Sclerosing lobular hyperplasia (SLH) occasionally forms a localized tumor (1,2) and may be associated with tenderness.

The lobules are enlarged, with an increased number of acini. The intralobular stroma is collagenized, with variable levels of sclerosis (Fig. 7.1). Adjacent lobules appear as minute FAs with a prominent glandular component (Fig. 7.2). The acini are lined by monostratified epithelium, and myoepithelial cells are evident. Secretory activity may be present. Calcifications are uncommon. SLH can occur near FAs and phyllodes tumors (PTs) (1,5).

SLH is a benign alteration of the breast parenchyma and does not require any specific treatment. Surgical excision might be considered if the needle core biopsy (NCB) sampling from a breast mass yields only SLH to rule out peripheral/inadequate sampling of a PT. Clinical and radiological correlation is necessary.

FA is a tumor of the specialized mammary stroma, associated with a secondary proliferation of the glandular elements. The stroma shows either intra- or pericanalicular growth pattern (Fig. 7.3). FAs with a prominent intracanalicular pattern can mimic benign PTs, especially in NCB samples. Within any given FA, the stroma has homogeneous cellularity, and the epithelium-to-stroma ratio is similar throughout the tumor (Fig. 7.3). In contrast, PTs have an uneven distribution of glands and heterogeneous stromal cellularity, including foci indistinguishable from a FA. Adipocytic differentiation does not occur in FAs, but it may occur in PTs.

Multinucleated stromal giant cells can be found in FAs (23) and PTs (23), in some benign breast tumors (24), as well as in nonlesional mammary stroma. The nuclei may be pleomorphic and hyperchromatic, or have a florette-like pattern. The presence of multinucleated stromal cells does not appear to influence the clinical course of the lesion. FAs with focal multinucleated stromal giant cells should not be misclassified as PTs, even if the cells are focally p53- and Ki67-positive (24).

The usual (adult-type) FA is the most common type of FA (Fig. 7.4). Usual FAs in postmenopausal women tend to be hypocellular and hyalinized, and they may harbor coarse dystrophic stromal calcifications (Fig. 7.5). FAs from women younger than 20 years of age usually have more cellular stroma. Epithelial hyperplasia is usually absent; focal secretory changes may be present (Fig. 7.6). Mitotic figures are uncommon in usual FAs, but scattered mitoses may be observed in usual FAs in adolescent girls (6,7).

A tubular adenoma is a variant of pericanalicular FA with adenosis (Fig. 7.7). It consists of closely approximated round or oval glandular structures lined by monostratified glandular epithelium and myoepithelium.

An adult-type FA with cellular stroma but no cytologic atypia is often referred to as cellular FA, but this diagnosis has low interobserver reproducibility. The differential diagnosis between cellular FA and benign PT can be problematic, especially if only NCB material is available for review (Figs. 7.8 and 7.9); surgical excision of the lesion is warranted for its definitive classification. Usual FAs rarely pose a diagnostic challenge in NCB material. A hyalinized FA with conspicuous epithelium may occasionally raise the differential diagnosis of a sclerosed papilloma, but the pseudopapillary fronds lack true fibrovascular cores.

The underlying architecture of an infarcted FA can usually be identified in H&E-stained sections and can be highlighted with CK stains (Fig. 7.10).

Myxoid FAs are characterized by diffuse and homogenous myxoid change of the stroma (Fig. 7.11). Myxoid FAs can occur in patients with Carney syndrome (19), but most patients with a myxoid FA do not have a known systemic abnormality. Myxoid FAs have uniformly hypocellular stroma with evident vascularity, whereas myxoid change in a PT tends to be less homogeneous, and stromal cellularity is increased. The differential diagnosis of myxoid FA in NCB specimens includes mucinous carcinoma (Fig. 7.12) and PT with focal myxoid stroma.

Complex FAs are FAs with at least one of the following histologic features: sclerosing adenosis (SA), papillary apocrine hyperplasia, cysts (≥3 mm), and epithelial calcifications (Fig. 7.13) (9,25). In a series of 63 complex FAs (10), 57% had SA, 8% had apocrine metaplasia, and 1.6% had cysts. Calcifications in SA were found in 9.5% of the cases. Fibrocystic changes (FCCs) such as papillary epithelial hyperplasia and SA can mask the basic fibroadenomatous nature of a complex



FA, especially in the limited sample of a NCB, and raise the differential diagnosis of FCCs (Fig. 7.13), juvenile papillomatosis, and papilloma (Fig. 7.14). The differential diagnosis of complex FAs with extensive SA also includes invasive carcinoma (Fig. 7.15). Surgical excision of a complex FA is not necessary, unless the epithelium shows evidence of atypia or the diagnosis is uncertain.

A juvenile fibroadenoma is characterized microscopically by increased stromal cellularity and epithelial hyperplasia. Pericanalicular architecture is more common than intracanalicular architecture (6,7). The tumor border is well defined. The stroma tends to be uniformly cellular, with scant separation between intralobular/periglandular stroma and interlobular stroma (6). The glandular element tends to be uniformly distributed, but some juvenile FAs can show slight stromal expansion as well as gland-rich areas (6), creating an overall impression of intratumoral heterogeneity that might raise the differential diagnosis of PT, especially on review of NCB material. The uniform quality of the stromal proliferation and lack of nuclear stromal atypia are features that support the diagnosis of FA. Epithelial hyperplasia is common in juvenile FAs and can be conspicuous, raising the differential diagnosis of atypical ductal hyperplasia (ADH) or cribriform ductal carcinoma in situ (DCIS), which are exceedingly rare in this setting. Necrosis and/or calcifications are uncommon. A definitive diagnosis of juvenile FA cannot be rendered based on review of NCB material alone (Fig. 7.16). Evaluation of the entire lesion is necessary. The differential diagnosis usually includes benign PT and papilloma. The epithelial hyperplasia in a juvenile FA may raise the differential diagnosis of ADH if the presence of the underlying stromal lesion is not appreciated, especially in NCB material.

The epithelium and stroma of FAs show some positivity for ER and PR, but these findings have no specific diagnostic applications. The stromal cells of FAs are CD34-positive and show immunoreactivity for actin in cases with myofibroblastic proliferation. Moderate-to-strong nuclear staining for β-catenin has been documented in the stroma cells of FAs (28). A few investigators have reported significant differences in the Ki67 indices of FAs and benign PTs in NCB (29,30), but substantial overlap exists, limiting the practical utility of this marker in the evaluation of NCB specimens.

Recent molecular studies suggest that some PTs might develop from FAs (31,32,33), but this occurrence is exceedingly rare. Correlation of the clinical, radiologic, and pathologic findings of the lesion is of foremost importance. In the absence of atypical findings, surgical excision is not warranted for radiologic-pathologic concordant lesions yielding the diagnosis of FA at NCB.