, Christopher VandenBussche2 and Syed A. Hoda3
CBL Path, Rye Brook, NY, USA
Department of Pathology, Johns Hopkins University Department of Pathology, Baltimore, MD, USA
New York Presbyterian Hospital Weill Cornell Medical College, New York, NY, USA
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FNA is used to obtain diagnostic material from solid and cystic breast lesions. In recent years, needle core biopsies have mostly replaced FNA for diagnosing most solid breast lesions – at least in the United States. However, FNA is still used to sample cystic breast lesions and other lesions that are difficult to access through needle core biopsy, such as in the retroareolar location. Additionally, some clinicians and pathologists continue to use FNA to sample breast lesions in the outpatient setting. Thus, virtually any breast entity can be encountered in a breast FNA.
The “triple test” is utilized to help diagnose breast lesions on FNA. The “triple test” means that the cytological findings on FNA are placed in the context of clinical and radiological findings. Relying on the results of the FNA alone can be treacherous.
FNA sampling of high-grade ductal carcinoma in situ (DCIS) often results in pleomorphic malignant cells that cannot be distinguished from invasive ductal carcinoma (IDC). Low-grade DCIS and even IDC contain relatively bland monotonous cells that may not reveal their malignant nature on FNA. Typically, if the clinician is suspicious of malignancy, needle core biopsies should be taken.
Upon FNA, cystic breast lesions should be drained of all fluid. If a residual solid mural component is detected, it should be sampled via FNA and needle core biopsy. Follow-up should ensure that the cystic lesion does not recur. If the cyst recurs, FNA or excisional biopsy may be required.
FNA of breast can be used to make conventional smear for rapid on-site evaluation, in which case the needle rinses can be processed as LBP. If rapid on-site evaluation is not performed, dedicated passes can be placed entirely into LBP preservative and submitted for processing.
Nipple discharge can be collected and submitted for processing. Ductal lavage can be performed to sample cells for cytological examination – if a lesion is visualized inside the duct upon galactography. In these cases, the fluid submitted to the laboratory can be processed using standard concentration techniques, including LBP.
Multiple studies have demonstrated the utility of LBP for breast FNA. Aside from some cytomorphological differences between LBP and conventional smears, LBP has been shown to be a reliable technique with a diagnostic accuracy equivalent to conventional smears [1, 2]. One study has shown that SP LBP provides better cellularity for cystic lesions than conventional smears .
Fibrocystic change with apocrine metaplasia. (a) Benign changes sampled on FNA are often typified by apocrine metaplasia. Here the epithelial cells contain abundant, amphophilic cytoplasm with round nuclei and bland chromatin. There are no nuclear irregularities, and the cells have an orderly arrangement (TP). (b) This larger fragment of epithelial cells demonstrates typical apocrine change; there is a minimal anisonucleosis, but otherwise the nuclei are benign-appearing, and the cells maintain an orderly arrangement (TP). Liquid-based preparation performs comparably to conventional smears for breast FNA specimen preparation and provides better cellularity for cystic lesions 
Lactational adenoma. (a) Lactational adenoma typically presents as a well-circumscribed mass during or immediately after pregnancy. FNA specimens, as seen here, are typically hypercellular. The cells have foamy cytoplasm, uniform nuclei, and prominent nucleoli. Foamy material may also be seen in the background on a conventional smear, but a clean background is more commonly seen on LBP (TP). Of note, prominent nucleoli can be seen in both malignant and benign lesions . (b) The background in this conventional smear is more bloody than foamy, but cytoplasmic vacuolization is prominent (DQ-stained conventional smear). (c) The cells here are monotonous, with prominent nucleoli; cytoplasm is foamy and delicate (TP). (d) The corresponding excisional biopsy shows hypersecretory change in mammary glands with abundant luminal secretions. The lesional cells are similar to those on cytology. (d, H&E)
Fibroadenoma. (a–c) Fibroadenoma is typified by staghorn arrangements of epithelial cells intermixed with spindled cells. The nuclei may be overlapping and can have atypia that can be mistaken for malignancy. Note the clean background. The diagnosis of fibroadenoma may be more difficult on liquid-based preparations, with studies showing a low diagnostic rate compared to conventional smears and an increased number of false-positive results . The number of myoepithelial cells and stromal fragments may be reduced in liquid-based preparations (a,TP; b,TP; c,TP). (d) Fibroadenoma with elongated epithelial lined cleft amid stromal proliferation (H&E)
Intraductal papilloma. (a) Cuboidal to columnar epithelial cells in a complex papillary-like cluster, showing round regular nuclei with fine chromatin and conspicuous nucleoli. In contrast to papillary carcinomas, papillomas usually have broader branching fragments as opposed to slender complex papillae and fewer columnar-shaped cells  (TP). (b) Ductal cells with vacuolated cytoplasm and bland round to oval nuclei and small nucleoli (TP). (c) Excisional biopsy specimen shows papilloma with multiple papillae containing vascularized fibroconnective tissue. Apocrine metaplasia can be seen (H&E)
Papillary carcinoma. (a) Multiple cellular fragments, some with thin branching structures, can be seen amid a clean background. Smaller clusters can also be seen (TP). (b) The cells around the edges are primarily columnar, as opposed to more epithelioid ones seen in (a). The nuclei are hyperchromatic and overlapping (TP). (c) The edges of these fragments are a mixture of columnar and epithelioid cells, both demonstrating hyperchromasia and anisonucleosis. Differentiating between benign and malignant papillary lesions on FNA can be challenging (TP). (d) Conventional smear shows a hypercellular specimen with columnar cells, many of which are loosely attached to thin papillary fibrovascular cores with complex branching (Pap-stained CS). (e) The monotony of cells and bland nuclear features may not suggest carcinoma; however, the specimen is hypercellular, and myoepithelial cells are absent (Pap-stained conventional smear). (f) Excisional biopsy specimen demonstrate complex papillae with columnar epithelium (H&E)
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