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Adenosis and Microglandular Adenosis


Introduction

The term adenosis is used to describe a non-neoplastic lobulocentric proliferation of ductules with epithelial and myoepithelial cells, usually formed from the terminal duct lobular unit. The clinical presentation is variable and numerous microscopic variants have been described. Most are benign. This chapter discusses adenosis and addresses the involvement of adenosis by other pathological entities. Microglandular adenosis (MGA) is described separately later in this chapter.

Adenosis

Clinical Presentation

Foote and Stewart used the terms sclerosing adenosis and sclerosing adenomatosis to describe the lesion in 1945. They described the lesions as occurring in one of two forms: as a palpable mass or as a lesion seen only on microscopic examination. These two forms correspond to our present terminology of adenosis tumor , used when adenosis takes the form of a palpable or macroscopically recognizable mass, and adenosis , a microscopic lesion that is most often detected clinically because it contains calcifications seen on mammography. Adenosis tumor is more common in premenopausal women. Adenosis tumor may present with bloody secretion of the nipple.

Clinical Imaging

There is no pathognomonic sign or appearance of adenosis presenting as a tumor. In a study of the mammographic features of adenosis tumor, most tumors appeared as an irregular density, some with a lobulated appearance ( Fig. 14.1 ). Other tumors were circumscribed, and some appeared as stellate masses. When presenting as a mass, the mean diameter was 2.1 cm (range 0.5–4.5 cm). Associated calcifications were also identified. Ultrasound examination may reveal an oval mass, lobular mass, or irregular mass. The masses are most likely to be hypoechoic and have posterior acoustic enhancement ( Figs. 14.2 and 14.3 ). Sclerosing adenosis is most commonly identified on clinical imaging studies as clustered, diffuse, or scattered calcifications, but it may also present as an asymmetric density, mass, or area of architectural distortion ( Figs. 14.4 and 14.5 ). Coarse heterogeneous calcifications amid an area of asymmetric density may be a clue to the diagnosis of sclerosing adenosis, but it is not specific. In a study of 20 cases showing atypical apocrine adenosis on core biopsy, 12 cases showed masses on ultrasound examination, one case showed asymmetry only, one case presented as a persistently enhancing focus on magnetic resonance imaging (MRI), and six cases presented as calcifications on mammography.

Fig. 14.1, Adenosis tumor on mammogram. Partially obscured ovoid mass with macrolobulated borders.

Fig. 14.2, Adenosis tumor on ultrasound. Hypoechoic mass with macrolobulated angulated borders.

Fig. 14.3, Adenosis tumor on ultrasound. Hypoechoic macrolobulated mass with ill-defined margins and posterior acoustic enhancement; tall = wide dimensions; no significant color Doppler flow (not shown).

Fig. 14.4, Sclerosing adenosis on mammogram. Coarse heterogeneous clustered microcalcifications.

Fig. 14.5, Sclerosing adenosis on mammogram. Coarse heterogeneous microcalcifications, loosely clustered, possibly associated with a mass. Excisional biopsy showed lobular carcinoma in situ involving sclerosing adenosis.

Gross Pathology

In an early description of 15 cases of adenosis or “fibrosing adenomatosis,” Heller and Fleming described the lesions as unencapsulated, well-circumscribed, firm nodular masses, with granularity, or a fibrous appearance with small (1–3-mm) cystic spaces.

Adenosis presenting as a tumor may be pale, homogeneous, tan, lobulated, and well circumscribed. Adenosis tumors are generally small; in one series of 27 cases, they ranged from 0.6 to 2.3 cm. Sclerosing adenosis, particularly when present in association with fibrocystic change, may be more firm and white than normal breast parenchyma, but there is no distinctive gross appearance. Adenosis is commonly associated with, and considered to be part of, the spectrum of fibrocystic change. Therefore, the gross appearance of dense, firm white breast parenchyma and variably sized cysts may be seen in areas that also show adenosis on histological sections.

Microscopic Pathology

Adenosis is a lobulocentric proliferation of small ductules with both epithelial and myoepithelial cells. The ductules may be compressed and distorted and may appear to invade the surrounding stroma. The degree of sclerosis and compression of the small ductules tends to increase with age.

Florid Adenosis

Epithelial cells are most prominent in florid adenosis. The proliferation is cellular and consists of small ductules with hyperplasia of both the epithelial and myoepithelial layers ( Fig. 14.6 ). The epithelial cells are small and usually cuboidal to columnar, with central, round nuclei and inconspicuous nucleoli. Cytoplasm is usually eosinophilic, but it may show clear cell change ( Figs. 14.7 and 14.8 ). Myoepithelial cells are usually easily identified as a layer of smaller cells with slightly darker, more angulated nuclei surrounding the epithelial cells ( Fig. 14.9 ). In adenosis tumor, the coalescence of the glandular proliferation into a mass is seen, sometimes with the appearance of fusion of discrete lobules of adenosis with varying growth patterns. Clues to the presence of adenosis tumor on needle core biopsy specimens include lobulated growth, the density of the proliferation, and a well-circumscribed border. Recognition of these features may help in correlation with imaging findings ( Figs. 14.10 and 14.11 ).

Fig. 14.6, Florid adenosis composed of closely packed glands with plump epithelial cells and smaller more hyperchromatic myoepithelial cells.

Fig. 14.7, Clear cell change in florid adenosis.

Fig. 14.8, Clear cell change in florid adenosis.

Fig. 14.9, Florid adenosis. The epithelial cells have round nuclei and somewhat prominent nucleoli. The myoepithelial cells at the periphery of the ductules are smaller, with more hyperchromatic nuclei.

Fig. 14.10, Adenosis tumor on needle core biopsy. Variably sized glands amid a mildly hypercellular stroma with a well-circumscribed border.

Fig. 14.11, In this needle core biopsy, the well-circumscribed border is evident in this more cellular example of adenosis tumor.

Sclerosing Adenosis

At low power, sclerosing adenosis has an infiltrative, swirling appearance, yet usually maintains a lobulocentric distribution ( Figs. 14.12 to 14.15 ). Foci of sclerosing adenosis are generally larger than normal lobules. The ductules may extend into adjacent adipose tissue, mimicking invasive carcinoma, but they are invariably invested by a delicate rim of collagenous stroma. The ductules are round to somewhat angular, small, and generally uniformly sized but may show dilatation of some or many ductules and may contain some luminal secretion ( Figs. 14.16 and 14.17 ). Although each ductule has an epithelial layer and a myoepithelial layer, the epithelial cells may show variable atrophy and the ductules may appear to be composed of only one layer ( Figs. 14.18 and 14.19 ). These cells are uniform, with pale to clear cytoplasm, prominent cell borders, round to angulated nuclei, and inconspicuous nucleoli. Atrophy of epithelial cells and compression of ductules by surrounding sclerosis may result in ductules that have the appearance of single cells with an infiltrative appearance, sometimes simulating the appearance of invasive carcinoma ( Fig. 14.20 ). The ductules are often surrounded by dense, hyalinized collagenous stroma ( Fig. 14.21 ). Both intraluminal and stromal calcifications may be identified ( Figs. 14.22 to 14.24 ). Sclerosing adenosis is commonly identified in association with fibrocystic change and may also involve benign fibroadenoma ( Figs. 14.25 to 14.27 ). Sclerosing adenosis is also a common component of radial sclerosing lesions, and the ductules in these cases may be surrounded by stromal elastosis ( Figs. 14.28 and 14.29 ). Collagenous spherulosis ( Fig. 14.30 ) and columnar cell change with usual ductal hyperplasia may be seen concurrently with sclerosing adenosis ( Fig. 14.31 ). On fine-needle aspiration (FNA) biopsy, sclerosing adenosis has been described as frequent acinar sheets and small, dense hyalinized stroma attached to epithelial sheets with scattered individual epithelial cells.

Fig. 14.12, This example of sclerosing adenosis shows variably sized round glands in a lobulocentric distribution in which both an epithelial layer and a myoepithelial layer are easily discerned.

Fig. 14.13, The lobulocentric distribution of sclerosing adenosis is evident in this example, with variably sized ductules and collagenous stroma.

Fig. 14.14, Sclerosing adenosis with a lobulocentric distribution and small cuboidal cells with round nuclei.

Fig. 14.15, Sclerosing adenosis with prominent epithelial atrophy and hyalinized stroma in a lobulocentric distribution.

Fig. 14.16, Adenosis composed of round ductules of variable size with intraluminal secretions.

Fig. 14.17, Adenosis composed of round ductules of variable size with intraluminal secretion and some extension into adjacent adipose tissue.

Fig. 14.18, ( A and B ) In this example of sclerosing adenosis, distinct epithelial and myoepithelial layers are visible on routine stain.

Fig. 14.19, Epithelial atrophy and compression of ductules result in prominent myoepithelial cells with clear cytoplasm and small dark nuclei, along with luminal obliteration.

Fig. 14.20, ( A to C ) Small, compressed ductules of sclerosing adenosis with epithelial atrophy and an infiltrative appearance.

Fig. 14.21, ( A to C ) Sclerosing adenosis with prominent hyalinized stroma surrounding individual ductules.

Fig. 14.22, ( A and B ) Sclerosing adenosis with scattered intraluminal microcalcifications.

Fig. 14.23, ( A to C ) Sclerosing adenosis with abundant intraluminal microcalcifications.

Fig. 14.24, ( A and B ) Prominent stromal microcalcifications in association with sclerosing adenosis.

Fig. 14.25, Small round glands of adenosis adjacent to fibrocystic change.

Fig. 14.26, Needle core biopsy of fibroadenoma with proliferation of small ductules of sclerosing adenosis in the center of the image.

Fig. 14.27, ( A and B ) Sclerosing adenosis involving a fibroadenoma.

Fig. 14.28, Sclerosing adenosis as a conspicuous component of this radial sclerosing lesion with central stromal elastosis.

Fig. 14.29, Sclerosing adenosis with microcalcifications involving a radial sclerosing lesion.

Fig. 14.30, ( A to C ) Collagenous spherulosis and stromal elastosis in sclerosing adenosis.

Fig. 14.31, Columnar cell change in sclerosing adenosis.

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