Secretory carcinoma (SC) of the salivary gland is a rare entity with limited published literature on cytomorphology. The authors present the largest cohort to date of SC fine-needle aspiration (FNA) cases.
FNA cases of histologically confirmed SC were retrospectively retrieved from 12 academic institutions in the United States, Italy, Finland, and Brazil. The collated data included patient demographics, imaging findings, cytopathologic diagnoses according to the Milan System for Reporting Salivary Gland Cytopathology, cytomorphologic characteristics, and immunohistochemical/molecular profiles.
In total, 40 SCs were identified (male-to-female ratio, 14:26) in patients with a mean age of 52 years (age range, 13-80 years). Ultrasound imagining revealed a hypoechoic, ovoid, poorly defined, or lobulated mass. The most common primary site was the parotid gland (30 of 40 tumors). Regional lymph node metastasis (9 patients) and distant metastasis (4 patients; brain, liver, lungs, and mediastinum) were noted. Two patients died of disease. FNA smears were cellular and demonstrated mainly large, round cells with intracytoplasmic vacuoles or granules and round-to-oval nuclei with smooth nuclear contour, minimal irregularities, and prominent nucleoli arranged predominantly in clusters, papillary formations, and single cells. The background was variable and contained inflammatory cells, mucin, or proteinaceous material. The diagnoses were malignant (19 of 38 tumors; 50%), suspicious for malignancy (10 of 38 tumors; 26%), salivary gland neoplasm of uncertain malignant potential (7 of 38 tumors; 18%), and atypia of undetermined significance (2 of 38 tumors; 6%) according to the Milan System for Reporting Salivary Gland Cytopathology. Two malignant cases (2 of 40 tumors; 5%) were metastases. The neoplastic cells were immunoreactive for S100 (23 of 24 tumors), mammaglobin (18 of 18 tumors), GATA-3 (13 of 13 tumors), AE1/AE3 (7 of 7 tumors), and vimentin (6 of 6 tumors). ETV6-NTRK3 fusion was detected in 32 of 33 tumors by fluorescence in situ hybridization (n = 32) and next-generation sequencing (n = 1).
Familiarity with cytomorphologic features and the immunohistochemical/molecular profile of SC can enhance diagnostic accuracy.

UNASSIGNED: GATA-3 is a potential marker for detection of metastatic breast carcinoma, reportedly more sensitive than mammaglobin (MAM) and GCDFP-15. We aim to compare the sensitivity of GATA-3, MAM and GCDFP-15 in determining the breast origin of malignant effusions.
UNASSIGNED: Cell blocks from 27 cases of serous effusions positive for metastatic breast cancer were retrieved. Immunohistochemistry for GATA-3, MAM, gross cystic disease fluid protein 15 (GCDFP-15), estrogen receptor (ER) and progesterone receptor (PR) was performed on cell-block micro-array. Statistical analysis using two ways Chi square, one-way ANOVA and multiple regression was performed.
UNASSIGNED: The detection rate of breast cancer in serous fluid was significantly higher with GATA-3 (88.8 %, X2=15.9, p=0.00034) than with MAM (51.8 %) and GCDFP-15 (37.0 %). All ER positive cases (19) were GATA-3 positive. Conversely, all GATA-3 negative cases (3) were ER negative. The intensity of stain and percentage of positive cells were significantly higher with GATA-3 (p<0.0001) than with MAM and GCDFP-15. The intensity and percentage of positive cells score of GATA-3 were statistically associated with ER stain intensity and percentage of positive cell scores.
UNASSIGNED: GATA3 is a sensitive marker, superior to MAM and GCDFP-15 in determining the breast origin of metastatic adenocarcinoma. It is also strongly associated with ER expression.

Diagnostic verification of breast cancer metastasis with histopathology and imaging analysis is essential to determine tumor staging. The aim of this study was to validate the utility of GATA3 immunohistochemistry as a diagnostic marker for breast cancer metastases and metastases of unknown primary origin. Retrospective immunohistochemical analysis of GATA3 expression in 164 breast cancer metastases diagnosed between 2004 and 2014 showed a striking difference between mammaglobin and GATA3 expression (51.2% vs 94% positivity). These findings highlight GATA3 as a more reliable and sensitive diagnostic marker for breast cancer metastases and possibly metastatic tumors of unknown origin than mammaglobin.

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.

BACKGROUND: Mammary analog secretory carcinoma (MASC) of the salivary gland has been recently described according to morphological, immunohistochemical, and molecular (ETV6-NTRK3 translocation) similarities with the mammary secretory carcinoma. The most important differential diagnostic considerations of MASC are low-grade adenocarcinoma not otherwise specified (NOS), cystadenocarcinoma, and acinic cell carcinoma (AciCC). These tumors may share an overlapping morphology with MASC, and additional immunohistochemical studies are required to reinforce the diagnosis. Mammaglobin, GCDFP-15, and p63 staining have been reported in MASC. Our study was designed to check the specificity of these antibodies in MASC compared to other frequent tumors of salivary glands.
METHODS: A series of 62 salivary gland tumors [10 MASCs, 5 adenocarcinomas NOS and 2 cystadenocarcinomas with MASC features and without ETV6 rearrangement, one low-grade cribriform cystadenocarcinoma (LGCCC), 9 AciCCs, 10 MECs, 10 adenoid cystic carcinomas (AdeCCs), 5 polymorphous low-grade adenocarcinomas (PLGAs), and 10 pleomorphic adenomas (PAs)] was analyzed by immunohistochemistry with mammaglobin, GCDFP-15, and p63 antibodies.
RESULTS: Positivity for mammaglobin was observed in all MASCs, cystadenocarcinomas, LGCCC, and PLGAs, in some adenocarcinomas NOS, PAs, and MECs, rarely in AciCCs and never in AdeCCs. Positivity for GCDFP-15 was observed in most of the tumor types except in AdeCCs. Interestingly, cytoplasmic positivity for p63 was observed in most of MASCs and PLGAs while rarely in adenocarcinomas NOS and PAs, and never in the other tumor types.
CONCLUSIONS: Our study revealed the usefulness of mammaglobin and p63 cytoplasmic staining to define which tumors are worth to be screened for ETV6 rearrangement.