Unusual Gastric Metastasis in Triple-Negative (Estrogen Receptor/Progesterone Receptor/HER2neu Negative) GATA-Binding Protein 3-Positive Breast Cancer

A 47-year-old woman presented with complaints of a lump in her left breast for 8 months and dyspepsia for 1month. Trucut biopsy from the left breast lump showed invasive ductal carcinoma (IDC). Immunohistochemistry(IHC) showed negative estrogen receptor(ER, Allred score 0/8), progesterone receptor (PR, Allred score 0/8), and Her2neu staining, but immunopositive for GATA-binding protein 3(GATA 3). ¹⁸F-fluorodeoxyglucose positron emission tomography–computed tomography (¹⁸F-FDG PET/CT) [Figure 1] was planned for staging. The maximum intensity projection image [Figure 1a] and axial sections of fused PET/CT [Figure 1b and c] revealed a mass in the left breast involving overlying skin and infiltrating underlying pectoral muscle with increased FDG uptake (maximum standardized uptake value [SUV_max] 15.5)[Figure 1a and b, red arrow], along with multiple skeletal metastases [Figure 1a, black arrows]. There is another nodular lesion with increased FDG uptake (SUV_max8.3) involving body of proximal stomach [Figure 1a, curved arrow and Figure 1c, white arrow]. Upper gastrointestinal (GI) endoscopy showed submucosal lesion along the greater curvature of stomach [Figure 1d, black arrow]. Biopsy from the gastric nodule showed fibrocollagenous tissue infiltrated by atypical cells [Figure 1e, black arrow]. The cells were immunopositive for GATA 3 [Figure 1f, black arrow] and ER, focal positive for gross cystic disease fluid protein 15 (GCDFP-15) [Figure 1g, black arrow], while negative for PR and HER2neu, which helped in establishing the metastatic nature of gastric nodule (from breast primary) rather than primary gastric malignancy.

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Figure 1 The maximum intensity projection image (a) and axial sections of positron emission tomography–computed tomography (b and c) revealed mass in the left breast with increased fluorodeoxyglucose uptake (maximum standard uptake value 15.5) (a and b, red arrow) with multiple skeletal metastases (a, black arrows). There is fluorodeoxyglucose avid nodular lesion (maximum standard uptake value 8.3) involving body of proximal stomach (a, curved arrow; and c white arrow). Upper gastrointestinal endoscopy showed submucosal lesion along the greater curvature of stomach (d, black arrow). Biopsy from the gastric nodule showed atypical cells (e, black arrow), which are immunopositive for GATA-binding protein 3 (f, black arrow) and focal positive for gross cystic disease fluid protein 15 (1g, black arrow)

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Triple-negative breast cancer (TNBC) accounts for 20%–25% of breast cancer cases. Lymph node, bone, and liver are common sites of metastasis in hormone receptor-positive breast cancer while lung, brain, and liver are common in TNBC.[1] Visceral metastasis is common in TNBC; however, metastasis to stomach is uncommon. Further, there is considerable difference in pattern of metastatic spread between invasive lobular carcinoma (ILC) and IDC, with common sites of metastases reported with IDC being bone, lungs, and liver. On the contrary, ILC has greater propensity for metastasis to GI tract, peritoneum, and pelvic organs.[234] Isolated gastric metastases are rare; they usually have multiple other sites of metastasis. A study done by Xu et al. has shown that breast cancer patients with gastric metastasis have simultaneous bone, liver, and lungs metastases in 50%, 20.4%, and 12.2%, respectively.[5] Linitis plastica (diffuse infiltration of muscle layer) is the most common subtype associated with gastric metastasis, while submucosal nodular variant is relatively uncommon. Morphological similarity of signet ring gastric carcinoma and invasive lobular breast carcinoma also complicates diagnosis and needs further immunostaining to avoid misdiagnosis. Primary gastric cancer can also show positivity for ER and ER in 32% and 12%, respectively, hence that is inadequate for confirming a definite metastasis from breast cancer.[6] GATA 3 is part of GATA family of zinc-finger binding transcription factors which are involved in the differentiation of many cell types.[7] It is expressed in many tissues at low level which is usually not detectable by IHC, and it has been shown as a specific IHC marker for breast and urothelial carcinomas.[8] Regarding breast cancer, it is of most significance in TNBC, where proving origin from the breast is difficult by IHC (ER−/PR−/Her2−). Positive cytoplasmic staining for GCDFP-15 has also been found to be a sensitive (55%–76%) and specific (95%–100%) marker to establish mammary origin and correctly identify lesion to be metastatic from breast primary.[9] Our patient has completed three cycles of chemotherapy (paclitaxel 175 mg/m² every 3 weeks) until now, and she is under regular follow-up.