Bilateral breast metastases from small cell lung carcinoma: Case report and review of the literature

Abstract

Differentiation of primary versus secondary breast cancer can be difficult, with the relative rarity of the latter representing a diagnostic challenge. Here, we present a case of small cell lung cancer with synchronous bilateral breast metastases in a 52-year-old female. There are less than 5 other cases of small cell lung cancer with bilateral breast metastases reported in the literature to date. The breast metastases represented the first clinical and imaging manifestation of malignancy in our case. We present the patient's disease course including multi-modal imaging, histopathologic analysis, and clinical management. We aim to highlight the entity of secondary breast cancer and how multidisciplinary collaboration can help arrive at the diagnosis, which is critical for prognosis and treatment planning in this patient population.

Keywords: BI-RADS, breast imaging reporting and data system; Breast metastases; CD45, cluster of differentiation 45; CDX-2, caudal type homeobox 2; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; Ki-67, proliferation index; LCA, leukocyte common antigen; Neuroendocrine; PD-L1, programmed death-ligand 1; PR, progesterone receptor; Secondary breast cancer; Small cell lung cancer; TTF-1, thyroid transcription factor1; WHO, world health organization.

Fig. 1

Diagnostic mammography was obtained utilizing tomosynthesis with reconstructed 2D composite views (C-views). Right breast full field (a) CC and (b) MLO C-views, and (c) conventional 2D spot compression CC view demonstrate two high density masses in the right upper outer breast (indicated by the arrows on the spot compression view). This included the patient-reported palpable, oval, circumscribed 1.5 cm mass at the 11-o'clock position, as well as a 0.4 cm oval but indistinctly marginated mass at the 10-o'clock position. These were new since prior screening mammogram 1.5 years ago, and findings were classified as BI-RADS 4.

Fig. 2

Diagnostic mammography was obtained utilizing tomosynthesis with reconstructed 2D composite views (C-views). Left breast full field (a) CC and (b) MLO views, and (c) conventional 2D spot compression MLO view demonstrate a 1.0 cm indistinctly marginated high density mass in the left upper breast at the 12-o'clock position (indicated by the arrow on the spot compression view). This was new since prior screening mammogram 1.5 years ago, and findings were classified as BI-RADS 4.

Fig. 3

Diagnostic high resolution sonography of both breasts confirmed ultrasound correlates for the mammographic masses, all classified as BI-RADS 4. This included (a) targeted sonography with color Doppler demonstrating an oval, circumscribed, parallel oriented, hypoechoic 1.5 cm right breast mass with internal vascularity at 11-o'clock, 9 cm from the nipple, corresponding to the patient's palpable complaint, (b) an irregular, spiculated 0.4 cm right breast mass with anti–parallel orientation at 10-o'clock, 10 cm from the nipple, and (c) an oval, circumscribed, parallel oriented, hypoechoic 1.0 cm left breast mass at 12-o'clock, 6 cm from the nipple.

Fig. 4

CT demonstrating a 2.2 cm right lower lobe pulmonary nodule abutting the bronchovascular bundle (arrow).

Fig. 5

PET/CT demonstrating FDG-avid subcarinal lymphadenopathy (arrow).

Fig. 6

Contrast-enhanced CT demonstrating a 1.1 cm hypoattenuating lesion in the right hepatic lobe abutting a branch of the right portal vein (arrow).

Fig. 7

T1-weighted fat-saturated post-contrast MRI sequence demonstrating a 1.6 cm enhancing lesion in the right temporal subcutaneous tissues (arrow). There is normal enhancement of the right sigmoid sinus. No intracranial lesion was identified.

Fig. 8

Diagnostic 2D full field CC and MLO mammograms of the right breast (a and b) and left breast (c and d) obtained 10 months after the initial diagnostic mammograms demonstrate interval increase in size of all biopsy proven bilateral metastatic sites (now containing biopsy clips), with representative palpable right breast mass now measuring 2.0 cm (previously 1.5 cm). There are 5 right and 3 left new, oval, circumscribed, high density masses. Findings were deemed compatible with disease progression and classified as BI-RADS 6, known biopsy-proven malignancy. Compare to prior diagnostic mammograms in Fig. 1 and 2.

Fig. 9

Targeted ultrasound of the left upper extremity at the level of the distal humerus demonstrates a 1.3 cm round hypoechoic lesion in the soft tissues with internal vascularity, corresponding to the palpable abnormality. The lesion is suspicious for metastasis, with an epitrochlear lymph node disfavored given the lateral location.

Fig. 10

CT demonstrating a subcutaneous nodule in the right abdominal wall (straight arrow) and a prominent mesenteric lymph node in the right abdomen (curved arrow).

Fig. 11

Histology of the excised subcutaneous abdominal wall nodule consistent with metastatic small cell carcinoma. (a) Low power magnification (4x) shows a sharply demarcated subcutaneous nodule of basaloid tumor cells. Tumor cell infiltration into the surrounding adipose tissue is noted (circle). (b) Spindly to ovoid basaloid tumor cells arranged in nests (loops). (c) Tumor cells amidst infiltrating cords and trabeculae (arrows). (d) Tumor cells with high nuclear to cytoplasmic ratio, hyperchromatic nuclei and brisk mitotic activity (circles).

Fig. 12

Immunohistochemistry of the excised subcutaneous abdominal wall nodule consistent with metastatic small cell carcinoma. (a and b) Tumor cells are strongly and diffusely positive for neuroendocrine markers, particularly (a) synaptophysin and (b) CD56. (c) The tumor is also positive for chromogranin, a more specific neuroendocrine marker, albeit weakly and with a dot-like staining pattern. (d) TTF-1 labels nearly 100% of tumor nuclei. Diffuse and strong TTF-1 immunostaining is noted in the vast majority of pulmonary small cell carcinomas, although a proportion of extrapulmonary small cell carcinomas can also express TTF-1, depending on the clone of antibody used .