Abstract
Gastric metastasis from breast cancer is rare and frequently misdiagnosed as primary gastric adenocarcinoma. Mixed ductal-lobular carcinoma demonstrates a unique metastatic pattern with a predilection for the gastrointestinal tract and serosal surfaces, creating significant diagnostic and therapeutic challenges. We describe a 77-year-old woman with a history of estrogen receptor–positive breast carcinoma who presented 3 years after mastectomy with epigastric pain, vomiting, and weight loss. Endoscopy revealed a malignant-appearing gastric ulcer and initial histology suggested primary gastric adenocarcinoma with signet-ring features. However, immunohistochemical analysis (pan-CK, CK7, mammaglobin, ER, PR positivity with CK20 and CDX2 negativity) confirmed metastatic breast carcinoma. Operative findings revealed diffuse peritoneal and omental metastases. The patient underwent palliative gastrojejunostomy but developed severe postoperative complications and died on postoperative day 51. This case highlights the importance of immunohistochemistry and multidisciplinary evaluation to avoid unnecessary radical surgery in metastatic breast carcinoma.
Introduction
Breast carcinoma is a leading cause of cancer-related deaths among women globally [1]. Invasive lobular carcinoma (ILC) and mixed ductal-lobular carcinoma (mDLC) account for 10%–15% and 5%–10% of invasive breast cancers, respectively [2], and carry a poor prognosis once distant metastasis occurs [3, 4]. Both ILC and mDLC exhibit increased tropism for the gastrointestinal tract, peritoneum, and serosal surfaces [5, 6]. Gastric metastases from breast cancer are rare (<1%) but far more common at autopsy (up to 18%), predominantly in ILC [4, 7]. These lesions mimic primary gastric adenocarcinoma, both endoscopically and histologically, particularly with signet-ring morphology, often contributing to diagnostic delay [8]. Therefore, immunohistochemistry is essential for accurate diagnosis and appropriate management. We present a case illustrating these challenges and highlighting the role of immunohistochemistry in confirming metastatic mDLC.
Case report
A 77-year-old female with a one-month history of epigastric pain, vomiting, and weight loss was referred to a tertiary surgical oncology clinic. Her medical history was significant for hypertension, hyperlipidemia, and type 2 diabetes mellitus complicated by peripheral neuropathy.
Three years earlier, she was diagnosed with right breast cancer after presenting with a palpable mass in the lower outer quadrant associated with skin tethering. Mammography demonstrated a 4 × 4 cm spiculated mass with multifocal deposits and no suspicious nodes. Core biopsy showed grade 3 invasive carcinoma with lobular features (single-file growth); E-cadherin was retained, raising suspicion of a mixed ductal-lobular phenotype (Fig. 1A and C). Given her poor functional status, she underwent right simple mastectomy with sentinel lymph node biopsy (negative). Final histopathology confirmed pT2N0 mDLC with single-file/targetoid growth pattern and weak, incomplete E-cadherin expression (Fig. 1B, D–F). Estrogen receptor (ER) and progesterone receptor (PR) were positive in 95% and 20% of cells, respectively, HER2 was negative, and a Ki-67 was 10% (Table 1). The patient began adjuvant anastrozole.
Histopathology and immunohistochemistry of primary breast tumor. (A) Low-power H&E of the core needle biopsy showing grade 3 invasive carcinoma with a diffusely infiltrative pattern at the periphery, initially classified as invasive lobular carcinoma. (B) High-power H&E of the mastectomy specimen demonstrating single-file linear cords and concentric targetoid growth around a benign duct, hallmarks of invasive lobular carcinoma. (C) E-cadherin immunostaining on the core biopsy showing retained membranous expression, contributing to the initial lobular classification. (D) Low-power H&E of the mastectomy specimen showing ill-defined, diffusely infiltrative tumor architecture without a well-circumscribed mass. (E) High-power H&E of the mastectomy specimen demonstrating discohesive tumor cells permeating the stroma in single-file cords without glandular formation, consistent with invasive mammary carcinoma with lobular features (pT2N0). (F) E-cadherin immunostaining of the mastectomy specimen showing weak, incomplete membranous expression in tumor cells with strong retained staining in adjacent benign ductal epithelium (internal positive control), supporting the lobular phenotype.
Immunohistochemical profile across primary and metastatic sites
| Marker | Breast (core) | Breast (mastectomy) | Gastric | Omentum | Ascites |
|---|---|---|---|---|---|
| pan-CK | Positive | Positive | Positive | Positive | N/A |
| CK7 | Positive | Positive | Positive | Positive | Positive |
| CK20 | Negative | Negative | Negative | Negative | Negative |
| CDX2 | N/A | N/A | Negative | Negative | N/A |
| ER | 95% (strong) | 95% (strong) | 90% (strong) | 90% (strong) | Positive |
| PR | 20% (weak-mod) | 40% (mod-strong) | 60% (weak-mod) | N/A | Negative |
| HER2 (IHC) | Score 1 (Neg) | Score 1 (Neg) | Score 1 (Neg) | Score 2 (Equiv) | N/A |
| HER2 (FISH) | Not done | Not done | Not done | Negative | N/A |
| mammaglobin | N/A | N/A | Positive | Positive | N/A |
| GCDFP-15 | N/A | N/A | Negative | Focal + | N/A |
| E-cadherin | Positive | Weak | N/A | N/A | N/A |
| Beta-catenin | N/A | Weak | N/A | N/A | N/A |
| HMWCK | N/A | N/A | N/A | Focal + | N/A |
| LCA | N/A | N/A | Negative | N/A | N/A |
+, positive; −, negative; N/A, not assessed; mod, moderate; Equiv, equivocal.
On current presentation, she was cachectic (ECOG 2), with a soft, non-tender abdomen and no abnormalities at the mastectomy site or axillae. Repeat breast imaging was deferred given her poor functional status.
Endoscopy demonstrated a large circumferential ulcer involving the gastric antrum causing luminal narrowing and food retention despite a patent pylorus. Endoscopic ultrasound revealed tumor invasion into the muscularis propria without transmural extension (T2) and no significant lymphadenopathy.
Despite this, immunohistochemistry showed a profile inconsistent with gastric origin: pan-cytokeratin (Fig. 2D) and CK7 positivity, mammaglobin positivity, and ER (90%)/PR (60%) positivity (Fig. 2E and F; Table 1), with CK20 and CDX2 negativity and reduced E-cadherin expression, consistent with the mixed ductal-lobular phenotype noted in the primary tumor (Table 1). Two independent gastric biopsies showed an identical profile.
Histopathology and immunohistochemistry of gastric biopsy. (A) Low-power H&E of the gastric antral biopsy showing multiple mucosal fragments with variable degrees of malignant infiltration and extensive replacement of native glandular architecture. (B) Medium-power H&E demonstrates dense lamina propria infiltration by malignant cells with residual entrapped benign gastric glands, closely mimicking primary gastric adenocarcinoma. (C) High-power H&E showing sheets of malignant cells with moderate pleomorphism, mitotic activity, and focal signet-ring morphology, representing a recognized diagnostic pitfall for metastatic lobular breast carcinoma. (D) Pan-cytokeratin immunostaining showing strong diffuse cytoplasmic positivity, confirming epithelial origin and excluding lymphoma and non-epithelial differentials. (E) Estrogen receptor immunostaining demonstrating moderate nuclear positivity in 90% of tumor cells. (F) Progesterone receptor immunostaining showing weak nuclear positivity in 60% of tumor cells, with concordant hormone receptor expression between the gastric lesion and the prior breast primary supporting a common origin.
Staging FDG PET/CT showed gastric uptake (SUVmax 6.3) with equivocal FDG-avid foci near the right hemidiaphragm, right iliac region, and left adrenal gland, raising concern for distant spread (Fig. 3). Diagnostic laparoscopy revealed diffuse peritoneal/omental metastases with ascites, with omental biopsies and ascitic cytology confirmed poorly differentiated carcinoma. A palliative gastrojejunostomy was performed to relieve obstructive symptoms (Fig. 4).
18F-FDG PET/CT for staging. (A) Coronal maximum intensity projection (MIP) whole-body PET image demonstrating focal hypermetabolic activity in the upper abdomen corresponding to the gastric antral lesion, with no suspicious distant hypermetabolic foci. Equivocal, low-grade FDG uptake fast noted adjacent to the right hemidiaphragm, in the right iliac region, and in the left adrenal gland, of uncertain significance; no other suspicious distant hypermetabolic foci were identified. (B) Axial fused PET/CT image showing intense circumferential FDG uptake in the gastric antrum (SUVmax 6.3) with associated food retention in the proximal stomach, consistent with the known gastric malignancy. No hypermetabolic nodal, osseous, or pulmonary lesions were identified.
CT abdomen and pelvis demonstrating gastric outlet obstruction and postoperative disease progression. (A) Preoperative contrast-enhanced CT (19 December 2022) showing irregular circumferential wall thickening of the gastric pylorus causing gastric outlet obstruction, with associated perilesional mesenteric fat stranding. (B) Early postoperative unenhanced CT (8 January 2023) demonstrate intact gastrojejunostomy with no anastomotic leak or pneumoperitoneum, and newly developed moderate ascites consistent with interval peritoneal disease progression.
The postoperative course was complicated by pulmonary edema, atrial fibrillation, and hospital-acquired pneumonia, necessitating ICU admission. The patient’s condition deteriorated, and she died on postoperative day 51.
Discussion
Metastatic breast carcinoma with a lobular component poses a significant diagnostic challenge when involving the stomach. Prior series show no significant difference in metastatic distribution between mDLC and pure ILC [6], with both more likely than invasive ductal carcinoma to metastasize to the peritoneum, pericardium, and gynecologic sites.
This tropism is attributed to loss of E-cadherin expression (CDH1), producing the discohesive, single-file growth, and signet-ring morphology characteristic of ILC, which mimics gastric adenocarcinoma endoscopically and histologically [9]. Notably, the present tumor did not follow that classic pattern: E-cadherin was weakly retained rather than absent, on both the primary and metastatic specimens, consistent with a mixed ductal-lobular rather than purely lobular phenotype. This distinction matters because aberrant (rather than absent) E-cadherin staining can obscure the lobular component, increasing reliance on ancillary markers. When this infiltrative phenotype involves the gastric mucosa and submucosa, the endoscopic findings are often subtle and overlooked, further complicating accurate diagnosis [9].
Clinically, gastric metastases from invasive breast cancers often present non-specifically (e.g. epigastric pain, dyspepsia, nausea, or melena), mimicking a primary gastrointestinal disorder [9, 10]. Diagnosis is further complicated by latency: gastric metastases may arise 10–20 years after primary treatment [10].
Distinguishing primary gastric cancer from metastatic breast carcinoma relies primarily on immunohistochemistry. A CK7-positive/CK20-negative profile favors breast origin [11]. Furthermore, ER/PR expression is characteristic of metastatic breast carcinoma and rare in primary gastric adenocarcinoma, and mammaglobin positivity provides additional confirmation [12]. p120-catenin, GATA-3, and Ki-67 were not assessed on the gastric or omental metastases, which would have further characterized the lobular component.
Hormone receptor expression showed progressive discordance: PR positivity of 20% in the core biopsy, 40% at mastectomy, and 60% in the gastric metastasis, and negative in ascitic fluid, consistent with intratumoral heterogeneity and clonal evolution under endocrine selective pressure [13]. Similarly, variable gross cystic disease fluid protein-15 staining (negative in the gastric biopsy, focally positive in the omental deposit) does not preclude a common breast origin [14]. This aberrant E-cadherin pattern supports the mDLC classification.
Gastric metastases from breast cancer remain frequently misdiagnosed, often leading to unnecessary radical surgery. Gastrectomy confers no survival benefit in disseminated disease and carries significant morbidity [4]. Consequently, management should be limited to palliative symptom control, as performed here.
Although germline CDH1 mutations link ILC and diffuse gastric carcinoma [15], genetic testing was not performed. While CDH1 analysis might have clarified the E-cadherin aberrancy, the patient’s poor status precluded systemic treatment. Moreover, the strong concordance of the immunohistochemical between the gastric, omental, and prior breast tumors, plus absence of family history suggestive of hereditary diffuse gastric cancer syndrome, supports a single metastatic breast origin.
Conclusion
Gastrointestinal metastases from breast carcinoma may occur years after initial diagnosis, particularly with a lobular component, whether classic ILC or mDLC. Morphology alone risks misdiagnosis; immunohistochemistry guides appropriate palliative management and helps avoid unnecessary radical surgery.
Acknowledgements
The authors thank the staff of the Histopathology and Nuclear Medicine departments at KCCC for their technical assistance.
Author contributions
H.S.A. conceived and designed the case report, collected and reviewed the clinical and radiological data, and drafted the manuscript. T.E. was the primary operating surgeon for the case and supervised the patient’s management. A.B. participated in the surgical management and acquisition of operative and clinical data. T.A. performed the histopathological and immunohistochemical analysis and provided the pathology images. A.S. contributed to the oncological management. All authors critically revised the manuscript for important intellectual content and read and approved the final version.
Conflicts of interest
None declared.
Funding
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Consent
Written informed consent for publication of this case report and the accompanying images was obtained from the patient’s next of kin. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
