CHICAGOThe diagnosis of ductal carcinoma in situ (DCIS) usually
is straightforward from a pathologic point of view. However,
microinvasion and histologically ambiguous lobular carcinoma in situ
(LCIS) lesions may be difficult to distinguish from DCIS, Stuart
Schnitt, MD, said at the Second Annual Lynn Sage Breast Cancer
Symposium, sponsored by Northwestern University Medical School.
Microinvasion was not clearly defined until 1997, said Dr. Schnitt,
associate professor of pathology, Harvard Medical School, and
director of surgical pathology, Beth Israel Deaconess Medical Center,
At that time, the AJCC/UICC staging manual created the T1mic
category for breast cancer cells that extend beyond the basement
membrane and have no single focus that is greater than 0.1 cm or that
exceeds 1.0 mm at its greatest dimension.
Because of the lack of agreement about the pathologic characteristics
of the microinvasion disease state, clinical studies applied a wide
variety of descriptions. These include evidence of stromal invasion,
limited microscopic stromalization invading less than 10% of the
surface of the histologic specimen, maximal invasion that is 2.0 mm
or less or represents less than 10% of the tumor, and site of
invasion that is 1.0 cm in size or less.
Pathologic changes associated with DCIS or tissue sampling also can
be mistaken for microinvasion, such as ductal branching, DCIS
involving lobules or benign sclerosing lesions, tangential sectioning
of the involved ducts, crush artifact, cautery effect, or water
The clinical significance of microinvasion is not known largely
because the literature contains so many different definitions of the
disease state, Dr. Schnitt said.
In about a dozen small clinical studies, the incidence of axillary
lymph node involvement in patients who were given the diagnosis of
microinvasion ranges from 0% to 20%. Outcomes studies of patients
with microinvasion provide few data about disease-free and overall
survival, and no clear survival comparisons with patients who have
Use of the AJCC/UICC T1mic stage should improve the
recognition of microinvasion as well as the understanding of the
effect of this form of breast cancer on patients, Dr. Schnitt said.
He believes that in centers that apply the strict AJCC/UICC
definition of microinvasion, patients should have a low rate of
axillary lymph node metastasis and a cure rate approaching 100% after
appropriate localized therapy.
Distinguishing From LCIS
Because of differences in treatment, lobular carcinoma in situ must
be differentiated from ductal carcinoma. However, pathologists are
more frequently encountering difficulty distinguishing between DCIS
and LCIS, perhaps because the increasing use of screening mammography
is revealing unusual forms of breast abnormalities, Dr. Schnitt said.
Although most cases of lobular carcinoma can be easily characterized
path-ologically, some lesions have indeterminate histologic features
that are similar to those of DCIS. LCIS may extend into extralobular
ducts, and DCIS may involve obvious lobules.
Even highly experienced pathologists have difficulty establishing a
diagnosis when small-cell in situ carcinoma lesions have features
that suggest microinvasion or features of both DCIS and LCIS, he
Immunostaining for the adhesion molecule E-cadherin may provide a
molecular basis for characterizing LCIS in questionable situations,
Dr. Schnitt said.
A number of recent clinical studies indicate that DCIS cells
consistently stain strongly for E-cadherin regardless of the stage of
the lesion, while invasive LCIS cells do not express the adhesion
molecule. Several studies have shown that invasive LCIS has a
mutation in the gene for E-cadherin expression.
Dr. Schnitt studied a series of DCIS tissue samples, as well as
samples of carcinoma in situ that were indeterminate, from his
pathologic consulting practice at Beth Israel Deaconess Medical
In all cases, immunostained DCIS samples were positive for
E-cadherin, showing intense membrane staining for the molecule. All
immunostained samples of LCIS were negative for E-cadherin, with no
evidence of adhesion molecule staining.
Some lesions that were indeterminate on hemoxylin and eosin staining
had strong E-cadherin expression, suggesting a closer kinship to DCIS
than LCIS, he said.
Dr. Schnitt concluded that immuno-staining for E-cadherin may be a
useful adjunct in determining whether an in situ lesion is LCIS or
DCIS in histologically ambiguous cases. Such testing, therefore, may
more definitively guide clinicians to attempt eradication of breast
lesions in women who most likely have DCIS or to follow patients with
suspected LCIS as a marker of an overall increased risk of breast