Introduction: Pleomorphic lobular carcinoma in situ (PLCIS), a rare variant of LCIS depicting a more aggressive morphology, has been recognized, for which controversy exists as to its biology, classification and management. In this study, we aimed to compare the immunophenotypic features of PLCIS with classical LCIS (CLCIS) and determine if PLCIS exhibits characteristics more closely associated with some forms of high grade ductal carcinoma in situ (DCIS) e.g. basal and HER2+ types.

Methods: A total of 46 lesions of in situ lobular neoplasia {23 PLCIS and 23 classical lobular neoplasia (CLN)} from 42 women (4 had both CLCIS and PLCIS) diagnosed in consultation from January 2005 to September 2009 were studied. A diagnosis of PLCIS required acinar distension by dyscohesive tumor cells with nuclear pleomorphism score 3 using the Nottingham grading system for invasive breast cancer. Immunohistochemistry for estrogen receptor (ER) (n=33), CK5/6 (n=34), CK14 (n=30), GCDFP‐15 (n=2), E‐cadherin (EC) (n=44), keratin 34BE12 (n=4) and HER2 (n=2) was performed with the biotin‐avidin method, and results were assessed with the H‐scoring system.

Results: PLCIS lesions were largely (16/17, 94%) and intensely ER positive {H‐score distribution:0–9 (n=1),10–49 (n=3), 50–99 (n=0), 100–199 (n=2), 200–300 (n=11)}. One PLCIS lesion was both ER (H‐score 225) and HER2 (H‐score 300) positive. The single ER negative case (H‐score=0) was GCDFP‐15 positive (H‐score 270) with overt apocrine histology. PLCIS lesions were uniformly negative (H‐scores=0) for CK5/6 (n=17) and CK14 (n=15). 18/23 (78%) PLCIS lesions were EC negative, while five disclosed patchy, attenuated EC reactivity (1+ intensity, H‐scores 10–50). In comparison, all lesions of CLN were ER positive (16/16) {H‐score distribution: 0–49 (n=0), 50–99 (n=1), 100–199 (n=3), 200–300 (n=12)}. They were similarly negative for CK5/6 (n=17) and CK14 (n=15) (H‐scores=0). 19/21(90%) CLN lesions were non‐reactive for EC, while two were weakly EC reactive (1+ intensity, H‐scores 10–50). CLN lesions were HER2 negative (n=1, H score 0), GCDFP‐15 negative (n=1) and keratin 34BE12 positive (n=4, H‐scores 200–300).

Conclusions: PLCIS exhibits a similar immunoprofile to CLN, a finding in keeping with recent molecular data, implying that it is more closely related to the LN family, rather than a variant of E‐cadherin negative high grade DCIS. Furthermore, PLCIS, despite expression of keratin 34BE12, exhibits consistent ER positivity with CK5/6 and CK14 negativity and therefore appears an unlikely precursor of basal‐like breast cancer. Like CLN, PLCIS may be amenable to therapeutic hormonal intervention.

Citation Information: Cancer Prev Res 2010;3(1 Suppl):B64.