Adenoid Cystic Carcinoma

Adenoid Cystic Carcinoma

Edi Brogi

Mammary adenoid cystic carcinoma (ACC) is morphologically similar to its counterpart in the salivary glands but has a more indolent behavior. Most ACCs of the breast and salivary glands carry a characteristic MYB-NFIB fusion gene, which results from a t(6:9)(q22-23;p23-24) translocation (1,2,3).



ACC is one of the least frequent forms of primary mammary carcinoma (4,5), with reported incidence ranging from less than one in a million (6) to about one in a thousand (7). The incidence rate of ACC was relatively constant between 1977 and 2006 (6).

Age and Ethnicity

ACC occurs in women of any age, but the mean and median ages of patients with ACC range from 50 years to 63 years in various studies (4,6,7,8,9). Between 70% and 96% of women with ACC in three separate series (6,10,11) were postmenopausal. Most (82%-87%) women with ACC are white (4,7,10). No association with familial syndromes has been described.


ACC can occur in men, including adolescents. ACC constituted 1% of 759 primary carcinomas of the male breast in one series (12).


The most frequent sites of ACC are the upper outer quadrant (6) and the retroareolar region (6,15,16).


ACC is usually unifocal, and only rarely consists of two (10,17) or more distinct foci (10). Bilateral ACC is uncommon.

Risk of Additional Malignancy

The frequency of subsequent carcinoma in either breast or of a solid nonmammary malignant tumor in patients with mammary ACC is not greater than that expected in the general population (6).


ACC presents mammographically as a well-defined lobulated mass or an ill-defined lesion (15,18,19); a mammographic spiculated mass can also be observed (14). Only 18% of ACCs in one series (10) were detected by mammography; in another study (19), 12.5% of ACCs were mammographically undetected. Calcifications are rarely associated with ACC.

The sonographic appearance of ACC is that of a heterogenous or hypoechoic mass (14,19). Eight of nine ACCs studied sonographically (19) appeared as irregularly shaped hypoechoic or heterogenous masses, oriented parallel to the skin, with no echogenic halo or posterior shadowing. Doppler sonography detected only minimal flow signal around and within the tumor. One tumor presented as an 8-mm hypoechoic nodule suggestive of an intramammary lymph node (20).

MRI is helpful for defining the extent of the ACC, especially in a dense breast (19). ACC tends to be irregular or lobulated, with rapid and heterogeneous enhancement after injection of gadolinium, and persistent or plateau kinetic (19). T2-weighted images show iso-intensity with the adjacent breast parenchyma or extensive high T2-weighted signal.


Most ACCs measure between 1 and 3 cm. In a recent series of 31 ACCs (21) the mean tumor size was 2.7 cm (range: 0.6-15 cm); the mean size of ACC with conventional histology was 2.9 cm (range: 0.7-12 cm), and that of ACC with basaloid morphology was 2.6 cm (range: 0.6-15 cm). In another series of six cases of solid ACC (22), the mean tumor size was 2 cm.

FIGURE 16.1 Adenoid Cystic Carcinoma, Cribriform Growth Pattern. A: A needle core biopsy specimen showing nests of predominantly cribriform adenoid cystic carcinoma. Cribriform growth with basement membrane spherules (arrows) and small glandular lumina (arrowheads) are shown in the inset. B: The surgically excised tumor has similar morphology. Note the diffuse infiltrative growth pattern and lack of stromal desmoplasia. A small duct is also present (arrow).

Microscopic Pathology

ACC is composed of glandular epithelium (adenoid component) and basaloid/myoepithelial cells, which produce abundant basement membrane material (Figs. 16.1 and 16.2). These components are heterogeneously distributed within any given tumor and produce different morphologic appearances.

FIGURE 16.2 Adenoid Cystic Carcinoma, Reticular Growth Pattern. A, B: The tumor in this needle core biopsy specimen has a reticular structure. Scattered small glandular spaces are evident (arrows) B. C: Only myoepithelial nuclei are immunoreactive for p63.

Cribriform Morphology

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.

Reticular Morphology

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).

Scirrhous Morphology

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

FIGURE 16.3 Adenoid Cystic Carcinoma, Coexisting Patterns. A: Three different growth patterns are present in this tumor. B: The cribriform pattern in this nest mimics cribriform ductal carcinoma in situ. Few small glandular lumina are evident (arrows), and there are numerous spherules of basophilic basement membrane material. C: A small nest has solid growth with scattered glandular lumina (arrows). Cribriform (right) and reticular (left) patterns are also represented. D: The prevalent growth pattern in this field is reticular. The basaloid solid nest in C is partially represented in the right upper corner.

Solid and Basaloid Morphology

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).

FIGURE 16.4 Adenoid Cystic Carcinoma, Solid and Basaloid Pattern. A: The carcinoma consists of solid nests composed of hyperchromatic cells. The stroma around the neoplastic nests is hypocellular, with a focally pale blue tinctorial quality. B: At higher magnification, the neoplastic cells show basaloid morphology. The pale blue staining of the stroma around the invasive nests is a feature commonly associated with high-grade adenoid cystic carcinoma and should not be mistaken for stromal mucin.

Metaplastic Alterations

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

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.

Adenoid Cystic Carcinoma In Situ

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.

FIGURE 16.5 Shrinkage Artifact Can Mimic Lymphovascular Invasion. Shrinkage artifact around nests of adenoid cystic carcinoma is common and can simulate lymphovascular invasion (arrows). On high-power examination (inset), the space around the nests of adenoid cystic carcinoma is devoid of endothelium.

Other Associated Carcinomas

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).


The glandular (luminal) and basaloid/myoepithelial components of ACC have different immunoprofiles.

FIGURE 16.6 Adenoid Cystic Carcinoma and Well-differentiated Ductal Carcinoma. A: This core biopsy sampled an invasive carcinoma with dual morphology. One half (right) consists of a well-differentiated invasive ductal carcinoma, and the other half (left) is adenoid cystic carcinoma. B: The two morphologic components merge in the center of the tumor. C: A close-up view of the adenoid cystic component with cylindromatous features.

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Nov 17, 2018 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Adenoid Cystic Carcinoma

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