Abstract
This population-based study uses data from the Surveillance, Epidemiology, and End Results database to analyze the typical clinical characteristics of mammary analog secretory carcinoma.
Mammary analog secretory carcinoma (MASC) is a rare salivary gland tumor that was initially described in 2010.1 These tumors are characterized by a chromosomal translocation that fuses the ETS variant 6 gene (ETV6) (OMIM 600618) to the neurotrophic tyrosine kinase receptor type 3 (NTRK3) gene (OMIM 191361) and have histologic features similar to those of breast secretory carcinoma, a low-grade ductal breast carcinoma. Thus far, fewer than 300 cases have been reported in the literature. Studies have primarily been case reports and case series that focused on histopathologic and epidemiologic data. We aimed to use a population-based study of MASC cases to elucidate characteristic clinical features of this malignant tumor.
Methods
We used the Surveillance, Epidemiology, and End Results (SEER) database (SEER-18 registry, November 2017) to identify cases of MASC diagnosed from January 1, 2010, to December 31, 2015. Patients with MASC were identified using the International Classification of Diseases for Oncology, Third Edition (ICD-O-3) code 8502 and primary site of salivary gland. Data collected included sex, race, age, primary site, primary surgery, lymph node surgery, lymph node involvement, stage, cause-specific survival, grade, and duration of follow-up. De-identified data were obtained using SEER*Stat, version 8.3.5 (http://www.seerstat.gov); therefore, institutional review board approval was not required according to the University of California, Irvine, Office of Research.
Results
Fifty-five patients with MASC (mean [SD] age, 48.6 [17.9] years; age range, 12-82 years; 31 [56.4%] male; 45 [81.8%] white) were identified in the SEER database. Patient demographic information, tumor characteristics, and treatment are summarized in the Table. Mean (SD) follow-up was 20.3 (14.9) months. Most patients had disease staged as American Joint Committee on Cancer stage I (25 [45.5%]) or II (18 [32.7%]) at diagnosis. Tumors were primarily located within the parotid gland (42 [76.4%]), and the most common primary operation performed was subtotal parotidectomy or subtotal removal of major salivary gland (25 [45.5%]). Thirty-four patients (61.8%) received a neck dissection for nodal management; however, nodal disease was found in only 3 patients (5.5%). No patients had distant metastatic disease. In patients for whom data were available, tumors were histologic grade I or II. All patients were alive at the conclusion of the study period, and length of survival correlated with year of diagnosis.
Table. Patient Demographics and Tumor Characteristics.
| Variable | Finding (N = 55)a |
|---|---|
| Sex | |
| Male | 31 (56.4) |
| Female | 24 (43.6) |
| Race | |
| White | 45 (81.8) |
| Black | 3 (5.5) |
| Otherb | 5 (9.1) |
| Unknown | 2 (3.6) |
| Age, mean (SD), y | 48.6 (17.9) |
| Age categories, y | |
| <50 | 26 (47.3) |
| 50-59 | 14 (25.5) |
| 60-69 | 8 (14.5) |
| 70-79 | 3 (5.5) |
| 80-84 | 4 (7.3) |
| Year of diagnosis | |
| 2011 | 1 (1.8) |
| 2012 | 13 (23.6) |
| 2013 | 7 (12.7) |
| 2014 | 17 (30.9) |
| 2015 | 17 (30.9) |
| Primary site | |
| Parotid gland | 42 (76.4) |
| Submandibular gland | 3 (5.5) |
| Major salivary gland, NOS | 10 (18.2) |
| Primary surgery | |
| No primary surgery | 7 (12.7) |
| Local tumor excision | 12 (21.8) |
| Less than total parotidectomy or less than total removal of major salivary gland | 25 (45.5) |
| Total parotidectomy or total removal of major salivary gland | 14 (25.5) |
| Radical parotidectomy or radical removal of major salivary gland | 2 (3.6) |
| Unknown | 1 (1.8) |
| Lymph node surgery | |
| Lymph node biopsy | 1 (1.8) |
| Neck dissection | 34 (61.8) |
| None | 20 (36.4) |
| Lymph node involvement | |
| Negative lymph node | 32 (58.2) |
| Positive lymph node | 3 (5.5) |
| Unknown or lymph node not examined | 20 (36.4) |
| Tumor size, mean (SD), cm | 1.95 (1.01) |
| Tumor size categories, cm | |
| ≤2 | 31 (56.4) |
| >2-4 | 19 (34.5) |
| >4 | 1 (1.8) |
| Unknown | 4 (7.3) |
| AJCC stage group | |
| I | 25 (45.5) |
| II | 18 (32.7) |
| III | 6 (10.9) |
| IVA | 1 (1.8) |
| Unknown | 5 (9.1) |
| T stage | |
| T1 | 27 (49.1) |
| T2 | 19 (34.5) |
| T3 | 3 (5.5) |
| T4a | 1 (1.8) |
| TX | 5 (9.1) |
| N stage | |
| N0 | 51 (92.7) |
| N1 | 3 (5.5) |
| NX | 1 (1.8) |
| M stage | |
| M0 | 55 (100) |
| M1 | 0 (0) |
| Grade | |
| I, well differentiated | 11 (20.0) |
| II, moderately differentiated | 14 (25.5) |
| Unknown | 30 (54.5) |
| Follow-up, mean (SD), mo | 20.3 (14.9) |
| Alive at follow-up | 55 (100) |
Abbreviations: AJCC, American Joint Committee on Cancer; NOS, not otherwise specified.
Data are presented as number (percentage) of patients or cases unless otherwise indicated.
American Indian, Alaska Native, Asian, or Pacific Islander.
Discussion
Because of the rarity of MASC, little information is available regarding the clinical characteristics of this neoplasm. To our knowledge, this study represents the largest described novel cohort of patients with MASC. Our results suggest that most patients have early-stage disease at presentation with rare nodal involvement. This finding is consistent with prior studies2,3 that have described MASC as a predominantly low-grade malignant tumor with an indolent clinical course. Although there have been case reports of MASC with high-grade transformation,4 no evidence of such aggressive cases was identified in this analysis.
Although 34 patients with MASC (61.8%) underwent neck dissection, only 3 patients (5.5%) had nodal metastasis. Other case series have demonstrated higher rates of nodal metastasis, with frequencies ranging from 6.7% to 25%.1,2,5 In this cohort, 61.8% of patients received neck dissections for nodal management, similar to the proportion reported by Chiosea et al (50%).5 However, Sethi et al6 described a lower rate of 22.8% in a combined analysis of 92 patients. Because many of the case series have a limited number of patients, further analysis is warranted to determine whether the frequency of neck dissections for clinical N0 disease is appropriate for the rate of nodal metastasis.
The duration of follow-up was limited because of the recent period in which this malignant tumor has been described. As a result, data were insufficient to determine prognostic factors that affect survival or disease management. Despite the limitations and small sample size of this study, our results suggest that MASC is a rare, indolent malignant tumor with a low rate of nodal metastasis.
References
- 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. Am J Surg Pathol. 2010;34(5):599-608. doi: 10.1097/PAS.0b013e3181d9efcc [DOI] [PubMed] [Google Scholar]
- 2.Luk PP, Selinger CI, Eviston TJ, et al. . Mammary analogue secretory carcinoma: an evaluation of its clinicopathological and genetic characteristics. Pathology. 2015;47(7):659-666. doi: 10.1097/PAT.0000000000000322 [DOI] [PubMed] [Google Scholar]
- 3.Skálová A, Gnepp DR, Lewis JS Jr, et al. . Newly described entities in salivary gland pathology. Am J Surg Pathol. 2017;41(8):e33-e47. doi: 10.1097/PAS.0000000000000883 [DOI] [PubMed] [Google Scholar]
- 4.Skálová A, Vanecek T, Majewska H, et al. . Mammary analogue secretory carcinoma of salivary glands with high-grade transformation: report of 3 cases with the ETV6-NTRK3 gene fusion and analysis of TP53, β-catenin, EGFR, and CCND1 genes. Am J Surg Pathol. 2014;38(1):23-33. doi: 10.1097/PAS.0000000000000088 [DOI] [PubMed] [Google Scholar]
- 5.Chiosea SI, Griffith C, Assaad A, Seethala RR. Clinicopathological characterization of mammary analogue secretory carcinoma of salivary glands. Histopathology. 2012;61(3):387-394. doi: 10.1111/j.1365-2559.2012.04232.x [DOI] [PubMed] [Google Scholar]
- 6.Sethi R, Kozin E, Remenschneider A, et al. . Mammary analogue secretory carcinoma: update on a new diagnosis of salivary gland malignancy. Laryngoscope. 2014;124(1):188-195. doi: 10.1002/lary.24254 [DOI] [PMC free article] [PubMed] [Google Scholar]