FISH is positive for ETV6 translocation.
Mammary Analogue Secretory Carcinoma of Salivary Gland, Stage pT1, N0, Mx.
In 2010, SkaŽlovaŽ et al described for the first time, the same balanced chromosomal translocation, t(12;15)(p13;q25), found in congenital fibrosarcoma and in secretory carcinoma of the breast, in a novel salivary gland tumor. This translocation results in the fusion of the transcriptional regulator, ETV6 gene (located in Chr12p13), with a membrane-receptor kinase, NTRK3 gene (located in Chr15q25) and leads to a constitutively active chimeric tyrosine kinase. This new entity was called mammary analogue secretory carcinoma (MASC)(1). The same translocation is also present in others tumor such as congenital (infantile) fibrosarcoma, cellular variant of congenital mesoblastic nephroma, some cases of thyroid papillary carcinoma, and acute myeloid leukemia[3-5].
The case described here is a MASC of the parotid gland in a child. MASC is more frequent in adults, but pediatric patients have been reported. Similar to the case described here the majority of the patients with MASC has clinical history of a painless, slow-growing mass, but cases with pain and facial paralysis have been described. The most frequent location of the tumor is the parotid (70% of cases) and the submandibular gland (7% of cases). Macroscopically the tumor is in general well-circumscribed but non-encapsulated, with a variable cystic component.
On microscopy, the characteristic morphology of MASC is similar to the case described here. This tumor has variable architecture, and solid, cribriform, tubular, microcystic and papillocystic patterns can be present in the same tumor[1,5]. Tumor cells of MASC are morphologically uniform; they have small to medium size, oval to round shaped nuclei, with pale chromatin and small nucleoli. The cytoplasm is pink and bubbly. The microcystic and tubular spaces are characteristically filled with eosinophilic colloid-like or frothy secretions. This tumor has a low mitotic rate, no necrosis, rare perineural invasion and occasional lymphovascular invasion.
On immunohistochemistry, MASC characteristically shows strong and diffuse expression of mammaglobin, GATA3 and S100 protein. Tumor cells of MASC also express pancytokeratin, CK7, epithelial membrane antigen, vimentin, and are typically negative for high-molecular weight keratin and basal cell markers, such as SMA, CK5/6, and p63[6-8]. A recurrent balanced chromosomal translocation t(12,15)(p13;q25), is the most specific diagnostic test. It can be detected by FISH using a break-apart probe for the ETV6 gene1 or by reverse transcription-polymerase chain reaction using ETV6 and NTRK3 gene-specific primers. In the case described here, the diagnosis was confirmed by IHC and by ETV6 FISH break-apart probe.
The most important differential diagnosis for MASC is acinic cell carcinoma (AcCC), but in general the tumor cells of AcCC have basophilic cytoplasm with zymogen granules and more cytological diversity than MASC. Zymogen-poor AcCC can be difficult to differentiate from MASC on H&E, but on IHC, AcCC will be negative for S100 protein and mammaglobin. Mucoepidermoid carcinoma, the most frequent salivary gland tumor in children and adolescents, is also a differential diagnosis of MASC in pediatric cases. In a surgical specimen the distinction between MASC and MEC based on H&E is not that difficult because they are morphologically distinct tumors, but on cytological samples, the differentiation can be more challenging. In cytological specimens IHC and molecular studies can help to differentiate MASC and MEC. In the cytological specimen of the case described here, MEC was excluded by negative FISH for MAML2 translocation.
Although MASC is currently regarded as a low-grade malignancy with favorable prognosis, it has a potential for an aggressive course. Cases with local recurrence, high-grade transformation, as well as regional lymph node and distant metastases have been reported. However, as with any newly described entity, the data on MASC management, outcomes and prognosis need studies with long-term follow up. In a recent systematic review after 7 years of the tumor description, Khalele concluded that close follow-up is recommended, " especially when necrosis, increased mitotic activity, and other classic caveats are conspicuous." Due to the negative surgical margins, and the absence of perineural and vascular invasion, the patient described here received no postoperative additional therapy. At six months of follow-up he has no evidence of recurrence.
Contributed by Claudia Maria Salgado, MD, PhD, Rita Alaggio, MD and Sarangarajan Ranganathan, MD