ACC of the breast is a rare histopathologic type of slow progression and represents only 0.1% of breast cancer cases. In sharp contrast to the extra-mammary counterpart, ACC of the breast has an excellent prognosis, as the incidence of lymph node metastasis is lower and distant metastases uncommon .
Even rarer are the cases of ACC intermingled with other types of breast cancer within a single lesion. Our case report is one of the few in the literature describing a patient with an ACC of the breast mixed with the ductal histological type. Furthermore, we present a review of the existing relevant cases of mixed breast cancers with an ACC component.
In the present study, the case of a 67-year-old woman with a non-palpable 1.7 cm right breast lesion is described. The radiologic evaluation was equivocal, but a mixed cancer with ACC and ductal components was found on biopsy. The patient agreed to proceed with a mastectomy (the patient's choice) and a sentinel node biopsy, which was negative. The hormone receptors were negative, and therefore there was no role for endocrine treatment.
Few cases of ACC have been described in the literature to date. Cabibi et al. first reported an ACC intermingled with a small-cell carcinoma in a 40-year old woman. Mates et al. later published a case report of a patient with bilateral breast cancer where the right side involved an ACC intermingled with a subtype of a ductal carcinoma (papillary). Another patient with ACC mixed with an "ordinary" invasive ductal and intra-ductal carcinoma was reported by Righi et al.. Noske et al. presented an ACC with spindle-cell carcinoma and melanoma (Table 1).
The diagnosis may be challenging in mixed ACC cases, as some clinical and radiological features can be misleading. Furthermore, ACC of the breast is known for occasional demonstration of "benign" clinical or radiological characteristics . Malignant lesions with ACC components can be well circumscribed on palpation, but careful radiologic evaluation and histopathology should set the diagnosis in experienced hands [3–6].
There is clearly no large experience with the treatment of mixed ACC of the breast. Surgical excision remains the cornerstone of treatment in operable cases, with two mastectomies and two cases of BCT reported in the literature [3–6]. Clear margins remain the desirable goal. A sentinel node biopsy was done in one case , and full axillary clearance was performed in three cases [3, 4]. Radiotherapy has been applied after BCT [3, 6] and after mastectomy with one affected node . Chemotherapy was administered in three cases, while typically the ERs and PRs are negative. Chemotherapy is not routinely used to treat ACC of the breast; however, in mixed cases, it is likely that to be used on the basis of hormone receptor negativity and the more aggressive potential of the non-ACC component. The four previous reports of mixed ACC breast cancers and the present study are summarized in Table 1.
Regarding the histogenesis of these rare dual tumors, the hypothesis of de-differentiation prevails at the moment. Righi et al. found that tumor morphology and immunohistochemical and clonality tests point toward the hypothesis that the two components are part of the same tumor and that part of the tumor underwent a progressive transformation, leading to the development of a more aggressive component. Cabibi et al. surmised that the two different histological and immunohistochemical patterns might represent an example of de-differentiation along neuroendocrine phenotype lines occurring in a multi-potential neoplastic stem line already committed toward a myoepithelial phenotype. This de-differentiation can progress as far as a spindle-cell carcinoma or melanoma . The de-differentiation of ACC to more aggressive types in salivary gland tumors was first reported by Cheuk et al. in 1999. Nagao et al. and Ide et al. also reported similar cases for ACC located outside the breast.
Much of the clinical significance of discovering mixed ACC breast tumors lies in their prognostic information. The existence of a de-differentiated component of higher malignancy grade worsens the prognosis [7, 8]. However, the exact magnitude of this is difficult to estimate because of the limited number of cases described in the literature and the wide diversity of the de-differentiation patterns. Another implication of mixed ACC breast cancers is the type of appropriate adjuvant treatment, as a chemotherapeutic agent or radiotherapy may not necessarily be effective for both components.