Pleomorphic lobular carcinoma of the breast: is it a prognostically significant pathological subtype independent of histological grade?

Abstract

Pleomorphic lobular carcinoma is regarded as a biologically aggressive variant of invasive lobular carcinoma of the breast. However, there is no consensus on the definition and whether this subtype adds useful information to histological grade. Two-hundred and two grade 2 or grade 3 invasive lobular carcinomas were studied. Tumours were categorised according to the components of histological grade: tubules, pleomorphism and mitoses. Pleomorphic lobular carcinoma was defined as a carcinoma with a lobular growth pattern and marked nuclear pleomorphism (pleomorphism 3). Breast cancer-specific survival was used in analysis of prognosis. Grade 3 pleomorphic lobular carcinomas (tubules 3, pleomorphism 3, mitoses 2 and tubules 3, pleomorphism 3, mitoses 3) had a worse prognosis than grade 2 (tubules 3, pleomorphism 2, mitoses 1) carcinomas. Grade 2 lobular carcinomas with marked nuclear pleomorphism (tubules 3, pleomorphism 3, mitoses 1) had a similar prognosis to grade 2 carcinomas with moderate pleomorphism (tubules 3, pleomorphism 2, mitoses 1). Survival was associated with mitotic score, but not with nuclear pleomorphism on both univariate and multivariate analysis. A non-classical growth pattern was seen more frequently in all subgroups with marked nuclear pleomorphism and was associated with worse survival. Histological grade and nodal status were independent of prognostic factors. This study shows that histological grade (in particular the mitotic component) in invasive lobular carcinomas is of prognostic importance, but pleomorphic type does not provide useful additional prognostic information.

Invasive Pleomorphic Lobular Carcinoma of the Breast: Pathologic, Clinical, and Therapeutic Considerations

“…Later publications, however, demonstrate hormone receptor statuses that closely approach those seen in classic ILC (57%-96%). 4,[15][16][17][18]20,[46][47][48] Only one outlying study, which included 10 cases of PLC, showed no ER positivity. 49 PR and ER expression can both be lost in PLC, with the majority of the studies demonstrating a PR loss in approximately one third of patients.…”

“…Florescence in-situ hybridization resulted in lower HER-2 positivity. 4,15,17,18,20,[46][47][48] Overall, PLC tumors are more often HER-2/neu amplified than classic ILC tumors.…”

“…17 Recent publications have adjusted patient outcomes in PLC to prognostic factors and have concluded that poorer outcomes are less likely related to pleomorphic histology and more likely related to negative prognostic factors. 15,48 Using the Cox proportional hazard model, Rakha et al 48 concluded that the pleomorphic nuclei of PLC did not have prognostic value. The authors concluded that although PLCs are known to be more aggressive, prognosis should be determined by total histologic grade.…”

“…The published data regarding PLC suggest that it presents with larger tumors at diagnosis, along with higher-grade tumors and increased lymph node involvement. 4,6,9,17,23,24,38,48 More aggressive surgical management could thus be expected. It is true that PLC patients are more likely to require mastectomy.…”

“…4,9,23,24,38,48 It remains to be determined, however, whether the pleomorphic histology of PLC independently predicts a worse outcome or whether other known negative prognostic factors that are common in PLC account for the poorer prognosis. 48 For example, PLC is known to have larger-size tumors, disease of higher grade, increased lymph node positivity, increased HER-2 expression, and possibly increased incidence of TNBC, as described above, and these are all negative prognostic factors in breast cancer.…”