High frequency of lobular breast cancer in distant metastases to the orbit

Abstract

Metastasis to the periocular soft tissue of the orbit is a rare manifestation of metastatic cancer. Infiltrating lobular breast cancer (ILBC) is a special breast cancer subtype, which accounts for 10-15% of all mammary carcinomas and for ~1% of all malignancies. Here, we report on a high frequency of lobular breast cancer in patients with orbital metastases identified in an original series of metastatic tumor specimens and by a systematic literature review. A series of 14 orbital metastases was compiled from formalin-fixed paraffin-embedded archival tissues. All cases were subjected to histological re-review and detailed immunophenotypical characterization. In addition, we performed a meta-analysis of 68 previously published case reports describing orbital metastases, with special reference to breast cancer subtypes. Based on clinical history, histomorphology, immunophenotype, and/or comparison with matched primary tumors, orbital metastases were derived from breast cancer in 8/14 cases, seven of which were classified as metastatic lobular breast cancer. Other entities included non-small cell lung cancer (4/14), infiltrating ductal breast cancer (1/14), prostate cancer (1/14) and adenocarcinoma of the esophagus (1/14). In line with this original series of orbital metastases, lobular breast cancer was the most common malignancy in 72 patients with orbital metastases described in 68 independent case reports. In conclusion, lobular breast cancer represents the cancer subtype with the highest prevalence among orbital metastases. The high frequency of ILBC in orbital metastases illustrates the special metastatic behavior of this tumor entity and may have implications for the understanding of the organotropism of metastatic lobular breast cancer.

Keywords: Immunophenotype; lobular breast cancer; meta-analysis; metastasis; orbit.

Figure 1

Magnetic resonance tomography (MRT) scans showing bilateral orbital metastases from infiltrating lobular breast cancer (ILBC). (A) MRT scan of a 61-year-old female patient, 11 years after bilateral mastectomy for ILBC and adjuvant therapy with tamoxifen and chemotherapy (cyclophosphamide, methotrexate, fluorouracil). The arrow indicates an ill-defined orbital tumor and exophthalmos. The patient underwent enucleation of the right bulbus oculi and resection of the periocular soft tissue, which confirmed a metachronous metastasis from ILBC. Subsequently, the patient was diagnosed with newly emerging hepatic metastases and was treated with second-line chemotherapy (paclitaxel). Twelve weeks after the enucleation of the right bulbus oculi, the patient was diagnosed with a newly emerging metastasis in the contralateral orbit. (B) MRT scan of the same patient, 12 weeks after enucleation of the right orbit. The arrow indicates an ill-defined lesion in the left orbit, suspicious for metastatic involvement.

Figure 2

(A) Representative photomicrographs of orbital metastases (OMs) from patients with a history of breast cancer. HE-stained sections are shown on the left side (400×), immunohistochemical stainings for E-cadherin (E-cad) and estrogen receptor (ER) are shown on the right side. (B) Overview showing the immunophenotypical characteristics of the 14 OM. Immunohistochemical markers are aligned along the bottom, primary tumor sites along the left side. Filled squares indicate positive staining. Empty squares indicate negative staining. Diagonal lines indicate missing data. (C) Proportion of infiltrating lobular breast cancer (ILBC) in a control group of randomly selected primary breast cancers (BC, n = 17/134) diagnosed at our institution, compared with the proportion of ILBC in OMs from patients with a history of breast cancer (n = 7/8). Statistical significance was assessed with the chi-square test using the actual numbers of observed cases.

Figure 3

Meta-analysis of previously published case reports. (A) Orbital metastases (OMs) analyzed for primary tumor entities. BC, breast cancer; ILBC, infiltrating lobular breast cancer; IDBC, infiltrating ductal breast cancer; HCC, hepatocellular carcinoma; SCC, squamous cell carcinoma (head and neck, 1 SCC of the cervix uteri). Lung cancers included small cell and non-small cell lung carcinomas. Thyroid carcinomas included follicular thyroid carcinoma, papillary thyroid carcinoma, and medullary thyroid carcinoma. Other entities included: renal cell carcinomas (not further specified), colorectal cancer (adenocarcinomas and one signet cell carcinoma), melanoma, neuroendocrine tumors of the gastrointestinal tract, transitional cell carcinoma of the bladder, adenocarcinoma of the esophagus, chorioncarcinoma, gastric carcinoma (not further specified), gastrointestinal stroma tumor of the stomach, leiomyosarcoma of the abdominal cavity, Merkel cell carcinoma and an osteosarcoma of the tibia. (B) Anatomical sites of metastases from ILBCs, as described in previous publications. *Other sites included: Anus, aorta, bone, cervix uteri, kidney, meninges, liver, muscle, salivary glands, skin, and vulva.