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Acta Cytol. 1994 Nov-Dec;38(6):898-908.

The spectrum of the "gray zone" in breast cytology. A review of 186 cases of atypical and suspicious cytology.

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Department of Pathology, Case Western Reserve University, Cleveland, Ohio 44106.


A "gray zone" exists in fine needle aspiration (FNA) cytology of breast; there an unequivocal diagnosis cannot be made. Previous studies have reported a gray zone incidence of 6.9-20%. We reviewed 2,197 fine needle aspirations (FNAs) of the breast performed at our institution to determine the incidence of the gray zone, analyze the sources of difficulty and establish guidelines to minimize the size of the gray zone. One hundred eighty-six (10%) of the total 2,197 FNAs were diagnosed as atypical (91) or suspicious for malignancy (95). The cytologic smears from all 186 equivocal cases and histopathologic sections from 156 of these patients who underwent a biopsy or mastectomy were reviewed. Clinical follow-up was obtained on the remaining 30 cases. Upon review, the causes of the equivocal diagnoses were divided into three categories: (1) technical, in which the smears were either markedly limited in cellularity or obscured by blood and/or drying artifact; (2) inexperience, which included cases that were reclassified by the reviewing cytopathologist as benign or malignant; and (3) the overlap of cytologic features of benign and malignant lesions due to the nature of the lesion, justifying a confirmational biopsy. Technical difficulties accounted for 103 equivocal diagnoses (4.5%); inexperience of the cytopathologist was responsible for 44 cases (2.4%). The third category, which represents the true gray zone in breast cytology, accounted for 39 cases (2%). Fibroadenomas constituted the largest single cause of equivocal diagnoses (17 cases). These fibroadenomas exhibited very cellular smears with marked discohesiveness and occasional nuclear atypia and prominent nucleoli. Other breast lesions in this category were intracystic papillary carcinoma, low grade apocrine carcinoma, solitary intraductal papilloma, and intraductal and atypical hyperplasia. The remaining lesions, and useful criteria of help with the differential diagnosis of the above categories, are discussed.

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