Pleomorphic lobular carcinoma: Morphology, immunohistochemistry, and molecular analysis

Infiltrating pleomorphic lobular carcinoma (PLC) is an aggressive variant o f infiltrating lobular carcinoma. Recently, in situ changes identical to PL C (PLCIS) have been described. The role of prognostic markers and their cor relation with therapeutics, clinical outcome, and genetic changes is not we ll established in PLC. The authors examined 38 cases of this entity to unde rstand better this tumor's biology. Immunohistochemical (IHC) analysis was performed in 21 specimens for estrogen and progesterone steroid receptors, p53, Her 2 (p185), and GCDFP-15. Genomic deoxyribonucleic acid was obtained from microdissected tumor as well as normal control cells, and loss of het erozygosity was investigated at the ESR (16q24), p53 (TP53 17p), Her 2 (17q 11-12), and BRCA 1 (17q12-25) loci. In this series, the average patient ag e was 57.5 years (age range, 24-92 years). Twenty-seven women were postmeno pausal. Tumor size ranged from 1.2 to 25 cm. Six patients were a pathologic stage I; 19, stage II; 12, stage III; and one, stage IV. Histologically, m ultifocal nodular aggregates of discohesive pleomorphic tumor cells were se en interspersed in dense and fibrotic breast parenchyma. Twenty-nine percen t of the specimens demonstrated associated signet ring cells. The remainder had dishesive, globoid, plasmacytoid cells with high-grade nuclear feature s. PLCIS was identified in 17 of 38 patients (45%), and lobular carcinoma i n situ (LCIS) was noted in 8 patients (21%). IHC analysis showed estrogen i mmunoreactivity in 81%, progesterone in 67%, GCDFP-15 in 71%, and Her 2 in 81% (2+ to 3+ membranous staining) of specimens. Antibodies to p53 stained the tumor cell nuclei in 48% of the tumors. Loss of heterozygosity was iden tified in 52% of the specimens at the p53 locus, 18% at the ESR locus, 19% to 24% at the Her 2 loci, and 27% to 32% at the BRCA 1 locus. Follow-up was available in 19 patients and ranged from 12 months to 15 years (mean, 73 m onths). Seven patients had no evidence of disease at last examination (rang e, 1-15 years), three patients were alive with disease (range, 2-14 years), and nine patients were dead of disease (range, 2 months-9 years). Six pati ents had subsequent diagnoses of tumor in the contralateral breast. Analysi s shows that PLC tends to appear in older postmenopausal women who present with locally advanced disease. PLCIS was found to be associated with PLC 45 % of the time, The aggressive clinical course of patients with PLC is suppo rted by tumor immunoreactivity with unfavorable markers Her 2 and p53. Over expression of Her 2 in PLC may be therapeutically relevant, enabling the us e of novel chemotherapeutic drugs like Herceptin. Interestingly, tumors tha t were Her 2, immunoreactive also maintained estrogen hormone immunoreactiv ity.