Fibrocystic change is the most common lesion to produce a breast mass in women aged over 30. Up to 50% of women have palpable 'lumpiness' and up to 90% show histological changes. The lesions of fibrocystic change, usually multiple and bilateral, are the most common palpable lesions sampled by FNA.
Histologic features include ductal dilatation, possibly resulting from periductal scarring, with subsequent formation of cysts, which are associated with apocrine metaplasia, ductal hyperplasia, fibrosis and chronic inflammation. FNA cytology is often poorly cellular because of the background fibrosis.
Cytological diagnostic features
- Low cellularity
- Flat, honeycomb epithelial sheets, with no loss of polarity and distinct cell borders
- Uniform small nuclei, low N/C ratio
- Bipolar naked nuclei
- Foamy cells and apocrine cells
- Fat and fibrous stromal tissue fragments
Apocrine cells can be arranged in flat sheets or as single cells, and show abundant granular cytoplasm and larger, more hyperchromatic nuclei with prominent nucleoli. Bipolar naked nuclei are often said to derive from myoepithelial cells, however they might also be derived from fibroblasts of the interlobular connective tissue. They are not specific of fibrocystic change, as they can be seen in other benign breast lesions (such as fibroadenoma).
Various degrees of epithelial proliferation occur in fibrocystic change, reflecting ductal hyperplasia, sclerosing adenosis, collagenous spherulosis, and atypical ductal hyperplasia. FNA smears of proliferative lesions show increased number of cohesive ductal cell groups and bipolar naked nuclei.
Cytological diagnostic features - proliferative fibrocystic change
- Moderate to high cellularity
- Cohesive epithelial groups with mild nuclear overlapping
- Myoepithelial cells within epithelial groups
- Bipolar naked nuclei in the background
- Apocrine and foamy cells
Aspirates of proliferative lesions can be a potential source of false-positive diagnoses of malignancy when the groups are hypercellular and show mild nuclear overlapping. The benign nature of the lesion should be suspected when a polymorphic population of cells is present, including apocrine, ductal and histiocytic cells, and especially when numerous bipolar naked nuclei are seen. FNA cytology is generally limited in its ability to subclassify proliferative breast lesions.
Collagenous spherulosis is a benign lesion characterized by the presence of acellular eosinophilic and fibrillary spherules, surrounded by a proliferation of bland, round to oval myoepithelial cells. It is usually an incidental finding associated with intraductal papilloma, sclerosing adenosis, radial scar, or lobular infiltrative carcinoma..
The aspirates contain scattered metachromatic hyaline globules, associated with numerous benign ductal cells. The differential diagnosis includes adenoid cystic carcinoma, although the clinical findings facilitate the correct diagnosis.
Atypical ductal hyperplasia
Intraductal epithelial proliferations of the breast represent a spectrum ranging from intraductal hyperplasia without atypia (conventional ductal hyperplasia) to atypical ductal hyperplasia (ADH), to ductal carcinoma in situ (DCIS).
Conventional hyperplasia can be mild, moderate or florid, depending on the degree of epithelial proliferation. Aspirates show increased cellularity, with cohesive epithelial groups and bipolar naked nuclei. Some variations in cell size and shape can be present within the groups, but single atypical epithelial cells are not seen.
Aspirates of ADH are usually highly cellular and contain crowded groups of cells with both bland and atypical features. However, the diagnosis of ADH belongs to histopathology diagnosis and this term and diagnosis should be avoided in cytology.
Cytological diagnostic features of ADH
- High cellularity
- Considerable cellular and nuclear overlapping
- Cellular monotony
- Prominent nucleoli
- Myoepithelial cells within the groups and stromal bipolar naked nuclei in the background
The cells show considerable variation in cell size and shape and some loss of polarity within the groups. Occasional single atypical cells can be present, however, in contrast with DCIS, bipolar naked nuclei are present.
Cytology is not usually believed to be reliable in sub-classification of proliferative breast disease. Aspirates deemed to be 'atypical' should lead to core-needle or surgical biopsies.