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Fibroadenoma masquerading carcinoma on fine-needle aspiration of the breast
D. Tamiolakis, G. Georgiou, S. Barbagadaki, Ch. Antoniou, S. Nikolaidou, N. Tsiminikakis, C. Economou, S. Bolioti, E. Alifieris (Chirurgia, 103 (2): 227-230)

Introduction
Fibroadenoma of the breast is the most common breast tumor in young women; the peak incidence occurs in the third decade of life. On fine-needle aspiration (FNA) cytology, many cases of fibroadenoma display characteristic morpho-logic features that lead to a definitive diagnosis. (1) However, some fibroadenomas show cytologic features (hypercellularity, lack of cohesion, single epithelial cells, and some nuclear atypia) that are suggestive of malignancy. As a result, cases of fibroadenoma are the most common cause of false-positive, suspicious, or atypical diagnoses in breast FNA cytology. (2)
On the other hand, some cases of breast carcinomas show bland cytology and can be confused with benign lesions. One such example is papillary carcinoma. (3) It is well recognized that benign and malignant papillary neoplasms can be difficult to separate using FNA. (4, 5) However, it has not been documented that papillary carcinomas and fibroadenomas of the breast share cytologic features and thus cause difficulty in differentiating the 2 entities. We report a case of histologically proven fibroadenoma with cytologic features that overlap with those previously described for benign and malignant papillary lesions of the breast.

Case study
FNA was performed by a surgeon with 23-gauge needles. The aspirated material was immediately smeared on slides. The slides were stained with the Hemacolor rapid staining kit. The surgical pathology report of the excisional biopsy was obtained. Clinical and radiologic data were obtained from the patient's medical record.

Results
The tumor size was 1.5 cm in greatest dimension. The tumor was a well-circumscribed solid nodule on radiological evaluation (mammography and ultrasound).

Cytology
The smears were moderately to highly cellular with both epithelial clusters and sheets and numerous intact single elongate/columnar cells (fig. 1, 2). The epithelial clusters displayed mild to moderate cellular crowding and overlapping with loss of cohesion at the periphery of the groups. The numerous single cells had intact cytoplasm and were elongated and columnar. All epithelial cells, including those present in groups and the single cells, possessed slightly enlarged nuclei with at most minimal chromatin aberration and inconspicuous nucleoli (fig. 3, 4). No stripped “bipolar“ nuclei were present in the background. No staghorn clusters were apparent, while rare papillae were noted.

Figure 1
Figure 2
Figure 3
Figure 4

Immunostaining was noncontributory, owing to the scant material present on the slides submitted for immunocytochemical staining.
The cytologic diagnosis was indicative of malignancy, with a microscopic description provided. The histologic diagnosis of the excisional biopsy was fibroadenoma (fig. 5, 6).

Figure 5
Figure 6

Discussion
Fibroadenomas show a wide spectrum of presentation on FNA cytology and thus are well-known diagnostic pit-falls that cause false-positive diagnoses on breast FNA. The slides from our case share many similarities, including cellularity presence of many single epithelial cells, arrangement of epithelial cell clusters, a background of proteinaceous material with macrophages, and columnar/elongate shape of epithelial cells, apparent nuclear atypia Nuclear membrane irregularities and chromatin aberration (clearing) was also noticeable.
Since only direct slides were made from each specimen, it is unknown whether distinguishing features can be better appreciated on Thin-Prep smears. The initial evaluation of ThinPrep preparations of breast indicated potential pitfalls for accurate diagnosis and a particularly poor correlation with histology for fibroadenomas. (6) However, a recent comparison based on 7464 conventional and 7903 ThinPrep breast FNA specimens showed comparable sensitivity, specificity, and positive and negative predictive values. (7) In addition, a significantly lower unsatisfactory rate was noted for the ThinPrep than for conventional smears (27.7% vs 33.9%, P < .01). Another recent study that compared features of conventional and ThinPrep preparations in 70 cases of breast FNA also demonstrated that ThinPrep was less likely to be unsatisfactory and superior in nuclear details. (8)
Immunocytochemistry is helpful . A reticulated pattern of staining of myoepithelial cells with antibody against actin has been shown to be present in the majority of epithelial cell clusters on FNA of benign breast lesions, such as fibroadenomas and ductal hyperplasia. (9, 10) This staining pattern has been noted to be either absent or present in a small percentage (<10%) of epithelial cell clusters of invasive carcinoma, including tubular carcinoma. Recently, 2 more antibodies, calponin and smooth muscle myosin heavy chain, which are more specific for the smooth muscle apparatus of myoepithelial cells, have been applied on FNA materials. (11)
However, calponin-positive myoepithelial cells may be noted in clusters of cells from ductal carcinoma in situ, although the smooth muscle myosin heavy chain reactivity is absent. (12) Thus, immunocytochemistry does not provide a definitive distinction between fibroadenoma and ductal carcinoma in situ. However, immunocytochemical staining may help to favor benign or malignant status.
Our case represents the epitome of the “gray zone“ of breast FNA. It has some, but not all, of the features that we require to be present before we render a definite positive diagnosis. (13) It is always tempting for a cytopathologist to render a definitive diagnosis, whether benign or malignant, to guide the clinician. However, it is more important not to mislead the clinician than to be definitive.

References
1. Maygarden, S.J., Novotny, D.B., Johnson, D.E., Frable, W.J. - Subclassification of benign breast disease by fine needle aspiration cytology: comparison of cytologic and histologic findings in 265 palpable breast masses. Acta Cytol., 1994, 38:115.
2. Wills, S.L., Ramzy, I. - Analysis of false results in a series of 835 fine needle aspirates of breast lesions. Acta Cytol., 1995, 39:858.
3. Layfield, L.J., Dodd, L.G. - Cytologically low grade malignancies: an important interpretative pitfall responsible for false negative diagnoses in fine-needle aspiration of the breast. Diagn. Cytopathol., 1996, 15:250.
4. Dawson, A.E., Mulford, D.K. - Benign versus malignant papillary neoplasms of the breast: diagnostic clues in fine needle aspiration cytology. Acta Cytol., 1994, 38:23.
5. Bardales, R.H., Suhrland, M.J., Stanley, M.W. - Papillary neoplasms of the breast: fine-needle aspiration findings in cystic and solid cases. Diagn. Cytopathol., 1994, 10:336.
6. Perez-Reyes, N., Mulfod, D.K., Rutkowski, M.A., Logan-Young, W., Dawson, A.E. - Breast fine-needle aspiration: a comparison of thin-layer and conventional preparation. Am. J. Clin. Pathol., 1994, 102:349.
7. Bedard, Y.C., Pollett, A.F. - Breast fine-needle aspiration: a comparison of ThinPrep and conventional smears. Am. J. Clin. Pathol., 1999, 111:523.
8. Biscotti, C.V., Shorie, J.H., Gramlich, T.L., Easley, K.A. - ThinPrep vs. conventional smear cytologic preparations in analyzing fine-needle aspiration specimens from palpable breast masses. Diagn. Cytopathol., 1999, 21:137.
9. Masood, S., Lu, L., Assaf-Munasifi, M., McCaulley, K. - Application of immuno-staining for muscle specific actin in detection of myoepithelial cells in breast fine-needle aspirates. Diagn. Cytopathol., 1995, 13:71.
10. Fischler, D.F., Sneige, N., Ordonez, N.G., Fornage, B.D. - Tubular carcinoma of the breast: cytologic features in fine-needle aspirations and application of monoclonal anti-alpha-smooth muscle actin in diagnosis. Diagn Cytopathol., 1994, 10:120.
11. Dabbs, D.J., Gown, A.M. - Distribution of calponin and smooth muscle myosin heavy chain in fine-needle aspiration biopsies of the breast. Diagn. Cytopathol., 1999, 20:203.
12. Myers, T., Wang, H.H. - Fibroadenoma mimicking Papillary carcinoma on Thin-Prep of Fine Needle Aspiration of the breast. Arch. Pathol. Lab. Med., 2000, 124:1667.
13. Wang, H.H., Ducatman, B.S. - Fine needle aspiration of the breast: a probabilistic approach to diagnosis of carcinoma. Acta Cytol., 1998, 42:285.


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