Combined Use of Mammography and FNA Eliminates Pitfalls in the Management of Metaplastic Breast Carcinoma

Discussion

As shown by a recent multicenter case–control study (8), MBC is characterized by larger size, more rapid growth, less frequent lymphovascular invasion, significantly lower positivity rates for ER, PR and HER2, and more frequent triple-negative subtype, in contrast to invasive ductal carcinomas (IDC). Conversely, epidermal growth factor receptor (EGFR), p53, and cytokeratin 5/6 (CK5/6) are found at higher rates in patients with MBC. Furthermore, MBC usually presents with a lower incidence of lymph node involvement compared with IDC, but it displays a higher rate of distant metastasis, as well as higher tumor grade (9). All these clinicopathological features, along with the unfavorable prognosis related to this specific subtype of breast cancer, render timely diagnosis imperative regarding its management (3).

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Figure 1.

Digital mammography showing a high-density region with indistinct margins in the right breast.

Due to its heterogeneity as a tumor, there are no known specific radiological features of MBC (10). All palpable masses should, therefore, be investigated with both mammography and ultrasound in order to increase the diagnostic accuracy, but most agree that definitive diagnosis is achieved by surgical excision (11).

Recent data from the Breast Cancer Surveillance Consortium have shown that the sensitivity and the specificity of digital mammography in breast cancer diagnosis lie at the level of 87.8% (95% confidence interval(CI)=87.3-88.4%) and 90.5% (95% CI=90.4-90.6%), respectively (12). On the other hand, FNA is a method highly dependent on the skill and training of the aspirator and the interpreter. Thus, reported sensitivity ranges from 43.8% to 95%, with specificity from 89.8% to 100% (13). Given the low possibility of occult disease in negative mammographies, it is essential that these two techniques be combined for all palpable breast lesions in order to minimize the risk of misdiagnosis.

Although many authors consider FNA a challenging and problematic procedure in diagnosing this specific subtype of breast cancer (3-5), its preoperative role should not be underestimated, as it seems to be a valuable diagnostic tool. According to the literature, cytological features of MBC are as follows: highly cellular smears; malignant cells in a myxoid background, which can be fibrillar or metachromatic; elongated, atypical and pleomorphic mesenchymal cells; multinucleated forms of malignant or benign nature; single or clustered carcinoma cells; and the presence of abnormal mitotic figures (14). In our case, only some of these features were revealed, therefore cytology was unable to establish an accurate diagnosis of MBC since both mesenchymal and squamous elements were not shown (14). However, FNA smear pointed out the mass as being positive for malignancy and, in combination with mammography findings, the diagnosis of MBC was highly suspected preoperatively. Consequently, the necessity for its surgical resection was established.

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Figure 2.

a: Fine-needle aspiration cytology leading to high suspicion of metaplastic breast carcinoma (MBC). b: Hematoxylin and eosin-stained section at ×40 magnification showing characteristics of MBC.

By definition, the term ‘metaplastic’ refers to differentiation of neoplastic epithelium into a non-epithelial phenotype comprising squamous cells and mesenchymal elements (1). Given the fact that MBC refers to a heterogenous group of neoplasms, as aforementioned, the cytological features are variable, and, therefore the cytological diagnosis is rendered fairly challenging. Nogueira et al. reported that some cytological findings, namely a liquid aspirate, a proteinaceous or chondromyxoid background, multinucleated giant cells from a poorly differentiated tumor and high nuclear pleomorphism, may suggest the diagnosis of MBC (15). Although these findings are relatively common in MBC cases, they are not specific and, for this reason, both carcinomatous and metaplastic components are required to be demonstrated in FNA smears in order for the diagnosis to be definite. Stanley et al. had earlier shown that FNA revealed both ductal carcinoma and metaplastic component only in four out of seven cases (57%) and, thus, accurate diagnosis was not feasible in almost half of the cases (16).

Another study showed that smears containing solely malignant glandular elements on cytological examination ultimately revealed malignant squamous components on surgical resection specimens, thereby leading to the conclusion that the combination of cytological and histological examination should always be considered as it could eliminate pitfalls in diagnostic procedure (17). Finally, Kato et al. suggested that FNA cytology may permit MBC diagnosis but in order to increase its effectiveness, the tumor should be aspirated from different positions so that several cell components are adequately sampled (6).

Since MBC usually presents as stage III and IV disease with a higher incidence than IDC (2, 9), improving timely diagnosis and initiating the appropriate treatment is considered crucial for increasing life expectancy. As many studies have shown, the response of MBC to both neoadjuvant and adjuvant chemotherapy has been poor over the years (2, 5, 9, 18). In that context, most agree that surgery should be the first therapeutic approach when facing this type of cancer (2, 18). However, in cases of HER2-positive and triple-negative breast tumors, neoadjuvant chemotherapy may be considered if the appropriate criteria are met (19). High preoperative suspicion of MBC through combination of mammography and FNA cytology could prevent the administration of neoadjuvant chemotherapy in cases of ambiguous indications.