Invasive lobular carcinoma: to grade or not to grade

Abstract

Grading of invasive ductal carcinoma of no special type using the Nottingham combined histologic grading system provides independent prognostic information. The prognostic utility of grading invasive lobular carcinomas, however, has not been fully elucidated. In addition, the relationship between grade in invasive lobular carcinomas and expression of predictive biomarkers is less certain. The purpose of this study was to correlate histologic grade in invasive lobular carcinoma with known prognostic and predictive markers. All primary resections for invasive mammary carcinomas diagnosed in Mount Sinai Hospital, Toronto, between the years 1996 and 2002 were reviewed (n ¼ 1053). Of these cases, 50 were pure invasive lobular carcinoma (incidence 4.7%). The median age at diagnosis was 64 years. These tumors were graded using the Nottingham combined histologic grading system and analyzed for estrogen receptor, progesterone receptor, HER2/neu and E-cadherin expression. Tumor grade was correlated with tumor size (P ¼ 0.03), and the American Joint Committee on Cancer nodal status (P ¼ 0.05). Assessment of the individual components of grade showed that the mitotic score was highly correlated with tumor size (P ¼ 0.02), lymph node positivity (P ¼ 0.02) and overall American Joint Committee on Cancer stage (P ¼ 0.01). Estrogen receptor and progesterone receptor were highly expressed irrespective of the grade of tumor. HER2/neu protein overexpression and E-cadherin protein expression was absent in all invasive lobular carcinomas studied. We conclude that pure invasive lobular carcinoma is uncommon and occurs predominantly in postmenopausal women. Increasing tumor grade is correlated with median tumor size and the American Joint Committee on Cancer nodal stage, but not correlated with the expression of estrogen receptor, progesterone receptor, E-cadherin or HER2/neu protein overexpression.

Invasive lobular breast cancer. Prognostic significance of histological malignancy grading

“…In our study, most classical invasive lobular carcinoma turned out to be grade II tumours, with a minor portion being grade I and only very few grade III tumours. This was to be expected, considering the grading method (tubule formation, number of mitoses and nuclear pleomorphism) and it correlates well with the findings in other studies [17,22,23]. However, the distribution within the group of nonclassical lobular carcinomas is different.…”

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

“…Histological grade was an independent prognostic factor in keeping with previous studies. 18,21,24,25 In our series, we observed heterogeneity of pleomorphism in a substantial proportion of pleomorphic lobular carcinomas in both the in situ and the invasive components. This is consistent with recently published genetic data, suggesting that pleomorphic lobular carcinomas may evolve through a genetic pathway similar to that of classical invasive lobular carcinomas, but with the acquisition of additional genetic events.…”

“…9 Our results are similar to previous studies of unselected invasive lobular carcinomas, which show that the majority of invasive lobular carcinomas (80-100%) are oestrogen receptor positive and lack ERBB2 overexpression. 13,18,21,[28][29][30] We based the diagnosis of invasive lobular carcinoma on the typical dyscohesive growth pattern. We did not base it on E-cadherin expression as there is good evidence that about 10-15% of invasive lobular carcinomas show some membranous expression.…”

“…Although some studies reported limited prognostic value for histological grading of invasive lobular carcinoma, 15 we and others have demonstrated that grading of these tumours, using the Nottingham grading system, is a strong and independent predictor of outcome, which supports the importance of routine assessment of histological grade in invasive lobular carcinoma. [16][17][18][19][20][21] Analysing the three components of grading separately revealed that mitotic count was of more prognostic power than the two other components. 16,21 This raises the question of whether pleomorphic lobular carcinoma as a distinct pathological subtype has any clinical value additional to grading, because conventional grading also includes cellular atypia and mitotic count as components.…”

“…[16][17][18][19][20][21] Analysing the three components of grading separately revealed that mitotic count was of more prognostic power than the two other components. 16,21 This raises the question of whether pleomorphic lobular carcinoma as a distinct pathological subtype has any clinical value additional to grading, because conventional grading also includes cellular atypia and mitotic count as components. The aim of this study was therefore to evaluate the prognostic significance of pleomorphic lobular carcinoma and to provide recommendations regarding the relevance of using this separate subtype.…”