FINAL DIAGNOSIS: ADENOID CYSTIC CARCINOMA, GRADE II OF III.
Adenoid cystic carcinoma of the breast (ACCB) is a rare tumor, accounting for <0.2% of all breast carcinomas (1). The lesion is more often located in the subareolar portion of the breast but is not usually associated with nipple discharge. The patient with ACCB often presents with a somewhat tender mass that has become apparent over weeks to months. Age at presentation has ranged from 25 to 80 years, with a median age in the late 50s. A family history of breast carcinoma is usually not present. Several cases of ACC in the male breast have been reported (2).
The gross and histologic appearance of ACCB is identical to that seen in the salivary glands. The lesions of ACCB generally range from 1 to 5 cm, with a grossly circumscribed appearance and grey-yellow cut surface. Histologically, the lesion is characterized by an invasive proliferation of circumscribed nests, islands, and cord-like clusters of tumor cells forming cribriform, tubular, and solid arrangements. The tumor islands are composed of two different cell types: a basaloid cell population which predominates and a smaller population of cells having a bright eosinophilic cytoplasm. The cribriform spaces or lumens are often filled with basement membrane material, mucoid secretions, or an eosinophilic band deposited on the lumenal surface of the cells. While it is likely that the basaloid cells have a myoepithelial derivation, ultrastructural evidence for this is lacking (3). The smaller, eosinophilic population of cells shows prominent desmosomes and luminal microvillous projections, suggesting that these are adenosquamous cells (4). Immunohisto-chemical studies reveal a variably positive reaction for actin and S-100, while the eosinophilic population shows a positive reaction for cytokeratin. Estrogen and progesterone receptor positivity is usually negative.
The differential diagnosis of ACCB includes intraductal carcinoma, invasive cribriform carcinoma and mucinous carcinoma, as well as the benign entity of collagenous spherulosis of the breast (CSB) and the much rarer pleomorphic adenoma (5,6). CSB is usually discovered as an incidental finding associated with benign proliferative processes such a sclerosing adenosis and radial scars. Histologically, CSB is characterized by the presence of acellular eosinophilic and fibrillar spherules comprised of basement membrane material, primarily type IV collagen, produced by flattened myoepithelial cells immediately surrounding the spherules. The lesion of CSB is confined to two or three ducts and usually does not present as a palpable mass identifiable on mammogram. ACCB, on the other hand, is invasive and often forms a palpable nodule. The easiest way to make a distincton is by strict adherence to the requirement of the presence of both the basaloid and eosinophilic cell types for a diagnosis of ACCB; the other lesions within the differential do not have these two cell types (1)
While the histologic appearance of ACCB is often characteristic, the cytologic diagnosis of this lesion in a fine needle aspirate biopsy (FNA) of the breast can be quite challenging. Several criteria for diagnosis ACCB have been proposed (5): (1) FNA smears should be highly cellular, comprised of small, uniform, monotonous cells having very little cytoplasm, smooth chromatin and few, if any, nucleoli. (2) Naked nuclei of these small cells should be present in the background; and there should be very little admixture of typical benign duct cell groups. (3) Extracellular metachromatic spheres are required for the diagnosis. (4) Overall, traditional cytologic features of malignancy should not be present. The spheres of acellular, homogenous material is generally translucent with a Papanicolaou stain and pink or metachromatic on Diff-QuikTM stain. The differential diagnosis of ACCB on cytology includes those entities discussed above. Intraductal and invasive cribriform carcinoma should have a greater degree of nuclear atypia than is seen with ACCB. From the standpoint of patient management, however, the most significant differential diagnosis is CSB (no further action with CSB versus segmental mastectomy with ACCB). Cytologically, CSB will show monolayered clusters of cells, with little branching architecture; and the cells will have a low nuclear/cytoplasmic ratio . In contrast, ACCB will be comprised of syncytial, multilayered, and branching clusters of cells having a high nuclear/cytoplasmic ratio. Additionally, the acellular spherules of CSB will often be surrounded only by a single layer of nuclei, whereas the spherules of ACCB are typically surrounded by several cell layers (7,8).
Compared with the aggressive, malignant nature of adenoid cystic carcinomas of the salivary glands, ACCB has a very good prognosis. The relatively low-grade nature of ACCB remains unexplained. ACCB rarely metastasizes to the axillary nodes, but it can recur. Distant metastases do occur, with lung by far the most common site; and long-term follow up is necessary. Grading of ACCB is the same as that for salivary gland lesions. Grade I tumors have glandular and cystic areas lacking a solid component. Grade II tumors have solid areas comprising less than 30% of the tumor, while Grade III tumors have a solid component comprising greater than 30% of the total tumor.
Contributed by : Karen K. Deal, MD, PhD, Anisa Kanbour, MD, and Manju E. Nath, MD