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

infiltrating lobular carcinomas expressed E-CD in their infiltrating cells, whereas they
showed only weak immunostains in areas of atypical lobular hyperplasia and lobular
carcinoma in situ.
However, the pathologists should keep in mind that in the some recent studies, a low
percentage of invasive lobular carcinomas have been shown to express E-cadherin
(58, 59). Therefore, E-cadherin positivity or negativity cannot be reliable factor by
itself for the classification of lobular and ductal carcinomas.
Of additional interest, p53 is rarely expressed in lobular carcinoma. Domagala et al.
(42) found striking differences between different histological types of breast cancer
when 263 invasive breast carcinomas were tested for nuclear p53 accumulation in
formaldehyde-fixed paraffin sections. Nuclear p53 accumulation was found in at least
10% of the tumor cells in 61% of the medullary carcinomas (22/36), 37% of grade 3
ductal not otherwise specified carcinomas (32/86), 4% of lobular carcinomas (2/47),
and 0% (0/7) of mucinous carcinomas. Strong cytoplasmic p53 staining was noted in
32% of lobular carcinomas. Medullary and high-grade ductal breast carcinomas
accumulated nuclear p53 in high percentages, but these tumors have favorable and
poor prognoses, respectively. Thus, while nuclear p53 accumulation can be associated
in these tumors with high morphological malignancy grades in general and with tumor
cell proliferation in particular; p53 accumulation is not necessarily correlated with
biological aggressiveness.
Differential Diagnosis: The diagnosis of the classical form of infiltrating lobular
carcinoma is seldom difficult, and experienced diagnostic pathologists concur in the
vast majority of cases. Yet, some invasive breast carcinomas contain features of both
infiltrating lobular carcinoma and infiltrating duct carcinoma, and (so far as this author
is concerned) those invasive tumors that maintain the invasive pattern of infiltrating
lobular carcinoma, yet have nuclear features approaching that of duct carcinoma,
represent the pleomorphic variant of lobular carcinoma. Infiltrating duct carcinomas
have a more solidly cohesive invasive pattern without the diffuse, single file,
multifocal, and periductal targetoid pattern of infiltrating lobular carcinoma.
Obviously, the distinction between mixed ductal and lobular carcinoma and the
pleomorphic variant of invasive lobular carcinoma could become quite subjective and
observer dependent. In an attempt to overcome the subjectivity in subclassifying
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