Gastrointestinal metastatic signet ring cell breast cancer in young females: a case report
Case Report

Gastrointestinal metastatic signet ring cell breast cancer in young females: a case report

Liang Zhang1,2, Lingyuan Wu3, Jiyu Li4, Shasha Song5, Huanyu Lu2, Chao Fang2, Kunbing Zhu2

1School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China; 2Department of Breast and Thyroid Surgery, Shandong Provincial Maternal and Child Health Care Hospital, Jinan, China; 3Reproductive Medicine Center, Shandong Provincial Maternal and Child Health Care Hospital, Jinan, China; 4Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China; 5Department of Pathology, Shandong Provincial Maternal and Child Health Care Hospital, Jinan, China

Correspondence to: Kunbing Zhu. Department of Breast and Thyroid Surgery, Shandong Provincial Maternal and Child Health Care Hospital, Jinan 250014, China. Email: zkb8321@163.com.

Background: Signet ring cell carcinoma (SRCC) is characterized by strong invasiveness and rapid progression. It occurs mostly in young and middle-aged patients, and early patients may have no clinical symptoms. Gastric SRCC with breast cancer metastasis is relatively rare. It often presents challenges for clinicians and pathologists and may lead to an absolutely different therapeutic strategy.

Case Description: In this paper, we report on a 37-year-old woman who was admitted to the hospital with a left breast mass discovered 5 days earlier, the mass was occasionally painful, and there was no skin swelling, skin depression, or other abnormalities. The initial diagnosis considered her to have a left breast tumor. The patient was previously healthy with no family history of tumor. Considering the possibility of malignant lesions, she underwent resection of the left breast tumor and surrounding tissue. Postoperative pathological findings suggested SRCC (left breast mass). Although the patient had no history of gastrointestinal tumors, considering that SRCC can also appear in the gastrointestinal tract and other organs. We performed gastroscopy on the patient, showed an ulcerative mass in the greater curvature of the gastric body, with irregular nodular uplift of the surrounding mucosa. The excised breast lesions were analyzed by immunohistochemistry, and the pathological result showed SRCC (left breast tumor). Combined with the results of immunohistochemistry, it was consistent with gastrointestinal metastasis. Through our multi-faceted differential diagnosis, the final diagnosis of the patient was clear, which not only bought time for the patient’s subsequent treatment, but also avoided misdiagnosis and blind treatment due to the particularity and rarity of the case.

Conclusions: Gastric cancer should be considered when breast tumors show SRCC without in situ lesion. Signet ring cell gastric cancer (occult) should be excluded even if the patient has no family history of gastric cancer. It is important to distinguish metastatic cancer from primary breast cancer to avoid misdiagnosis and blind treatment due to the particularity of the case, at which point an early recognition can be made and an optimal treatment plan can be chosen.

Keywords: Signet ring cell carcinoma (SRCC); breast cancer; gastrointestinal metastatic; case report

Submitted Mar 21, 2022. Accepted for publication May 13, 2022.

doi: 10.21037/gs-22-242

Introduction

Signet ring cell carcinoma (SRCC) is a poorly differentiated and weakly cohesive cancer characterized by a large amount of mucus within the cell that pushes the nucleus to one side, creating a crescent shape or signet ring cell morphology (1,2). SRCC is a type of gastric cancer with a high degree of malignancy, which has a low incidence rate. Patients with early stage gastric cancer may not have clinical symptoms, and are typically in the advanced stage when they are discovered. Gastric SRCC with breast cancer metastasis is relatively rare.

We reviewed previously published articles on signet ring cell breast cancer combined with gastric cancer. Simple gastric SRCC is more common in young and middle-aged women, while gastric SRCC with breast cancer metastasis is more common in perimenopausal women. Gastrointestinal discomfort is the first symptom in most cases when found. There have also been reports of breast masses and calcified microfocals as the first symptoms, but they were misdiagnosed as inflammatory breast cancer, and received breast cancer treatment (3). The pathological results of this case report suggest that the patient had gastrointestinal metastatic signet ring cell breast cancer. This case is the first of its kind in Shandong Provincial Maternal and Child Health Care Hospital. We report this case to improve the diagnostic experience and reduce the misdiagnosis rate of such special cases, so as to provide a reference experience for clinical diagnosis and treatment. We present the following article in accordance with the CARE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-22-242/rc).

Case presentation

A 37-year-old female presented with a left breast mass during physical examination, and was admitted to the Department of Breast and Thyroid Surgery of Shandong Provincial Maternal and Child Health Care Hospital in May 2021. This study was approved by the institutional ethics board of Shandong Provincial Maternal and Child Health Care Hospital (approval No. 2021-097). All procedures performed in this study were in accordance with the ethical standards of the institutional research committee and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

The patient had unintentionally discovered a left breast mass 5 days prior to hospitalization. The mass was occasionally painful, and there was no skin swelling, skin depression, or other abnormalities. The patient was otherwise healthy and had no history of other diseases. There was no family history of cancer, no history of genetic and infectious diseases. Her occupation is in legal consulting, and she has no bad eating habits such as high fat, no history of smoking, and no history of drinking. She had no abnormal mental status, diet, urine and feces, and no recent change in weight. Specialist physical examination showed that the bilateral breasts were symmetrical, and there was no redness, ulcers, hyperpigmentation, or scarring. Also, the bilateral nipples were symmetrical, and there was no retraction and retraction. A mass (approximately 3.5 cm × 2.5 cm in size) was palpated in the upper outer quadrant of the left breast; it was hard, with unclear borders, and poor mobility. There was no palpable mass in the right breast and no abnormal discharge. Abnormally enlarged lymph nodes were not palpated in the bilateral axillae and supraclavicular fossa.

In the outpatient department, breast ultrasound examination showed the following: (I) a patchy low echo area was detected in the gland layer of the upper quadrant of the left outer breast, with a range of about 3.9 cm × 2.6 cm × 1.8 cm, unclear boundary, irregular shape, uneven internal echo, and multiple mildly dilated catheter echoes Breast Imaging Reporting and Data System category 4A (BI-RADS category 4A); (II) bilateral mammary hyperplasia and left breast duct dilation; and (III) the echo of a lymph node was detected in the left axilla, about 1.7 cm × 0.8 cm in size, with thickened cortex and clear portal structure. After admission, relevant tests were carried out and mammography was performed, which suggested focal asymmetry of the left breast and catheter dilation (BI-RADS category 4A), suggesting a high possibility of inflammatory lesions. Carcinoembryonic Antigen (CEA), Carbohydrate Antigen 199 (CA199), and Carbohydrate Antigen 724 (CA724) were significantly increased in the serum tumor markers, of which CA724 was significantly increased by 99.77 U/mL (reference value: 0–6.9 U/mL).

Other examinations, such as abdominal ultrasound, routine blood, and biochemical tests, showed no obvious abnormalities. Considering the large volume of the left breast mass, the possibility of malignant lesions, clear indications of surgery, communication of the disease, and consent of the patient, resection of the left breast mass and some surrounding tissues was performed. Rapid intraoperative pathological diagnosis suggested that clumps and cords of signet ring cells could be seen in the fibrous stroma of the breast (left breast mass), and malignant or metastatic lesions could not be ruled out. The intraoperative rapid frozen pathological diagnosis is shown in Figure 1.

Figure 1 Rapid pathological diagnosis results of frozen breast tissue (hematoxylin and eosin staining) showed clusters and cord-shaped signet ring cells (×200).

We then inquired again about whether the patient had gastrointestinal-related symptoms and family history, and she denied them all. In order to further confirm the diagnosis, under our recommendation, the patients underwent electronic gastroscopy. Gastroscopy showed an ulcerative mass of about 3.0 cm × 4.0 cm in size in the greater curvature of the gastric body, with irregular nodular uplift of the surrounding mucosa, as well as yellow and white fur on the bottom. Six biopsies were taken, which were tough and bled easily. We considered the possibility of gastric malignancy. At the same time, the pathological results of the patient’s breast lesions showed SRCC (left breast tumor), which, combined with the immunohistochemical results, were consistent with gastrointestinal metastasis.

The pathological immunohistochemical results showed the following: estrogen receptor (ER)(−), progesterone receptor (PR)(−), Human epidermal growth factor receptor 2 (HER-2)(2+), Ki67 (30% hot spot area), GATA-binding protein 3 (GATA3)(−), Cytokeratin 7 (CK7)(+), Cytokeratin 20 (CK20)(+), villin(+) and CDX-2(+). Among these, we were interested in CK7(+), CK20(+), and villin(+), which, combined with other immunohistochemical indicators, proved that the first breast lesions found in this patient were metastatic cancer, and were considered to be gastric cancer metastasis. The immunohistochemical results of the breast tumor are shown in Figure 2. Finally, the histopathological diagnosis of gastroscopic biopsy was as follows: poorly differentiated carcinoma, some of which were SRCC [HER-2(2+)]. The immunohistochemical results of the gastroscopic biopsy tissue are shown in Figure 3, which confirmed our previous diagnosis.

Figure 2 Pathological diagnosis results of the breast tissue in this case. (A) Signet ring cell infiltration beside the milk duct (hematoxylin and eosin staining, ×100); (B) CK7 staining positive (immunohistochemical staining, ×40); (C) CK20 staining positive (immunohistochemical staining, ×40); (D) positive for Villin staining (immunohistochemical staining, ×40); (E) positive for CDX-2 staining (immunohistochemical staining, ×40); and (F) positive for HER-2 staining (immunohistochemical staining, ×40).
Figure 3 Histopathological results of gastroscopic biopsy in this case. (A) Signet ring cell infiltration (hematoxylin and eosin staining, ×100); (B) positive for HER-2(2+) staining (immunohistochemical staining, ×100).

Through our multi-faceted differential diagnosis, the final diagnosis of the patient was clear, which not only bought time for the patient’s subsequent treatment, but also avoided misdiagnosis and blind treatment due to the particularity and rarity of the case. Considering that the latter treatment in this case was mainly chemotherapy and radiotherapy, the patient was transferred to the medical oncology department for follow-up treatment. HER-2 gene fluorescence in situ hybridization test was negative, and the patient received XELOX (capecitabine + oxaliplatin) for 6 cycles. The efficacy evaluation after treatment was stable disease (SD).

Discussion

According to the Classification of Tumors by the World Health Organization (WHO), SRCC is a poorly differentiated and weakly cohesive carcinoma characterized by a large amount of mucus in the cells that pushes the nucleus to one side, forming a crescent shape or signet ring cell morphology (1,2). Primary SRCC can originate in many organs, most commonly in the stomach, followed by the colon, esophagus, rectum, lung, pancreas, breast, bladder, small intestine, and gallbladder. Primary SRCC in the breast accounts for only 1.5% (4-6).

SRCC is a type of gastric cancer with a high degree of malignancy. It is characterized by strong invasion and rapid disease progression, and is more common in middle-aged and young people, especially young women (7-9). Patients without a family history of gastric cancer may also have a high incidence of occult signet ring cell gastric cancer if they carry mutant reproductive genes (10). In the present case, the pathological findings suggested SRCC (left breast mass). Considering that SRCC may also appear in other organs, the primary lesion should be further identified for differential diagnosis.

Signet ring cell breast cancer with gastric cancer is rare, with fewer than 60 cases having been reported so far. We performed a literature search of the PubMed, MEDLINE, Embase, Google Scholar databases using keywords such as “stomach or gastric cancer”; “tumor or cancer or carcinoma or adenocarcinoma”; “breast cancer or breast”; and “transfer”. As of December 2021, a total of 33 cases of SRCC had been diagnosed with either the stomach or breast as the primary site, including 22 cases of primary gastric cancer and 11 cases of primary breast cancer. Breast mass and calcification microfoci were the first symptoms in 15 cases, and gastrointestinal discomfort was the first symptom in 14 cases. Also, three patients with ovarian cancer as the first symptom were diagnosed as primary SRCC of the stomach with breast and ovarian cancer metastasis, and another case was diagnosed as primary SRCC of the stomach with breast and cervical cancer metastases. The ages of the patients ranged from 23 to 67 years, with a mean of 45.16±11.25 years. The retrieved cases and statistics are shown in Table 1.

Table 1

Thirty-three cases of SRCC with stomach or breast as primary site

Case Age/gender Initial symptom Primary carcinoma Histologic type Immunohistochemistry Treatment
Arifa Abid et al., 2013 (11) 59/F Stomach Breast Lobular carcinoma CK7+, AE3+, AE−, ER+, PR+, CK20−, CDX2−, HER2− Endocrine therapy
Tetsuji Kudo et al., 2005 (12) 59/F Stomach Breast Signet ring-cell carcinoma GCDFP15+ Chemotherapy, 2 years
Idrees Khan et al., 2017 (13) 56/F Stomach Breast Signet cell carcinoma – Chemotherapy
S. Di Cosimo et al., 2003 (14) 39/F Ovarian Stomach Signet cell carcinoma GCDFP15−, ER−, c-erbB-2− Chemotherapy
Yoichiro Kondo et al., 1984 (15) 51/F Stomach Breast Signet cell carcinoma – Bilateral mastectomy and partial gastrectomy
Tomoi Sato et al., 2008 (16) 67/F Breast Stomach Poorly differentiated adenocarcinoma with signet ring cells inside the lymphatics ER−, PR−, HER2−, CK20−, MUC 5AC−, GCDFP15+, CK7+, MUC2+ Chemotherapy
Hyunee Yim et al., 1997 (17) 48/F Stomach Breast Signet cell carcinoma GCDFP15+, ER− Chemotherapy
Sibel K. Cetintas et al., 2006 (18) 48/F Breast Breast Signet cell carcinoma ER+, PR+, CK+, CD20−, CR-A− Chemotherapy
Kwangil Yim et al., 2017 (19) 65/F Stomach Breast Signet ring cell carcinoma GCDFP15−, GATA3+, ER−, PR−, c-erbB-2+ Chemotherapy
Oya Kayacan et al., 2008 (20) 28/F Left breast Stomach Signet ring cell carcinoma – –
Huanhuan Yan et al., 2017 (21) 39/F Left breast Stomach Signet ring cell carcinoma CK7−, CK20−, villin++, CAM5.2+, Ki-67 (50%), P53+, c-erbB-2− Chemotherapy
Qiuhong Tian et al., 2016 (22) 37/F Breast Stomach Signet ring cell carcinoma CK7+, CK20−, villin++, ER−, PR−, HER2− Chemotherapy
Qiuhong Tian et al., 2016 (22) 31/F Right breast Stomach Signet ring cell carcinoma CK7(−), CK20(3+), villin(3+), PR(−), S100(−), Vim(−), ER(−), Ki-67(+), c-Erb-B2(−), CD34(−), E-cadherin(2+) Chemotherapy
Audrius Dulskas et al., 2019 (23) 34/F Stomach Stomach Signet ring cell type of adenocarcinoma CDX-2+, CK20+, ER−, CK7−, GATA 3− Chemotherapy, Radiation therapy
Gregory E. Jones et al., 2007 (24) 51/F Stomach Breast Adenocarcinoma of a signet-ring pattern ER+, PR+, CK7+, GCDFP15+, CK20−, HER2− Palliative care
Gregory E. Jones et al., 2007 (24) 61/F Stomach Breast Poorly differentiated adenocarcinoma of signet ring cell type ER+, PR+, CK7+, CK20−, HER2− Chemotherapy and radiotherapy to her brain
CH Park, et al., 1996 (25) 48/F Right Breast Breast Signet ring cell carcinoma – Chemotherapy
SS Qureshi et al., 2005 (26) 34/F Stomach Stomach Signet ring cell carcinoma Ck20+, GCDFP−, ck7−, S-100−, ER−, PR− Gastrectomy, chemotherapy
C. Gregoire et al., 2014 (27) 66/F Stomach Breast Signet ring cell adenocarcinoma ER+, PR+, E-cadherin− Stop chemotherapy, Hormonal therapy
Anastasios L Boutis et al., 2006 (28) 37/F Left breast Stomach Signet ring cell carcinoma ER−, PR−, c-erbB-2−, CK7+, CK20+, Chemotherapy
HH Buerba-Vieregge et al., 2021 (29) 38/F Stomach Stomach Signet ring cell carcinoma HER2−, GATA3−, ER−, ACE+, CK7+, CK20+ Chemotherapy
S. Krichen Makni et al., 2007 (30) 40/F Stomach Stomach Signet ring cell carcinoma ACE−, CK20−, CK7+, ER−, PR− Chemotherapy
Doval et al., 2009 (31) 34/F Ovarian Stomach Signet ring cell carcinoma GCDFP-15−, ER−, PR−, HER-2/neu (ERBB2)−, CA125− Chemotherapy
Li-Yuan Wei et al., 2017 (32) 49/F Breast Stomach Signet ring cell carcinoma ER−, PR−, c-erbB-2−, CK20−, CK7+, CK19+, CK20+, GATA3−, GCDFP-15−, MMG− Chemotherapy
Asumi Iesato et al., 2015 (33) 41/F Pelvic and breast Stomach Signet ring cell carcinoma MUC5AC+, HIK1083+ Chemotherapy
Asumi Iesato et al., 2015 (33) 34/F Cervical polyp Stomach Signet ring cell carcinoma HER2−, ER−, PR−, HIK1083+, GCDFP15+, MUC6+ Chemotherapy
Chun-Lan He et al., 2015 (34) 48/F Left breast Stomach Signet ring cell breast carcinoma CK7+, CK20+, villin+, EGFR+, ErbB2/HER2+, ER−, PR−, GCDFP-15−, CEA−, (CA) 153−, CA125−, CA199− Chemotherapy
Susanne Briest et al., 1999 (35) 46/F Both breasts Stomach Signet ring cell carcinoma ER−, PR−, CK7+, CK20+, CEA+ Chemotherapy
Jin-Young Kwak et al., 2000 (36) 41/F Left breast Stomach Signet ring cell carcinoma ER−, GCDFP− –
Jin-Young Kwak et al., 2000 (36) 23/F Right breast Stomach Signet ring cell carcinoma ER−, GCDFP− –
Yiu Shiobhon Luk et al., 2012 (37) 54/F Right breast Stomach Signet ring cell carcinoma ER−, c-erbB-2−, AE1/AE3+, PAS-D+, E-cadherin+, CK7+, CK20+ Chemotherapy
Atul K Madan et al., 2002 (38) 39/F Abdomen Stomach Signet ring cell carcinoma GCDFP-15−, c-erg−, ER−, PR−, BRST-2−, CK20+, CK7+ Palliative surgery
Karl J. Schmutzer et al., 1973 (39) 22/F Stomach Stomach Krukenberg tumors – Gastrectomy, oophorectomy, mastectomy, chemotherapy

SRCC, signet ring cell carcinoma; F, female.

It has been reported that simple SRCC of the stomach is more likely to occur in young and middle-aged women, while SRCC of the stomach with breast cancer metastasis is more likely to occur in perimenopausal women (40-42). In this case, the age of onset was 37 years old, which was relatively young and consistent with the age characteristics of SRCC of the stomach with breast cancer metastasis. Therefore, for young breast disease patients, especially those with BI-RADS 4A imaging diagnosis, professional surgeons cannot ignore detailed medical history collection and related professional examinations, such as mammography, breast Magnetic Resonance Imaging, serum tumor-related markers, etc. Single tumor marker detection has limited application value in the early diagnosis of breast cancer. Combined detection of serum tumor markers significantly improves the sensitivity of tumor diagnosis, especially for liver, biliary, pancreatic tumors, lung cancer, breast cancer, gastric cancer, colorectal cancer, and other digestive tract tumors. Moreover, the combined detection of CA15-3, CA125, and CEA can complement each other and effectively improve the performance indicators of breast cancer diagnosis (43,44), which is of certain value for the early diagnosis and treatment of breast cancer.

Breast cancer diagnosis relies on histopathological examination, and pathological specimens can be obtained through a variety of surgical methods, including core needle biopsy (CNB) and open surgical biopsy. In this case, the patient underwent excision of the left breast mass and some surrounding tissue, considering the possibility of malignant lesions of the left breast mass. Signet ring cells can be seen locally in the fibrous stroma of the breast as indicated by pathological diagnosis. The choice of complete tumor resection here can avoid misdiagnosis due to the particularity of the case.

Pathological diagnosis based on histopathological features has always been the “gold standard” of tumor diagnosis and the basis of clinical treatment. It plays an important role in the pathological diagnosis of special types of malignant tumors, such as breast SRCC. SRCC of the breast needs to be differentiated from mucinous cystadenocarcinoma, metastatic mucinous carcinoma, and metastatic SRCC, which can be combined with clinical history and immunohistochemical results (45-48). According to the literatures we searched, CK20+ and CDX2+ were indicative of gastric cancer as the primary focus, while ER+, PR+, and gross cystic disease fluid protein-15 (GCDFP-15)+ were supported by breast cancer as the primary focus. GATA3 has only been used as the main differential indicator in recent years to differentiate primary breast cancers from gastrointestinal tumors. The study by Hui et al. reported that ER and GATA-3 are effective methods for differentiating signet ring tumors of the breast and gastrointestinal tract (49). In this case, the immunohistochemical results of ER, PR and GATA-3 were negative, which suggested that breast SRCC was not the primary lesion. Meanwhile, CK20 and CDX2 also helped to support the gastrointestinal origin of the signet ring tumors. This case report is consistent with the findings of Hui. It is important to differentiate between metastatic and primary breast cancer at pathological diagnosis.

SRCC is a type of gastric cancer with a high degree of malignancy, which has a low incidence rate. Patients with SRCC early stage may not have clinical symptoms, and are typically in the advanced stage when they are discovered. Through our multi-faceted differential diagnosis, the final diagnosis of the patient was clarified earlier, which not only bought time for the patient’s subsequent treatment, but also avoided misdiagnosis and blind treatment due to the particularity and rarity of the case.

Conclusions

Gastric cancer should be considered when breast tumors show SRCC without in situ lesion. Signet ring cell gastric cancer (occult) should be excluded even if the patient has no family history of gastric cancer. It is important to distinguish between metastatic carcinoma and primary breast cancer, also can avoided misdiagnosis and blind treatment due to the particularity and rarity of the case. For patients with advanced metastatic breast cancer patients, the optimal treatment option involves making an appropriate and early diagnosis, and prolonging the patient’s life with tumor control, while at the same time improving their quality of life.

Acknowledgments

Funding: The work was supported by the Shandong Province Medical and Health Science and Technology Development Program (No. 2017WSB03002) and the Special Fund Project of Breast Disease Research of Shandong Medical Association (No. YXH2021ZX052).

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-22-242/rc

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-22-242/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was approved by the institutional ethics board of Shandong Provincial Maternal and Child Health Care Hospital (approval No. 2021-097). All procedures performed in this study were in accordance with the ethical standards of the institutional research committee and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

  1. Fléjou JF, Classification OMS. 2010 des tumeurs digestives: la quatrième édition Ann Pathol 2011;31:S27-31. [WHO Classification of digestive tumors: the fourth edition]. [Crossref] [PubMed]
  2. Tan PH, Ellis I, Allison K, et al. The 2019 World Health Organization classification of tumours of the breast. Histopathology 2020;77:181-5. [Crossref] [PubMed]
  3. Hamby LS, McGrath PC, Cibull ML, et al. Gastric carcinoma metastatic to the breast. J Surg Oncol 1991;48:117-21. [Crossref] [PubMed]
  4. Wu SG, Chen XT, Zhang WW, et al. Survival in signet ring cell carcinoma varies based on primary tumor location: a Surveillance, Epidemiology, and End Results database analysis. Expert Rev Gastroenterol Hepatol 2018;12:209-14. [Crossref] [PubMed]
  5. Zhang M, Zhu G, Zhang H, et al. Clinicopathologic features of gastric carcinoma with signet ring cell histology. J Gastrointest Surg 2010;14:601-6. [Crossref] [PubMed]
  6. Machlowska J, Pucułek M, Sitarz M, et al. State of the art for gastric signet ring cell carcinoma: from classification, prognosis, and genomic characteristics to specified treatments. Cancer Manag Res 2019;11:2151-61. [Crossref] [PubMed]
  7. Allemani C, Matsuda T, Di Carlo V, et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet 2018;391:1023-75. [Crossref] [PubMed]
  8. Chen CL, Xue DX, Chen HH, et al. Nomograms to Predict Overall and Cancer-Specific Survival in Gastric Signet-Ring Cell Carcinoma. J Surg Res 2021;266:13-26. [Crossref] [PubMed]
  9. Torre LA, Siegel RL, Ward EM, et al. Global Cancer Incidence and Mortality Rates and Trends--An Update. Cancer Epidemiol Biomarkers Prev 2016;25:16-27. [Crossref] [PubMed]
  10. Gamble LA, Rossi A, Fasaye GA, et al. Association Between Hereditary Lobular Breast Cancer Due to CDH1 Variants and Gastric Cancer Risk. JAMA Surg 2022;157:18-22. [Crossref] [PubMed]
  11. Abid A, Moffa C, Monga DK. Breast cancer metastasis to the GI tract may mimic primary gastric cancer. J Clin Oncol 2013;31:e106-7. [Crossref] [PubMed]
  12. Kudo T, Matsumoto T, Nakamura S, et al. Solitary minute metastasis from breast cancer mimicking primary intramucosal gastric signet-cell cancer. Gastrointest Endosc 2005;62:139-40. [Crossref] [PubMed]
  13. Khan I, Malik R, Khan A, et al. Breast Cancer Metastases to the Gastrointestinal Tract Presenting with Anemia and Intra-abdominal Bleed. Cureus 2017;9:e1429. [Crossref] [PubMed]
  14. Di Cosimo S, Ferretti G, Fazio N, et al. Breast and ovarian metastatic localization of signet-ring cell gastric carcinoma. Ann Oncol 2003;14:803-4. [Crossref] [PubMed]
  15. Kondo Y, Akita T, Sugano I, et al. Signet ring cell carcinoma of the breast. Acta Pathol Jpn 1984;34:875-80. [Crossref] [PubMed]
  16. Sato T, Muto I, Fushiki M, et al. Metastatic breast cancer from gastric and ovarian cancer, mimicking inflammatory breast cancer: report of two cases. Breast Cancer 2008;15:315-20. [Crossref] [PubMed]
  17. Yim H, Jin YM, Shim C, et al. Gastric metastasis of mammary signet ring cell carcinoma--a differential diagnosis with primary gastric signet ring cell carcinoma. J Korean Med Sci 1997;12:256-61. [Crossref] [PubMed]
  18. Cetintas SK, Kurt M, Ozkan L, et al. Gastric metastasis of signet ring cell carcinoma of the breast. Saudi Med J 2006;27:259-61. [PubMed]
  19. Yim K, Ro SM, Lee J. Breast cancer metastasizing to the stomach mimicking primary gastric cancer: A case report. World J Gastroenterol 2017;23:2251-7. [Crossref] [PubMed]
  20. Kayacan O, Karnak D, Ayşe Can B, et al. Gastric signet-ring cell adenocarcinoma presenting with left arm deep-vein thrombosis and bilateral chylothorax. Clin Appl Thromb Hemost 2008;14:476-80. [Crossref] [PubMed]
  21. Yan H, Liu J, Ming X, et al. Metastatic gastric carcinoma to the breast: A case report and review of the Chinese literature. Mol Clin Oncol 2017;7:221-4. [Crossref] [PubMed]
  22. Tian Q, Zeng J, Tao X, et al. Clinical pathology of metastatic gastric carcinoma to the breast: A report of two cases and a review of literature. Oncol Lett 2016;11:3081-4. [Crossref] [PubMed]
  23. Dulskas A, Al Bandar M, Choi YY, et al. A case of gastric cancer metastasis to the breast in a female with BRCA2 germline mutation and literature review. Acta Chir Belg 2019;119:59-63. [Crossref] [PubMed]
  24. Jones GE, Strauss DC, Forshaw MJ, et al. Breast cancer metastasis to the stomach may mimic primary gastric cancer: report of two cases and review of literature. World J Surg Oncol 2007;5:75. [Crossref] [PubMed]
  25. Park CH, Whang HS, Park HB. Bilateral signet-ring cell carcinoma of the breast: scintigraphic findings. Clin Nucl Med 1996;21:115-7. [Crossref] [PubMed]
  26. Qureshi SS, Shrikhande SV, Tanuja S, et al. Breast metastases of gastric signet ring cell carcinoma: a differential diagnosis with primary breast signet ring cell carcinoma. J Postgrad Med 2005;51:125-7. [PubMed]
  27. Gregoire C, Muller G, Machiels JP, et al. Metastatic signet-ring cell carcinoma of unknown primary origin. Acta Clin Belg 2014;69:135-8. [Crossref] [PubMed]
  28. Boutis AL, Andreadis C, Patakiouta F, et al. Gastric signet-ring adenocarcinoma presenting with breast metastasis. World J Gastroenterol 2006;12:2958-61. [Crossref] [PubMed]
  29. Buerba-Vieregge HH, Fernández-Ferreira R, Soberanis-Piña PD, et al. Breast Metastasis of Gastric Signet Ring Cell Carcinoma: A Case Report and Literature Review. Case Rep Oncol 2021;14:165-72. [Crossref] [PubMed]
  30. Krichen Makni S, Abbes K, Khanfir A, et al. Metastatic signet ring cell carcinoma to the breast from stomach. Cancer Radiother 2007;11:276-9. [Crossref] [PubMed]
  31. Doval DC, Pande SB, Sharma JB, et al. Metastatic Signet-Ring Cell Gastric Carcinoma Masquerading as Breast Primary. Case Rep Gastroenterol 2009;3:21-5. [Crossref] [PubMed]
  32. Wei LY, Kong M, Zhang Z, et al. Breast metastasis of gastric signet-ring cell carcinoma. J Zhejiang Univ Sci B 2017;18:1026-30. [Crossref] [PubMed]
  33. Iesato A, Oba T, Ono M, et al. Breast metastases of gastric signet-ring cell carcinoma: a report of two cases and review of the literature. Onco Targets Ther 2015;8:91-7. [PubMed]
  34. He CL, Chen P, Xia BL, et al. Breast metastasis of gastric signet-ring cell carcinoma: a case report and literature review. World J Surg Oncol 2015;13:120. [Crossref] [PubMed]
  35. Briest S, Horn LC, Haupt R, et al. Metastasizing signet ring cell carcinoma of the stomach-mimicking bilateral inflammatory breast cancer. Gynecol Oncol 1999;74:491-4. [Crossref] [PubMed]
  36. Kwak JY, Kim EK, Oh KK. Radiologic findings of metastatic signet ring cell carcinoma to the breast from stomach. Yonsei Med J 2000;41:669-72. [Crossref] [PubMed]
  37. Luk YS, Ka SY, Lo SS, et al. An unusual case of gastric cancer presenting with breast metastasis with pleomorphic microcalcifications. J Breast Cancer 2012;15:356-8. [Crossref] [PubMed]
  38. Madan AK, Ternovits C, Huber SA, et al. Gastrointestinal metastasis to the breast. Surgery 2002;132:889-93. [Crossref] [PubMed]
  39. Schmutzer KJ, Zaki AE, Regan JF. Gastric carcinoma in a 22-year-old Negro woman with metastases to ovaries and breast. A case report. J Natl Med Assoc 1973;65:426-8. [PubMed]
  40. Smith RA. The value of modern mammography screening in the control of breast cancer: understanding the underpinnings of the current debates. Cancer Epidemiol Biomarkers Prev 2014;23:1139-46. [Crossref] [PubMed]
  41. Pace LE, Keating NL. A systematic assessment of benefits and risks to guide breast cancer screening decisions. JAMA 2014;311:1327-35. [Crossref] [PubMed]
  42. Niell BL, Freer PE, Weinfurtner RJ, et al. Screening for Breast Cancer. Radiol Clin North Am 2017;55:1145-62. [Crossref] [PubMed]
  43. Lee JS, Park S, Park JM, et al. Elevated levels of serum tumor markers CA 15-3 and CEA are prognostic factors for diagnosis of metastatic breast cancers. Breast Cancer Res Treat 2013;141:477-84. [Crossref] [PubMed]
  44. Stieber P, Nagel D, Blankenburg I, et al. Diagnostic efficacy of CA 15-3 and CEA in the early detection of metastatic breast cancer-A retrospective analysis of kinetics on 743 breast cancer patients. Clin Chim Acta 2015;448:228-31. [Crossref] [PubMed]
  45. Tot T. The role of cytokeratins 20 and 7 and estrogen receptor analysis in separation of metastatic lobular carcinoma of the breast and metastatic signet ring cell carcinoma of the gastrointestinal tract. APMIS 2000;108:467-72. [Crossref] [PubMed]
  46. Chu PG, Weiss LM. Immunohistochemical characterization of signet-ring cell carcinomas of the stomach, breast, and colon. Am J Clin Pathol 2004;121:884-92. [Crossref] [PubMed]
  47. Fukui Y. Mechanisms behind signet ring cell carcinoma formation. Biochem Biophys Res Commun 2014;450:1231-3. [Crossref] [PubMed]
  48. Ma YR, Ren Z, Conner MG, et al. Reduced E-Cadherin and Aberrant β-Catenin Expression are Associated With Advanced Disease in Signet-Ring Cell Carcinomas. Appl Immunohistochem Mol Morphol 2017;25:432-8. [Crossref] [PubMed]
  49. Hui Y, Wang Y, Nam G, et al. Differentiating breast carcinoma with signet ring features from gastrointestinal signet ring carcinoma: assessment of immunohistochemical markers. Hum Pathol 2018;77:11-9. [Crossref] [PubMed]

(English Language Editor: A. Kassem)

Cite this article as: Zhang L, Wu L, Li J, Song S, Lu H, Fang C, Zhu K. Gastrointestinal metastatic signet ring cell breast cancer in young females: a case report. Gland Surg 2022;11(5):943-952. doi: 10.21037/gs-22-242

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