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Signet ring morphology in gastric biopsies may mask metastatic invasive lobular carcinoma from breast cancerExpert Review Helps Identify Breast Cancer Spreading to Stomach

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Key Takeaway
Use IHC panels including GATA3 and TRPS1 to differentiate metastatic breast cancer from primary gastric cancer.

This case report describes a 52-year-old woman with de novo metastatic, grade 1, luminal A invasive lobular carcinoma (ILC) who presented with a gastric lesion. The lesion was initially interpreted as primary gastric cancer based on its signet ring morphology. However, expert review of immunohistochemistry (IHC) markers revealed GATA3 and TRPS1 positivity, strong ER/PR expression, CDX2 negativity, and loss of E-cadherin, confirming the diagnosis of metastatic breast cancer.

The authors emphasize that signet ring morphology in gastric biopsies is not pathognomonic for primary gastric carcinoma. They recommend utilizing IHC panels including GATA3, TRPS1, CDX2, CK20, and E-cadherin to avoid misdiagnosis of metastatic breast cancer in patients presenting with gastric lesions.

A significant limitation of this evidence is that it is a single case report. The findings are based on one patient and do not provide sufficient data to establish broad clinical patterns or generalizable outcomes for the wider population.

How this fits prior evidence

This case report addresses a gap in diagnostic certainty regarding gastric lesions with signet ring morphology. While prior coverage noted that CDK4/6 inhibitors show therapeutic potential in advanced gastrointestinal cancers, this report highlights the necessity of accurate primary site identification via IHC panels to ensure correct management of metastatic disease.

Doctors recently reviewed a case involving a 52-year-old woman who was initially thought to have primary gastric cancer. However, specialized testing revealed that the cancer in her stomach had actually spread from a type of breast cancer known as invasive lobular carcinoma.

The study highlights how certain physical features in tissue samples can sometimes look like stomach cancer even when they are actually from breast cancer. By using specific markers like GATA3 and TRPS1, and checking for others like CDX2, doctors were able to make the correct diagnosis.

Because these two types of cancer can look very similar under a microscope, this case serves as a reminder for doctors to use full testing panels. This ensures patients receive the most accurate treatment possible. Because this was a single case report, it is not a broad study, but it highlights an important step in diagnostic accuracy.

What this means for you:
Specific lab tests help doctors tell the difference between stomach cancer and metastatic breast cancer.

Study Details

Study typeSystematic review
EvidenceLevel 1
PublishedJun 2026
View Original Abstract ↓
BackgroundInvasive lobular carcinoma (ILC) is a distinct breast cancer subtype with a characteristic infiltrative growth pattern linked to loss of E-cadherin. GI metastases may clinically and histologically mimic primary GI malignancies, creating significant diagnostic pitfalls.Case presentationA 52-year-old woman with de novo metastatic, grade 1, luminal A ILC (ER+/PR+, HER2 0; Ki-67 5%) diagnosed in 2022 achieved durable disease control with systemic therapy and maintenance ribociclib plus ovarian suppression. In late 2025, she developed progressive epigastric discomfort and rising tumour markers. Gastroduodenal endoscopy demonstrated erythematous gastric mucosa with focal whitish areas. Biopsies showed diffuse-type adenocarcinoma with signet ring morphology, initially interpreted as primary gastric cancer. Expert review with comparative pathology and extended immunohistochemistry demonstrated GATA3 and TRPS1 positivity, strong ER/PR expression, CDX2 negativity, and loss of E-cadherin, supporting gastric metastasis from ILC. Despite no clear radiologic progression on CT, symptomatic gastric involvement and weight loss prompted initiation of second-line weekly paclitaxel.ConclusionSignet ring morphology in gastric biopsies is not pathognomonic for primary gastric carcinoma. In patients with current or prior ILC, an IHC panel incorporating breast-lineage markers (e.g., GATA3, TRPS1) and GI markers (e.g., CDX2, CK20), alongside E-cadherin status, is pivotal to avoid misdiagnosis, inappropriate surgery, and delay of systemic therapy.
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