Background: Mammary analogue secretory carcinoma (MASC) is defined as a rare lump of salivary gland that most generally affects the parotid gland, followed by the submandibular gland and also other minor salivary glands. Since 2017, MASC has been included in the World Health Organization's ( WHO) Bracket of Head and Neck Tumors. It's a veritably rare subtype of malignancy of salivary gland. Here we report a case of a 13 yr old female who presented to ENT OPD with right side parotid swelling, managed surgically and diagnosed as secretory carcinoma parotid on HPE.
Mammary analogue secretory carcinoma (MASC) is a novel entity when it comes to the opinion of salivary gland malignancies [1].Found almost equal in both genders. MASC is an indolent salivary gland malignancy, in which maximum number of cases presents as a slow- growing, painless mass, with a duration ranging from 2 months to several years. Certain cases have been reported having pain and facial palsy[2].
It's quite difficult to make a definitive preop diagnosis due to the uncertain pathophysiology and a lack of distinct clinical and imaging characteristic features. It’s a lipid-rich excrescence containing large lipid droplets which are enclosed by adipophilin or adipocyte differentiation- related protein, suggesting that MASC can have lactation- like properties [3]. Cytologically the features are analogous to the histological findings which includes moderate cellular sheets of S100-positive cells arranged in papillary, tubular, cystic and solid growth configurations.It’s several histological features are shared with those of other salivary gland malignancies including acinic cell carcinoma, adenocarcinoma not otherwise defined, and low- grade mucoepidermoid carcinoma.Hence accurate and comprehensive immunohistochemistry( IHC) will help in distinguishing MASC from other primary salivary gland tumors[4]. According to Khurram et al. the IHC technique helps to properly detect MASC tumor and also differ them from acinic cell carcinoma , which nearly act as MASC.It's immunoreactive for S100 as well as mammaglobin( 70% time) and these markers are infrequently positive in case of acinic cell carcinoma[5].On the contrary, DOG- 1 is generally positive in acinic cell carcinoma whereas it's generally negative in MASC.
A 13yr old female presented to ENT OPD with chief complaint of right side pre auricular swelling from last 3yrs. swelling was progressively increasing in size and was associated with on and off pain. There was history of loss of appetite but no history of fever, trauma, any discharge from swelling. No history of ear discharge, facial asymmetry was present. On palpation swelling around 3*3cm was palpable in right parotid region, tender, firm in consistency, overlying skin was normal, no discharge or ulceration noted. Facial nerve was normal on examination
Further workup was done by sending the tissue blocks for IHC (IMAGE 5) which was suggestive of-
IHC MARKER(S) RESULT
S100 Immunoreactive, score 4+ in lesional cells
P63 Non-immunoreactive, score 0 in lesional cells
DOG-1 Non-immunoreactive, score 0 in lesional cells
P40 Non-immunoreactive, score 0 in lesional cells
Secretory Carcinoma is a malignant tumor of salivary gland. It is a rare tumor and is associated with the translocation t( 12; 15)( p13; q25), which results in the fusion gene ETV6- NTRK3. It is extensively known fact that this tumor is related to certain specific immunohistochemical features including positive Mammaglobin, S- 100, and Vimentin stains [6]. In general, secretory carcinoma have a indolent course. Risk of local recurrence and lymph node metastasis is around 15- 20%. The risk of distant metastasis varies around 5% and cases with high- grade transformation have a poor prognosis.
The gold standard to establish a definite diagnosis is flourescence in situ hybridization( FISH) test for the ETV6- NTRK3 fusion which is present in nearly 99% of MASC tumors while NTRK gene fusion are rare in other cancer subtypes(less than 1%)[7]. The biological significance of this translocation is the presence of fusion oncogene which promotes cell proliferation and their survival. The use of cytogenetics to diagnose MASC may be minimized or avoided, If IHC can facilitate the diagnosis of MASC.
Its treatment depends on the stage of the tumor and on the histological and molecular characteristics of the tumor. The treatment of choice for low- grade Secretory Carcinoma is complete surgical resection. But many cases can show recurrence [8]. Locoregional radiation therapy may be considered for large tumors or in cases where it have shown perineural invasion or positive margins. The need for lymph node dissection depends on each case. In cases of SC with high- grade transformation, total resection of the affected gland and adjuvant radiotherapy is recommended [9]. In addition, this type of malignancy shows a great propensity to metastasize to the cervical lymph nodes, which would suggest the need for lymph node dissection for optimal management of these cases
Typical presentation of secretory carcinoma is 40- 50yrs age group. Equal distribution of sex or a slight male predominance (1.5:1), depending on the series. Most frequent site is Parotid gland. They present as slow growing painless mass .Erythema and ulceration of the overlying skin are not common. A firm rubbery mass on macroscopic characteristics. The cut surface is gray -white and may present with small cystic spaces with secretions which are yellowish in color.
Microscopic characteristics shows Eosinophilic cell proliferation forming lobules separated by thin septa and showing microcystic, tubular, papillary, or solid patterns . Cells having oval nuclei with loose chromatin and a single prominent central nucleolus[10]
In Immunohistochemistry S- 100 protein, mammaglobin, and vimentin are seen to be positive, DOG- 1, p63, and calponin are negative. Characteristic t( 12; 15)( p13; q25) translocation with ETV6- NTRK3 gene Fusion is seen in molecular pathology.
Secretory carcinoma is a rare and quite recently defined entity which arise most generally in the parotid gland. It is characterized as a low- grade malignancy. Maximum number of cases are diagnosed at an early stage, without any regional or distant metastasis and the prognosis is fairly good. MASC should be included in the differentials of oncocytic tumors of salivary glands. IHC is helpful in ruling out the histopathological differentials such as papillary variant of ACC and oncocytic variant of MEC.
1. Skálová A., Vanecek T., Sima R., et al. Mammary analogue secretory carcinoma of salivary glands, containing the etv6-ntrk3 fusion gene: a hitherto undescribed salivary gland tumor entity. The American Journal of Surgical Pathology. 2010;34(5):599–608. doi: 10.1097/pas.0b013e3181d9efcc.
2. Bishop J. A., Taube J. M., Su A., et al. Secretory carcinoma of the skin harboring ETV6 gene fusions. The American Journal of Surgical Pathology. 2017;41(1):62–66. doi: 10.1097/PAS.0000000000000734.
3. Stevens T. M., Kovalovsky A. O., Velosa C., et al. Mammary analog secretory carcinoma, low-grade salivary duct carcinoma and mimickers: a comparative study. Modern Pathology. 2015;28(8):1084–1100. doi: 10.1038/modpathol.2015.64.
4. Dettloff J., Seethala R. R., Stevens T. M., et al. Mammary analog secretory carcinoma (MASC) involving the thyroid gland: a report of the first 3 cases. Head & Neck Pathology. 2017;11(2):124–130. doi: 10.1007/s12105-016-0741-6.
5. Baneckova M., Agaimy A., Andreasen S., et al. Mammary analog secretory carcinoma of the nasal cavity. The American Journal of Surgical Pathology. 2018;42(6):735–743. doi: 10.1097/PAS.0000000000001048.
6. Hyrcza M. D., Andreasen S., Melchior L. C., Tucker T., Heegaard S., White V. A. Primary secretory carcinoma of the lacrimal gland: report of a new entity. American Journal of Ophthalmology. 2018;193:178–183. doi: 10.1016/j.ajo.2018.06.019.
7. Seethala R. R., Stenman G. Update from the 4th edition of the world health organization classification of head and neck tumours: tumors of the salivary gland. Head & Neck Pathology. 2017;11(1):55–67. doi: 10.1007/s12105-017-0795-0.
8. Montalvo N., Posso V., Redrobán L. Secretory carcinoma in a 79- year-old woman: an exceptionally rare type of breast carcinoma. Rare Tumors. 2017;8(4):188–190. doi: 10.4081/rt.2016.6650.
9. Majewska H., Skálová A., Stodulski D., et al. Mammary analogue secretory carcinoma of salivary glands: a new entity associated with ETV6 gene rearrangement. Virchows Archiv. 2015;466(3):245–254. doi: 10.1007/s00428-014-1701-8.
10. Chi H. T., Ly B. T., Kano Y., Tojo A., Watanabe T., Sato Y. ETV6–NTRK3 as a therapeutic target of small molecule inhibitor PKC412. Biochemical and Biophysical Research Communications. 2012;429(1-2):87–92. doi: 10.1016/j.bbrc.2012.10.087.