Metastatic non-small cell lung carcinoma a mimic of primary breast carcinoma—case series and literature review

Abstract

Metastatic tumors to the breast are rare but constitute a major diagnostic dilemma. Of these, non-mammary carcinomatous metastases to the breast are particularly challenging and, without a clinical history, may be extremely difficult to distinguish from primary breast carcinoma (PBC). We specifically studied metastatic tumors of pulmonary origin, as the lung is one of the major primary sites for carcinomatous metastasis to breast. Sixteen metastatic lung tumors to the breast were identified in our archives between 1996 and 2017 including 12 non-small cell lung carcinomas (NSCLC), one large-cell neuroendocrine, one atypical carcinoid, and two small-cell carcinomas. Adenocarcinoma was the most frequent amongst the NSCLCs (11/14). We retrieved the clinical information of these cases and reviewed the pathological characteristics to provide practical tools for pathologists to aid in their identification. Even in the absence of a clinical history of lung cancer, metastatic pulmonary adenocarcinoma to the breast should be considered in at least one of the following scenarios: (1) single or multiple well-circumscribed lesions of the breast that lack an in situ component and that are accompanied by distant metastases but negative axillary lymph nodes, (2) breast tumors that are triple negative yet not high-grade, or (3) breast tumors presenting as stage 4 disease and/or having an unusually aggressive clinical course on standard breast therapy. Accurate and timely diagnosis of these tumors is mandatory because of treatment and prognostic implications.

Three Cases of Breast Metastases from Lung Cancer and Systematic Review of the Literature

“…Alva and Shetty Alva (12) reported 78 cases in their literature review from 1855 to 1998. The most recent and largest review published in 2018 has reported 169 cases from 1999 to 2017 (13). In the cases of Alva and Shetty Alva (12), we have found 180 additional cases of metastatic lung tumors in the breast and made a summary of a total of 258 cases published in English until 2019.…”

“…Lung cancer, which is a common malignancy and one of the leading cancer-related causes of death worldwide, frequently spreads to other organs but metastasizes to the breast very rarely. A few reviews have previously been published on lung cancer metastasizing to the breast (3,4,(10)(11)(12)(13). Alva and Shetty Alva (12) reported 78 cases in their literature review from 1855 to 1998.…”

<p>Metastases to the Breast from Extramammary Nonhematological Malignancies: Case Series</p>

“…29 Biomarkers of TTF-1 for lung cancer, CDX2 for gastric cancer, CD56(+), Syn, CgA for neuroendocrine cancer and WT-1 and CA125 for ovarian cancer are common markers for identification of the origin of metastatic lesions. 3,9,22,30 TTF-1 is expressed in most lung adenocarcinomas and small cell carcinomas accounting for 70-80%, and usually most cells are positive. 25,31,32 TTF-1 is rarely expressed in other types of lung cancers.…”

“…2,[4][5][6] Breast metastases have also been reported in primary cancers such as melanoma, lung cancer, ovarian cancer, gastric cancer and neuroendocrine cancer. [7][8][9] To avoid unnecessary and potentially harmful treatments, accurate diagnosis of secondary breast carcinoma is very important. Identification of the primary and secondary breast tumors is crucial.…”

Metastatic adenocarcinoma to the breast from the lung simulates primary breast carcinoma—a clinicopathologic study

“…According to sporadic case reports, the breast was reported as a metastatic site for primary lung adenocarcinomas and the incidence of breast metastases from an extramammary primary tumor can be as low as 0.5-3.0% (2)(3)(4)(5)(6)(7). Because of its rarity, even with known history of lung cancer, breast metastases would have been easily misdiagnosed as primary breast cancer and thus leads to unnecessary mastectomies (6,8,9). Due to the distinct biological mechanisms, advanced lung adenocarcinoma and breast cancer are treated with different therapies, such as EGFR tyrosine kinase inhibitors (TKIs) for lung cancer, and estrogen receptor (ER), progesterone receptor (PR) related endocrine treatment or human epidermal growth factor receptor 2 (HER-2) related target therapy for breast cancer.…”