Invasive lobular carcinoma with extracellular mucin production and HER-2 overexpression: a case report and further case studies

Abstract

Invasive lobular carcinomas (ILC) of breast typically demonstrate intracytoplasmic mucin. We present a unique case of classical type ILC with abundant extracellular mucin and strong ERBB2 (HER2/neu) expression confirmed by immunohistochemistry and fluorescent in situ hybridization. Dual E-cadherin/p120 immunohistochemical stain demonstrated complete loss of membranous E-cadherin and the presence of diffuse cytoplasmic p120 staining, confirming the lobular phenotype. The tumor cells showed ductal-like cytoplasmic MUC1 staining, but were negative for MUC2 and other mucin gene markers. In addition, studies of tissue microarrays of 80 breast carcinomas with mucinous differentiation revealed 4 pure mucinous carcinomas showing significantly reduced E-cadherin staining without redistribution of p120 into cytoplasm. The findings suggest that the presence of extracellular mucin does not exclude a diagnosis of lobular carcinoma, and the morphologic and molecular characteristics of lobular and ductal carcinomas are more complex than previously appreciated.

Figure 1

A case of invasive lobular carcinoma of breast with extracellular mucin. The tumor showed discohesive (A, H&E, ×100) and nested (B, ×200) growth with abundant extracellular mucin. At the periphery, the tumor cells formed cords and single files (C, ×100). Cytologically, the tumor cells were small to medium in size and relatively uniform (D, ×400), with scattered signet ring cells present (D inset, arrows, ×400). A sentinel lymph node showed metastatic focus of uniform tumor cells (E inset, ×40) in dissociated infiltrating pattern (E, ×200). Immunohistochemical stain revealed complete absence of membranous E-cadherin staining (brown) and the presence of diffuse cytoplasmic p120 staining (pink); a normal duct with membranous staining for both E-cadherin and p120 served as an internal control (F, immunohistochemistry, ×400). Alcian Blue (G, ×200) and Mucicarmine (H, ×200) stains highlighted both extracellular and intracellular mucin.

Figure 2

Characteristics of the invasive lobular carcinoma with extracellular mucin. The tumor cells revealed strong cytoplasmic MUC1 staining (top left, immunohistochemistry, ×200), but were negative for MUC2, MUC4, MUC5AC and MUC6 (images not shown). The tumor cells were positive for ER (top right, ×400), negative for PR (image not shown), and positive for HER-2/neu with 3+ staining (bottom left, ×400). FISH study confirmed the amplification of HER-2 gene (bottom right, ×1,000).

Figure 3

Cases of pure mucinous carcinoma with significantly reduced membranous E-cadherin and p120 staining without redistribution of p120 into cytoplasm (A, H&E, ×400; B, inset is a typical mucinous carcinoma with strong membranous E-cadherin staining, immunohistochemistry, ×400).