Study Informs How to Diagnose Underrecognized Breast Tumor

Pathologists can struggle to correctly classify a certain type of tumor known as adenomyoepithelioma that can hide in plain sight among far more common, benign findings. However, a closer look at the tumor’s microscopic features, along with its distinctive molecular and genetic signatures, can improve how confidently doctors diagnose it, a new Yale School of Medicine study finds.

In the study, recently published in the American Journal of Surgical Pathology, researchers aimed to bring this often-misunderstood tumor into sharper focus. They evaluated several cases of adenomyoepithelioma of the breast that were classified into different categories. Upon closer review, however, 35% of cases were reclassified from their original diagnoses.

The findings, the researchers say, can inform how adenomyoepithelioma tumors are diagnosed going forward.

Lorraine Colón Cartagena, MD, assistant professor of pathology, led the study, working with Uma Krishnamurti, MD, PhD; Nichelle Perera, MD, MS; Yuanxin Liang, MD, PhD; and Haiying Zhan, MD, PhD.

Adenomyoepithelioma is composed of two different cell types, epithelial and myoepithelial, growing together in the same tumor. No two cases look alike.

In the study, the researchers analyzed 26 cases of adenomyoepithelioma of the breast that were assessed via biopsy. Of those samples, 54% were initially classified as benign, 27% were atypical, 12% belonged to a special subtype, and 8% were cancerous.

After closer examination, several of these tumors were reclassified, a finding that is useful for practice, the researchers say. Tumors that were benign, atypical, or of a special subtype tended to be smaller, with a median size of 12 to 18 millimeters, and had wavy, lobe-like borders. Cancerous AMEs told a different story: They were larger, with a median size of 27.5 millimeters, and infiltrated surrounding tissue rather than forming as a contained mass.

Surgical removal of the tumor corrected six diagnoses: four benign AMEs that were initially identified as other conditions, one benign AME that went unidentified altogether, and one atypical AME that mimicked a different type of benign growth.

Retrospective expert review of the biopsied tissue turned up three more corrections: Two benign AMEs were upgraded to atypical and a cancerous AME was identified once it metastasized to the lungs.

Even under the microscope, AMEs can stay elusive. Typical methods for labeling tissue to determine whether it is AME did not work in 19% of cases, a reminder that the very markers pathologists lean on can sometimes blur the picture. In those situations, alternative markers may need to be evaluated, the researchers say.

The takeaway for pathologists and physicians is that a diagnosis of AME based on a biopsy is worth a second look before it's treated as final. Given the 35% reclassification rate, the researchers observe, surgical removal is the safer path, especially for tumors measuring more than 20 millimeters. This closer evaluation could reduce the likelihood that tumors with recurrent or metastatic potential slip through.