Clinicopathologic and Immunophenotypic Classification of Invasive Lobular Carcinoma with Histiocytoid Features

Histiocytoid lobular breast carcinoma is a rare subtype of invasive lobular carcinoma characterized by relatively bland, uniform nuclei, single small eosinophilic nucleolus, and ample granular cytoplasm. These cancers are typically triple negative, show frequent androgen receptor (AR) positivity, and are therefore theorized to represent a variant of apocrine differentiation in invasive lobular carcinoma. Anecdotal evidence suggests that these tumors have excellent outcomes, though some studies suggest a variable clinical outcome.

Inclusion criteria included women with a histologic diagnosis of invasive lobular carcinoma with histiocytoid features, regardless of immunohistochemical profile, diagnosed at our institution between 2008 and 2021 with additional tissue still available for ancillary studies. We reviewed patients meeting these criteria and investigated hematoxylin and eosin-stained slides and a panel of immunohistochemical stains (estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 [HER2], AR, endothelial growth factor receptor, and keratin 5/6), as well as outcomes including survival and metastatic disease.

Overall, 12 eligible patients were identified. The classical immunophenotype (triple negative with AR positivity) was noted in 4 out of 12 tumors. The majority of the remaining tumors (7 out of 12) showed a luminal B immunohistochemical profile, while 1 out of 12 was HER2-enriched. No patients in the cohort died from disease-related causes and 2 out of 12 presented with distant metastatic disease during their disease course.

Histiocytoid lobular breast carcinoma is a morphologic variant of lobular carcinoma with apocrine features that shows a variable immunohistochemical profile and variable clinical behavior. Further subclassification and stricter diagnostic criteria may be helpful in the distinction between truly indolent tumors and those with more aggressive clinical features.