CASE REPORTS IN GI ONCOLOGY
Metastatic Breast Cancer Masquerading as Primary Gastric Cancer: Case Report and Review of the Literature Alexander C. Black,1 Danielle Lu,2 Susan Murakami2 1 Division of Hematology-Oncology Department of Medicine David Geffen School of Medicine at UCLA Los Angeles, CA 2 Department of Pathology Huntington Medical Center Pasadena, CA Copyright © 2014 by International Society of Gastrointestinal Oncology
CASE REPORT An 84-year-old woman on postmenopausal hormone replacement therapy (HRT) had an abnormal screening mammogram of the left breast. The patient underwent an ultrasound-guided core biopsy confirming a diagnosis of invasive breast cancer. HRT was discontinued, and she underwent a lumpectomy with sentinel lymph node mapping. Pathology revealed a 0.9-cm, well-differentiated, lobular carcinoma (Figure 1) with 33 of 36 sampled axillary lymph nodes demonstrating cancer, including several with extracapsular extension. The cancer was estrogen receptor (ER) and progesterone receptor (PR) positive and Her2 negative by immunohistochemistry (IHC) and chromogenic silver in situ hybridization (SISH). The patient received 6 cycles of adjuvant chemotherapy with docetaxel and cyclophosphamide, followed by postlumpectomy radiation therapy and then aromatase inhibitor antiestrogen therapy with anastrozole. She also was enrolled in a clinical study in which she was randomized to either denosumab, a monoclonal antibody to the RANK (receptor activator of nuclear factor -B) ligand that inhibits osteoclasts, or placebo. The primary end point was to delay or prevent relapse of breast cancer to the bone. As part of the study, the patient underwent annual computed tomographic (CT) scans of the chest, abdomen and pelvis, and bone.
Figure 1. H&E staining of the axillary lymph node tissue from the initial breast cancer surgery.
May–August 2014
Approximately 2.5 years after the breast surgery, the patient began experiencing dysphagia. She saw a gastroenterologist who performed an esophagogastroduodenoscopy (EGD). A tumor along the lesser curvature of the stomach was biopsied, with pathology from another lab showing poorly differentiated signet ring–type adenocarcinoma (Figure 2), consistent with a gastric primary and negative for Helicobacter pylori. Repeat CT scans, which were obtained 5 months after the previous study-mandated scans, showed a new 1.7-cm proximal stomach mass but no other abnormalities. The patient underwent a laparotomy with the intention of performing a partial gastrectomy and regional lymph node dissection, but aggressive surgery was aborted because of visible, unresectable omental disease. The clinical impression was that the patient had regionally metastatic, unresectable gastric cancer. Omental biopsies were sent to pathology (Figure 3). Given the patient’s history of breast cancer, a panel of immunostains was performed to confirm tissue of origin. The omental biopsy specimen was positive for the highly breast cancer–specific gross cystic disease fluid protein (GCDFP)-15 (Figure 4), as well as cytokeratin (CK)-7 and estrogen receptor (ER), and was focally positive for mammaglobin and negative for CK20, TTF-1, and CDX-2. The EGD specimen was obtained from the outside lab and reanalyzed by IHC and was also positive for GCDFP-15 (Figure 5), CK7, and ER and
Figure 2. H&E staining of the gastric biopsy specimen.
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Case Reports in GI Oncology
Figure 3. H&E staining of an omental biopsy specimen.
Figure 5. GCDFP-15 immunostaining of the gastric biopsy specimen.
cancer and newly diagnosed adenocarcinoma of the stomach, to spare the patient an unnecessary, aggressive, risky surgical approach for potential cure of presumptive stomach cancer. Pathologists can provide invaluable assistance in screening for a possible breast primary with appropriate IHC stains. In addition to the standard ER and PR, GCDFP and CK-7 and -20 can help confirm a breast primary, as in our case and in previously reported cases.5,6 Screening for a possible breast primary when stomach adenocarcinoma is discovered in a breast cancer survivor, particularly one with lobular histology, should arguably become the standard of care. Figure 4. GCDFP-15 immunostaining of the omental biopsy specimen.
REFERENCES negative for CK20 and CDX-2, similar to the omental specimen and the original breast cancer. Having a diagnosis of metastatic ER and Her2 breast cancer, the patient was started on fulvestrant, an ER downregulator. Her dysphagia resolved, and she remained otherwise asymptomatic. She did not have bone metastases on a repeat bone scan, and she continued on the double-blind, randomized, clinical study of denosumab.
1. Ambroggi M, Stroppa EM, Mordenti P, et al: Metastatic breast cancer to the gastrointestinal tract: report of five cases and review of the literature. Int J Breast Cancer 2012:439023, 2012
DISCUSSION
5. Arrangoiz R, Papavasiliou P, Dushkin H, et al: Case report and literature review: metastatic lobular carcinoma of the breast an unusual presentation. Int J Surg Case Rep 2:301–305, 2011
Although breast cancer is quite common, metastases to the stomach are rare.1 An Italian single-institution retrospective review of 980 breast cancer cases demonstrated a 0.3% incidence of gastric metastases.1 When stomach spread occurs, lobular carcinoma is by far the most common breast cancer histology, with an estimated prevalence of 852 to 97%3. Autopsy studies of patients with metastatic lobular cancer showed a 6 –18% incidence of gastrointestinal (GI) metastases,4 suggesting that the GI lumen is a relatively common eventual site of progressive metastases. As our case illustrates, it is important to have a clinical suspicion of possible gastric metastases in women with a history of breast
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Gastrointestinal Cancer Research
2. Hussain T, Elahi B, McManus P, et al: Gastric obstruction secondary to metastatic breast cancer: a case report and literature review. J Med Case Rep 6:232, 2012 3. Hara F, Kiyoto S, Takabatake D, et al: Metastatic breast cancer to the stomach resembling early gastric cancer. Case Rep Oncol 3:142–147, 2010 4. Ghirarduzzi A, Sivelli R, Martella E, et al: Gastric metastasis from breast carcinoma: report of three cases, diagnostic-therapeutic critical close examination and literature review. Ann Ital Chir 81:141–146, 2010
6. Pectasides D, Psyrri A, Pliarchopoulou K, et al: Gastric metastases originating from breast cancer: report of 8 cases and review of the literature. Anticancer Res 29:4759 – 4763, 2009
Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest.
Address correspondence to: Alexander C. Black, MD, Clinical Professor of Medicine, UCLA/Pasadena Healthcare, 625 S. Fair Oaks Avenue, Suite 320, Pasadena, CA 91105; E-mail: [email protected]
Volume 7 • Issue 3– 4
Metastatic Breast Cancer Masquerading as Primary Gastric Cancer: Case Report and Review of the Literature Alexander C. Black,1 Danielle Lu,2 Susan Murakami2 1 Division of Hematology-Oncology Department of Medicine David Geffen School of Medicine at UCLA Los Angeles, CA 2 Department of Pathology Huntington Medical Center Pasadena, CA Copyright © 2014 by International Society of Gastrointestinal Oncology
CASE REPORT An 84-year-old woman on postmenopausal hormone replacement therapy (HRT) had an abnormal screening mammogram of the left breast. The patient underwent an ultrasound-guided core biopsy confirming a diagnosis of invasive breast cancer. HRT was discontinued, and she underwent a lumpectomy with sentinel lymph node mapping. Pathology revealed a 0.9-cm, well-differentiated, lobular carcinoma (Figure 1) with 33 of 36 sampled axillary lymph nodes demonstrating cancer, including several with extracapsular extension. The cancer was estrogen receptor (ER) and progesterone receptor (PR) positive and Her2 negative by immunohistochemistry (IHC) and chromogenic silver in situ hybridization (SISH). The patient received 6 cycles of adjuvant chemotherapy with docetaxel and cyclophosphamide, followed by postlumpectomy radiation therapy and then aromatase inhibitor antiestrogen therapy with anastrozole. She also was enrolled in a clinical study in which she was randomized to either denosumab, a monoclonal antibody to the RANK (receptor activator of nuclear factor -B) ligand that inhibits osteoclasts, or placebo. The primary end point was to delay or prevent relapse of breast cancer to the bone. As part of the study, the patient underwent annual computed tomographic (CT) scans of the chest, abdomen and pelvis, and bone.
Figure 1. H&E staining of the axillary lymph node tissue from the initial breast cancer surgery.
May–August 2014
Approximately 2.5 years after the breast surgery, the patient began experiencing dysphagia. She saw a gastroenterologist who performed an esophagogastroduodenoscopy (EGD). A tumor along the lesser curvature of the stomach was biopsied, with pathology from another lab showing poorly differentiated signet ring–type adenocarcinoma (Figure 2), consistent with a gastric primary and negative for Helicobacter pylori. Repeat CT scans, which were obtained 5 months after the previous study-mandated scans, showed a new 1.7-cm proximal stomach mass but no other abnormalities. The patient underwent a laparotomy with the intention of performing a partial gastrectomy and regional lymph node dissection, but aggressive surgery was aborted because of visible, unresectable omental disease. The clinical impression was that the patient had regionally metastatic, unresectable gastric cancer. Omental biopsies were sent to pathology (Figure 3). Given the patient’s history of breast cancer, a panel of immunostains was performed to confirm tissue of origin. The omental biopsy specimen was positive for the highly breast cancer–specific gross cystic disease fluid protein (GCDFP)-15 (Figure 4), as well as cytokeratin (CK)-7 and estrogen receptor (ER), and was focally positive for mammaglobin and negative for CK20, TTF-1, and CDX-2. The EGD specimen was obtained from the outside lab and reanalyzed by IHC and was also positive for GCDFP-15 (Figure 5), CK7, and ER and
Figure 2. H&E staining of the gastric biopsy specimen.
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Case Reports in GI Oncology
Figure 3. H&E staining of an omental biopsy specimen.
Figure 5. GCDFP-15 immunostaining of the gastric biopsy specimen.
cancer and newly diagnosed adenocarcinoma of the stomach, to spare the patient an unnecessary, aggressive, risky surgical approach for potential cure of presumptive stomach cancer. Pathologists can provide invaluable assistance in screening for a possible breast primary with appropriate IHC stains. In addition to the standard ER and PR, GCDFP and CK-7 and -20 can help confirm a breast primary, as in our case and in previously reported cases.5,6 Screening for a possible breast primary when stomach adenocarcinoma is discovered in a breast cancer survivor, particularly one with lobular histology, should arguably become the standard of care. Figure 4. GCDFP-15 immunostaining of the omental biopsy specimen.
REFERENCES negative for CK20 and CDX-2, similar to the omental specimen and the original breast cancer. Having a diagnosis of metastatic ER and Her2 breast cancer, the patient was started on fulvestrant, an ER downregulator. Her dysphagia resolved, and she remained otherwise asymptomatic. She did not have bone metastases on a repeat bone scan, and she continued on the double-blind, randomized, clinical study of denosumab.
1. Ambroggi M, Stroppa EM, Mordenti P, et al: Metastatic breast cancer to the gastrointestinal tract: report of five cases and review of the literature. Int J Breast Cancer 2012:439023, 2012
DISCUSSION
5. Arrangoiz R, Papavasiliou P, Dushkin H, et al: Case report and literature review: metastatic lobular carcinoma of the breast an unusual presentation. Int J Surg Case Rep 2:301–305, 2011
Although breast cancer is quite common, metastases to the stomach are rare.1 An Italian single-institution retrospective review of 980 breast cancer cases demonstrated a 0.3% incidence of gastric metastases.1 When stomach spread occurs, lobular carcinoma is by far the most common breast cancer histology, with an estimated prevalence of 852 to 97%3. Autopsy studies of patients with metastatic lobular cancer showed a 6 –18% incidence of gastrointestinal (GI) metastases,4 suggesting that the GI lumen is a relatively common eventual site of progressive metastases. As our case illustrates, it is important to have a clinical suspicion of possible gastric metastases in women with a history of breast
118
Gastrointestinal Cancer Research
2. Hussain T, Elahi B, McManus P, et al: Gastric obstruction secondary to metastatic breast cancer: a case report and literature review. J Med Case Rep 6:232, 2012 3. Hara F, Kiyoto S, Takabatake D, et al: Metastatic breast cancer to the stomach resembling early gastric cancer. Case Rep Oncol 3:142–147, 2010 4. Ghirarduzzi A, Sivelli R, Martella E, et al: Gastric metastasis from breast carcinoma: report of three cases, diagnostic-therapeutic critical close examination and literature review. Ann Ital Chir 81:141–146, 2010
6. Pectasides D, Psyrri A, Pliarchopoulou K, et al: Gastric metastases originating from breast cancer: report of 8 cases and review of the literature. Anticancer Res 29:4759 – 4763, 2009
Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest.
Address correspondence to: Alexander C. Black, MD, Clinical Professor of Medicine, UCLA/Pasadena Healthcare, 625 S. Fair Oaks Avenue, Suite 320, Pasadena, CA 91105; E-mail: [email protected]
Volume 7 • Issue 3– 4
