Case report
We report a 77-year-old lady with negative past medical history for malignancy, presented with bilateral breast lesions.  A mammogram revealed highly suspicious masses in both breasts, bilateral BI-RADS 5. Computerized tomography scan ( CT Scan) Guided core needle biopsies from both breasts were done, they revealed fibro adipose tissue infiltrated by adenocarcinoma, the malignant cells are arranged in glands, trabeculae, and cords, no carcinoma in situ is seen and no lymphovascular invasion. No normal residual breast issue is seen in Figure 1. Immunohistochemical study showed the adenocarcinoma cells to be reactive for pan-cytokeratin (PCK) and cytokeratin 7 (CK7) While stains for estrogen, progesterone receptors (ER, PR), And Her2 Neu antibodies were all negative, with low Ki-67 index. The initial impression was triple-negative breast cancer, but when a CT scan chest was performed it revealed left hilar lung mass with a metastatic nodule in the right upper lobe. In addition, a metastatic lytic lesion in the rib was found Figure 3. Due to the CT scan findings, a TTF1 immunohistochemical stain was performed on the breast biopsy that turned out to be positive confirming primary lung adenocarcinoma with breast metastasis. Figure 2. A molecular study revealed epidermal growth factor (EGFR) Exon 19 mutation.

Rola et.al have searched for metastatic lung cancer to breast between the years 1996 and 2017. Within the 21 years search, she has found 16 cases in their hospital files. Adenocarcinoma was the most common histologic type to metastasize to the breast. She summarized some histologic and prognostic points that help in suspecting or diagnosing these lesions; A triple-negative tumor with low-grade morphology, a tumor that lacks an in-situ component, with the absence of elastosis [3,5,6,14,21,22]. More features include a tumor presenting with the high stage but has negative axillary lymph node involvement and or not responding to standard breast cancer therapy [7,8]. More morphologic features on imaging studies include superficial location in subcutaneous tissue immediately adjacent to glandular breast, presence of multiple lymphatic tumor emboli, well- circumscribed tumor, smooth contour with multiple satellite foci, lack of architectural distortion, speculations and microcalcifications [14,23]. A predilection for the upper outer quadrant is noted by many authors [3,7,9,15]. An even very rare presentation reported by some authors is lung metastasis presenting as inflammatory carcinoma (IBC) of the breast [7,13,24,25].

This mode of presentation confirms that the tumor has reached the breast via the lymphatic route, a predilection for the ipsilateral breast, and upper outer quadrant have been noticed by many authors. Moreover, in patients with bilateral metastasis, both breasts can be affected again due to extensive lymphatic spread [7,14,24].

Ota et al described a 69 years old patient who underwent left lower lobectomy for primary adenocarcinoma of the lung that was epidermal growth factor (EGFR) exon 21 mutated. Initially, she responded well to tyrosine kinase inhibitors (TKI). But she had a recurrence 2 years later in the form of IBC. CT- Guided core needle biopsy from breast, confirmed lung primary as the tumor was TTF1 positive and harbour the same EGFR mutation. He also postulated that when metastatic tumor reaches the breast through blood supply it will form a single mass, but when it reaches the breast through lymphatics it tends to form multiple nodules [13].

Metachronous and synchronous presentation of metastasis are correlated with histologic type, initial staging at diagnosis, treatment histories, and outcomes, therefore it has clinical relevance [7,23].

Jennifer et al reported 39 cases of breast metastasis from lung cancer, 31 were adenocarcinoma, and 8 of which are small cell carcinoma (SCC), while 80 % of the SCC metastasized synchronously only 33 % of the adenocarcinoma did so [23].

In most situations, metastatic disease to the breast occurs after the diagnosis of the primary tumor i.e., metachronous. In approximately 25 % of patients, a breast mass is a cause for the initial presentation just like our patient. In these patients, metastases to the breast can mimic benign disease or primary breast malignancies. In the study by Babu all of his three cases, a breast mass was the initial mode of presentation [15]. This is further supported by the study of Williams who mentioned that 88.2 % of patients who presented with breast metastasis had a prior history of known malignancy [9].

Nicoletta et al reported a micropapillary adenocarcinoma that presented synchronously. This histologic type of primary lung adenocarcinoma is a high grade with a poor prognosis, so such a presentation is expected [24].

In Jennifer’s study 8/31 cases of metastatic lung cancer to the breast were SCC, 80 % of them presented synchronously, a similar observation noted by Alessandro and Nicoletta [7,23,24].

As the prognosis and management of primary mammary carcinoma versus metastatic carcinoma to the breast are different, all authors have agreed that an immunohistochemical panel is needed for differentiation between them; the recommended panel is displayed in Table 1. [8,13,14,26].

It is evident that the TTF-1 antibody is the most reliable antibody, it is positive in up to 85 % of lung carcinoma, the other tumor that can be positive is thyroid carcinoma, but breast metastasis of primary thyroid cancer is extremely rare [27]

The primary lung adenocarcinoma with metastasis to the breast in the series reported by Rola has unilateral metastasis in 11/13 while only 2 presented with bilateral metastasis [8]. Li Wang et.al have reported 2 patients with bilateral metastasis to the breast, but his patients had neuroendocrine carcinomas and not adenocarcinomas, moreover, his patients were found to have synchronous breast and lung masses at the time of presentation, unlike our patient who was found to have the lung mass discovered by CT-Scan later [28].

Biyuan reported a female patient who was discovered late to have primary lung adenocarcinoma with bilateral breast metastasis and skin deposits after being managed with many treatment lines [29]. Moreover, Xiao Wu reported two cases of primary adenocarcinoma with breast metastasis one of them had bilateral breast metastatic deposits [30]. Assi also reported a metastatic small cell carcinoma of the lung in a 52 years old smoker female patient, who presented with respiratory symptoms rather than breast mass, she received chemotherapy, after 6 months, at follow up visit she was found to have bilateral breast metastasis, manifesting as Inflammatory breast cancer with fixed breast mass, the left breast showed swelling redness and inverted nipple, the right breast had smaller masses [25].

Among the histologic types of primary lung cancer, adenocarcinoma is the commonest to metastasize to the breast. However, all histological subtypes may metastasize to the breast especially small cell carcinoma which tends to spread early, extensively through lymphatics, and is more likely to be synchronous with breast lesion in 80 % of cases [23]

The observation of bilateral breast metastasis from solid organ cancer is described in the Toombs review. He reported 21 metastatic lesions from solid organ cancer, he found 26 % of cases presenting initially with bilateral breast lesions [31].

The case presented by Dansin is very much similar to our patient in many aspects. She is a 52 years old patient who presented with IBC, diagnosed initially as triple-negative primary breast cancer. She received chemotherapy and progressed, later she was discovered to have a primary lung cancer during workup for cancer progression and examination of the pleural fluid proved a TTF-1 positive primary lung cancer with Exon 19 EGFR mutation. [32] This is the same as our patient’s scenario, however, our patient was found to have a lung mass on CT- Scan during workup for her disease progression, we did not have additional tissue, but we applied TTF-1 and Napsin on the first biopsy from the breast and it proved to be positive for these markers with even Exon 19 EGFR mutation. Breast carcinoma can acquire EFGR mutation, particularly the triple-negative type; an incidence of 1.4 % and 11.4 % is described in two Asian studies. Therefore, not all triple-negative breast cancer with EGFR mutation should be suspected to be metastasis from the lung, IHC panel confirmation is the gold standard [32]. Other case reports of breast metastasis from lung adenocarcinoma with EGFR mutation are available in the literature [23,33,34].

The age range of metastatic lung cancer to the breast as seen in the literature is 40-77 years. The two young patients below 30 years reported in the literature are for Diego & Wang SC [14,26]. Diego reported a 29-year-old patient, diagnosed with breast and lung cancer at the same time, she survived for 20 months after first and second-line chemotherapy for lung cancer, in his literature search since 2000 he found 62 cases, eight of them were for male patients (12.7 %) [14]. Kannan et al. Reported a male patient with lung cancer metastasized to the breast after 4 years [35]. This literature review showed approximately seven hundred cases Table 2. [23,7,9,8] More individual case reports are available that are not included in those big series, which means more cases are available and attention to this problem has to be paid when dealing with patients known to have malignancy and presenting with breast lesion.