Secretory carcinoma (SC) is a recently recognized type of salivary gland tumor characterized by t(12;15) (p13;q25) translocation resulting in an ETV6-NTRK3 gene fusion. Most SCs are located in a main salivary gland, and primary sinonasal secretary carcinoma is rare. We describe three cases of primary SC in the sinonasal cavity with high-grade transformation (HGT) in one case, and the first case in the pharynx. All tumors comprised slightly atypical cells with solid, tubular, microcystic growth patterns. The case with HGT included two components with distinct sharp boundaries and comedo necrosis, high mitotic figures and obvious cellular atypia. Tumor cells were positive for vimentin, S100, and Gata-3 and negative for p63 and DOG-1. Three cases showed nuclear staining of pan-TRK and one showed cytoplasmic staining. All cases harbored ETV6 gene rearrangement, and ETV6-NTRK3 gene fusion was detected in three cases. Most patients were treated with radical resection and adjuvant therapy. After excision, all remained tumor-free for 65-164 months (medium 98.5 months). SC in the sinonasal cavity and pharynx is a low-grade malignant tumor with histologic features overlapping those of other salivary gland tumors. Immunohistochemical analysis and fluorescence in situ hybridization are useful techniques for its differential diagnosis.

Background: Mammary analogue secretory carcinoma (MASC) is characterized by similar histologic, immunohistochemical, and molecular features with breast secretory carcinoma. MASC usually occurs in adults. Case report: A 4-year-old boy presented with a right infra-auricular mass. Features of the tumor include solid, tubular, and papillary growth patterns, with homogenous eosinophilic secretions inside microcystic structures. Immunohistochemical stains showed strong, diffuse staining for CK7, S100, pan-TRK protein. P63 was positive in a peripheral pattern. Fluorescence in situ hybridization (FISH) analysis showed the characteristic ETV6-NTRK3 gene fusion. Conclusion: Typical histological, immunohistochemical, and molecular features are present in MASC occurring early in childhood.

OBJECTIVE: The present study aimed to characterize and differentiate the ultrasonography (US) and computed tomography (CT) features of mammary analogue secretory carcinoma (MASC) and acinic cell carcinoma (AciCC).
METHODS: A total of 83 patients with clinically proven MASC and AciCC were analyzed. The following characteristics were assessed on US, CT, and magnetic resonance imaging: lesion size, shape, margin, echogenicity, echotexture, cystic components, posterior echo, vascularity, density, degree of enhancement, enhancement pattern, signal intensity (SI) on T1- and T2-weighted images (WI), hemorrhages, and lymph node enlargement.
RESULTS: Similarities were observed between the imaging performance of MASC and AciCC. Differences between the two characteristics of shape on US and cystic components on CT were statistically significant. The proportion of MASC to regular shape on US (p = 0.006) and cystic components on CT (p = 0.027) was significantly higher than that of AciCC. Regular shape on US had the highest sensitivity in the identification of MASC and AciCC, while regular shape on US + cystic component on CT had the highest specificity.
CONCLUSIONS: The shape on US and cystic components on CT are key characteristics for distinguishing MASC and AciCC.

BACKGROUND: Mammary analogue secretory carcinoma (MASC) is a rare low-grade malignant salivary gland tumor. The morphological and immunohistochemical features of MASC closely resemble those of breast secretory carcinoma. The key characteristics of the lesion are a lack of pain and slow growth. There is no obvious specificity in the clinical manifestations and imaging features. The diagnosis of the disease mainly depends on the detection of the MASC-specific ETV6-NTRK3 fusion gene.
METHODS: This report describes a rare case of a 32-year-old male patient who presented with a gradually growing lesion that was initially diagnosed as breast-like secretory carcinoma of the right parotid gland. Imaging and histological investigations were used to overcome the diagnostic difficulties. The lesion was managed with right parotidectomy, facial nerve preservation, biological patch implantation to restore the resulting defect, and postoperative radiotherapy. On postoperative follow-up, the patient reported a mild facial deformity with no complications, signs of facial paralysis, or Frey\'s syndrome.
CONCLUSIONS: The imaging and histological diagnostic challenges for MASC are discussed.

Mammary analog secretory carcinoma (MASC), or secretory carcinoma of the thyroid is an extremely rare disease harboring ETV6-NTRK3 gene fusion with TRK activation. Here we report the twelfth case of MASC of the thyroid worldwide. A 36-year-old female was diagnosed with poor-differentiated thyroid carcinoma (PDTC). Pathology consultant and immunochemical workups showed the tumor cells were negative for TTF1, TG, PAX8, positive for S100, Vimentin, GATA-3, and focally positive for mammaglobin. Fluorescence in situ hybridization (FISH) assay using a dual-color break-apart probe showed ETV6 translocation t(12p13) (ETV6) was present and established the diagnosis of MASC. Next-generation sequencing (NGS) of a 47-gene panel identified exon 1-5 of ETV6 gene were fused with exons 15-19 of NTRK3 gene. The patient experienced three loco-regional recurrences within 12 months and eventually developed inoperable local disease as well as bilateral lung metastasis. She is currently receiving anti-TRK treatment with a follow-up time of 33 months. A literature review of MASC in the thyroid was also conducted.

Mammary analogue secretory carcinoma (MASC) of the salivary glands is rarely reported. In this article, the histopathological features of 5 cases of parotid MASC were retrospectively analyzed. AB/PAS and immunohistochemical staining of S-100, mammaglobin and P63 was performed, which were validated by the ETV6-fluorescent FISH detection of NTRK3 gene. The tumors were composed of two kinds of tumor cells. One kind of cells was rich in cytoplasms, transparent or vacuole-like, partial basophilic double tropism, but another type of cellular cytoplasm was acidophilic. The karyotype was consistent between two types of tumors in the vacuolar pattern. Although the tumor cells were arranged in different forms, the cystic (capsule or microcapsule) structures were constantly observed. Two kinds of tumor cells produced different secretions, which were distributed among the tumor cells. Tumor tissues were divided by hardened collagen interstitial, even in the infiltration lesion, collagen and tumor cells mass was also inseparable. The expression of mammaglobin and S-100 significantly differed between the two types of tumor cells. These characteristics contribute to the differential diagnosis of MASC. ETV6-NTRK3 gene detection can be applied in the diagnosis of atypical cases, but it should not be done routinely.

Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumour notable for a balanced chromosomal translocation t(12;15)(p13;q25) that contributes to ETV6 gene rearrangements. It was first reported in 2010 by Skalova et al. with histological features resembling secretory carcinoma of the breast and was acknowledged and referred to as \"secretory carcinoma\" in the updated 2017 WHO classification. It is reported that MASC accounts for <0.3% of all salivary gland tumours, with a finite number of published reports on it. MASC has a range of histological features and clinical behaviours. The histopathological diagnosis of MASC can be difficult with current immunohistochemical methods. One case was located in the left palate, and 1 case was located in the soft palate. The maximum diameter of the tumour was 1.4~3.7 cm. CT demonstrated a mass that had not invaded into the palate bone, and the patients underwent palate neoplasm expanded ectomy without neck dissection or postoperative radiation therapy. Histopathological examination revealed that the tumour cells consisted of a mixed arrangement of microcystic, papillary-cystic, follicular, and solid lobular growth patterns. Eosinophilic cytoplasm and intraluminal or intracytoplasmic colloid-like secretions were observed. The final pathology confirmed the diagnosis of MASC with immunohistochemically neoplastic cells staining positive for S-100 and mammaglobin. The patients were asymptomatic at their 12-month follow up. More studies are needed to identify the typical behaviour of this tumour and establish the standard treatment regimen. This study aims to reinforce the awareness of this tumour by analysing its clinicopathologic features, immunophenotype, and diagnosis.

OBJECTIVE: The prognostic factors of salivary (mammary analogue) secretory carcinoma (SC) are unclear because of the rarity of the tumor. This report presents the largest case series to investigate the prognosis-related clinicopathologic factors in conventional SC.
METHODS: This study was based on a retrospective cohort study from 1993 to 2015 of patients whose sections were reviewed and who were newly diagnosed as having SC by the detection of ETV6 rearrangement. Clinicopathologic features, including age, gender, involvement site, tumor category, node category, histopathologic subtype, cellular atypia, tumor necrosis, growth pattern (noninvasive vs invasive), perineural invasion, margin, hyalinized fibrous septa, Ki67 expression, and postoperative treatment, were analyzed as primary predictors. Patients\' final outcomes-including no evidence of disease, recurrence, metastasis, and death-were collected during follow-up. Survival analysis was performed only for conventional SC using the Kaplan-Meier method and the Cox proportional hazards regression model.
RESULTS: Sixty-two cases of SC were retrospectively confirmed. Fifty-nine cases were identified as conventional SC, whereas 3 cases were identified as high-grade SC. In conventional SC, univariate analyses showed that nodal metastasis, invasive growth, and a Ki67 index of at least 10% were related to decreased recurrence-free survival (RFS), distant disease-free survival (DDFS), and disease-free survival (DFS). Age older than 44 years, T3 and T4 stages, and markedly hyalinized fibrous septa were associated with decreased DDFS. T3 and T4 stages, positive margins, and tumor necrosis were associated with decreased overall survival. By multivariate analysis, the Ki67 index was found to be an independent prognostic factor for RFS (P = .008) and DFS (P = .003).
CONCLUSIONS: Although most patients with conventional SC had a favorable clinical prognosis, patients with nodal involvement, invasive growth, and a Ki67 index higher than 10% showed a poor clinical outcome by exhibiting local recurrence or distal metastasis. Patients with a higher Ki67 index especially need close observation for local recurrence.

Objective: To investigate the clinicopathologic and molecular genetic features of secretory carcinoma of salivary gland (SCSG). Methods: Six cases of SCSG were collected from Zhejiang Provincial People\'s Hospital from January 2011 to March 2018. The clinical, histopathological and immunohistochemical features were analyzed and fluorescence in situ hybridization (FISH) was used to detect ETV6 gene rearrangement. Results: Four out of 6 tumors originated in the parotid gland and one of each in the minor salivary glands of soft palate and the buccal mucosa. Grossly, 4 cases were solid and 2 were partially cystic with maximum diameter ranging from 1.0 to 4.0 cm. Microscopically, 5 tumors showed typical features of low grade SCSG with tumor divided by thin fibrous septa into lobules composed of solid acinar, microcystic, follicular and papillary structures with abundant extracellular mucinous secretions. The tumor cells had cuolated or hobnail cytoplasm with low-grade nuclei and scarce mitoses. Perineural invasion was present in 1 case. The remaining tumor showed about 30% of the tumor areas with high-grade transformation characterized by proliferation of a distinct population of anaplastic cells arranged in irregular glandular, small nested and single cell patterns that were surrounded by desmoplastic stroma and invaded into surface mucosa with ulceration. Immunohistochemistry showed that all 6 tumors had diffuse and strong reactivities to S100 protein and cytokeratin 7, and 4 cases showed focal reactivity to gross cystic disease fluid protein 15 (GCDFP15), all were negative for discovered on gist 1 (DOG1), cytokeratin 20, p63 and calponin. High grade transformation cases were analysed, the high grade SCSG components showed a significantly increased Ki-67 index and cyclin D1 positive tumor cells compared to the conventional SCSG components. FISH analyses showed that 4 cases had ETV6 gene rearrangement. Eleven to seventy one months\' follow-up showed no evidence of tumor recurrence nor metastasis. Conclusions: SCSG harbors characteristic genetic abnormalities with ETV6 gene rearrangement and typically shows a low grade morphology with occasionally, high grade transformation can be present.
目的： 探讨唾液腺分泌性癌（secretory carcinoma of salivary gland，SCSG）的临床病理和分子遗传学特征。 方法： 收集2011年1月至2018年3月于浙江省人民医院杭州医学院附属人民医院就诊的6例SCSG，观察其临床、组织学和免疫组化染色特点，应用荧光原位杂交检测ETV6基因重排。 结果： 6例SCSG中4例发生于腮腺区，2例位于小唾液腺区（软腭和颊部内各1例）。大体上4例实性，2例囊实性，直径1.0~4.0 cm。镜下可见5例肿瘤由薄的纤维性间质分隔呈小叶状，小叶内瘤细胞呈实性腺泡状、微囊状、滤泡样及乳头状排列，胞外可见丰富的黏液聚集，瘤细胞常见空泡状或鞋钉样胞质，核异型性轻微，罕见核分裂象，1例可见神经侵犯，1例可见约30%肿瘤区域呈高级别转化，瘤细胞异型性明显，呈不规则腺样、小巢状或单个细胞浸润伴表面溃疡形成，可见促结缔组织增生性间质反应。免疫组化染色示6例弥漫强表达S100蛋白和细胞角蛋白7，4例局灶表达特异性囊肿病液体蛋白15，均不表达DOG1蛋白、细胞角蛋白20、p63基因和钙调蛋白等。高级别转化的SCSG成分Ki-67增殖指数和细胞周期蛋白D1阳性表达均较无高级别转化的SCSG病例增加。荧光原位杂交检测4例SCSG均显示ETV6基因重排。4例SCSG随访11~71个月均未见复发和转移。 结论： SCSG有特征性的ETV6基因重排，以低级别组织学表现为主，可伴高级别转化。.

Mammary analogue secretory carcinoma of salivary gland (MASC) is a tumor with histopathologic and immunophenotypic features mimicking secretory carcinoma of the breast harboring the ETV6 split. The expression of mammaglobin, S-100, Ki-67, P63 and ETV6 split were detected in twelve cases of acinar cell carcinoma and fourteen cases of mammary analogue secretory carcinoma of salivary gland by immunohistochemistry and fluorescence in situ hybridization respectively. The expression of ETV6 gene split was detected in fourteen mammary analogue secretory carcinomas of salivary gland with positive expression of mammaglobin. Eight of mammary analogue secretory carcinomas of salivary gland also tested positive for the ETV6 gene split via fluorescence in-situ hybridization (FISH). The concordance rate of the immunohistochemistry and FISH was 72.3%. Mammaglobin and ETV6 gene split detection could help to distinguish mammary analogue secretory carcinoma of salivary gland. The mammary analogue secretory carcinoma of salivary gland specimens were also examined under transmission electron microscope. And apical junctional complexes were observed in the loosely connected tumor cells.