and Aysegul A. Sahin2
Division of Pathology, Singapore General Hospital, Singapore, Singapore
The University of Texas, M. D. Anderson Cancer Center, Houston, TX, USA
KeywordsSclerosing adenosisRadial scarComplex sclerosing lesion
Many different types of both benign and malignant breast lesions can be associated with stromal fibrosis and collagen deposition and can be broadly classified as sclerosing lesions [1–3]. Recognising the aetiology of the fibrosis on excisional biopsy is usually not very difficult; however, extensive fibrosis and related histologic changes may create major diagnostic challenges on a limited sample such as a core needle biopsy. Sclerosing adenosis and radial scar/complex (radial) sclerosing lesion are two benign entities that will be described in this chapter. The main clinical significance of these lesions is that they may mimic invasive carcinoma clinically and radiographically as well as in gross and microscopic evaluations.
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Adenosis is defined as a relative increase in the number of acinar units in a terminal ductal lobular unit. Sclerosing adenosis refers to adenosis with extensive fibrosis that includes compression and distortion of acinar units . When proliferating glands expand lobular units significantly and form nodules or mass lesions, the terms nodular adenosis and adenosis tumour are used .
Sclerosing adenosis is a frequent incidental microscopic finding in breast specimens removed for other indications. Sclerosing adenosis has been reported in 15–20 % of breast biopsies without carcinoma. It occurs in a wide age group but is most frequent in perimenopausal women. Regression of sclerosing adenosis has been noted in postmenopausal women. Most lesions are less than 2 cm and can be unifocal or multiple. The majority are associated with microcalcifications and/or architectural distortion that leads to biopsy. Therefore, screen detection in an asymptomatic patient is the most common mode of discovery. Less commonly, the presenting symptom may be a mass lesion on palpation or on imaging. Rarely, sclerosing adenosis may be associated with breast pain.
Sclerosing adenosis may present as microcalcifications, architectural distortion, or mass lesions (Fig. 5.1) . Microcalcifications are typically described as amorphous and clustered; pleomorphic and punctate microcalcifications can also be associated with sclerosing adenosis. This latter pattern cannot be differentiated from that of carcinoma, and biopsy is required for definitive diagnosis. Increased density with irregular margins with or without microcalcifications can also be a radiographic finding of sclerosing adenosis. This pattern closely mimics invasive carcinoma, especially tubular carcinoma. Mass-forming lesions are typically well circumscribed or lobulated. There are usually no significant MR findings. Twenty percent of cases of sclerosing adenosis may show intermediate enhancement.
Sclerosing adenosis. (a) Mammography shows a mix of powdery, punctate and rounded types of microcalcifications in this cluster. Stereotactic-guided percutaneous biopsy revealed that the calcifications were associated with sclerosing adenosis. (b) Ultrasound examination shows a group of lobulated and tubular-oriented nodules that can mimic ductal pathology on imaging. When sclerosing adenosis forms nodules or mass lesions, it is referred to as nodular sclerosing adenosis.(Courtesy of Dr. Lester Leong)
The gross appearance of sclerosing adenosis depends on the size and microscopic composition of the lesion. Since the majority of sclerosing adenosis lesions are small and have a combination of stromal and glandular components, they are imperceptible on macroscopic evaluation. If a lesion has extensive fibrosis, it may appear as white and vaguely nodular (Fig. 5.2). Lesions composed predominantly of glandular components with epithelial proliferation may appear as circumscribed, rubbery, pale tan nodules.
Adenosis tumour. Gross and imaging features. (a) Imaging and specimen show a partially-circumscribed white nodule. (b) Higher magnification of specimen displays a mixture of grey-white and yellow tissue. Note that the grey-white tissue blends into adjacent fat
Sclerosing adenosis is characterised by enlarged lobular units due to nodular proliferation of ducts and acini that are compressed and distorted by stromal collagen (Figs. 5.3, 5.4, and 5.5) [4, 7]. The normal lobular appearance is distorted by fibrosis, particularly in the centre of the lesion, where distorted glands may have an angulated appearance and mimic invasive carcinoma (Fig. 5.6). However, the lobulocentric nature of the lesion, which is best appreciated on low magnification, is maintained and can be the most important histologic feature to differentiate it from invasive cancer (Fig. 5.6). The ducts have both luminal epithelial and peripheral myoepithelial cells. Although the presence of a dual cell population is easy to appreciate on haematoxylin and eosin (H&E) sections in most cases, confirmation by immunohistochemistry may be helpful in selective instances to illustrate the preservation of myoepithelial cells (Fig. 5.7). The ratio of epithelial and myoepithelial cells can vary significantly from case to case (Fig. 5.8).
In some cases, there is significant epithelial atrophy and preferential proliferation of myoepithelial cells. In others, both epithelial and myoepithelial components appear hyperplastic. The basement membrane around glands of sclerosing adenosis is usually thickened and prominent. Occasionally, both epithelial and myoepithelial cells undergo metaplastic changes. Apocrine metaplasia of epithelium, spindle cell morphology, and myoid differentiation of myoepithelium are commonly seen in sclerosing adenosis. The term apocrine adenosis is used when the entire lesion of sclerosing adenosis shows apocrine metaplasia (Fig. 5.9) [8–10]. Microcalcifications are a common microscopic feature of sclerosing adenosis and can be present either in fibrotic stroma or in ductal lumens. Atypical ductal and atypical lobular hyperplasia or in situ carcinoma may involve sclerosing adenosis. These may cause major diagnostic difficulties, especially on core needle biopsies. Involvement of sclerosing adenosis by ductal carcinoma in situ may mimic invasive carcinoma, and it is one of thecommonly mistaken diagnoses on core needle biopsies. Ductal carcinoma in situ involving sclerosing adenosis can be high grade and arise within sclerosing adenosis. The integrity of the individual acini and preservation of myoepithelium may be difficult to appreciate on H&E sections alone (Figs. 5.10, 5.11, and 5.12). Lobulocentric architecture of sclerosing adenosis versus infiltrative growth pattern of invasive carcinoma, a background of dense fibrotic stroma of sclerosing adenosis versus the more cellular (desmoplastic) stroma of invasive carcinoma, should be useful in arriving at the correct diagnosis. Using immunohistochemical stains to highlight myoepithelial cells will be helpful [11–14].
Perineural pseudoinvasion has been reported in 2 % of sclerosing adenosis cases (Fig. 5.13) . Sclerosing adenosis glands and ducts may be present around nerves, most commonly in the perineurium, but rarely in nerve fibres. The benign appearance of the glands and the preserved myoepithelial layer around the ducts will be helpful to differentiate these glands from invasive carcinoma.
Sclerosing adenosis. (a) Core biopsies show cellular areas at low magnification. (b) Medium magnification shows a dense population of cells with slightly spindled appearances, merging with small tubules with patent lumens. (c) Higher magnification shows small tubules among ovoid to spindle cells of myoepithelial origin. (d) CK14 immunohistochemistry shows prominent myoepithelial cells rimming the small tubules and compressed epithelial nests. (e) Immunohistochemistry for p63 also shows retention of myoepithelial cells. (f) Higher magnification shows p63 immunostaining of many myoepithelial nuclei among the luminal epithelial cells. Myoepithelial hyperplasia is often encountered in sclerosing adenosis
Sclerosing adenosis. Microscopic features. (a) Low magnification of lobulocentric growth. (b) Medium magnification of (a) shows that some glands have collapsed closed lumens, while others have open tubular structures
Sclerosing adenosis. Microscopic features. (a) Low magnification shows a distinct nodule with sharp demarcation from adjacent breast parenchyma. (b) Medium magnification shows distorted small glands that have predominantly closed lumens. (c) High magnification of the same case shows a small glandular proliferation surrounded by dense collagenized stroma
Sclerosing adenosis. Microscopic features. (a) Low magnification of core needle biopsy shows a crowded glandular proliferation with fibrotic areas and a pseudo-infiltrative pattern (arrows). (b) Glands with open as well as compressed lumens are present, rimmed externally by spindled myoepithelial cells. Occasional luminal calcifications are seen. (c) High magnification shows the compressed ductules to be lined by bilayered epithelium – an inner luminal layer that is composed of cuboidal to flattened cells, and an outer layer of myoepithelial cells with spindled morphology and pink cytoplasm indicating myoid metaplasia. (d) Atypical lobular hyperplasia is seen superimposed on sclerosing adenosis. Inset shows negative immunohistochemical staining of lobular neoplastic cells for E-cadherin
Sclerosing adenosis. Immunohistochemical features. (a, b) Lower and higher magnification shows positive staining for smooth muscle myosin that highlights peripheral myoepithelial cells
Sclerosing adenosis. Microscopic features. (a) Low magnification shows sclerosis of several small atrophic glands associated with hypocellular stroma (upper field). (b) Closer view shows that the small glands are bilayered, with variably prominent myoepithelial cells. (c) High magnification shows compressed glands with myoepithelial cells in a linear distribution, which may mimic an invasive carcinoma growth pattern
Sclerosing adenosis with apocrine metaplasia (apocrine adenosis). Microscopic features. (a) Low magnification shows a lobulocentric proliferation of small glands in a fibrotic background. (b, c) Higher magnification shows apocrine metaplasia
Ductal carcinoma in situ (DCIS) involving sclerosing adenosis. Gross and microscopic features. (a) Specimen shows a haemorrhagic area (arrow) corresponding histologically to foci of glandular proliferation. (b, c) Low magnification of different areas of the prior core biopsy showing a glandular proliferation in a fibrous background. (d) Higher magnification indicates a proliferation of low-to-intermediate grade ductal carcinoma in situ cells expanding the glands. (e) A few scattered glands are not involved by DCIS (arrows). (f) Immunohistochemistry for CK14 decorates an intact outer layer of myoepithelial cells around DCIS
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