Worldwide, lung cancer is the most common cancer in terms of both incidence and mortality (1.6 million new cases per year and 1.378 million deaths) . Approximately one fifth, of newly diagnosed lung adenocarcinomas, present with distant metastases. The most common sites of metastasis are brain, bone, liver, and adrenal glands, in decreasing order. However autopsy series have demonstrated that NSCLCs may spread to virtually any organ.
Breast metastases from extra-mammary malignancies are rare accounting for 0.4 to 1.3% of all breast malignancies [2–5]. Nearly 700 cases have been reported in small series and case reports [2–5, 7, 12, 16, 17].
According to the international literature the most common sources of primary tumors were haematological malignancies, malignant melanoma, lung tumors, renal cell carcinoma, ovarian tumors, thyroid carcinomas and small bowel carcinoids [3, 7, 17]. Williams et al in the largest published series of 169 cases with metastases to the breast from extramammary solid tumors reported that the most common histological type was malignant melanoma .
Review of the literature (1990-2010) includes approximately 30 NSCLCs as case reports or part of a series of secondary breast tumors [4, 5, 9–12, 18–26]. Twelve of the above cases were classified as adenocarcinomas [5, 9, 12, 18, 20–22, 24]. Additionally, 53 cases of breast metastasis from lung tumors were presented however, no detailed histological classification was provided [7, 17, 27–29]. The majority of breast metastases present as palpable, rapidly growing, well circumscribed, painless breast masses with predilection to the upper outer quadrant [2, 7, 12, 16, 21]. Unlike primary tumors, in the vast majority of metastases retraction of the skin or nipple is not demonstrated despite their superficial location [5, 21]. However, in our patient, the lesion was poorly defined and skin redness was observed. Other authors have rarely reported similar findings [7, 16, 24, 29].
Distinguishing a breast metastasis from a primary mammary adenocarcinoma, based on mammographic findings, may be extremely difficult because of the wide range of imaging manifestations of the metastatic lesion [4, 5, 17]. Thus, metastasis can mimic a primary malignancy or even a benign breast tumor [4, 5, 17]. The most commonly described mammographic presentation is usually single but sometimes multiple well circumscribed lesions with smooth margins [3, 17, 29]. Microcalcifications are very uncommon but have been reported in patients with metastatic serous ovarian papillary carcinoma [17, 28, 29]. In our case, mammography showed diffuse asymmetrical density and skin thickening. In cases such as ours the differential diagnosis includes inflammation, lymphoma and inflammatory breast carcinoma.
As sited in the literature, histological features that may aid in the recognition of secondary tumors are the following: The absence of in situ carcinoma strongly supports a metastatic tumor, although it may not be present in all primary invasive carcinomas. Additionally, metastatic malignancies are often sharply circumscribed from the surrounding breast tissue. Furthermore, elastosis is common in primary tumors but rare in extramammary malignancies [2, 4, 5, 12, 18]. Occasionally, metastases to the breast demonstrate features that can lead pathologists to the correct diagnosis such as presence of pigmentation and intranuclear inclusions in malignant melanomas. Nevertheless, many extramammary malignancies such as adenocarcinoma of the lung lack specific histological features.
Carcinomas with a micropapillary component have been described in many organs including the breast, urinary bladder, ovary and salivary glands . Amin et al. in 2002, was the first to report lung adenocarcinomas with micropapillary component . Histologically, the latter is characterized by small papillary tufts lying freely within alveolar spaces or encased within the thin walls of connective tissue. These small, cohesive nests lack fibrovascular connective tissue cores . In our case all biopsies examined demonstrated an extensive micropapillary component. Although psammoma bodies have not been observed in invasive micropapillary pattern carcinoma of the urinary bladder and salivary glands they have rarely been reported in cases of lung adenocarcinoma with micropapillary morphology [13, 14, 30]. Multiple psammoma bodies were demonstrated in the tissue sections of our samples examined. To the best of our knowledge this is the first report of a breast metastasis from lung adenocarcinoma with micropapillary pattern diagnosed concomitantly with the primary tumor.
The distinction between metastasis from lung adenocarcinoma, particularly with extensive micropapillary pattern, and primary mammary adenocarcinoma may cause a significant diagnostic dilemma. The contribution of immunohistochemstry to the correct diagnosis is crucial.
TTF-1 is expressed in 68-80% of lung adenocarcinomas, and besides a single case published by Klingen TA et al, has never been reported to stain positive in breast adenocarcinoma [31–33]. The sensitivity of SP-A is substantially less. It is expressed in approximately 45% of lung adenocarcinomas [32, 33]. A negative expression of thyroglobulin excludes the diagnosis of papillary carcinoma of the thyroid, which stains positive to both markers. ERs are expressed in 80% and GCDFP-15 in 45-53% of breast carcinomas [32, 34]. As recently published, ER expression in the lung adenocarcinoma, by using the monoclonal antibodies 1D5 and 6F11 is low (7,6-14,1%) [32, 35]. Additionally, 5,2-15% of lung adenocarcinomas express GCDFP-15 [34, 36]. Finally, mammaglobin is expressed in 48-72,1% of mammary adenocarcinomas but stains negative in pulmonary adenocarcinomas [32, 34, 37]. Consequently, a panel of markers must be used as no single antibody is 100% sensitive and false negative results do occur. In our case, all the tumor specimens (lung, pleura and breast) showed positive nuclear staining for TTF-1 and cytoplasmic staining for SP-A. The neoplastic cells lacked expression of GCDFP-15, ER and mammaglobin.
Overall metastasis to the breast has been associated with poor prognosis with most patients dying within a year of diagnosis . Our patient survived 6 months following the diagnosis of both the primary lung tumor and the breast metastasis.