33 Special Types of Invasive Breast Carcinoma: Diagnostic Criteria ...

cancerous change (43-47). To some extent, this reflects a tendency in some studies to
include orderly papillary carcinomas in the group of papillomas. Yet in some cases,
carcinoma and a papilloma are in such close proximity that they must be regarded as
parts of a single lesion. Usually, the carcinomatous component is in situ. It is
important that in a detailed 3-D reconstruction study of intraductal papillomas, Ohuchi
et al. (44) "accidentally" discovered that 6 of 16 patients (37%) with peripheral duct
papillomas had carcinomas in "close anatomic continuity" to the benign papillomas,
whereas none of the 9 patients with central duct papillomas had cancers. Thus, these
observations suggest that multiple peripheral duct papillomas may be a form of
"benign" breast disease deserving of complete, yet conservative, local excision,
especially, when palpable and/or cytoarchitectural atypia is present. Haagensen (45)
advised that "when local excision of the lesion is carried out, the surgeon must take
great care to try to remove all of the grossly evident disease."
Standard histologic criteria for atypia and/or malignancy should be used in evaluating
areas of duct hyperplasia that occur in conjunction with intraductal papilloma. Finally,
it is important to add that in and around the bases of papillomas there may be
considerable fibrosis and epithelial entrapment, resulting in a pseudoinvasive pattern.
When the glands in these pseudoinvasive areas have a double cell layer cytologically
identical to those found in the papilloma, their benign nature is secure. Over
diagnosing the pseudoinvasive areas as invasive carcinoma (especially on frozen
sections) must be avoided. But please remember that true invasive papillary carcinoma
(48) and invasive micropapillary carcinoma (49) should not be underdiagnosed as
benign. If there is any doubt, defer the final diagnosis until permanent sections are
available, when special studies can be performed, and/or when consultation can be
obtained from a trusted colleague and/or an expert in breast pathology.
Although the above criteria may seem straightforward, controversial and/or borderline
cases do arise. In some cases, the double cell layer may be inconspicuous. To
delineate the double-cell layer, Papottie et al (50) were among the first to propose
using immunohistochemical staining with carcinoembryonic antigen (CEA) to
highlight carcinoma cells and actin to highlight myoepithelial cells. Benign papillomas
have a basal layer of actin-rich, myoepithelial cells, and the cytoplasm of the benign
luminal epithelial cells are CEA-negative. Papillary carcinomas, including intracystic
papillary carcinoma, lack the myoepithelial layer. CEA was detected in 85% of the
papillary carcinomas in Papottie's study. Two of their cases of "suspected" carcinoma
lacked myoepithelial cells and were interpreted as carcinomas. Other
immunohistochemical studies of papillomas and papillary carcinomas have found that
antibodies to muscle actin (HHF-35) were reliable markers for myoepithelial cells
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