898
Chapter 33
subsequently reported.
99–103
Carcinoma occurs in less than
0.5% of FA,
101,104
and in 1% to 2% of PT.
101,102
Clinical Presentation
The age of patients with carcinoma arising in a FA ranges
from 15 to 70 years, with a mean age of 42 to 44 years.
101,104
Women with
in situ
carcinoma have a mean age of 42 to
45 years, and the mean age for patients with invasive carci
noma in a FA is 47 to 52 years.
99
Because patients who have
carcinoma in a FA tend to be somewhat older than those
with FA that lack carcinoma, the possibility of encountering
carcinoma should be anticipated when a FA is excised from
a patient 35 years or older. The age distribution of women
with carcinoma in or associated with a PT is not appreciably
different from women with PT generally, reflecting the older
age distribution of PT.
There are no specific clinical or radiologic clues to indi
cate the presence of
in situ
carcinoma within a FA or a PT.
Invasive carcinoma in or associated with a FA may distort or
blur the margin of the tumor in a mammogram.
105,106
Rarely,
the pattern of calcifications in a FA can suggest intraductal
carcinoma.
105,107
Carcinoma is more likely to be detected in a
fine-needle aspirate from a FA if the carcinomatous compo
nent is extensive. The diagnosis depends upon recognizing
neoplastic cells in the customary background of benign epi
thelium and stromal cells obtained from a typical FA.
108,109
If the lesion consists of
in situ
carcinoma limited to a small
part of the tumor, there may not be sufficient material in
a FNA or a needle core biopsy specimen to be diagnos
tic.
110
Because there are no good clinical indicators of the
presence of carcinoma in a fibroepithelial tumor, the diag
nosis is generally not suspected until a needle core biopsy
has been obtained or the excised tumor has been examined
pathologically.
Gross Pathology
When
in situ
carcinoma is present in a FA or PT, it will of
ten not be apparent on gross inspection.
99
FA that harbor
carcinoma may not be especially large and many do not
exceed 2 cm. Unusual firmness may develop at the site of
intraductal carcinoma, particularly in those which are of
high-grade with necrosis and calcifications. Invasive carci
noma confined to a FA is generally inconspicuous grossly,
but invasion into the adjacent breast tissue can distort the
tumor enough to be evident.
Microscopic Pathology
The distinction between atypical hyperplasia and
in situ
carcinoma in a FA or PT is based on the same criteria that
are used to assess epithelial proliferation in the mammary
parenchyma. The characteristics of epithelial abnormalities
within a FA or PT do not necessarily reflect the proliferative
status of the surrounding breast tissue.
More information about secretory carcinoma can be found
in Chapter 22.
Among the 132
BRCA-positive women
with breast
carcinoma who participated in a high-risk protocol at The
University of Texas M.D. Anderson Cancer Center, 106
second-generation women could be paired with a family
member in the previous (first) generation who was diagnosed
with a BRCA-related carcinoma in either breast or ovarian
carcinoma.
93
The median age of carcinoma diagnosis in the
first-generation patients was 48 years (range, 30 to 72 years)
and in the second-generation patients, it was 42 years (range,
28 to 55 years). This trend was found in subgroups with
either a
BRCA1
or
BRCA2
mutation. The statistically sig
nificant difference in age at diagnosis suggests that
BRCA
-
mutation–related carcinomas in at least one subsequent
generation occur at an earlier age after the first case is identi
fied. The prognosis of breast carcinoma patients in
BRCA 1
and
BRCA 2
carriers has been controversial. In a large inter
national population-based cohort study
BRCA1
and
BRCA2
mutation carriers were found to have no significant differ
ence in outcome when compared with patients with sporadic
breast carcinoma after adjusting for age, stage and grade of
tumor, lymph node and hormone receptor status, and year
of diagnosis.
94
Li–Fraumeni syndrome
is a rare autosomal dominant
disorder that is linked to germline mutations of the
p53
tumor suppressor gene. The syndrome increases sus
ceptibility to certain forms of cancer, including those of
the breast, bone, and soft tissues. A cohort of eight breast
carcinoma patients with a median age at diagnosis of 30
from Li–Fraumeni families with the associated germline
p53
mutations was studied in France.
95
Six of eight received
radiation (including three after mastectomy). After a median
follow-up of 6 years, an extraordinarily high incidence
of subsequent events occurred in the six radiated patients
consisting of three ipsilateral breast recurrences; three
contralateral breast carcinomas; two radiation-associated
sarcomas; one thyroid carcinoma in field. The data suggest
that bilateral mastectomy is appropriate and that radiation
therapy is contraindicated in this setting because the patients
appear to have a genetic predisposition to develop radiation-
associated malignant neoplasms.
CARCINOMA ARISING IN FIBROEPITHELIAL
NEOPLASMS
Fibroepithelial neoplasms consist of proliferating epithelial
and stromal mammary tissues. Fibroadenomas (FA) arise
from the stroma and epithelium of lobular-terminal duct
units, whereas phyllodes tumors (PT) are composed pre
dominantly of periductal stroma and duct epithelium.
In 1931, Cheatle and Cutler
96
described carcinoma aris
ing in a FA, and similar lesions were reported in 1940 by
Harrington and Miller.
97
The first series, consisting of 26
patients, was published in 1967.
98
Numerous cases have been
