Breast-nonmalignant

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Breast-nonmalignant

Procedures

Cytology of breast lesions

Editor: Hind Nassar, M.D., Johns Hopkins Medical Institute (see Reviewers page)

Revised: 26 September 2012, last major update April 2010

General

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● See also discussion under specific diagnoses

● Usually refers to fine needle aspiration (FNA); also imprints of core biopsies, cytology touch imprints for evaluating margins, ductal lavage cytology

● Relatively quick with minimal equipment needed

Terminology

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● Stereotactic (Greek/Latin-“touching in space") refers to sampling of nonpalpable or indistinct breast lesions using techniques that enable the spatial localization of the lesion within the breast

Fine needle aspiration (FNA)

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● Uses 23 or 27 gauge needles (Breast 2006;15:567)

● “Time out” for verification recommended by JCAHO at start of procedure (Cytojournal 2007;4:19)

● 90% sensitive, 95%+ specific

● Difficult to differentiate ADH or invasive carcinoma from DCIS, or papillary carcinoma from fibroadenoma (Archives 2000;124:1667)

● Less sensitive for tumors with extensive fibrosis, DCIS or cribriform carcinoma; also for women age 35 and under with malignancy (Pathology 2008;40:359)

● Rapid cell blocks may be superior to on site evaluation (Diagn Cytopathol 2008;36:523)

● Monolayer preparation using cytocentrifuge may increase diagnostic accuracy (J Clin Pathol 2009;62:931)

● Reliable but underutilized for male breast lesions (Acta Cytol 2009;53:369)

● Cell blocks can be used to evaluate basal phenotype (Diagn Cytopathol 2010 Jan 20 [Epub ahead of print]), or p63 to categorize cases problematic by Pap staining (Am J Clin Pathol 2007;128:80)

● Breast aspiration fluid CEA concentration may be helpful in determining malignancy (Archives 2004;128:1251)

False positives for malignancy:

● Florid epithelial hyperplasia

False negatives:

● Tubular carcinoma, lobular carcinoma (Cancer 2008;114:111), low grade ductal carcinoma (Cancer Cytopathol 2009;117:491)

● Small tumor size may cause sampling error (Cytopathology 2008;19:279)

Core biopsy imprint cytology

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● Useful as adjunct to core biopsy (Cytopathology 2008;19:311)

● May reduce diagnostic waiting time and increase sensitivity of core biopsy (Eur J Surg Oncol 2009;35:1037)

● Core wash cytology may be superior to touch imprint (Cancer Cytopathol 2009;117:333)

Ductal lavage cytology

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● Variable sensitivity in detecting intraductal malignancies (high-Breast Cancer Res Treat 2009;118:9; low-Acta Cytol 2009;53:410)

● May be useful in distinguishing benign versus malignant lesions in patients with unilateral, spontaneous nipple discharge (Int Surg 2003;88:83)

● Presence of epithelial cells in nipple aspirate fluid is associated with higher risk for subsequent breast cancer (Breast Cancer Res Treat 2006;98:63)

● Combination of visualization through ductoscopy and pathologic analysis of washings provides the highest predictive value for the diagnosis of papilloma (Breast J 2009;15:254)

● Limited value in screening high risk patients overall (Am J Surg 2007;194:463)

Cytology touch imprints for margin evaluation

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● Quick, easy, inexpensive, no frozen section artifact, doesn’t sacrifice tissue, can sample entire margin (Archives 2002;126:846)

Recommendations

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● Fine needle aspiration preferred for benign appearing lesions, suspected recurrent disease (Diagn Cytopathol 2008;36:855), children / adolescents (Acta Cytol 2008;52:681) and clinically suspicious lymph nodes prior to neo-adjuvant therapy

● Use core biopsy for indefinite cases (Br J Cancer 2008;98:1182, Cytopathology 2008;19:271, Ann Surg Oncol 2009;16:281) or malignant appearing lesions

● In United States, core biopsy has replaced FNA in many centers due to inability to diagnose invasive disease by FNA

● Negative FNA should not rule out biopsy if clinical suspicion of malignancy persists, but negative cytology, negative clinical examination and negative radiologic findings (“triple negative test”) together have a negative predictive value close to 100% (Breast J 2004;10:487) [note: triple negative also refers to basal-like breast carcinomas that are ER-, PR-, HER2-]

● Cytopathologists may be able to perform ultrasound guided FNAs and core biopsies (Diagn Cytopathol 2008;36:317, Diagn Cytopathol 2009;37:262)

FNA Artifacts

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● Displaced epithelium, which simulates stromal and vascular invasion (Am J Surg Pathol 1994;18:896, Mod Path 1995;8:380)

● Hemorrhage, infarction, necrosis, hemosiderin deposition (Am J Surg Pathol 1994;18:1039)

Cytology description

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● Detailed analysis of a single morphologic characteristic has limited diagnostic value (Cancer 2005;105:152)

● Helpful features for malignancy are cohesive clusters of tumor cells with irregular margins, pleomorphic cells with enlarged and hyperchromatic nuclei, mitotic figures, necrosis, microcalcifications, lack of naked nuclei, lack of apocrine metaplasia

● In elderly patients, background of single epithelial cells with atypia and absence of bipolar nuclei in the background have a strong association with malignancy (Pathology 2008;40:573)

Cytology images

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Displaced #2-simulating vascular #3-displaced papillary carcinoma

epithelium #1 invasion

Cytology imprints from core biopsy - malignant

Cytology imprints from core biopsy - benign

Differential diagnosis of malignancy by cytologic examination

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● Gynecomastia with chemoradiation induced atypia (Archives 2002;126:613), micro image

● Tissue infarction (Diagn Cytopathol 2008;36:586)

● Herpes zoster / chicken pox infection (Acta Cytol 2008;52:337)

Additional references

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● eMedicine

End of Breast-nonmalignant > Procedures > Cytology

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