Mammary Analogue Research Articles

Macrocystic (Mammary Analogue) Secretory Carcinoma: An Unusual Variant and a Pitfall in the Differential Diagnosis of Cystic Lesions in the Head and Neck.

Mammary analogue secretory carcinoma (MASC) is a relatively recently described salivary gland adenocarcinoma characterized by ETV6-NTRK3 gene fusion and in most cases indolent clinical behavior. The majority of tumors show an admixture of microcystic, solid, and tubular growth patterns but only a few cases with dominant macrocystic growth have been reported. We report 15 cases of macrocystic MASC. There were 11 men and 4 women (17 to 88 y age range, average 47 y). The patients presented with a painless cystic mass, the majority in the region of the parotid gland (n=13), as well as in submandibular gland (n=1) and the neck (n=1). All tumors were circumscribed measuring 1.0 to 4.0 cm in greatest diameter (mean: 1.75 cm). Twelve tumors were unilocular, while 3 were multilocular. The cystic spaces were predominantly lined by a single epithelial cell layer with focal areas in which the epithelium was multilayered with papillary and hobnail features. In 3 of the cases there were more solid foci of intracystic tumor characterized by papillary and/or microcystic growth. The neoplastic cells were round to oval with hyperchromatic to vesicular nuclei with centrally located nucleoli and eosinophilic or vacuolated cytoplasm. Tumor cells showed strong positivity for S100 protein and mammaglobin, while DOG1 was uniformly negative. A minority of cases showed focal p63 reactivity predominantly limited to the periphery of the cystic lining. ETV6 gene rearrangement was identified in 9 cases. Macrocystic MASC can simulate benign and malignant salivary gland lesions and needs to be included in the differential diagnosis of cystic lesions in the head and neck. To the best of our knowledge, our report represents the first series of macrocystic MASCs wholly focusing on this unusual variant.

Clinical characteristics of acinic cell carcinoma and secretory carcinoma of the parotid gland

Mammary analogue secretory carcinoma (SC) of the parotid gland is a relatively uncommon cancer associated with the ETV6-NTRK3 fusion product similar to breast cancer. The clinical characteristics and outcome of treatment were reviewed for patients with this tumor at our hospital. In this retrospective case series, 24 patients with a diagnosis of acinic cell carcinoma (AcCC) of the parotid gland were classified as having either SC or AcCC based on analysis of the ETV6-NTRK3 fusion gene. These two groups were compared with respect to their clinical and imaging characteristics (MRI/US), cytologic findings, accuracy of fine-needle aspiration cytology and frozen section, treatment outcomes, and immunohistochemical findings. Based on re-classification by ETV6-NTRK3 fusion gene analysis, the diagnosis was SC in 14 patients and AcCC in 10 patients. The SC group had a significantly higher proportion of male patients and was also significantly younger than the AcCC group. Imaging studies revealed that SC was significantly more likely to show internal heterogeneity. Correct grading of both tumors was comparable by fine needle aspiration, with the rate being 60% for AcCC and 50% for SC. Diagnosis by frozen section biopsy diagnosis obtained the correct grade in 90% of the AcCC group and 93% of the SC group. In 24 patients previously diagnosed with AcCC, re-analysis of the ETV6-NTRK3 fusion product indicated that 14 patients actually had SC. Although AcCC and SC show similarities of their biological aggressiveness and prognosis, patients with SC were significantly more likely to be male and younger.

EXTRAPARENCHYMAL EXTENSION, LYMPH NODE INVOLVEMENT, AND A HIGHER KI67 INDEX WERE HIGH RISK FACTORS FOR WORSE PROGNOSIS IN CONVENTIONAL MAMMARY ANALOGUE SECRETORY CARCINOMA

Objective The prognostic factors of salivary gland (mammary analogue) secretory carcinoma (SC) are unclear because of the rarity of the tumors. Here we presented the largest case series to investigate the prognosis related clinicopathological factors in salivary conventional SC. Findings The study was based on a retrospective cohort of patients whose sections were reviewed and newly diagnosed as SC by the detection of ETV6 rearrangement from 1993 to 2015. The clinicopathological features were analysed as the primary predictors and patients’ final outcome was collected. Survival analysis was performed in conventional SC by using Kaplan-Meier method and Cox proportional hazards regression model. In our study, totally sixty-two cases of SC were confirmed. Fifty-nine out of 62 cases were conventional SC with a mean age of 43.2 years, showing significant male predilection (49/59, 83.1%) and mostly occurred in parotid glands (49/59, 83.1%). Additional 3 cases were identified as SC with high-grade transformation (HG-SC), with a mean age of 20 years older than that of patients with conventional SC. Lymph node metastasis and Ki67 expression ≥10% were related to poor recurrence-free survival (RFS), distant disease-free survival (DDFS) and disease-free survival (DFS) in conventional SC. Significantly decreased RFS and DFS were seen in patients with extraparenchymal extension. T3/T4 stage, age greater than 44 years and markedly hyalinized fibrous septa were associated with worse DDFS. By using multivariate analysis, the Ki67 index was found to be an independent prognostic factor for RFS (p = 0.008) and DFS (p = 0.003) in conventional SC. Much more worse RFS and DFS were presented in HG-SC due to its aggressive behaviour. Conclusion In conventional SC, patients with extraparenchymal extension, lymph node involvement, and higher Ki67 index exhibited poor clinical outcome. Moreover, Ki67 was a potential predictor of RFS and DFS of conventional SC.

SECRETORY CARCINOMA OF THE PAROTID GLAND IN A 9-YEAR-OLD FEMALE PATIENT: A CASE REPORT AND REVIEW OF THE LITERATURE

Introduction Formerly known as mammary analogue carcinoma (MASC), secretory carcinoma of the salivary glands (SCSG) is a low-grade malignancy harboring the ETV6-NTRK3 translocation. SCSG shares morphological and genetic features with secretory carcinoma of the breast. It shows a characteristic protean histological phenotype reminiscent of acinic cell carcinoma, mucoepidermoid carcinoma, and adenocarcinoma, NOS. We report a case of SCSG in a pediatric patient showing a pure zymogen-poor acinic cell carcinoma morphology. Clinical presentation A 9-year-old female patient presented to the ENT clinic with 8 months history of left facial swelling. Imaging studies showed a 2.7 cm lesion of the left parotid gland with no lymphadenopathy. Left lateral lobe parotidectomy with facial nerve dissection and preservation was performed. Gross examination of the tumor revealed a tan, hemorrhagic ill-defined mass, measuring 2.5 × 2.4 × 2 cm. Microscopic examination showed lobulated growth pattern consisting of papillary architecture and microcystic spaces. Lobules of tumor cells were identified in the intraparotid lymph node. The tumor was negative for DOG-1 and strongly positive for Mammaglobin, S-100, GATA-3, CK 7, and Pan cytokeratin. The ETV6 gene translocation was subsequently detected by FISH. Literature review A total of 17 cases of pediatric SCSGs (age range: 8-18 years) have been reported in the literature. The parotid gland (88%) is the most common location. The mainstay of treatment is surgical resection. Based on the limited number of documented cases, SCSG appears to show an indolent biological behavior rarely occurring in pediatric patients. Conclusion Because of the spectrum of histological patterns of SCSG, immunohistochemical markers and genetic documentation of the ETV6-NTRK3 gene fusion are essential to correctly diagnose this tumor.

MAMMARY ANALOG SECRETORY CARCINOMA OF SALIVARY GLANDS:A CASE REPORT.

Objective Mammary analog secretory carcinoma(MASC), is a distinctive low-grade malignant salivary cancer. Microscopically, most cases of MASC consist of a circumscribed mass divided by thin fibrous septa into lobules composed of microcystic, tubular, and solid structures. Due to the scarcity of reported cases, however, little information exists regarding this lesion in the salivary gland. Here, we report a case of MASC occurring in the parotid gland. Clinical Presentation Our patient is a 28-yer-old male who presented with a 3.0 × 2.5 × 2.0cm in the right parotid gland, referred slowly growing, painless approximately one year duration. The tumor is rubbery, with a white-tan to gray cut surface. On the cut surface of the mass, many small cystic spaces may be seen, containing yellow to whitish fluid. The borders of the tumor is circumscribed but not encapsulated. Conclusion Most cases of MASCs were diagnosed as AciCC or adenocarcinoma not otherwise specified. Many MASC were found to harbor an ETV6-NTRK3 fusion gene because of a t(12;15) (p13,q25) translocation, a finding identical to secretory carcinoma of the breast. The most recent version of the World Health Organization (WHO) Classification of Head and Neck Tumours utilizes the terminology of “secretory carcinoma” for consistency. In addition to the case report, we review the past and current cases enrolled of MASC. Awareness of such a clinical presentation is important for the clinician.

Immunohistochemistry with a pan-TRK antibody distinguishes secretory carcinoma of the salivary gland from acinic cell carcinoma.

Secretory carcinoma (previously known as mammary analogue secretory carcinoma) is characterised by ETV6 rearrangements, most often ETV6-NTRK3 fusion. Given its histological overlap with other salivary gland tumours, secretory carcinoma can be difficult to diagnose without genetic confirmation. A recently developed pan-TRK antibody shows promise for identifying tumours with NTRK fusions. The aim of this study was to evaluate the utility of pan-TRK immunohistochemistry in distinguishing secretory carcinoma from mimics. We examined whole-tissue sections from 86 tumours, including 14 secretory carcinomas (12 parotid primaries and one buccal primary, and one metastasis; five with ETV6 rearrangement confirmed by fluorescence in-situ hybridisation, and one with ETV6-NTRK3 fusion and one with ETV6-RET fusion detected by targeted sequencing), 14 acinic cell carcinomas, 18 polymorphous adenocarcinomas, 20 low-grade mucoepidermoid carcinomas, and 20 pleomorphic adenomas. Immunohistochemistry was performed with a pan-TRK rabbit monoclonal antibody. Pan-TRK staining was detected in nine (64%) secretory carcinomas, all with a nuclear pattern and four with diffuse staining (>50% of cells). Among other tumour types, pan-TRK immunoreactivity was observed in all (100%) pleomorphic adenomas (particularly myoepithelial cell-rich, myxoid areas), 15 (83%) polymorphous adenocarcinomas, and four (20%) low-grade mucoepidermoid carcinomas, all with predominantly membranous/cytoplasmic immunoreactivity; only six cases showed focal (<10%) nuclear staining. All acinic cell carcinomas were entirely negative. Although pan-TRK expression is not entirely sensitive or specific for secretory carcinoma, nuclear staining distinguishes secretory carcinoma from mimics. Acinic cell carcinomas are negative for pan-TRK, though membranous expression of TRK is common in other salivary gland neoplasms. The lack of pan-TRK immunoreactivity in a subset of secretory carcinomas may suggest non-NTRK fusion partners.

Dectection of fusion gene ETV6-NTRK3 in seven cases of mammary analogue secretary carcinomas of salivary glands

目的： 比较逆转录聚合酶链反应（RT-PCR）与荧光原位杂交（FISH）两种方法检测涎腺乳腺样分泌性癌（MASC）ETV6-NTRK3融合基因的阳性率。 方法： 收集十堰市太和医院病理科2004—2017年诊断的MASC 7例，10例同期诊断的腺泡细胞癌作为对照。采用免疫组织化学检测S-100蛋白、乳腺球蛋白、波形蛋白、DOG1、CD117、Ki-67、SOX10；MASC病例行RT-PCR及FISH检测，对照组仅行RT-PCR检测。 结果： S-100蛋白、乳腺球蛋白、波形蛋白、DOG1四种标志物有助于区分典型MASC与腺泡细胞癌；7例MASC均至少有1种分子检测结果阳性，5例ETV6分离探针阳性，6例RT-PCR检测阳性；4例RT-PCR与FISH检测均阳性。 结论： FISH与RT-PCR在检测MASC中ETV6-NTRK3融合基因时具有互补性，联合检测可提高检出率。.

Diagnostic utility of fluorescence in situ hybridization testing on cytology cell blocks for the definitive classification of salivary gland neoplasms

Fine needle aspiration biopsy (FNAB) is a minimally invasive modality to evaluate salivary gland neoplasms and help guide clinical management. However, significant overlap in the cytomorphology findings among salivary gland neoplasms often renders the definitive diagnosis challenging. Recently, a number of benign and malignant salivary gland tumors have been characterized by specific chromosomal aberrations detectable using fluorescence in situ hybridization (FISH) testing. In the present study, we evaluated the role of FISH testing performed on cytology cell blocks in the diagnosis of salivary gland neoplasms by FNAB. The data from 57 cases of primary salivary gland tumors diagnosed using FNAB at our institution and sent for ancillary FISH testing between 2012 and 2017 were retrospectively reviewed. The FISH studies were performed on cytology cell blocks, and break-apart probes were used to detect characteristic gene rearrangements for PLAG1, MYB, MAML2, and ETV6 for pleomorphic adenoma, adenoid cystic carcinoma, mucoepidermoid carcinoma, and secretory carcinoma (mammary analogue secretory carcinoma), respectively. Of the 57 cases sent for FISH testing, 6 were excluded because of FISH analysis failure (insufficient cell block cellularity). Of the 51 cases included in the analysis, 15 samples were successfully subclassified after FISH testing, and 10 of these 15 FISH-positive cases were diagnostically confirmed by the surgical pathology review of excision material. Forty cases overall had undergone subsequent excision with the histopathologic follow-up diagnosis available, and all subclassified cases had concordant FNAB, FISH, and excision diagnoses. FISH testing performed on cytology cell blocks is a useful adjunct in establishing the diagnosis of salivary gland neoplasms by FNAB.

Higher Ki67 Index, Nodal Involvement, and Invasive Growth Were High Risk Factors for Worse Prognosis in Conventional Mammary Analogue Secretory Carcinoma

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. 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. 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 44years, 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). 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.

Neurotrophic tropomyosin or tyrosine receptor kinase (NTRK) genes

The neurotrophic tropomyosin or tyrosine receptor kinase (NTRK) genes (1-3) are proto-oncogenes that when activated are encountered in a wide array of tumours. The recent advent of very specific and...

Two Cases of Mammary Analogue Secretory Carcinoma Arising from the Parotid Gland

Two Cases of Mammary Analogue Secretory Carcinoma Arising from the Parotid Gland

Fine-needle Aspiration Cytology of Mammary Analog Secretory Carcinoma of the Parotid Gland: A Diagnostic Conundrum.

Fine-needle Aspiration Cytology of Mammary Analog Secretory Carcinoma of the Parotid Gland: A Diagnostic Conundrum.

TRK Fusion Cancers in Children: A Clinical Review and Recommendations for Screening.

Chromosomal translocations involving the NTRK1, NTRK2, and NTRK3 genes (TRK fusions), which encode the neurotrophin tyrosine kinase receptors TRKA, TRKB, and TRKC, can result in constitutive activation and aberrant expression of TRK kinase. Certain cancers almost universally harbor TRK fusions, including infantile fibrosarcoma, cellular congenital mesoblastic nephroma, secretory breast cancer, and mammary analog secretory carcinoma of the salivary gland. TRK fusions have also been identified at lower frequencies across a broad range of other pediatric cancers, including undifferentiated sarcomas, gliomas, papillary thyroid cancers, spitzoid neoplasms, inflammatory myofibroblastic tumors, and acute leukemias. Here we review the prevalence and diseases associated with TRK fusions and methods of detection of these fusions in light of the recent development of selective TRK inhibitors, such as larotrectinib, which demonstrated a 75% response rate across children and adults with TRK fusion cancers. We provide recommendations for screening pediatric tumors for the presence of TRK fusions, including the use of immunohistochemistry or fluorescence in situ hybridization for patients with tumors likely to harbor TRK fusions. Further, we recommend next-generation sequencing for tumors that have a relatively low prevalence of TRK fusions, both to identify patients who may benefit from TRK inhibition and to identify other targetable oncogenic drivers that exist in the same tumor types.

Analysis of Clinical Features of Mammary Analog Secretory Carcinoma Using the Surveillance, Epidemiology, and End Results Database

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.

Molecular Profiling of Salivary Gland Intraductal Carcinoma Revealed a Subset of Tumors Harboring NCOA4-RET and Novel TRIM27-RET Fusions: A Report of 17 cases.

Intraductal carcinoma (IC) is the new World Health Organization designation for tumors previously called "low-grade cribriform cystadenocarcinoma" and "low-grade salivary duct carcinoma." The relationship of IC to salivary duct carcinoma is controversial, but they now are considered to be distinct entities. IC is a rare low-grade malignant salivary gland neoplasm with features similar to mammary atypical ductal hyperplasia or ductal carcinoma in situ, that shows diffuse S100 protein and mammaglobin positivity and is only partially defined genetically. (Mammary analogue) secretory carcinoma harboring ETV6-NTRK3, and in rare cases ETV6-RET fusion, shares histomorphologic and immunophenotypical features with IC. Recently, RET rearrangements and NCOA4-RET have been described in IC, suggesting a partial genetic overlap with mammary analogue secretory carcinoma. Here, we genetically characterize the largest cohort of IC to date to further explore this relationship. Seventeen cases of IC were analyzed by next-generation sequencing using the FusionPlex Solid Tumor kit (ArcherDX). Identified fusions were confirmed using fluorescence in situ hybridization break apart and, in some cases, fusion probes, and a reverse transcription polymerase chain reaction designed specifically to the detected breakpoints. All analyzed cases were known to be negative for ETV6 rearrangement by fluorescence in situ hybridization and for ETV6-NTRK3 fusion by reverse transcription polymerase chain reaction. Next-generation sequencing analysis detected a NCOA4-RET fusion transcript joining exon 7 or 8 of NCOA4 gene and exon 12 of RET gene in 6 cases of intercalated duct type IC; and a novel TRIM27-RET fusion transcript between exons 3 and 12 in 2 cases of salivary gland tumors displaying histologic and immunohistochemical features typical of apocrine IC. A total of 47% of IC harbored a fusion involving RET. In conclusion, we have confirmed the presence of NCOA4-RET as the dominant fusion in intercalated duct type IC. A novel finding in our study has been a discovery of a subset of IC patients with apocrine variant IC harboring a novel TRIM27-RET.

Secretory Carcinoma of the Salivary Gland: a Rare Entity

According to the new classification proposed by the World Health Organization, mammary analogue secretory carcinoma is designated as secretory carcinoma (SC). This tumor is a recently recognized malignancy of the salivary glands and shows striking resemblance to SC of the breast. A 44-year-old man presented with a painless, pedicled, nodular lesion on the anterior maxillary mucosa, measuring approximately 10 mm and a 1-year evolution. The provisional diagnosis was fibroma. A biopsy was performed; the histopathologic specimen showed proliferation of round to elliptical, large-sized neoplastic epithelial cells with eosinophilic cytoplasm and nuclei exhibiting slight pleomorphism and prominent central nucleoli organized in a lobular pattern containing pale mucoid secretion. Immunoreaction for vimentin, S100, CK7, and mammaglobin confirmed the diagnosis. The patient underwent surgery and is currently being followed-up with no apparent signs of recurrence.

Secretory Carcinoma in the Buccal Mucosa

Secretory carcinoma (SC) is a malignancy of the salivary glands, described by Skálová et al in 2010 as mammary analogue secretory carcinoma (MASC). Previously, the lesion was diagnosed as an unusual variant of acinic cell carcinoma (AciCC). The World Health Organization Classification of Head and Neck Tumors in 2017 simplified the name from MASC to SC. We described the case of a 27-year-old woman showing a round, circumscribed lesion in the buccal mucosa, resembling a mucocele. After an incisional biopsy, the microscopic analysis exhibited circumscribed lobulated masses under the epithelium, composed of microcystic structures. The cells presented a pale eosinophilic cytoplasm and vesicular nuclei with distinctive centrally located nucleoli. Immunohistochemistry analysis showed positivity for S-100 and mammaglobin. Fluorescence in situ hybridization detected the ETV6 gene rearrangement, confirming the diagnosis of secretory carcinoma. The patient underwent non-radical surgical excision, is under a follow-up for 10 months, and shows no local recurrences.

Hemorrhage of MRI and Immunohistochemical Panels Distinguish Secretory Carcinoma From Acinic Cell Carcinoma.

ObjectivesSecretory carcinoma (SC, mammary analogue secretory carcinoma) is a salivary gland tumor with ETV6‐NTRK3 gene fusion, and its differential diagnosis includes acinic cell carcinoma (ACC). As hemorrhage is often seen in SC, we hypothesized that magnetic resonance imaging (MRI) and immunohistochemical analyses could distinguish SC from ACC.Study DesignRetrospective study.MethodsWe used ETV6‐NTRK3 gene fusion analyses to reclassify 19 parotid gland tumors that had previously been diagnosed as SC or ACC, and then investigated hemorrhage in both hematoxylin‐eosin (H&E)‐stained sections and MRIs, and immunohistochemical expression of S‐100, mammaglobin, DOG1, and α‐amylase.ResultsThe 19 tumors were genetically reclassified into 11 (58%) SC and 8 (42%) ACC. Combined S‐100 and mammaglobin were specific for SC; whereas DOG1 was specific for ACC, and α‐amylase was expressed only in 4 ACC cases (50%). H&E staining showed hemorrhage with hemosiderin deposition in all SC cases, and T2‐weighted MRI showed hypointense areas in all investigated SC cases, but not in ACC.ConclusionHemorrhage with hemosiderin deposition is frequently present in SC, and hemorrhage findings in MRI and an immunohistochemical panels for S‐100, mammaglobin and DOG1 can distinguish SC from ACC.Level of Evidence3b

Salivary Secretory Carcinoma With a Novel ETV6-MET Fusion

Secretory carcinoma of the salivary glands, also known as mammary analogue secretory carcinoma, is a recently described tumor characterized by generally indolent clinical behavior and recurrent ETV6-NTRK3 fusions. However, a small subset of recent cases with high-grade histology, aggressive behavior, or alternate molecular findings are expanding the spectrum of this entity. In this case, a 59-year-old female presented with an infiltrative submandibular gland tumor that was originally classified as a high-grade acinic cell carcinoma, papillary-cystic variant. She developed persistent local disease and, 11 years after initial presentation, was found to have widespread metastases. Rereview of her primary tumor highlighted microcystic, papillary, and solid architecture, eosinophilic cytoplasm, vesicular nuclei with prominent nucleoli, abundant mitotic figures, and necrosis. Immunostains showed the tumor cells to be positive for S100 and mammaglobin and negative for DOG-1, and fluorescence in situ hybridization highlighted an ETV6 rearrangement, supporting a diagnosis of high-grade secretory carcinoma. Finally, next-generation sequencing demonstrated a novel ETV6-MET fusion. To our knowledge, this is the first ETV6-MET fusion reported in secretory carcinoma. This finding further expands the definition of secretory carcinoma while carrying implications for selecting appropriate targeted therapy.

Clinicopathological characteristics and outcome of 31 patients with ETV6-NTRK3 fusion gene confirmed (mammary analogue) secretory carcinoma of salivary glands

ObjectivesIn 2010, a new subtype of salivary gland cancer (SGC), (mammary analogue) secretory carcinoma (SC), was defined, characterized by the ETV6-NTRK3 fusion gene. As clinical behavior and outcome data of this histological subtype tumor are still sparse, we aimed to describe the clinicopathological course and outcome of a series of translocation positive SC patients. Patient and methodsWe re-evaluated the pathological diagnosis of a subset of SGCs, diagnosed in 4 of 8 Dutch head and neck centers. Subsequently, tumors with a morphological resemblance to SC were tested for the ETV6-NTRK3 fusion gene using RT-PCR. Furthermore, patients prospectively diagnosed with SC were included. The clinical characteristics and outcomes were retrieved from the patient files. ResultsThirty-one patients with ETV6-NTRK3 fusion gene positive SC were included. The median age was 49 years, 17 patients (55%) were male. Eighteen tumors (58%) arose in the parotid gland. One patient presented with lymph node metastasis. All patients underwent tumor resection and 4 patients had a neck dissection. Four patients had re-resection and 15 patients (48%) received postoperative radiotherapy. One patient developed a local recurrence, no regional recurrences or distant metastases were observed. After a median follow-up of 49 months the 5- and 10-year overall survival were 95%, the 5- and 10-year disease free survival were 89%. ConclusionThe clinical course of SC is favorable with a low rate of locoregional recurrence and excellent survival. Given the low incidence of nodal metastases, elective neck treatment, i.e. surgery and/or radiotherapy, does not seem to be indicated.