Case report: Characterization of the immunologic and molecular landscape in a unique presentation of invasive lobular carcinoma with concurrent uterine carcinosarcoma treated with immunotherapy

Abstract

Invasive lobular breast cancer (ILC) is characterized by a relatively high risk for late recurrence and a unique metastatic pattern with an increased risk for metastasis to gynecologic organs and peritoneum. We present a unique case of recurrent ILC with metastasis to the abdominal peritoneum as well as the uterine myometrium and cervix. Treatment was complicated by the discovery of concomitant uterine carcinosarcoma. This patient was effectively treated with a combination of hormonal therapy for her metastatic ILC and a combination of chemotherapy and immunotherapy for uterine carcinosarcoma. Molecular evaluation revealed a characteristic CDH1 mutation within the ILC and a PI3KCA mutation within the uterine carcinosarcoma, both of which have been linked to epithelial-to-mesenchymal transitions. Examination of the tumor immune microenvironment revealed proportionally more cytotoxic NK cells. This robust immune infiltration may be an indicator of the response to immunotherapy observed in this tumor or a result of the metastatic breast cancer within the uterus. This report provides a characterization of the molecular and immunologic landscape in this case with metastatic ILC and uterine carcinosarcoma.

Keywords: NK cell (NKC); carcinosarcoma; epithelial to mesenchymal (EMT); immunotherapy; lobular breast cancer.

Figure 1

Timeline of patient’s oncologic care and collection of specimens for pathologic and molecular evaluation.

Figure 2

Histopathologic Data. (A) Uterine curettage with biphasic high-grade neoplasm with mixed high-grade carcinoma (*) and associated undifferentiated sarcomatous component (#) (200X). (B) Skin biopsies with classic lobular carcinoma with discohesive, small monomorphic tumor cells infiltrating the dermis (*) (400X). (C) Uterine tumor with high-grade carcinoma component (*) and sarcomatous component with spindled and rhabdoid morphology(#) (200X). (D) Metastatic lobular carcinoma (*) within the uterine myometrium (#) (400X). (scale bar=50 microns). (E) Summary of histopathologic and immunohistochemical (IHC) staining of various pathologic specimens. Abbreviations: Epithelial membrane antigen (EMA), Test not performed (–).

Figure 3

Immune cell phenotyping by flow cytometry. (A) Proportion of NK (Live, Lineage-CD56+NKp46+) cells and T (Live CD3+) cells in patient blood, normal uninvolved adjacent tissue (NAT), and uterine tumor. (B) Mean Fluorescence Intensity (MFI) of Perforin and Granzyme B by intracellular flow cytometry among three patient tissue origins. (C) Proportion of tissue-resident NK cells (trNK) (Live, Lineage-CD56+NKp46+CD103+) and cytotoxic NK cells (cNK) (Live, Lineage-CD56+NKp46+CD103-) cells among three patient tissue origins. (D) MFI of Perforin and Granzyme B by intracellular flow cytometry of trNK and cNK cells among three patient tissue origins. (E) Flow cytometry gated for NKp46+, CD56+, and CD3+ cells demonstrating proportion of NK and T cells with tonsil used for control. (F) Flow cytometry gated for CD16+, CD103+, and CD49a+ cells demonstrating cNK and trNK with tonsil used for control.