Metastasis to the breast from colonic adenocarcinoma

Metastases to the breast from extramammary malignancies are rare and account for 0.43% of all breast malignancies [1]. Lymphoma, melanoma, sarcoma, lung carcinoma and ovarian tumor are common extramammary primary malignancies that metastasize to the breast [1-3]. Cases of metastasis from primary colorectal neoplasm to the breast is extremely rare. In searching MEDLINE and EMBASE including non-English literature, and handsearching the references, only 22 cases were identified. We describe the features of metastatic breast cancer from adenocarcinoma of the colon in a 63-year-old woman.

A 63-year-old woman was referred to a breast surgeon due to a mass with suspicious metastatic axillary lymph node discovered incidentally on positron emission tomography-computed tomography for follow-up study after colon cancer surgery without other metastatic lesion (Fig. 1). Four years ago, she underwent a subtotal colectomy for stage T3N1M0 sigmoid colon cancer with colonic obstruction and subsequent chemotherapy with 5-fluorouracil and leucovorine. Two years after the operation, a 2.8 cm sized solitary metastatic lung nodule on the right middle lobe was identified on chest computed tomography for follow-up study for which she underwent pulmonary wedge resection, followed by chemotherapy with oxaliplatin and 5-fluorouracil.

Fig. 1
Mild hypermetabolic lesion was seen in lower inner quadrant of right breast (arrow) and focal hypermetabolic lymph node was seen in right axillary area (arrow head).

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Physical examination revealed a 2 cm sized firm nodule in the lower inner quadrant of the right breast without evidence of axillary or supraclavicular lymphadenopathy. The contralateral breast and axilla were normal.

The mass was not identified on mammography, but ultrasonography showed 1.1 cm sized mass in the lower inner quadrant of the right breast without enlarged lymph node in the ipsilateral axilla. Sonography guided core needle biopsy of the breast mass revealed invasive adenocarcinoma. Serum tumor markers were all in normal ranges (carcinoembryonic antigen 4.2 ng/mL, carbohydrate antigen 15-3 6.2 U/mL). Subsequent magnetic resonance imaging showed 1.8 cm sized ill-defined irregular shaped enhancing mass in the lower inner quadrant of the right breast and enlarged lymph node at the ipsilateral axilla compatible with a nodule suspicious for metastasis. Breast specific gamma imaging using ^99mTc-MIBI showed a lesion with increased uptake in the lower inner portion of the right breast with no lesion uptake in the axilla.

Wide excision of the tumor and sentinel lymph node biopsy was performed (Fig. 2).

Fig. 2
1.7 cm sized irregular, whitish-gray, firm mass was identified in lower inner portion of right breast, 3.5 cm apart from nipple.

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On histopathological examination, the tumor cells in the breast mass were cuboidal to columnar with eosinophilic cytoplasm and pseudostratification, compatible with the features of adenocarcinoma of colorectal origin (Fig. 3). The harvested sentinel lymph node did not contain tumor cells.

Fig. 3
Cuboidal to columnar tumor cells with eosinophilic cytoplasm and pseudostratification were seen on hematoxylineosin stain (×100).

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Immunohistochemical study revealed the following results: tumor cells were strongly positive for CDX2, cytokeratin (CK)20 and negative for CK7, thyroid transcription factor-1, estrogen receptor, progesterone receptor, c-erbB2 (Fig. 4). These findings are consistent with metastatic adenocarcinoma of the colon or rectum.

Fig. 4
Immunohistochemistry showed neoplastic cells were positive for CDX2 immunostaining (A, ×200) and cytokeratin 20 immunostaining (B, ×200).

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Currently, she is receiving systemic chemotherapy with irinotecan and 5-fluorouracil.

Primary breast cancer is one of the most common malignancies and leading cause of death from malignant disease in women. A malignant mass in the breast can easily be misinterpreted as breast cancer and inappropriate surgical intervention could be carried out. Although there are few instances of breast metastasis from colorectal malignancy, correct diagnosis is crucial to avoid unnecessary surgical intervention.

Generally, metastases to the breast from extramammary malignancies are characterized by rapidly growing, mobile masses that are easily palpable but do not cause overlying skin or nipple retraction, or bloody nipple discharge [4, 5]. Core biopsy allows histological assessment of the tissue, helping in identifying the origin of the carcinoma. On the histologic finding, the periductal and perilobular location of the tumor with the absence of in situ ductal carcinoma in the surrounding breast specimen favor a metastasis [4, 5]. Immunohistochemistry enables a more confident differentiation between a primary breast adenocarcinoma and a colorectal adenocarcinoma metastasis to the breast. For our patient, diagnosis was finally reached after immunohistochemistry finding. The majority of colorectal carcinomas are usually CK7-negative and CK20-positive, while the majority of primary breast carcinomas is CK7-positive and CK20-negative [6]. And the positive immunostaining for CDX2 is a highly sensitive and specific marker of colorectal carcinoma [7]. Our case showed these findings as well; tumor cells were positive for CDX2, CK20 and negative for CK7. Recently, some authors have suggested that the expression of CK20 can be identified in primary breast cancer in contrast to the conventional immunohistochemistry results. So, clinicians and pathologists should examine multiple immunohistochemistry markers and combine them as an approach for final diagnosis [8].

According to recent reports, the management of metastatic breast mass from colorectal adenocarcinoma should be diagnostic and palliative. Barthelmes et al. [9] advocated that surgical excision should be avoided in the view of short life expectancy and risk of seeding to the skin. Fernández de Bobadilla et al. [10] suggested that excisional biopsy was usually appropriate and provided adequate local control. If the diagnosis for the breast mass is unclear, unnecessary intervention, for example mastectomy or lymph node dissection of axilla, can be performed. Therefore, when breast mass is identified incidentally on radiologic study during follow-up after operation for colorectal carcinoma, clinicians should keep the possibility of breast metastasis from colorectal adenocarcinoma in mind. Additionally, periodical examination of the breast after colorectal cancer surgery may be helpful to detect the metastasis early.