Evaluation of nipple secretions

A nipple discharge may be unilateral or bilateral; unilateral ones are more likely to be malignant. The secretion can be milky, serous, purulent or bloody. Cancer is most prevalent when the discharge is macroscopically bloody.

Benign nipple secretions – cytologic diagnostic features

Usually sparsely cellular
Ductal cells
Foamy cells
Inflammatory cells
Red blood cells

Benign ductal cells are molded around one another and arranged in tight clusters, which can be small and spherical or large and branching; isolated cells are very uncommon. The cells are usually small, with scant cytoplasm, but sometimes they are larger with abundant cytoplasm. Foamy cells are histiocytes with abundant vacuolated cytoplasm and round or oval nuclei. When the secretion contains several groups of benign ductal cells, especially in large, branching clusters, an intraductal papilloma or a florid intraductal hyperplasia are likely to be present. These lesions can only be distinguished histologically.

Malignant nipple secretions – cytologic diagnostic features

Clusters and single enlarged ductal cells
Nuclear pleomorphism
Stripped nuclei
Nucleoli
Acute inflammation
Blood
Necrotic debris

Evaluation of FNA specimens

Low power evaluation

Cellularity
Cell arrangements
Background elements

Cellularity is important, although there is considerable overlap between categories. Hypocellular aspirates are commonly obtained from fibroadenoma, fibrocystic changes, fat necrosis, radiation changes and carcinoma (particularly scirrhous, tubular and lobular types). Moderately cellular aspirates are seen with fibroadenoma, phyllodes tumor, fibrocystic changes and carcinoma. Hypercellular aspirates are common in some fibroadenomas, phyllodes tumors and invasive carcinoma.

Cells can be arranges in sheets (such as in fibroadenoma, fibrocystic changes, or lobular carcinoma in situ), tightly cohesive three-dimensional clusters (fibroadenoma, phyllodes tumor, intraductal papilloma and hyperplasia, lobular and ductal carcinoma in situ, mucinous carcinoma), loosely cohesive clusters (phyllodes tumor, ductal carcinoma in situ), branching papillary clusters (fibroadenoma, intraductal papilloma, papillary carcinoma). Numerous isolated cells are characteristic of breast carcinoma. Regular nuclear spacing in clusters suggest a benign lesion, whereas irregular spacing is characteristic of malignancy.

Background elements include inflammatory cells, amorphous debris, fresh and old blood, and mucin. Acute inflammatory cells are seen with mastitis and necrotic carcinomas, whereas chronic inflammatory cells can be seen with intramammary lymph nodes and medullary carcinoma. An amorphous granular debris suggests malignancy, but it can also be found in benign conditions, such as apocrine metaplasia. Blood suggests an intraductal papilloma or a carcinoma. Mucin is observed with fibroadenoma or mucinus carcinoma.

High power evaluation

Types of single cells
Nuclear features
Cytoplasmic features

Isolated cells are epithelial or mesenchimal in origin; they may be intact or stripped of cytoplasm (bare nuclei). Single epithelial cells are seen with carcinoma, whereas mesenchimal cells suggest fibroadenoma, phyllodes tumor or sarcoma, but they can also be present in invasive carcinoma. Bare nuclei are common in fibroadenoma. Inflammatory cells, including histiocytes, are common in fat necrosis, mastitis and fibrocystic changes.

Nuclear atypia (nuclear enlargement and pleomorphism, large nucleoli) is observed in moderately and poorly differentiated ductal carcinomas. However, some malignant tumors, such as tubular, lobular and mucinous carcinoma, show very little nuclear atypia, and the recognition of other features (architecture, abundant extracellular mucin) is important in the diagnosis of these tumors.

Some cytologic features are characteristic of some breast lesions. Apocrine change is seen in apocrine metaplasia and apocrine carcinoma. A vacuolated cytoplasm is observed with some carcinomas, including mucinous and lobular carcinoma.