SA is a lobulocentric proliferation of distorted acini around a central duct with preservation of myoepithelial cells, accompanied with varying degrees of epithelial atrophy and stromal fibrosis.
Incidence: SA is often an incidental finding in breast tissue removed for other reasons. In autopsy studies performed on patients with no history of breast disease, the incidence of SA was in a range of 7–20%. The lesion is present in 12–28% of breast biopsies without cancer and in 5–7% of malignant biopsies.
Age: Most patients are in their forties and fifties with a peak in the 45–55 age group (34%), versus 28.3% of older women and 21.6% of women less than 45.
Sex: SA is predominant in women and more common in obese and in women using hormone replacement therapy and with a higher fibroglandular breast tissue density at mammography (>25%). Because of increased estrogen receptor (ER) expression observed compared with normal glandular breast tissue, it is assumed that hormone imbalance and dysregulation of ER may play a role in development of SA.
Patients with a clinically palpable mass, termed as nodular SA or adenosis tumor, are generally younger, often in their pre- or perimenopausal age. The lesion is usually solitary, although multiple and bilateral nodular SA were reported. It may be ill-defined and can be somewhat fixed within the breast parenchyma.
The main features of SA are multiple, punctuate microcalcifications (i.e., powdery, cotton ball-like, “skipping stone-like”) (Fig. 1a). Thick-section images demonstrate that the radiologically detected microcalcifications can have “onion ring” like psammomatous appearance (Fig. 1b), and they are localized within enlarged and distorted lobules (Fig. 1c, d). Rarely mammographic calcifications may be amorphous and pleomorphic and in such cases indistinguishable from non-comedo DCIS. SA is less commonly detected as a mass lesion, which is generally circumscribed or lobulated and may be associated with microcalcifications. In rare cases, SA presents as an architectural distortion.
Nodular SA often appears as a circumscribed, hypoechoic solid lesion. In cases with asymmetrical density on mammography, the typical ultrasound feature is focal acoustic shadowing without a mass configuration. Mass-like lesions with irregular contour in association with marked posterior acoustic shadowing are also observed, and the distinction from infiltrating carcinoma is impossible.
Magnetic resonance imaging (MRI)
Typical SA lesions are indistinguishable from breast parenchyma, but the enhancement may increase moderately or rapidly over time making it difficult to distinguish nodular SA from malignant lesions.
Treatment: Some evidence suggests that SA may regress after the menopause. When SA associated with non-proliferative lesions as a part of fibrocystic change, further excision is not recommended. If SA is diagnosed in a core needle biopsy (CNB), surgical excision of the lesional area is recommended to rule out carcinoma, particularly in cases associated with radiographically suspicious calcifications, a spiculated contour, or combined with radial sclerosing lesions, or atypical epithelial hyperplasia. In the absence of the foregoing features, clinical follow-up is recommended.
Outcome: There is still disagreement as to whether SA is a risk factor for subsequent breast carcinoma. When only a small area of SA is present, there may be no evidence that risk is elevated beyond that of other non-proliferative lesions (no increased breast cancer risk, 4% lifetime risk) such as usual ductal hyperplasia. The combination of SA with atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia (ALH) increases the risk of cancer development (4.8–6.7×). The association with lobular neoplasia is found to occur almost three times more commonly than would be expected by chance. In addition, positive family history of breast cancer (2.85× risk), patient age (2.24× risk in 45–55 years old group), and other risk factors such as the degree of lobular involution (2.67× risk in non-involutionary breast) and higher Ki-67 expression in SA and/or adjacent normal breast can increase the risk of subsequent invasive carcinoma (Nassar et al. 2015).
There are no distinctive gross appearances, the breast tissue either appearing normal or showing features of associated fibrocystic change. In cases with nodular SA firm, lobulated but often ill-defined rubbery mass can be seen varying in size up to 5 cm. A nodular and whorled appearance may be appreciated on the cut surface.
Due to its origin, SA maintains the immunophenotype of normal lobules (i.e., CK7, CK 8/18, p63, p40, smooth muscle actin, calponin, and high-molecular weight cytokeratins (CK5/6, CK14)). Using of more than one myoepithelial marker or “cocktail” of markers can be helpful (Pavlakis et al. 2006). Basement-membrane material is immunoreactive for collagen IV and laminin.
A recent gene expression profile study revealed overexpression of DLK2, EXOC6, KIT, RGS12, and SORBS2 in SA at risk of cancer development (Winham et al. 2017).
Normal Breast Versus SA
(1) Adenosis: lobules are enlarged; the number of acini is increased. It occurs in normal circumstances such as pregnancy (“Adenosis”). (2) Lobules involution: involuting lobules appear more eosinophilic than SA, being dominated by luminal cells with plump blue nuclei.
The features favoring SA against invasive carcinoma are the following: lobulocentric architecture, myoepithelial cells on hematoxylin and eosin (HE) slides or by immunohistochemistry (IHC), and dense rather than desmoplastic stroma.
SA can mimic tubular carcinoma (TC) (“Tubular Carcinoma”). TC does not recapitulate the lobulocentric architecture and shows haphazardly infiltrating growth pattern, edges are irregular rather than circumscribed or lobulated, and the tubules are more widely spaced. In addition, TC shows angulated tubules with open lumens and no myoepithelial cells. Invasive apocrine carcinoma can be misdiagnosed in cases of atypical apocrine adenosis. However, in atypical apocrine adenosis, the organoid appearance is obvious and specific IHC markers can demonstrate myoepithelial cells.
Microglandular Adenosis (MGA)
MGA (“Microglandular Adenosis”) is composed of small round tubules scattered around normal breast structures. Luminal spaces are opened with round contours and eosinophilic secretions without obvious stromal response. MGA can be distinguished from SA by lacking myoepithelial cells, ER negativity, and S100 strong positivity with IHC.
References and Further Reading
- Nassar, A., Hoskin, T. L., Stallings-Mann, M. L., Degnim, A. C., Radisky, D. C., Frost, M. H., Vierkant, R. A., Hartmann, L. C., & Visscher, D. W. (2015). Ki-67 expression in sclerosing adenosis and adjacent normal breast terminal ductal lobular units: A nested case-control study from the Mayo Benign Breast Disease Cohort. Breast Cancer Research and Treatment, 151, 89–97.CrossRefGoogle Scholar
- Winham, S. J., Mehner, C., Heinzen, E. P., Broderick, B. T., Stallings-Mann, M., Nassar, A., Vierkant, R. A., Hoskin, T. L., Frank, R. D., Wang, C., Denison, L. A., Vachon, C. M., Frost, M. H., Hartmann, L. C., Aubrey Thompson, E., Sherman, M. E., Visscher, D. W., Degnim, A. C., & Radisky, D. C. (2017). NanoString-based breast cancer risk prediction for women with sclerosing adenosis. Breast Cancer Research and Treatment, 166, 641–650.CrossRefGoogle Scholar