Indeterminate and erroneous fine-needle aspirates of breast with focus on the 'true gray zone': a review

To review our experience and the literature on inconclusive/erroneous fine-needle aspirates (FNAs) of breast with the focus on the 'true gray zone'. To describe the cytology, differential diagnosis, pitfalls and limitations of common and rare lesions.

We conducted a literature search focusing on breast FNAs with statistical data of C3 and C4 categories including false-positive and false-negative cases. Similar data from 2003 to 2009 was obtained from our institution.

C3 and C4 categories account for 3-17% of breast FNAs. Contributing factors are technical difficulties, inexperienced pathologists interpreting FNAs of breast and overlap of cytologic features of certain benign and malignant conditions; this last, 'true gray zone' accounts for 2% of cases. Fibroadenoma, proliferative breast lesions, gynecomastia, infiltrating and in situ low-grade adenocarcinomas and tubular, cribriform, lobular and mucinous carcinomas are the most common problematic lesions. Granular cell tumor, adenomyoepithelioma, pregnancy-related lesions, fat necrosis, inflammatory and radiation changes, adenoid cystic carcinoma, spindle-cell lesions and Phyllodes tumor are less common.

Inconclusive/erroneous FNAs of breast due to the 'true gray zone' are rare. Most are due to the overlapping cytologic features of some benign and malignant conditions. Practical features that may help arrive at the correct diagnoses are elucidated.