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BACKGROUND Mammary analogue secretory carcinoma (MASC) with an ETS variant gene 6 ( ETV6)-neurotrophic tyrosine kinase receptor type 3 ( NTRK3) translocation is a newly described type of salivary gland cancer. It is known that overexpression of signal transducer and activator of transcription 5a (STAT5a) occurs in secretory carcinoma of the breast and MASC, and STAT5a expression may be related to the ETV6- NTRK3 translocation. It was hypothesized that phosphorylated signal transducer and activator of transcription 5 (p-STAT5) might be specifically expressed in MASC of the salivary gland. METHODS The expression of p-STAT5 and mammaglobin (MMG) was examined with immunohistochemistry (IHC)/immunocytochemistry (ICC) in tissue sections from 58 salivary gland cancers (8 MASCs and 50 other salivary gland cancers) and in cytological smears from 17 salivary gland cancers (7 MASCs with paired histologic samples and 10 other salivary gland cancers). RESULTS p-STAT5 IHC was clearly increased in MASC versus normal salivary gland tissue and other salivary gland cancers. p-STAT5 expression was found in 7 of 8 MASCs (87.5%) and in none of the 50 other salivary gland cancers (0%) by IHC. On cytology, p-STAT5 expression was found in all cases of MASC (7 of 7 or 100%) but in none of the 10 other salivary gland cancers (0%) by ICC. The expression rate of MMG by histology and cytology was higher than that of p-STAT5 in the other salivary gland cancers. CONCLUSIONS p-STAT5 might be useful as a detection marker of MASC in the differential diagnosis of salivary gland cancers, and initial screening with p-STAT5 IHC/ICC, combined with auxiliary fluorescence in situ hybridization confirmation, is a reliable, economical approach to identifying MASC of the salivary gland. Cancer (Cancer Cytopathol) 2015;123:603-11. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

Mammary analogue secretory carcinoma (MASC) has a specific ETV6-NTRK3 translocation and morphologically overlaps with acinic cell carcinoma (AciCC). Before the recognition of MASC, in AciCC, four histologic patterns were identified including microcystic, solid, papillary-cystic, and follicular. The aim of this study was to evaluate histologic patterns in these two neoplasms through comprehensive histologic subtyping. Using fluorescence in situ hybridization (FISH), we identified 14 cases of MASC and 21 cases of AciCC. We used comprehensive histologic subtyping to provide a semiquantitive assessment of histologic patterns in each tumor and performed immunohistochemical analyses including S100/vimentin/mammaglobin/DOG1. MASC often presented papillary-cystic patterns without a solid component, previously considered to be one of the four major patterns associated with AciCC. However, in our study, this histologic feature was rarely seen in AciCC and more characteristic of MASC. In aspiration cytology samples, MASC was associated with more cellular atypia. An immunohistochemical panel of S100/mammaglobin/DOG1 was found useful for differential diagnosis. Comprehensive subtyping of histologic patterns is a useful screening method prior to initiation of molecular testing. [ABSTRACT FROM AUTHOR]

Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumour that harbours the recurrent ETV6- NTRK3 translocation. This is the first series of MASC cases identified in the historic cohort of carcinomas of salivary glands with clinical/pathological correlation and follow-up data. We reviewed 183 primary carcinomas of major and minor salivary glands resected at the Medical University of Gdańsk, Poland, between 1992 and 2012. Based on morphology and immunohistochemistry, cases suspicious for MASC were selected, and the diagnosis was confirmed by fluorescence in situ hybridization (FISH) for ETV6 rearrangement and by RT-PCR for the ETV6- NTRK3 fusion transcript. Seven carcinomas met the criteria of MASC, as they exhibited a typical appearance with solid/microcystic and papillary architecture and intraluminal secretions, and cells completely devoid of basophilic cytoplasmic zymogen granules indicative of true acinar differentiation. The only paediatric case was an unencapsulated tumour composed of macrocystic structures covered by a mostly single but, focally, double layer of cells with apocrine morphology. In all cases, the neoplastic cells revealed immunoreactivity for S100, mammaglobin, cytokeratin CK7, CK8, STAT5a and vimentin. FISH for ETV6 gene rearrangement was positive in six out of seven cases, and RT-PCR was positive in three cases. MASC is a new entity of malignant epithelial salivary gland tumours not included in the 2005 WHO Classification of Head and Neck Tumours. There is a growing body of evidence that it is not as rare as was assumed, as is also indicated by our series (3.8 %). In most cases, MASC shares some microscopic features with AciCC, adenocarcinoma/cystadenocarcinoma NOS and low-grade MEC. In rare cases, MASC with high-grade transformation may mimic the morphological appearances of high-grade salivary gland malignancies, such as salivary duct carcinoma. [ABSTRACT FROM AUTHOR]

The recently described mammary analogue secretory carcinoma (MASC) is a low-grade salivary gland malignancy that harbors the recurrent cytogenetic abnormality t(12;15) (p13;q25) ETV6- NTRK3. Confirmation of this is currently considered the gold standard for diagnosis. Some have postulated that morphology together with supporting immunohistochemistry is sufficient to diagnose MASC. In this study we retrospectively review a series of 19 MASCs diagnosed based on histology in conjunction with immunohistochemistry; subsequently we performed in situ hybridization using an ETV6 break-apart probe. Immunohistochemistry for S100 protein and mammaglobin as well as fluorescence in situ hybridization using the Vysis ETV6 Dual Color Break-Apart FISH Probe Kit were performed on all cases. The 19 cases were from 12 females and 7 males with ages ranging from 16 to 76 years (mean = 45 years). Sixteen cases were from the parotid gland, 1 case was from a periparotid lymph node and 2 cases were from the submandibular gland. All 19 cases demonstrated moderate to strong expression of S100 protein. Eighteen cases demonstrated strong, diffuse expression of mammaglobin, while one case had only rare tumor cells that strongly expressed mammaglobin. Eighteen of 19 cases (95 %) demonstrated the ETV6 rearrangement by fluorescence in situ hybridization. Given that morphology together with immunohistochemistry is highly correlated with the ETV6 gene rearrangement, we conclude that molecular confirmation is not required to diagnose MASC. [ABSTRACT FROM AUTHOR]

Mammary analogue secretory carcinoma is a rare malignant tumor of the salivary glands that typically involves the major glands. The aim of the current study is to report a rare case of mammary analogue secretory carcinoma that presented with left cervical lymphadenopathy. A 59-year-old lady presented with left cervical lymphadenopathy. Tissue biopsy and immunohistochemistry revealed metastatic carcinoma, favoring ovarian origin. Staging workup was performed and, ultimately, the patient was treated as having a carcinoma of unknown primary. After showing partial response to therapy, left side neck dissection was performed. Based on better assessment of the histologic picture and a broader panel of immunohistochemistry performed on the excision specimen, the final diagnosis was that of mammary analogue secretory carcinoma. Mammary analogue secretory carcinoma is usually an indolent salivary gland carcinoma, with the majority of patients presenting with a slow-growing, painless mass measuring approximately 2 cm in size, and a reported duration ranging from 2 months to several years. In certain cases, pain and facial paralysis have been reported. It could also be found incidentally during radiologic assessment for thyroid illness or routine dental screening. Diagnosing mammary analogue secretory carcinoma is challenging, and this should be in the differential diagnosis list of metastatic carcinomas to cervical lymph nodes. • Mammary analogue secretory carcinoma (MASC) is a rare malignant salivary gland neoplasm. • MASC has similar histologic and molecular characteristics to breast secretory carcinoma. • MASC was first reported in 2010 by Skalova et al. • In this report, a brief review regarding this condition is discussed. [ABSTRACT FROM AUTHOR]

Mammary analogue secretory carcinoma (MASC) is a recently identified salivary gland neoplasm that can mimic other salivary gland tumours such as acinic cell carcinoma and cystadenocarcinoma. It is distinguished from these by differences in immunohistochemical profile and the identification of an ETV6-NTRK3 translocation (12;15)(p13;q25), which is also found in secretory carcinomas of the breast. Previous publications have suggested that MASC tumours have similar biological behaviour to acinic cell carcinoma. We report two cases of MASC that affected the upper lip, and showed an infiltrative and locally aggressive growth pattern that required several operations to ensure clearance of microscopic tumour cells. [ABSTRACT FROM AUTHOR]

We report the first case of mammary analogue secretory carcinoma (MASC) arising as a secondary malignancy in a 14 years old child with a history of atypical teratoid rhabdoid tumor (ATRT). Although MASC and ATRT are both rare malignancies, they do not share the same genetic and molecular profiles. MASC is a salivary malignancy characterized by a t(12;15)(p13;q25) translocation, resulting in an ETV6-NTRK3 fusion product encoding for a tyrosine kinase. ATRT is a highly malignant pediatric tumor characterized by a chromosome 22 mutation in the hSNF5/INI1 gene, encoding for a chromatin remodeling protein. Additionally, although mucoepidermoid carcinoma has been described as a secondary malignancy post-therapy for head and neck tumors, MASC has only been reported as a primary malignancy. Our patient was treated with a complete resection of his left sided ATRT at age 3 followed postoperatively with chemoradiotherapy. At age 14 he underwent a parotidectomy for his 1 year history of a left sided preauricular mass and was subsequently diagnosed with MASC. We not only report a case of two rare malignancies in one patient, but also the first case of MASC arising as a secondary malignancy. [ABSTRACT FROM AUTHOR]

Mammary analogue secretory carcinoma (MASC) is a recently described malignancy of the salivary glands characterized by an ETV6-NTRK3 (EN) fusion gene. Morphologically, MASC is sometimes difficult to distinguish from acinic cell carcinoma. Consequently, identifying the chromosomal translocation is essential for diagnosis. We present a case of parotid gland MASC in a 13-year-old boy. To the best of our knowledge, this is the youngest case reported in the literature. Histologic evaluation showed a tumor composed of microcysts, tubular structures, solid nests, or papillary architecture, with secretions within the lumens of the cysts or tubules. Immunohistochemically, tumor cells showed diffuse positive staining of S-100 protein, cytokeratin 19, and vimentin. ETV6 rearrangement was detected by fluorescence in situ hybridization and EN fusion transcripts were verified by reverse transcription (RT-PCR) assay. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis To review the known histopathologic findings and clinical behavior of mammary analogue secretory carcinoma (MASC). Data Sources PubMed. Review Methods Literature search using the terms 'Mammary analogue secretory carcinoma,' 'Mammary analog secretory carcinoma,' and 'MASC' to identify all relevant publications. Results MASC is an unusual and rare malignant salivary gland tumor first described in 2010. It shares histologic, immunohistochemical, and genetic features with secretory carcinoma of the breast. The clinical behavior of MASC ranges from slowly growing tumors that infrequently recur after surgical resection to aggressive tumors that cause widespread metastasis and death. Many cases of MASC were discovered in archived cases previously classified as acinic cell carcinoma, mucoepidermoid carcinoma, and adenocarcinoma not otherwise specified. Conclusion MASC is a newly recognized variant of salivary gland malignancy. Further research is needed to better delineate its overall prevalence and to define an appropriate treatment algorithm for this new clinical entity. Level of Evidence NA. Laryngoscope, 124:188-195, 2014 [ABSTRACT FROM AUTHOR]

GATA3 is a zinc finger transcription factor that regulates the normal development of many tissues and cell types. Recent studies have shown that immunohistochemical nuclear staining for GATA3 among tumors is highly restricted to carcinomas of breast and urothelial origin; however salivary gland tumors have not been tested. Given that breast and salivary gland tissues are very similar with respect to embryologic development and structure, we performed GATA3 staining on a spectrum of salivary gland neoplasms. GATA3 immunohistochemistry was performed on a diverse collection of 180 benign and malignant salivary gland neoplasms including 10 acinic cell carcinomas, 2 adenocarcinomas not otherwise specified, 41 adenoid cystic carcinomas, 2 epithelial-myoepithelial carcinomas, 1 low grade cribriform cystadenocarcinoma, 15 mammary analogue secretory carcinomas, 7 metastatic squamous cell carcinomas, 27 mucoepidermoid carcinomas, 2 oncocytic carcinomas, 5 oncocytomas, 34 pleomorphic adenomas, 4 polymorphous low grade adenocarcinomas, 25 salivary duct carcinomas, and 5 Warthin tumors. Staining for GATA3 was observed in 92/180 (51 %) of salivary gland tumors. GATA3 staining was observed in most of the tumor types, but diffuse immunolabeling was consistently seen in salivary duct carcinoma (25 of 25) and mammary analogue secretory carcinoma (15 of 15)-the two tumor types that most closely resemble breast neoplasia. Background benign salivary gland tissue was also usually weakly positive in both acini and ducts. GATA3 immunostaining is not restricted to tumors of breast and urothelial origin. Rather, it is expressed across many different types of salivary gland neoplasms. As a result, salivary gland origin should be considered in the differential diagnosis of a GATA3-positive carcinoma, particularly in the head and neck. Although GATA3 immunohistochemistry is not helpful in resolving the differential diagnosis between a primary salivary gland neoplasm and metastatic breast cancer, it may have some utility in subtyping salivary gland tumors, particularly salivary duct carcinoma and mammary analogue secretory carcinoma. [ABSTRACT FROM AUTHOR]

Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor characterized by ETV6 translocation. It appears that prior studies have identified MASC by reviewing salivary gland carcinomas, such as acinic cell carcinoma and adenocarcinoma, not otherwise specified. To address the possibility of MASC mimicking benign salivary neoplasms we reviewed 12 salivary gland (cyst)adenomas diagnosed prior to the discovery of MASC. One encapsulated (cyst)adenoma of the parotid gland demonstrated features of MASC. The diagnosis was confirmed by fluorescence in situ hybridization with an ETV6 break-apart probe. An unusual complex pattern of ETV6 rearrangement with duplication of the telomeric/distal ETV6 probe was identified. This case illustrates that MASC may mimic salivary (cyst)adenomas. To more accurately assess true clinical and morphologic spectrum of MASC, future studies may have to include review of salivary (cyst)adenomas. The differential diagnosis of MASC may have to be expanded to include cases resembling salivary (cyst)adenomas. [ABSTRACT FROM AUTHOR]

Aims Mammary analogue secretory carcinoma ( MASC) of salivary glands shows morphological similarities to milk-secreting mammary epithelial cells. The aim of this study was to analyse the immunohistochemical expression of adipophilin (a component of milk lipid globule membranes) and of proteins related to secretory mechanisms ( STAT5a and mammaglobin) in MASC and other salivary tumours. Methods and results Ten cases of MASC (all with ETV6 translocation) and 83 other salivary carcinomas were studied. In all MASC cases, adipophilin stained numerous large lipid droplets. These droplets were minute in other salivary carcinomas, except for sebaceous carcinoma. Overexpression of STAT5a was detected in all MASC cases, but only occasionally in other carcinomas. Mammaglobin expression occurred frequently in MASC (70% of cases), whereas, in other carcinomas, it was uncommon and limited. Only MASC showed cytoplasmic reactivity for p63, particularly in papillary-cystic areas. Positivity for S100, vimentin and high molecular weight keratin was observed in 100% of MASC cases. Conclusions MASC is a lipid-rich tumour containing large lipid droplets covered by adipophilin. This finding can be included among its defining immunohistochemical features, and possibly represents lactation-like secretory differentiation. Strong expression of STAT5a and cytoplasmic p63 in MASC reinforces this hypothesis. [ABSTRACT FROM AUTHOR]

Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor that has morphologic features similar to secretory carcinoma of the breast and that also harbors the same ETV6 translocation. Diffuse mammaglobin and S-100 immunoreactivity are used to differentiate MASC from its morphologic mimics, especially acinic cell carcinoma and adenocarcinoma, not otherwise specified. However, the combination of mammaglobin and S-100 immunoreactivity has not been well studied in other types of salivary gland carcinomas that may have focal areas reminiscent of MASC. Here we evaluated mammaglobin and S-100 immunoreactivity in 15 cases each of polymorphous lowgrade adenocarcinoma, adenoid cystic carcinoma and mucoepidermoid carcinoma, and also in 2 cases of adenocarcinoma, not otherwise specified, and 1 mucinous adenocarcinoma. Cases with significant coexpression of mammaglobin and S-100 (moderate or strong immunoreactivity in N25% of tumor cells) were further analyzed by fluorescence in situ hybridization using the ETV6 (12p13) break-apart probe. Nine cases (60%) of polymorphous low-grade adenocarcinoma and two (13.3%) of adenoid cystic carcinoma met the criteria for significant co-expression of mammaglobin and S-100. All were negative for the ETV6 translocation by fluorescence in situ hybridization. Although mammaglobin and S-100 positivity was seen in the majority of polymorphous low-grade adenocarcinomas and a minority of adenoid cystic carcinomas, none were positive for the ETV6 translocation characteristic of MASC. This indicates a need for caution in the use of immunohistochemistry for diagnosing MASC, especially in the absence of cytogenetic confirmation. [ABSTRACT FROM AUTHOR]

Mammary Analogue Secretory Carcinoma (MASC) is a recently described salivary gland tumor frequently sampled via fine-needle aspiration. The cytologic features of MASC are not entirely distinctive and can simulate acinic cell carcinoma, but the tumor harbors an ETV6 gene rearrangement resulting in an ETV6-NTRK3 fusion gene. We present a case of MASC arising in a 31 year old man with a history of multiple radio-embolization procedures. • MASC is a recently described salivary gland tumor frequently sampled via fine-needle aspiration • The cytologic features of MASC are not entirely distinctive, and ancillary studies are required to confirm the diagnosis • The granular cytoplasm of MASC presents a pitfall relative to the differential diagnosis of acinic cell carcinoma [ABSTRACT FROM AUTHOR]

Mammary analogue secretory carcinoma is a recently described salivary gland neoplasm defined by ETV6-NTRK3 gene fusion. Mammary analogue secretory carcinoma's morphology is not entirely specific and overlaps with other salivary gland tumors. Documenting ETV6 rearrangement is confirmatory, but most laboratories are not equipped to perform this test. As mammary analogue secretory carcinomas are positive for mammaglobin, immunohistochemistry could potentially replace molecular testing as a confirmatory test, but the specificity of mammaglobin has not been evaluated across a large and diverse group of salivary gland tumors. One hundred thirty-one salivary gland neoplasms were evaluated by routine microscopy, mammaglobin immunohistochemistry, and ETV6 break-apart fluorescent in situ hybridization. The cases included 15 mammary analogue secretory carcinomas, 44 adenoid cystic carcinomas, 33 pleomorphic adenomas, 18 mucoepidermoid carcinomas, 10 acinic cell carcinomas, 4 adenocarcinomas not otherwise specified, 3 polymorphous low-grade adenocarcinomas, 3 salivary duct carcinomas, and 1 lowgrade cribriform cystadenocarcinoma. All 15 mammary analogue secretory carcinomas harbored the ETV6 translocation and were strongly mammaglobin positive. None of the 116 other tumors carried the ETV6 translocation; however, mammaglobin staining was present in 1 (100%) of 1 low-grade cribriform cystadenocarcinoma, 2 (67%) of 3 polymorphous low-grade adenocarcinomas, 2 (67%) of 3 salivary duct carcinomas, 2 (11%) of 18 mucoepidermoid carcinomas, and 2 (6%) of 33 pleomorphic adenomas. Mammaglobin is highly sensitive for mammary analogue secretory carcinoma, but immunostaining can occur in a variety of tumors that do not harbor the ETV6 translocation. Strategic use of mammaglobin immunostaining has a role in the differential diagnosis of salivary gland neoplasms, but it should not be indiscriminately used as a confirmatory test for mammary analogue secretory carcinoma. © 2013 Elsevier Inc. All rights reserved. [ABSTRACT FROM AUTHOR]

Mammary analogue secretory carcinoma of salivary gland origin (MASC) is a recently described tumor with ETV6 translocation. Akin to secretory breast cancer, MASC expresses S-100 protein, mammaglobin, vimentin, and harbors a t(12;15) (p13;q25) translocation which leads to ETV6- NTRK3 fusion product. Histologically, MASC displays a lobulated growth pattern and is often composed of microcystic, tubular, and solid structures with abundant eosinophilic homogeneous or bubbly secretions. Colloid-like secretory material stains positive for periodic acid-Schiff (PAS) with and without diastase and for Alcian blue. The cells of MASC are devoid of PAS-positive secretory zymogen granules. These features help to exclude the most important differential diagnostic considerations, namely acinic cell carcinoma, low-grade cribriform cystadenocarcinoma, cystadenocarcinoma (not otherwise specified), and low-grade mucoepidermoid carcinoma. To date the presence of the ETV6- NTRK3 fusion gene has not been demonstrated in any other salivary gland tumor than MASC. It is likely that MASC is more common than currently recognized and with further studies, the clinical need for molecular studies of the ETV6- NTRK3 fusion may diminish. However, molecular testing is recommended at this time to arrive at the diagnosis of MASC. [ABSTRACT FROM AUTHOR]

BACKGROUND Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland neoplasm that is defined by ETV6-NTRK3 gene fusion. To the best of the authors' knowledge, only rare case reports of the cytopathologic features of MASC have been published to date. METHODS A wide variety of archival salivary gland tumors were tested for ETV6 translocation by break-apart fluorescent in situ hybridization. Positive cases with preoperative fine-needle aspiration (FNA) specimens or intraoperative touch preparations were retrieved from the archives of The Johns Hopkins Hospital. All smears were reviewed and the cytologic characteristics were described. RESULTS Five cases of MASC with cytopathologic material (4 FNA specimens and 1 touch preparation) were identified. The cases occurred in 3 men and 2 women ranging in age from 21 years to 78 years (mean, 52 years). On the cytologic smears, the MASCs were variably cellular and exhibited 2 different architectural patterns: 1) intact tissue fragments with isomorphic cells arranged in a sheet-like or papillary configuration; and 2) dispersed and dissociated cells with a mostly 'histiocyte-like' appearance with large cells containing abundant vacuolated cytoplasm. No matrix tissue or stromal spindled cells were present. The cells did not display acinic differentiation in the form of cytoplasmic zymogen granules. In each case, the preoperative FNA correctly identified a neoplasm, and the most frequent diagnostic considerations were acinic cell carcinoma, mucoepidermoid carcinoma, and pleomorphic adenoma. CONCLUSIONS MASC is a newly described salivary gland tumor that should be considered in the differential diagnosis of low-grade salivary gland neoplasms. Its cytologic features overlap considerably with those of other tumors, especially acinic cell carcinoma and mucoepidermoid carcinoma. Cancer (Cancer Cytopathol) 2013;121:228-33. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND Mammary analogue secretory carcinoma (MASC) of the salivary glands is a newly described tumor entity associated with the t(12;15)(p13;q25) ETV6-NTRK3 translocation. Early studies have shown this tumor to be a distinct entity with histologic, biologic, and clinical differences from acinic cell carcinoma and adenocarcinoma, not otherwise specified. Because this tumor was described only recently, it remains relatively unknown outside of head and neck specialty pathology centers. METHODS In the current study, 6 cases of fine-needle aspiration cytology from histologically and/or molecularly confirmed cases of MASC are presented. RESULTS Using cytomorphology, MASC primarily raises the differential diagnosis of an oncocytic salivary gland tumor but there are some features that can suggest the specific diagnosis of MASC. The 6 cases presented in the current study all demonstrated at least focal cytoplasmic vacuolization and papillary formations on smears. MASC can be differentiated from acinic cell carcinoma by a lack of periodic acid-Schiff diastase-positive zymogen granules and S-100 protein positivity. CONCLUSIONS The results of the current study the ability of ETV6 break-apart fluorescence in situ hybridization to detect gene rearrangement on cell block material. This is the first report of a case of MASC prospectively diagnosed on a cytology specimen. Cancer (Cancer Cytopathol) 2013;121:234-41. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland neoplasm that is characterized by its striking morphologic and molecular similarities to secretory carcinoma of the breast. This review highlights the characteristic clinical, histologic, immunophenotypic, and molecular features of MASC, and draws attention to the differential diagnosis of this increasingly recognized tumor. [ABSTRACT FROM AUTHOR]

Differentiation of salivary gland acinic cell carcinoma from mucoepidermoid carcinoma can be diagnostically challenging as both may have prominent mucin production. P63 is a p53 homologue required for limb and epidermal morphogenesis. It is expressed in basal and myoepithelial cells of normal salivary gland tissues. In this immunohistochemical study, we examined the expression of p63 in salivary gland acinic cell and mucoepidermoid carcinomas (MEC) and its use in differentiating these two entities. A search was performed and appropriate cases were selected from Lifespan Hospital System archives as well as the consult archives of one author (DRG). 31 salivary gland acinic cell carcinomas (ACC) and 24 MEC were examined for p63 expression by immunohistochemistry. The nuclear immunoreactivity was examined by both authors and was graded semi-quantitatively with negative being less than 10 % of cells staining. Positive staining was graded as follows: 10-25 % of tumor cells staining was weakly positive, 26-75 % of tumor cells staining was moderately positive, and 76-100 % of tumor cells staining was strongly positive. Negative nuclear staining of the tumor cells was seen in 30/31 (96 %) of salivary gland ACC while 1/31 (3 %) showed diffuse nuclear staining of the tumor cells. This latter case was later reclassified as mammary analogue secretory carcinoma following confirmatory molecular testing for the ETV6-NTRK3 fusion gene. Strong positive nuclear staining of the tumor cells was seen in 24 (100 %) of salivary gland MEC cases. P63 is an immunohistochemical stain that can potentially aid in differentiating unusual ACC with prominent mucin production from MEC of the salivary gland. According to this study, acinic cell carcinoma is always negative for p63 immunoreactivity while mucoepidermoid carcinoma is always positive. [ABSTRACT FROM AUTHOR]

Chiosea S I, Griffith C, Assaad A & Seethala R R (2012) Histopathology 61, 387-394 Clinicopathological characterization of mammary analogue secretory carcinoma of salivary glands Aims: Mammary analogue secretory carcinoma (MASC) is a recently described tumour with ETV6 translocation. We aimed to characterize the clinical significance of recognizing MASC. Methods and results: Thirty-six patients with MASC (27 identified retrospectively and nine prospectively) are presented. Historically, MASC mimicked other salivary tumours, as follows: 14 of 37 (37.8%) adenocarcinoma, not otherwise specified, 11 of 89 (12.4%) acinic cell carcinomas (AciCC), one of five (20%) mucin-producing signet ring adenocarcinomas, and one of 165 (0.6%) mucoepidermoid carcinomas. Demographically, MASC affected males more commonly (1.4:1). The average age at diagnosis was 45.7 years. Parotid gland was the most common site of involvement (26 of 36, 72.2%), although other head and neck sites, including the base of tongue, were affected. Of 18 patients with neck dissection, lymph node involvement was identified in four patients (four of 18, 22.2%). Survival analysis of MASC cases presented here, combined with those reported previously, revealed a mean disease-free survival for patients with MASC of 92 months [ n = 29; 95% confidence interval (CI) 71-115 months], compared with a mean DFS of 121 months for patients with AciCC ( n = 38; 95% CI 92-149, P = 0.43). Conclusions: Although perhaps slightly more aggressive, MASC clinical outcome mimics that of AciCC. [ABSTRACT FROM AUTHOR]

Abstract: The review summarizes the new findings in salivary gland pathology with particular reference to molecular genetic developments. In particular, newly recognized entities and specific chromosomal translocations associated with salivary gland carcinomas are discussed. Firstly, there are three types of salivary gland carcinomas which harbour important oncogenic translocations: mucoepidermoid carcinoma with the translocation t(11; 19)(q21; p13) CRTC1-MAML2 (as well as several other less frequent ones), adenoid cystic carcinoma with the translocation t(6; 9)(q22–23; p23–24) MYB-NFIB, and the recently described entity of mammary analogue secretory carcinoma (MASC) characterized by the translocation t(12; 15)(p13; q25) ETV6-NTRK3. Secondly, sclerosing polycystic adenosis was described in 1996 as possibly a salivary counterpart to benign fibrocystic disease of the breast, but recent molecular evidence of clonality suggests it is neoplastic in nature. Finally, new molecular developments in salivary duct carcinoma and molecular mechanisms responsible for high grade transformation and tumour progression in other neoplasms will be addressed. [Copyright &y& Elsevier]

Abstract: Salivary gland neoplasms are a morphologically heterogeneous group of lesions that are occasionally diagnostically challenging. This review describes the clinicopathologic features of a selected group of salivary gland carcinomas with a focus on their distinctive molecular characteristics. Mammary analogue secretory carcinoma is a recently described entity characterized by a t(12;15)(p13;q25) translocation with formation of an ETV6–NTRK3 fusion gene. Hyalinizing clear cell carcinoma is a low-grade tumour with infrequent nodal and distant metastasis, recently shown to harbour an EWSR1–ATF1 fusion gene. The MECT1–MAML2 fusion gene resulting from a t(11;19)(q21;p13) translocation, is now known to be a feature of both low and high-grade mucoepidermoid carcinomas which has been associated with improved survival. A recently detected t(6;9)(q22-23;p23-34) translocation resulting in the MYB–NFIB fusion gene has been identified in at least a subset of adenoid cystic carcinomas. Evidence that increased MYB expression may be significantly correlated with poor survival is emerging. [Copyright &y& Elsevier]

Mammary analogue secretory carcinoma (MASC) was recently identified as a distinct salivary gland neoplasm, morphologically resembling intercalated duct cell predominant acinic cell carcinoma (AciCC). To determine how frequently MASC has mimicked an intercalated duct cell predominant AciCC, we reviewed AciCC diagnosed from 1956 to 1975. Nine AciCC consecutively diagnosed in that period were identified. Based on morphologic examination, one case diagnosed as AciCC in a male patient in 1960 was re-classified as MASC [confirmed by fluorescence in situ hybridization (FISH) showing ETV6 translocation]. Another case diagnosed as AciCC of the palate in a female patient in 1975 was re-classified as mucoepidermoid carcinoma (based on the lack of acinar differentiation, presence of mucous cells, and confirmed by FISH showing MAML2 translocation). In this proof-of-principle study, we show that 1 in 9 cases historically designated as AciCC represents a MASC. 'Intercalated duct cell predominant AciCC', especially among male patients, most likely represent examples of MASC. For anatomic sites outside of the parotid glands, broader differential diagnoses should be considered before accepting morphologic variants of AciCC as the final diagnosis. [ABSTRACT FROM AUTHOR]

Mammary analogue secretory carcinoma (MASC) is a rare malignant tumour of the salivary glands, with only few cases reported in the literature to date. Initial preoperative staging is crucial for all patients with an oral malignancy to visualize the tumour, detect lymph node or distant metastases and plan therapeutic interventions. In the case presented herein, radiological imaging revealed a tumour of the right hard palate with suspected positive contralateral lymph nodes. Therefore, local tumour resection comprising hemimaxillectomy and bilateral neck dissection was performed. The diagnosis of MASC was finally based on characteristic histopathological and immunohistochemical findings, such as S100 protein and mammaglobin positivity. The diagnosis of MASC may be challenging, as such findings lack specificity. To confirm the diagnosis, molecular genetic examinations may be performed to detect a highly specific ETV6-NTRK3 fusion gene. Depending on the results of these examinations, surgery, alone or combined with adjuvant radiation or chemoradiation, is the recommended approach. In summary, MASC should be treated similarly to other low-grade salivary gland tumours, such as acinic cell carcinoma, as they exhibit biological and histopathological similarities. [ABSTRACT FROM AUTHOR]