Unusual Gastric Metastasis from Invasive Ductal Carcinoma Breast Mimicking as Metachronous Primary on ¹⁸F-FDG PET/CT

Introduction

Breast cancer is the most common primary malignancy in women. The most common sites of metastatic disease include the bones, lungs, liver, and brain. Breast cancer metastasizing to the gastrointestinal (GI) tract is rare, with invasive lobular carcinoma (ILC) being the predominant histologic subtype to show that tendency.[1]

The mean interval from primary breast cancer diagnosis to gastric metastasis is reported to be around 5–7 years.[2] Even in patients with a known history of breast cancer, it may be difficult to attribute them to a common cause due to this long latency.

In this report, we present an uncommon case of gastric metastasis in a patient with invasive ductal carcinoma (IDC) breast, which was suspected to be a gastric primary on ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT). This case highlights the importance of considering gastric metastasis as a differential diagnosis in patients who present with a gastric lesion and a history of breast cancer.

Case Report

A woman in her early 40s was diagnosed with invasive ductal carcinoma of the right breast, with a favorable molecular subtype – luminal B (ER +, PR +, HER2/neu –) with a Ki67 index 30% [Figure 1]. She underwent breast conservative surgery and adjuvant chemotherapy including four cycles of adriamycin and cyclophosphamide, followed by four cycles of taxane-based chemotherapy. She also received adjuvant radiation therapy to the rest of the right breast parenchyma (4272 cGy over 16 fractions with tumor bed boost of 1250 cGy over 5 fractions) with concurrent tamoxifen 20 mg once daily, which was later changed to tablet anastrozole 1 mg once daily. She also received bisphosphonates (injection zoledronic acid 4 mg intravenous) regularly every 6 months. She was compliant with the scheduled treatment and follow-up, showing no signs of disease recurrence.

Close

Figure 1 (a) Invasive ductal adenocarcinoma of the breast with tubular pattern (H and E, ×40), (b) Neoplastic cells with moderate pleomorphism and frequent mitoses (H and E, ×400), neoplastic cells express estrogen receptor (inset)

Export to PPT

Four years later, she developed loss of appetite and pain in her upper abdomen. ¹⁸F-FDG PET CT whole body scan was done which revealed multiple FDG avid right axillary and subpectoral lymph nodes with no definite suspicious lesions in the residual right breast. Along with them, focal FDG avid mural thickening along the greater curvature of the stomach was noted with multiple lymph nodes, liver, lung, adrenal, ovarian, and skeletal lesions with peritoneal carcinomatosis [Figure 2]. Suspicion of a second primary gastric neoplasm with disseminated metastases was raised due to the morphological resemblance of the gastric lesion to be a primary. Metastatic breast carcinoma was thought to be unlikely due to clinically favorable sub-type and initial good response to treatment. However, the gastric biopsy revealed metastatic carcinoma from the breast, with IHC analysis positive for ER, PR, CK 7, GATA and negative for HER2/neu and CK 20 [Figure 3]. She was started on palliative chemotherapy; however, succumbed to the disease 6 months after the diagnosis of metastatic disease.

Close

Figure 2 Maximum intensity projection (a) and representative coronal (b), sagittal (c and d), and axial (e and f) images of contrast-enhanced computed tomography (CT) and fused positron emission tomography/CT images showing focal fluorodeoxyglucose (FDG) avid enhancing nodular mural thickening along the greater curvature of the stomach (highlighted in red arrows). FDG avid disseminated disease also seen involving lymph nodes (green), liver (blue), ovaries (yellow), and bones (orange) with omental caking (purple) and ascites

Export to PPT

Close

Figure 3 Gastric mucosal biopsy with infiltrating neoplastic cells in the lamina propria. Overlying foveolar mucosa is unremarkable (H and E, ×200). Neoplastic cells express CK7, GATA3 with weak expression of estrogen receptor (×200)

Export to PPT

Discussion

In breast carcinoma, metastatic patterns of ductal and lobular subtypes have been reported to differ significantly. Ductal carcinoma most frequently metastasizes to the bone, lungs, liver, and brain, while lobular carcinoma has a relatively greater propensity to GI tract, gynecological organs, and the peritoneum.[3] The estimated rate of breast-to-stomach metastasis is variable with as low as 0.3% reported in a retrospective series of 12,001 patients with carcinoma breast.[4] Due to the low incidence, only sporadic cases and few small series of gastric metastases from breast cancer had been reported. Taal et al. reported a series of 51 patients with gastric metastases from breast carcinoma, which included ILC (n = 36; 70.6%), IDC (n = 10; 19.6%), and other subtypes (n = 5; 9.8%), confirming the preponderance of ILC subtype.[5] In a similar case series of 35 patients, Almubarak et al. reported that 97% (n = 34) had the ILC subtype.[6]

Gastric metastasis from the breast primary is often a part of a disseminated disease. Taal et al.[5] reported that up to 94% of breast carcinoma patients with gastric metastasis show disseminated disease, mostly involving the skeleton (60%), liver (20%), and also the lungs (18%). Almubarak et al.[6] reported 28% patients had bone metastases and 45% had peritoneal carcinomatosis at the time of detection of gastric metastases.

The most common radiological pattern of breast cancer metastasis to the stomach is a linitis plastica appearance (72.6%) with diffuse infiltration of the submucosa and muscularis propria.[7] Solitary lesions were more commonly observed than multiple lesions.[2]

¹⁸F-FDG PET/CT is a useful imaging tool for staging locally advanced breast cancer, locoregional or metastatic recurrence, and treatment response evaluation. However, its sensitivity is reported to be relatively lower for the diagnosis of gastric neoplasms compared to other cancer types due to nonspecific FDG uptake due to gastric peristalsis or mucosal inflammation, leading to false positives. Moreover, ¹⁸F-FDG may appear false negative in some malignant conditions like GI tumors with more signet ring cells and mucinous tissue.[8]

The incidence of gastric metastases in clinical and autopsy series is reported to vary between 0.2% and 1.7%. Due to this rarity and nonspecificity of symptoms, gastric metastases are often misdiagnosed, and patients are not treated promptly. The mechanisms underlying gastric metastasis have not been clearly understood and are probably different for each primary tumor. Malignant melanoma is the most frequently metastasized tumor to the stomach (27%–30%). It is followed by lung (18.9%), breast (13.5%; predominantly lobular subtype), and esophageal (8.1%) carcinoma, even though the risk is reported to be very low.[910]

Our case of gastric metastasis from carcinoma breast shares similarities with findings in literature such as disseminated presentation and late occurrence. However, it is of interest for three main reasons. First, metastasis to the stomach from IDC is very rare. Second, the Luminal B subtype which is generally considered to have a good prognosis showed disseminated metastasis (including stomach) within 4 years of diagnosis and the patient died within 6 months after the diagnosis of metastatic disease. Third, the appearance of gastric metastasis is like a discrete FDG avid mural thickening in the stomach, unlike the most frequently reported linitis plastica morphology.

Conclusion

Although gastric metastasis of breast carcinoma is uncommon, clinicians may encounter them, as the prevalence of breast cancer is increasing with more screening and advanced treatment. In patients with a history of breast cancer, a high index of suspicion for potential metastasis to the stomach should be maintained when new GI symptoms develop or when suspicious gastric lesions are seen on imaging modalities.