How to differentiate between invasive lobular carcinoma metastasis and type 4 advanced gastric cancer: The importance of immunohistochemistry

Abstract

Key Clinical Message

Gastric metastases derived from breast carcinomas and type 4 advanced gastric cancers are often difficult to distinguish because of their similar endoscopic and pathologic findings. Therefore, immunohistochemical analyses are key to diagnosis.

Abstract

Gastric metastases originating from breast carcinomas and type 4 advanced gastric cancers are often difficult to distinguish because of their similar endoscopic and pathologic characteristics. This often delays early intervention and accordingly affects prognosis. Immunohistochemical analyses are important for both diagnosis and treatment of breast carcinomas.

Immunohistochemical features of metastatic invasive lobular mammary carcinoma to the stomach.

A 74‐year‐old woman was diagnosed with stage IV breast carcinoma at our hospital in 2016 and is currently undergoing chemotherapy. Chest and abdominal computed tomography (CT) showed axillary lymph node metastases and osteolytic bone metastases in the skull and the spine. There were no obvious metastasis in the gastrointestinal tract. In December 2022, she visited her previous doctor for treatment of anorexia. An esophagogastroduodenoscopy (EGD) conducted by her previous doctor revealed sclerosis and poor extension of the gastric wall, which indicated that it was a type 4 advanced gastric cancer (AGC; Figure 1). EGD was performed again at our facility, and eight biopsies were taken. All these biopsies showed poorly differentiated adenocarcinoma, indicating that the metastasis originated from the breast carcinoma. Furthermore, to confirm this diagnosis, the expression levels of hormone receptors in cancer tissues were examined by immunohistochemical (IHC) analyses. The proportions of estrogen‐ and progesterone‐receptor‐positive cells were 60% and 5% (Allred's total scores: 6 and 4), respectively. Human epidermal growth factor receptor 2 (HER2) score was estimated at 2+ (equivocal), and FISH analysis revealed no HER2 gene amplification. Ki‐67 (MIB‐1) labeling index was 25% in the hot spot (so‐called luminal B‐like subtype). E‐cadherin was mostly negative, or weakly positive; GATA binding protein 3 was diffusely positive; gross cystic disease fluid protein 15 was variously positive; and mammaglobin was focally positive. In addition, cytokeratin 7 was positive, whereas cytokeratin 20 was negative (Figures 2 and 3). Based on these pathological findings, the diagnosis of gastric metastasis derived from invasive lobular carcinoma was confirmed.

FIGURE 1.

Endoscopic images. Type 4 advanced gastric cancer‐like sclerosis and poor extension of gastric wall are observed.

FIGURE 2.

Pathologic findings of invasive lobular carcinoma metastasis. Hematoxylin and eosin (H&E)‐stained images show poorly differentiated adenocarcinoma infiltrating into the gastric lamina propria in a trabecular or an isolated pattern. Estrogen receptor (ER) shows varying degrees of positive expression in carcinoma cells, whereas progesterone receptor (PgR) expression is restricted to a few carcinoma cells. E‐cadherin is mostly negative, but weak and incomplete expression can be seen in some carcinoma cell membranes.

FIGURE 3.

Pathologic findings of invasive lobular carcinoma metastasis. GATA binding protein 3 (GATA3) is diffusely positive. Gross cystic disease fluid protein 15 (GCDFP15) is reactive. Cytokeratin 7 is positive, and cytokeratin 20 is negative.

Currently, endocrine therapy for breast carcinoma contributes significantly to mortality reduction and recurrence control. ¹ However, the endoscopic and pathologic findings of gastric metastases derived from breast carcinomas are often mistaken to be the findings of type 4 AGC, thereby delaying correct diagnosis and therapeutic intervention. Gastric metastases derived from breast carcinomas should be especially kept in mind in cases of women with a history of breast carcinoma. ² Accurate endoscopic diagnosis, EGD‐biopsies, and pathological examinations, including IHC, are important for differentiating between gastric metastases derived from breast carcinomas and type 4 AGCs. The use IHC can help to determine the tissue of origin of the adenocarcinoma and thereby direct treatment.

In addition to highlighting the importance of IHC, we have focused on another interesting point in the present study: owing to EGD‐biopsies, cases of gastric metastases derived from breast carcinomas are easier to diagnose than cases of type 4 AGCs. In our current case, cancer tissue was abundant in all eight biopsy specimens. In the case of type 4 AGC, the diagnosis of adenocarcinoma using EGD‐biopsy specimens is not so common, as clinical reports have shown that the proportion of definitive diagnoses made on the basis of EGD‐biopsy results is approximately 50%. ³ , ⁴ In the future, examining the proportion of diagnosis by EGD‐biopsies in both may contribute to the rapid diagnosis of gastric metastases derived from breast carcinomas.

AUTHOR CONTRIBUTIONS

Ryuhei Jinushi: Conceptualization; writing – original draft; writing – review and editing. Tomonori Kawasaki: Conceptualization; writing – review and editing. Shomei Ryozawa: Writing – review and editing.

FUNDING INFORMATION

This work was supported by JSPS KAKENHI Grant Number JP21K06910.

CONFLICT OF INTEREST STATEMENT

The authors have no conflicts of interest to declare.

CONSENT

Written informed consent was obtained from the patient to publish this report in accordance with the journal's patient consent policy.

Jinushi R, Kawasaki T, Ryozawa S. How to differentiate between invasive lobular carcinoma metastasis and type 4 advanced gastric cancer: The importance of immunohistochemistry. Clin Case Rep. 2023;11:e7529. doi: 10.1002/ccr3.7529

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author (TK) upon request