Indeterminate and Erroneous Fine-Needle Aspirates of Breast with Focus on the ‘True Gray Zone': A Review

Abstract

Objective: 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. Study Design: 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. Results: 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. Conclusion: 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.

Stratification of risk of malignancy in atypical breast fine needle aspiration: a cytomorphological approach

“…We, like others have shown a heterogeneous mix of pathological outcomes during the follow up of C3 (5,(9)(10)(11)(12)(13)(14). In our earlier study, of 230 atypical (C3) cases, we found 37.4% to be malignant on follow-up and the remaining 62.6% yielded benign outcomes.…”

“…al. note the finding of tubular structures should be interpreted with caution as they can also be found in fibroadenomas, sclerosing adenosis and complex sclerosing lesions but are more frequently observed in tubular carcinoma (9,22). Kundu also warns against over-interpreting tubular structures as they can mimic malignancy in cases of sclerosing adenosis but states that these should also contain myoepithelial cells.…”

“…These outcomes were established by correlating the histology in 87%, repeat FNA in 3.5% and clinical and radiological follow-up 2 years post index FNA episode in 9.5%. The main reasons for placing these cases into the C3 category were suboptimal in 34.8% of the cases and the remaining 65.2% were diagnostically challenging, making interpretation difficult (9,15).…”

Role of fine needle aspiration cytology in diagnosis of breast lumps

“…Different studies have documented fibroadenoma as being one of the most commonly misdiagnosed lesions that appear as the grey zone lesions. 14,15 Fibroadenoma with atypia was reported in 2 cases. These on histopathology were diagnosed as usual ductal hyperplasia and duct carcinoma in situ (Figure 1a and 1b).…”

“…There are numerous factors that contribute to the indefinite, FN and FP categories. 15 These include: (1) technical difficulties where the smears are limited by cellularity or obscured by drying artefact and or blood, (2) inexperience or unfamiliarity of the pathologist with the cytologic features of breast FNAs and (3) the overlap of cytologic features of certain benign and malignant conditions due to the nature of the lesion (true grey zone).…”