FA is the most common neoplasm of the breast in the first two decades of life, and the overwhelming majority of cases are diagnosed in the interval from early puberty into late adolescence and beyond. There is a predilection for these tumors to occur in young African and African American females in whom the tumor commonly presents as a rapidly enlarging mass, which may be multifocal and even bilateral (45). Both FA and PT are seemingly more common in several tumor predisposition syndromes including Li-Fraumeni, Maffucci, and Beckwith-Wiedemann syndromes and Carney complex (40,46).

In most cases, there are relatively few difficulties in the histopathologic recognition of an FA in a young patient, but there is a thicket of largely semantic issues in the distinction, if any, among the juvenile, cellular, and giant FA from the FA, ordinary, and benign PT since the clinical and pathologic criteria are seemingly not burdened by a consensus or established criteria (47,48). Such qualifications as “increased stromal cellularity,” “massive,” and “juvenile” are both vague and subjective in their application to FAs in young individuals between the ages of 12 and 20 years (49).

Most FAs are well circumscribed from the surrounding breast parenchyma with a seeming cleft between the tumor and adjacent soft tissues. A true capsule is not present in most cases. The external surfaces often have a bosselated appearance that corresponds to the bulging multinodular or lobulated cut surface (Figure 20-2). A glistening, mucoid yellowish-tan to whitish surface characterizes most tumors although extensive hemorrhage may indicate the presence of infarction (50). The majority of tumors measure 2 to 5 cm in greatest dimension although some have applied the designation of “giant” to those tumors measuring 5 cm or greater (up to 20 cm). Some of the larger FAs can ulcerate the overlying skin and present as a fungating mass (49). Two basic histologic patterns are recognized in FAs: an intracanalicular pattern with a prominent stroma compressing strands of epithelium in various configurations including the phyllodes or leaflike pattern of a benign PT (Figure 20-3) and the periductal or pericanalicular pattern whose stroma separates individual terminal ductal lobular units (Figure 20-4). One or the other of these patterns is exclusive in any one
FA, or alternatively, there are FAs with a mixed pattern of phyllodes-like profiles and intracanalicular and/or pericanalicular patterns. The cellularity of the stroma is the usual source of concern in FAs in young individuals. In most cases, the stroma has a bland fibrous appearance with or without edema or a predominant myxoid stroma (Figure 20-5). The stroma adjacent to the epithelium is typically more cellular and less fibrotic than is the more remote, fibrous stroma. The occasional mitotic figure can be found in the stroma adjacent to the epithelium. When the stroma is more uniformly cellular, attention is directed to the presence or absence of mitotic figures since the latter separates the so-called cellular or juvenile FA from the borderline or low-grade PT (Figure 20-6A, B). Mitotic activity generally should not exceed 2 mitoses per 10 high-power (400×) fields (HPF) nor the leaflike phyllodes epithelial pattern, but in a needle core biopsy, the latter epithelial configuration may be difficult to appreciate (51). Mitotic figures become a concern when they are found in the stroma without difficulty, which usually translates into 10 mitoses in 10 HPF. An infiltrating stromal border at the periphery should be viewed with concern. Pleomorphic stromal giant cells are found infrequently, similar in some respects, to those stromal cells in nasal polyps or lamina propria of the bladder (52).

While there is considerable focus on the stroma of FAs, the epithelium may be quite hyperplastic with a degree of complexity and papillary profiles, which are especially notable in those tumors from adolescent or young adult women. Fibrocystic changes with cysts, apocrine metaplasia, and sclerosing adenosis are seen in some FAs in young individuals though they are more commonly observed in FAs from older women (Figure 20-7A, B). As a final note, there are examples of intraductal papillary lesions with FA-like features in young females (Figure 20-8) (53,54). Some have questioned the relationship in younger individuals between the intraductal papilloma and FA.

Immunohistochemistry has a very limited role in the diagnosis of FA. Those cases with an unsettling degree of cellularity and mitotic activity may benefit with Ki-67 and p53 staining (55). The stroma cells in FAs are rich in CD34+ fibroblasts, factor XIIIa+ dendrocytes, and smooth muscle actin + myofibroblasts (56). It has been noted that CD10+ stromal cells are uncommon in cellular FAs (57).

A recurrence rate of 10% to 15% is reported after resection of an FA in young patients; however, the “recurrence” may represent a new lesion. There are rare examples, principally in adults, of malignant progression of a recurrent FA to a malignant PT (58).

Benign PT is basically defined as a fibroepithelial neoplasm whose architecture is defined by the leaflike epithelial-lined structures and a stroma with a variable degree of cellularity (Figure 20-9). The periductal stroma is usually more cellular than in the stroma of the FA. An isolated mitotic figure in the mesenchymal cells adjacent to the epithelial component is permissible, which is also the case in an FA.

Adenomas constitute at least two general categories of breast lesions: one a monotypic fibroepithelial neoplasm arising from the terminal duct lobular unit in the absence of an intralobular stroma. The tubular and lactational adenomas are examples of the latter category (59,60). Tubular or pure adenoma is uncommon compared to FA, but is seen in the same young age group and is undistinguishable clinically from the FA (Figure 20-10). The distinctive histologic features are those of a multinodular tumor, which is composed of small uniform tubuloglandular structures with a variably prominent stroma in the background (Figure 20-11). In fact, some fibroepithelial neoplasms have a mixed pattern of tubular adenoma and FA. Lactational or secretory changes are the

features of the so-called lactational adenoma (Figure 20-12). Similar cellular changes are seen in the FA during pregnancy or in the postpartum period. Both the FA and tubular adenoma may uncommonly undergo partial or total infarction spontaneously in association with pregnancy, lactation, or following a fine needle biopsy (50,61).

The second category of adenomas are those tumors that are analogs, if not homologs, of sweat gland tumors of the skin whose occurrence is not all that surprising when one considers the common morphogenesis of the breast and skin (62). Syringomatous adenoma of the nipple, formerly nipple duct adenoma, is a rare rumor regardless of age at clinical presentation, but has been reported in later childhood (63). The microscopic appearance of elongated and tubular glands within a fibrous stroma with infiltrative features in the subareolar location can be mistaken for tubular-ductal carcinoma. At least in the setting of an older child or adolescent, the concern for malignancy should be quite low. Other sweat gland analog tumors of the breast constitute a spectrum from the typical syringocystadenoma papilliferum, eccrine spiradenoma, clear cell hidradenoma, and mixed tumor (pleomorphic adenoma).