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 Table of Contents  
CASE REPORT
Year : 2017  |  Volume : 50  |  Issue : 2  |  Page : 69-73

Invasive lobular carcinoma of breast with synchronous colon metastasis


1 Department of Surgery, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
2 Department of Internal Medicine, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
3 Department of Pathology, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
4 Department of Radiology, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
5 Department of Nuclear Medicine, College of Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan

Date of Submission22-Apr-2016
Date of Decision11-Jul-2016
Date of Acceptance28-Sep-2016
Date of Web Publication18-Apr-2017

Correspondence Address:
Hui-Ping Hsu
No. 138, Sheng Li Rd., Tainan City 704
Taiwan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/fjs.fjs_22_17

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  Abstract 

Secondary colon malignancy is rare and has a nonspecific presentation. Breast cancer is the second most common malignancy that metastasizes to the gastrointestinal (GI) tract. Here, we present the case of a 54-year-old woman diagnosed with breast cancer and synchronous colon metastasis through a positive result obtained from stool occult blood screening. Colonoscopy revealed a subepithelial tumor of the colon. Biopsy revealed metastatic cancer with positive cytokeratin and GATA-binding protein 3 staining, as well as negative caudal-type homeobox 2 staining. A palpable right breast mass with nipple retraction was found, and invasive lobular carcinoma (ILC) was diagnosed. Multiple bone, left adrenal gland, para-aortic lymph node, and contralateral breast metastases were detected. Multimodality treatment involving systemic chemotherapy, hormone therapy, and modified radical mastectomy was applied. In our clinical experience, colon metastasis from breast cancer is rare and usually mimics primary colon cancer. High-alert speculation and aggressive biopsy for patients with abnormal GI bleeding are indicated for diagnosis. Patients with colon metastasis from ILC of the breast have a poor prognosis. Therefore, multimodality treatments should be applied to improve their prognosis.

Keywords: Colon metastasis, gastrointestinal tract bleeding, invasive lobular carcinoma, multimodality treatment


How to cite this article:
Loh ZJ, Lee KT, Chung WP, Chen WC, Kuo HL, Chen PJ, Lu HH, Hsu HP. Invasive lobular carcinoma of breast with synchronous colon metastasis. Formos J Surg 2017;50:69-73

How to cite this URL:
Loh ZJ, Lee KT, Chung WP, Chen WC, Kuo HL, Chen PJ, Lu HH, Hsu HP. Invasive lobular carcinoma of breast with synchronous colon metastasis. Formos J Surg [serial online] 2017 [cited 2019 Oct 19];50:69-73. Available from: http://www.e-fjs.org/text.asp?2017/50/2/69/204661


  Introduction Top


Breast cancer is the most common cancer in women and the fourth main cause of cancer death in Taiwan.[1] The most common types of invasive breast carcinomas are invasive ductal and lobular carcinoma (IDC and ILC, respectively). A large-scale epidemiological study compared the survival of stage-matched patients and determined that the prognosis of patients with ILC is similar or slightly more favorable than that of those with IDC.[2] However, patients with luminal ILC (positive expression of estrogen receptor [ER]) have worse outcomes than those with luminal IDC.[3] The metastatic patterns of ILC are different from those of IDC.[2] The liver, lung, bone, and brain are the most common metastatic sites in patients with IDC or ILC. Metastasis to the gastrointestinal (GI) tract and gynecological organs is more common in patients with ILC.[4] Secondary GI tract metastasis is rare in patients with breast cancer, and metastasis to the upper GI tract occurs more frequently than that to the lower GI tract.[5] The presenting symptoms are typically nonspecific, making early detection difficult. A delayed diagnosis in patients with ILC is the main concern. Here, we present a case report of ILC of the breast with colon metastasis that mimics primary colon cancer. Multimodality treatment was administered and led to favorable results.


  Case Report Top


A 54-year-old woman underwent stool occult blood screening, and the result was positive. She did not experience abdominal discomfort or report any change in bowel habits. Serum carbohydrate antigen 125 (CA125) and CA153 levels were elevated, but the carcinoembryonic antigen (CEA) level was within the reference range (CA153, 561 U/mL; CA125, 203.49 U/mL; and CEA, 2.91 ng/mL). Colonoscopy revealed a 2 cm subepithelial tumor over the hepatic flexure of the colon [Figure 1]a. Abdominal computed tomography revealed a flat subepithelial lesion with fair enhancement over the hepatic flexure of the colon, irregular thickening of the urinary bladder posterior wall, a left adrenal gland nodule, and multiple osteoblastic lesions over the pelvic girdle. Biopsy of the subepithelial colon tumor was performed, and the pathological report revealed metastatic carcinoma, suggesting mammary or urothelial origin. Microscopically, the tumor cells were poorly cohesive and infiltrated into the lamina propria of the colonic mucosa. Some signet-ring cells were observed [Figure 1]b. An immunohistochemical study showed that the tumor cells were positive for cytokeratin and GATA-binding protein 3 [GATA3; [Figure 1]c and negative for caudal-type homeobox 2 [CDX2; [Figure 1]d. Transurethral biopsy with cystoscopy revealed cystitis cystica without evidence of malignancy. By contrast, the patient reported a palpable right breast mass with nipple retraction that she has noted for 1 month but she has chosen to ignore. Breast sonography detected a 2 cm irregular isoechoic mass with an indistinct margin over the lower inner quadrant of the right breast [Figure 2]a. Core needle biopsy of the right breast mass revealed ILC [Figure 2]b with positive ER, positive progesterone receptor, and negative human epidermal growth factor receptor 2 (Her-2/Neu) expression [Figure 2]c. The breast tumor showed the same morphology as the subepithelial tumor of the colon, with positive GATA3 and negative CDX2 staining. Moreover, immunohistochemical staining of the colon tumor revealed positive ER expression [Figure 2]d. Thus, the diagnosis of ILC of the right breast with colon metastasis was confirmed.
Figure 1: Colon tumor. (a) Colonoscopy revealed a subepithelial tumor of the colon, (b) hematoxylin and eosin staining of the colonic lesion confirmed the diagnosis of metastatic carcinoma, (c) positive GATA3 expression. Note the negative staining of the internal colonic glands, (d) negative CDX2 expression. Note the positive staining of the internal colonic glands

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Figure 2: Invasive lobular carcinoma of the breast. (a) Irregular isoechoic mass with an ill-defined margin of the right breast on sonography, (b) hematoxylin and eosin staining showed invasive lobular carcinoma of the right breast, (c) strongly positive estrogen receptor expression in breast carcinoma cells, (d) positive estrogen receptor expression in colon metastasis

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A bone scan and 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography (18 F-FDG PET/CT) showed right breast cancer with multiple bone, left adrenal gland, para-aortic lymph node, and contralateral breast metastases [cT1cNxM1, cStage IV; [Figure 3]a,[Figure 3]b,[Figure 3]c. The patient was treated with six cycles of combination chemotherapy with cyclophosphamide, epirubicin, and 5-fluorouracil. She also received hormone therapy with letrozole and was prescribed denosumab to prevent skeletal-related events. One year after the initial diagnosis,18 F-FDG PET/CT revealed the partial response of the right breast cancer and the reduced activity of the left adrenal nodule. Moreover,18 F-FDG-avid lesions were not detected in the bone, left breast, colon, and urinary bladder, and reactive lymphadenopathy in the abdomen was favored [Figure 3]d,[Figure 3]e,[Figure 3]f. Right modified radical mastectomy was performed for definitive breast management. The patient was in a stable condition 14 months after the diagnosis of colon metastasis.
Figure 3: 18-Fluoro-2-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) images performed before (a-c) and after (d-f) systemic treatment. The initial scan showed heterogeneous FDG accumulation in the vertebrae, with multiple sclerotic lesions indicating bone metastases (a). Increased FDG uptake in the right breast was consistent with biopsy results (b). Increased FDG uptake in the left adrenal gland (c). The posttreatment scan showed a resolution of FDG uptake in the vertebrae (d); a partial response with reduced standardized uptake values in the right breast tumor (e) and the left adrenal gland (f)

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  Discussion Top


Breast cancer is the second most common malignancy that metastasizes to the GI tract, following malignant melanoma.[2] A series of autopsies revealed a variable incidence rate of 8%–35% for GI tract metastasis.[6] The initial diagnosis of breast cancer is difficult, and its precise incidence is unclear. The most common site of GI tract metastases is the stomach (15% at autopsy [2],[6]), followed by the small bowel and colon. Only 39 cases of colon metastases have been reported.[7] The clinical symptoms exhibit variable severity and are nonspecific, from an alteration of bowel habits to bowel obstruction. Systemic symptoms, including anemia or weight loss, are the only indications in some patients, thus complicating the early diagnosis of secondary colon metastasis.[8]

Diagnostic imaging is currently nonspecific for differentiating primary tumors of the GI tract from metastatic tumors of the GI tract. Colon metastasis typically presents as an invasion of the submucosal layer through blood vessels or the lymphatic system. Consequently, endoscopic examination may result in a misleading diagnosis if the specimen is superficially biopsied, resulting in the diagnosis of benign colitis. Moreover, the prolonged interval from the initial diagnosis of breast cancer to GI metastasis can range from 4 to 28 years.[7] The prolonged interval can easily lead to misleading diagnosis by clinicians. Breast cancer is usually diagnosed initially, followed by a much later diagnosis of GI metastasis. Detecting primary breast cancer is rare after the histopathological examination of colon metastasis.[9]

Patients with a history of breast cancer have an increased incidence of second primary colon cancers relative to that of colorectal metastases.[10] Therefore, histopathological comparison between primary breast cancer and GI specimens plays a crucial role in obtaining a correct diagnosis. ILC is the most common type of breast cancer with GI metastases although patients with IDC exhibit a higher prevalence of GI metastases.[2],[4] McLemore et al. reported 41 cases of GI metastases among 12,550 cases of breast cancer, and 61% of the patients (25/41) were diagnosed as having ILC.[4] In our patient, histopathological and immunochemical comparison played a vital role in the diagnosis of breast cancer with synchronous colon metastasis. Initially, the colonic lesion showed strong staining for GATA3 but negative staining for CDX2. GATA3 is a specific marker of urothelial and breast carcinomas, whereas CDX2 is a molecular marker of GI malignancy, particularly colorectal adenocarcinoma. Subsequently, no urothelial lesion was identified in our patient. Finally, the histopathological image of the breast tumor confirmed that the breast tumor was the ILC type, and the breast tumor was morphologically and immunohistochemically consistent with the colon tumor.

Because of the extreme rarity of colon metastasis, the treatment principle for this metastasis remains controversial.[8] Previous studies have reported the use of surgery or systemic therapy. The prognosis is typically poor, and the median survival time is only 1–2 years following diagnosis. Isolated colorectal metastasis is often initially treated with surgery. Resection is also indicated for tumor-related complications, such as bowel obstruction, bleeding, and perforation.[11] Colostomy or bypass surgery is required for palliation; multiple metastases may require systemic therapy. In our patient, biopsy was successfully performed to obtain a correct diagnosis. Combination chemotherapy with an anthracycline-based regimen for Stage IV breast cancer was administered. The aromatase inhibitor letrozole was indicated for our postmenopausal patient with hormone receptor-positive metastatic disease. Denosumab was prescribed for bone metastases. The radioactivity in 18 F-FDG PET/CT of bone, lymph node, and left adrenal metastasis was decreased. A well-controlled Stage IV breast cancer was diagnosed, and definite breast cancer treatment with modified radical mastectomy was appropriate. The patient was stable after multimodality treatment with endoscopic biopsy, chemotherapy, hormone therapy, and surgery.

The relevant literature indicates that the prognosis of ILC is similar or slightly more favorable than that of IDC in stage-matched patients. However, early detection of ILC is difficult, and patients with ILC often have more involved nodes, a larger tumor size, and multifocal cancer on initial presentation than those with IDC. The recurrence rate, disease-free survival, and overall survival are similar in ILC and IDC, but the underestimation of the disease extent is a concern in patients with ILC. Two recent studies have reported contrasting outcomes for ILC and IDC. A large-scale study in 2010 demonstrated a more favorable prognosis for stage-matched patients with ILC.[12] This observation may be attributed to the favorable factors in patients with ILC, such as old age, low nuclear grade, low proliferative index, and high expression of ER receptors. In another large-scale study in 2016, patients with luminal ILC exhibited worse outcomes than those with luminal IDC, but other cell types (Her-2 overexpression or triple-negative breast cancer) were not evaluated.[3] Therefore, patients with ILC have more favorable prognosis than those with IDC under certain conditions. Additional studies should be conducted to obtain more definite conclusion.

In conclusion, colon metastasis from breast cancer is rare and challenging to diagnose. Experienced pathologists play a crucial role in the differential diagnosis between primary and secondary colon malignancies. The prognosis of breast cancer patients with colon metastasis is typically poor; however, an appropriate multimodality treatment may improve their quality of life and delay disease progression.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Acknowledgments

We are grateful for the support provided by Professor Pin-Wen Lin, the late superintendent of National Cheng Kung University Hospital.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
2015 Statistics of Causes of Death, Ministry of Health and Welfare, Republic of China. Available from: http://www.mohw.gov.tw/cht/DOS/Statistic.aspx?f_list_no=312 & fod_list_no=6201. [Last accessed on 2016 Oct 10].  Back to cited text no. 1
    
2.
Arpino G, Bardou VJ, Clark GM, Elledge RM. Infiltrating lobular carcinoma of the breast: Tumor characteristics and clinical outcome. Breast Cancer Res 2004;6:R149-56.  Back to cited text no. 2
    
3.
Adachi Y, Ishiguro J, Kotani H, Hisada T, Ichikawa M, et al. Comparison of clinical outcomes between luminal invasive ductal carcinoma and luminal invasive lobular carcinoma. BMC Cancer 2016;16:248.  Back to cited text no. 3
    
4.
McLemore EC, Pockaj BA, Reynolds C, Gray RJ, Hernandez JL, Grant CS, et al. Breast cancer: Presentation and intervention in women with gastrointestinal metastasis and carcinomatosis. Ann Surg Oncol 2005;12:886-94.  Back to cited text no. 4
    
5.
Critchley AC, Harvey J, Carr M, Iwuchukwu O. Synchronous gastric and colonic metastases of invasive lobular breast carcinoma: Case report and review of the literature. Ann R Coll Surg Engl 2011;93:e49-50.  Back to cited text no. 5
    
6.
Washington K, McDonagh D. Secondary tumors of the gastrointestinal tract: Surgical pathologic findings and comparison with autopsy survey. Mod Pathol 1995;8:427-33.  Back to cited text no. 6
    
7.
Wang G, Wang T, Jiang J, Zhou L, Zhao H. Gastrointestinal tract metastasis from tubulolobular carcinoma of the breast: A case report and review of the literature. Onco Targets Ther 2014;7:435-40.  Back to cited text no. 7
    
8.
Uygun K, Kocak Z, Altaner S, Cicin I, Tokatli F, Uzal C. Colonic metastasis from carcinoma of the breast that mimics a primary intestinal cancer. Yonsei Med J 2006;47:578-82.  Back to cited text no. 8
    
9.
Shakoor MT, Ayub S, Mohindra R, Ayub Z, Ahad A. Unique presentations of invasive lobular breast cancer: A case series. Int J Biomed Sci 2014;10:287-93.  Back to cited text no. 9
    
10.
Agarwal N, Ulahannan MJ, Mandile MA, Cayten CG, Pitchumoni CS. Increased risk of colorectal cancer following breast cancer. Ann Surg 1986;203:307-10.  Back to cited text no. 10
    
11.
Efthimiadis C, Kosmidis C, Fotiadis P, Anthimidis G, Vasiliadou K, Mekras A, et al. Breast cancer metastatic to the rectum: A case report. Tech Coloproctol 2011;15 Suppl 1:S91-3.  Back to cited text no. 11
    
12.
Wasif N, Maggard MA, Ko CY, Giuliano AE. Invasive lobular vs. ductal breast cancer: A stage-matched comparison of outcomes. Ann Surg Oncol 2010;17:1862-9.  Back to cited text no. 12
    


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