Amyloidosis of the breast: predominantly AL type and over half have concurrent breast hematologic disorders

Amyloidosis is a disorder characterized by extracellular deposition of proteins in an abnormal fibrillar configuration. Amyloidosis can be localized or systemic and may affect any organ. Breast involvement by amyloidosis has rarely been reported. In this study, we described the characteristics of 40 cases of breast amyloidosis that were reviewed at the Division of Anatomic Pathology at Mayo Clinic from 1995 to 2011. The cohort included 39 women and 1 man with a mean age of 60 years. The type of amyloidosis, determined by immunohistochemistry or mass spectrometry-based proteomics in 26 patients, was immunoglobulin-associated in all cases (AL-kappa type in 15 (58%) cases, AL-lambda in 10 (38%) and mixed heavy and light chains (AH/AL) in 1 (4%) case). Mass spectrometry-based proteomics was able to determine the type of amyloidosis in 95% of cases tested compared with 69% of cases by immunohistochemistry. In addition to amyloidosis, the breast biopsy showed a hematologic disorder in 55% of cases, most commonly MALT lymphoma. One patient had concurrent intraductal carcinoma, but none had invasive carcinoma. Of the 15 patients seen in our institution, 53% had localized amyloidosis and 47% had extramammary amyloid involvement, which was diagnosed before breast amyloidosis in most patients. M-spike was detected in the blood in 62%. After a median follow-up of 33.5 months in 12 patients, 5 died, mostly of complications of lymphoma or leukemia. In conclusion, our findings indicate that breast amyloidosis is of the AL type in the vast majority of patients (usually kappa). It is associated with systemic amyloidosis in close to half of patients and with hematologic malignancy in the breast in over half of patients. Therefore, further work up to rule out hematologic malignancy and/or systemic amyloidosis is recommended. Mass spectrometry-based proteomics is superior to immunohistochemistry for typing of breast amyloidosis.