A 70-year-old woman presented with a left breast mass and left lung mass. The breast mass was excised. Computed tomography (CT) and mammographic images of the lungs and left breast, as well as hematoxylin and eosin and immunohistochemical stained slides of the breast mass, are shown in the figures below.
The correct answer is ...
Metastatic lung adenocarcinoma.
The histologic sections in this case demonstrate an infiltrative neoplasm composed of glands and papillae within a desmoplastic stroma. The cells show mild to moderate cytologic atypia, with nuclear pleomorphism, occasional prominent nucleoli, hyperchromasia, and rare intranuclear inclusions.
By immunohistochemistry, the neoplastic cells are strongly and diffusely positive for TTF-1, and are negative for ER, PR, and thyroglobulin. The overall morphology and immunophenotype are most consistent with an adenocarcinoma of lung metastatic to the breast.
Metastases to the breasts from extramammary sites are rare, and incidences of such have been reported as 0.4%-3%. The most common malignancies to secondarily involve the breasts are leukemia/lymphoma and malignant melanoma.1,2 Carcinomas may metastasize to the breast as well, including ovarian, lung, renal, and thyroid.2,3 Metastases to the breasts are most often encountered in patients with advanced and disseminated disease. In such settings, the patient’s extramammary primary malignancy is generally known to the care team. When the extramammary primary is occult, the distinction of a metastasis from a primary carcinoma of the breast is especially important for prognosis and therapeutic decisions.3
The morphologic distinction between metastatic lung adenocarcinoma and primary breast carcinoma in the breast can be extremely difficult. In cases in which knowledge of a lung mass is unknown to the pathologist, metastatic lung carcinomas may be confused with triple negative primary breast carcinomas. Morphologic features that may suggest a primary breast carcinoma include the presence of an in-situ component and elastosis.1 Assessment of these helpful features may be limited in core biopsy specimens.
In this case, a papillary architectural component was noted with positivity for TTF-1 confirmed. These findings were consistent with metastatic lung carcinoma but also raised the differential diagnosis of a metastatic thyroid carcinoma. Thyroglobulin IHC testing was also performed, with a negative result, making a metastatic thyroid carcinoma unlikely.
Finally, while TTF-1 carries a high sensitivity and specificity for primary lung adenocarcinoma, aberrant TTF-1 expression has been described in a number of other entities, including extra-pulmonary neuroendocrine tumors and carcinomas arising from the bladder, prostate, gastrointestinal tract, and gynecologic organs.5,6 In the breast, carcinoma diagnoses, particularly those that are hormone receptor negative, may trigger expanded immunohistochemistry panels to confirm breast origin, including addition of markers such as mammaglobin, GATA3, or TRPS1.1-4
Radiology of the breast itself may not always be of help, as metastases to the breast may present as a solitary nodule or multiple nodules, with well- or ill-defined borders. More extensive imaging to include other sites may be useful, and other metastatic deposits may be identified.3,4 In this case, a single mass lesion was identified in the left breast, ipsilateral to the patient’s confirmed lung mass.
Kaitlyn Nielson, M.D.
Fellow, Surgical Pathology
Charles Sturgis, M.D.
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science