Some areas have a predominantly glandular arrangement that closely simulates invasive or in situ cribriform carcinoma (Fig. 16.1). This form of ACC can be mistaken for cribriform carcinoma when the basaloid element and basement membrane material are sparse, especially in the limited material in a needle core biopsy (NCB) sample.

The carcinoma consists of trabeculae with a nearly linear arrangement, surrounded by expanded extracellular basement membrane matrix, often with myxoid to mucoid tinctorial quality. Scattered minute glands are visible (Fig. 16.2).

Occasionally, different patterns coexist in the same case (Fig. 16.3).

Abundant basement membrane material can produce a cylindromatous pattern that may be mistaken for dense stromal fibrosis in a scirrhous carcinoma.

Solid growth of the basaloid cells yields a pattern referred to as the “solid variant of ACC with basaloid features” (23) (Fig. 16.4). The neoplastic cells have scant cytoplasm, relatively large hyperchromatic nuclei, and frequent mitoses. Scattered small glands are usually appreciable, as well as focal minute eosinophilic deposits of basement membrane material.

Ro et al. (24) suggested that ACC be stratified into three grades on the basis of the proportion of solid growth within the lesion: grade I, no solid elements; grade II, less than 30% solid growth; and grade III, solid areas composing more than 30% of the tumor. The authors (24) found that tumors with
a larger proportion of solid component (grades II and III) tended to be larger and were more likely to have recurrences than those without a solid component (grade I). In their series, none of the five patients with a grade I ACC developed distant metastases, whereas two of six patients with grade II ACC had a recurrence distally; the only patient with a grade III ACC also developed distant metastases. The grading scheme proposed by Ro et al. (24) was not prognostically significant in a subsequent study (16).

Some ACCs have focal sebaceous metaplasia or squamous differentiation. Adenomyoepitheliomatous (25) and syringomatous areas can be present. Adipocytic differentiation and myofibroblastic hyperplasia can also occur in the stroma of ACC. A high-grade basaloid ACC showed morphologic transition into a metaplastic spindle cell and glandular adenocarcinoma with melanomatous differentiation (26). Another basaloid ACC merged with a “small cell carcinoma” (27). Foschini et al. (22) have suggested that conventional and solid ACCs have a good prognosis, but the latter is more likely to involve lymph nodes (LNs) and recur locally, whereas ACC with areas of overtly malignant transformation has aggressive behavior. This grading scheme needs further validation.

Perineural and lymphovascular invasion is uncommon in mammary ACC with conventional morphology, and it is very rarely detected in NCB material. Shrinkage artifact is common, especially in fibrotic portions of ACC, and can mimic lymphovascular invasion (LVI) (Fig. 16.5). Three of six solid ACCs in one series (22) had LVI, including two tumors that also showed perineural invasion.

It is difficult to distinguish invasive from in situ ACC. ACC in situ lacks the periductal cuff of cellular myxoid stroma that typically surrounds the nests of invasive ACC, but this finding can be very subtle. Calponin decorates the native myoepithelium of the ducts and acini harboring in situ ACC, but it is absent within and around the nests of invasive ACC. Lobules and ducts adjacent to invasive ACC can display adenoid cystic traits, with small cylindromatous areas, which represent in situ carcinoma.

Patients with ACC can also develop other types of breast carcinoma in the same or opposite breast coincidentally or asynchronously. Merging of ACC with well-differentiated ER-positive invasive ductal carcinoma has been observed (Fig. 16.6).