Fibrocystic change encompasses a group of morphologic changes
that often produce palpable lumps and which are characterized
by various combinations of cysts, fibrous overgrowth, and epithelial
proliferation. Some of these changes are entirely innocuous while
others are associated with increased risk of subsequent carcinoma.
A diagnosis of fibrocystic change should therefore specify the
components of the morphologic changes present. The changes involve
the terminal duct lobular unit are common microscopic findings
in otherwise normal breasts.
The cause of fibrocystic change is not known. It is the single
most common disorder of the breast. The condition is diagnosed
frequently between the ages of 20 and 55 and decreases progressively
after the menopause. Fibrocystic change presents with asymptomatic
masses in the breast, which are discovered by palpation. The masses
vary from diffuse small irregularities (lumpy bumpy breast) to
a discrete mass or masses. It may also present with pain, which
may be cyclical with midcycle or premenstrual discomfort. Pain
may be focal or diffuse and may or may not be associated with
Fibrocystic change. Low power view showing multiple cysts and
foci of epithelial hyperplasia.
The cysts, which arise in the TDLU, usually unilocular. Smaller
cysts are not discernable on gross examination but clusters of
small cysts may be palpable. Large cysts often contain brown fluid,
which gives a blue color to the intact cyst, the blue-domed cyst
Histologically, cysts may be lined by flattened epithelium, columnar
epithelium with features of apocrine cells or may completely lack
an epithelial lining.
Single cyst without epithelial lining.
Multiple cysts some lined by metaplastic apocrine cells (lower
This refers to a histologic alteration of the epithelium of TDLUs
in which the cells resemble apocrine sweat gland epithelium. Embryologically,
the breasts arise from the same anlage that produces apocrine
glands. However, apocrine glands are not part of the normal histologic
components of the breast, nevertheless any benign proliferative
lesion may contain cells with the cytologic features of apocrine
There are no specific gross features associated with apocrine
metaplasia. The condition is seen most frequently in the epithelial
lining of cysts. It consists of cuboidal to tall columnar cells
with fine granular, eosinophilic cytoplasm, and round, uniform,
basally placed nuclei with single central, small nucleoli. Snouts
or blebs protrude from the apical surface into the
glandular lumen. Cells lining cysts may be flattened or may form
florid papillary proliferations, which may show bridging. Mitoses
are almost never seen in ordinary apocrine metaplasia.
This condition most often occurs as an incidental microscopic
finding but may manifest as a palpable mass that may be mistaken
clinically for cancer. It is almost always associated with other
forms of fibrocystic change. Diffuse microcalcifications are commonly
seen in the lesion, which may mimic carcinoma on mammography.
Microscopically, sclerosing adenosis consists of proliferation
of ductular structures and stroma with distortion of the TDLU.
Multiple altered lobules may be seen. The proliferated ductules
may be compressed and deformed producing whorls and cords that
may mimic infiltrating carcinoma, particularly in the center of
Epithelial or ductal hyperplasia describes a proliferative condition
that is manifested histologically as an increase in the cellularity
of the epithelium of the TDLU. It is a microscopic finding, which
cannot be predicted clinically or by mammographic examination.
The lesion may coexist with other features of fibrocystic change,
but in some cases may form the predominant pattern.
Epithelial hyperplasia ranges from mild through florid but typical
(i.e. without atypia) to cytologic atypia short of malignancy.
There is increase in epithelial layer lining, which distends the
terminal ducts and ductules. The epithelial proliferation may
either form papillary tufts projecting into the lumen with a tendency
to bridge and create arcades or form solid masses which fill the
lumen and may have irregular fenestrations. Individual cell borders
are inconspicuous so that the cell mass has a syncytial appearance.
Nuclear spacing is uneven leading to overcrowding and nuclear
overlap in areas and nucleoli are inconspicuous or absent. Often
two distinct cell populations, epithelial and myoepithelial cells,
may be discerned.
Atypical hyperplasia has some of the architectural and cytologic
features of carcinoma in situ but lack the complete criteria for
that diagnosis and is categorized as ductal or lobular in type.
Page and Dupont have studied the relationship between fibrocystic
change and the relative risk of developing subsequent invasive
carcinoma (NEJM 312:146-151, 1985). The study has formed the basis
of a consensus statement adopted by the College of American Pathologists
and the American Cancer Society (Arch Pathol 110:171, 1986). The
statement is summarized below:
No increased risk
Cyst, apocrine metaplasia, sclerosing adenosis, fibrosis and
mild hyperplasia (more than 2 but less than 4 cells thick)
Slightly increased risk (1.5 to 2X)
Hyperplasia- moderate or florid, solid or papillary (refers
to extensive degrees of epithelial proliferation)
Papilloma with fibrovascular core (peripheral papilloma)
Moderately increased risk (5X)
Atypical hyperplasia (AH) ductal or lobular
Note: Central intraduct papilloma is not included in the consensus
statement because there were not enough cases for analysis.
The risk of cancer subsequent to unilateral biopsy-proven proliferative
changes affects both breasts.
Relative risk is modified by other factors. In the Page and Dupont
- The additional presence of calcification increased the relative
risk of AH from 4.0 to 6.5.
- AH with a family history has 8.4 times the risk of nonproliferative
change with a family history and 11 times the risk of nonproliferative
without a family history.
It must be noted that although frequency of breast cancer in
previously biopsied women with proliferative changes exceeds that
of unbiopsied normal controls, only a small proportion of patients
with proliferative lesions (rarely exceeds 10%) develop cancer.
This is because the relative risks obtained in the Page and Dupont
studies are based on the assumption that relative risk remains
constant over time. If it is assumed that relative risk varies
with time (as it ought to), then the relative risk of a woman
with AH who remains free of breast cancer for 10 years after the
diagnosis is halved (Dupont and Page Human Pathology 20:723-725,
1989). AHs are therefore not obligate precursor lesions for breast
cancer, but they can progress to cancer, remain unchanged or possibly
regress over time.