates are commonly
found clinically in the skin.
265
Inflammatory changes are not
specific for mammary carcinoma, since they have been re
ported in skin metastases from carcinoma of the pancreas,
stomach, lung, and other sites.
266,267
Gross Pathology
Patients with primary IBC have an underlying invasive mam
mary carcinoma. The primary tumor is typically indistinct—
clinically, radiologically, and pathologically. If a mastectomy
is performed, the size of the tumor may not be recorded be
cause the gross margins cannot be defined (Fig. 33.33). Fre
quently, the breast is said to be diffusely involved, or a large
tumor is described.
268
As a consequence, accurate data about
the size distribution of the primary tumors are unavailable. In
one series, localized tumors measured 2 to 12 cm (averaging
FIG. 33.32.
Recurrent inflammatory carcinoma.
Inflam-
matory carcinoma appears to be restricted to the area of
radiation on the chest wall and clavicular region.
