Mammary analog secretory carcinoma, low-grade salivary duct carcinoma, and mimickers: a comparative study.

Mammary analog secretory carcinoma (MASC) is a recently recognized low-grade salivary carcinoma characterized by a specific ETV6 rearrangement. We describe 14 new MASCs and examine their immunophenotypic and genetic profiles in the context of look-alikes, namely, low-and high-grade salivary duct carcinoma and acinic cell carcinoma. ETV6 rearrangement, and robust expression of mammaglobin and S100, were demonstrated in 11/11, 14/14, and 12/14 MASCs, respectively. All low-grade salivary duct carcinomas coexpressed S100/mammaglobin (6/6); none harbored ETV6 rearrangements (0/5). Given that S100/mammaglobin coexpression and absence of zymogen granules are features of both MASC and low-grade salivary duct carcinoma, these two are best distinguished histologically. The former is predominantly an extraductal neoplasm with bubbly pink cytoplasm, whereas the latter is a distinct intraductal micropapillary and cribriform process. Querying ETV6 gene status may be necessary for difficult cases. No acinic cell carcinoma expressed mammaglobin (0/13) or harbored an ETV6 rearrangement (0/7); only 1/13 acinic cell carcinomas weakly expressed S100. DOG1 expression was limited or absent among all tumor types, except acinic cell carcinoma which expressed DOG1 diffusely in a canalicular pattern. Therefore, histology and immunohistochemistry (mammaglobin, S100, DOG1) suffices in distinguishing acinic cell carcinoma from both MASC and low-grade salivary duct carcinoma. HER2 (ERBB2) amplification was detected in only 1/10 acinic cell carcinomas, but none of the MASCs or low-grade salivary duct carcinomas tested. High-grade salivary duct carcinomas frequently expressed mammaglobin (11/18) and harbored HER2 amplifications (13/15); none harbored ETV6 rearrangements (0/12). High-grade salivary duct carcinomas can easily be distinguished from these other entities by histology and HER2 amplification.

Searching for mammary analogue [corrected] secretory carcinoma of salivary gland among its mimics.

Mammary analog secretory carcinoma of salivary gland is a recently described entity with unique morphologic, clinical, and genetic characteristics, including the characteristic t(12;15)(p13;q25) with ETV6-NTRK3 translocation found in secretory carcinomas of the breast. Before their initial description, these salivary gland tumors were generally diagnosed as acinic cell carcinoma or adenocarcinoma. For the purpose of this study, all cases of salivary gland acinic cell carcinoma, cribriform cystadenocarcinoma, and adenocarcinoma, not otherwise specified (NOS), diagnosed over a 10-year period were retrieved from our surgical pathology files. There were a total of 11 cases diagnosed as acinic cell carcinoma, 10 cases of adenocarcinoma, NOS, and 6 cases of cribriform cystadenocarcinoma. All slides were reviewed by two pathologists (AP, CGF) and tumors that show morphologic features of mammary analog secretory carcinoma according to the recent literature were selected. This process narrowed down the initial number to six cases originally diagnosed as acinic cell carcinoma, three cases originally diagnosed as adenocarcinoma, NOS, and one case originally diagnosed as cribriform cystadenocarcinoma. The 10 cases were subjected to immunohistochemistry for S-100, mammaglobin, and ANO1, as well as fluorescence in situ hybridization analysis for t(12;15)(p13;q25) with ETV6-NTRK3 fusion rearrangement. The ETV6-NTRK3 gene rearrangement was detected in three tumors. These three tumors, initially diagnosed as acinic cell carcinomas, stained positive for S-100 and mammaglobin, and negative for ANO1 by immunohistochemistry. Two of the three patients were male (2/3). In summary, mammary analog secretory carcinoma is a newly described diagnostic entity that should be in the differential diagnosis of salivary gland tumors that morphologically mimic other neoplasms, mainly acinic cell carcinomas. They differ from conventional acinic cell tumors immunohistochemically and molecularly. Positivity for mammaglobin and S-100, and negativity for ANO1 are useful screening tools before confirmatory molecular studies.

Differential expression of secretoglobins in normal ovary and in ovarian carcinoma--overexpression of mammaglobin-1 is linked to tumor progression.

Secretoglobins (SCGB), such as mammaglobin 1 (MGB1, SCGB2A2), mammaglobin 2 (MGB2, SCGB2A1) and lipophilin B (LIPB, SCGB1D2), have been related to carcinogenesis. We profiled expression of MGB1, MGB2 and LIPB in human tissues and ovarian carcinoma and explored the impact of SCGB overexpression on cell proliferation. MGB1, MGB2 and LIPB mRNA are expressed at variable levels in most human tissues and we observed significant bilateral correlations between the different secretoglobins. Concerted overexpression of MGB1 and LIPB resulted in significant increase in cell proliferation. In clinical specimens of ovarian carcinoma we measured elevated concentrations of secretoglobin mRNA and for MGB1 this up-regulation was confirmed on the protein level. Overexpression of MGB1 positively correlated with the FIGO stage, the tumor grade and the mitotic index suggesting a patho-physiological role of the protein. Our data indicate that MGB1, MGB2 and LIPB mRNAs are expressed at low levels in human tissues but basal expression is upregulated in ovarian cancer. The in vivo correlation between nuclear MGB1 localization and the mitotic rate in ovarian cancer as well as the increased cell proliferation induced by secretoglobin overexpression in ovarian cancer cell lines suggest a pathophysiological role of these proteins in ovarian cancer.

Characterisation of GATA3 expression in invasive breast cancer: differences in histological subtypes and immunohistochemically defined molecular subtypes.

AIMS: GATA-binding protein 3 (GATA3) is a sensitive and relatively specific marker in breast and urothelial carcinomas. Its diagnostic utility in primary and metastatic breast cancers has been explored and confirmed. However, the relationship between GATA3 expression and different breast carcinoma intrinsic subtypes has not been specifically defined in the literature despite a few reports with a small number of cases. The aim of the current investigation is to clarify GATA3 expression among different histological subtypes and surrogate molecular breast carcinoma subtypes in a large series of cases. METHODS: Immunohistochemical staining of GATA3, GCDFP15 and mammaglobin was performed in a cohort of 1637 cases of primary invasive breast carcinoma. The association of GATA3 expression with different histological and surrogate intrinsic subtypes was assessed and compared with the expression of GCDFP15 and mammaglobin. RESULTS: The overall positivity of GATA3 across the various immunohistochemistry-based surrogate intrinsic subtypes was 99.51% for luminal A-like, 97.70% for luminal B-like, 68.50% for HER2 overexpression and 20.16% for triple negative breast cancers. GATA3 expression was positively correlated with estrogen receptor (ER)-positive (luminal subtypes) breast carcinomas. For luminal-like and HER2 overexpression subtypes, GATA3 was much more sensitive than GCDFP15 and mammaglobin. For triple negative tumours, GATA3 was less sensitive than GCDFP15. CONCLUSIONS: GATA3 exhibits a relatively high sensitivity for breast carcinomas. It is more sensitive than GCDFP15 and mammaglobin in luminal-like and HER2 overexpression subtypes. GATA3 expression is associated with breast carcinomas of luminal subtype and low histological grade.

Immunohistochemical Differentiation of Plasmacytoid Urothelial Carcinoma From Secondary Carcinoma Involvement of the Bladder.

Plasmacytoid urothelial carcinoma (UC) is a rare variant of UC that can histologically mimic metastatic cancer involving the urinary bladder. A total of 45 cases of plasmacytoid UC were collected and reviewed histologically. The following immunohistochemical markers were performed: CDX2; polyclonal carcinoembryonic antigen (p-CEA); gross cystic disease fluid protein 15 (GCDFP-15); mammaglobin; estrogen receptor (ER); progesterone receptor (PR); GATA 3 and uroplakin II. In all cases, the plasmacytoid variant of UC lacked expression of ER and mammaglobin. In contrast, GCPDFP-15, PR, CDX2 and p-CEA showed positive staining in 11 (24.4%), 6 (13.3%), 8 (17.7%), and 22 (48.8%) cases, respectively. GCPDFP-15 was expressed in 4/8 female cases with 1 concurrently focally (+2) expressing PR. GATA 3 and uroplakin II was positive in 37/45 cases (82.2%) and 15/45 (33.3%) cases, respectively. A tissue microarray with 40 cases of infiltrating lobular carcinoma of the breast was stained for uroplakin II, and was negative in all cases. Tissue microarrays with 46 cases of gastric signet ring cell adenocarcinomas were all negative for GCDFP-15, ER, PR, GATA3, uroplakin II, and mammaglobin. A panel of stains including mammaglobin, ER, and uroplakin II is recommended to exclude metastatic lobular breast carcinoma to the bladder in cases where a conventional UC component is not present. Immunohistochemistry for CDX2 and p-CEA cannot be utilized to differentiate signet ring cell adenocarcinoma of the gastrointestinal tract from plasmacytoid UC; GATA3 or uroplakin II immunoreactivity can rule out a gastric primary given their negativity in signet ring cell adenocarcinoma of the stomach.

A rare case of a recently described entity: mammary analogue secretory carcinoma (MASC) of the parotid gland / Un caso raro de una entidad descrita recientemente: carcinoma secretorio análogo mamario (CSAM) de la glándula parótida

MASC is a salivary gland tumour which shares histological, immunologic and genetic characteristics with mammary secretory carcinoma including an ETV6 translocation and immunocytochemical positivity for S-100 protein, CK7, and mammaglobin as well as negativity for DOG1. This is a rare tumour with uncommon characteristics when compared to other salivary gland tumours. The case reported here is of a 28-year-old female patient who presented in the ER due to a palpable mass in the left parotid region. She underwent a superficial parotidectomy with using a mini-lifting approach, with tumour resection, followed by radiotherapy. The identified tumour shared most of the clinical characteristics with other cases of MASC described in the literature

CSAM es un tumor de glándula salival que comparte características histológicas, inmunológicas y genéticas con el carcinoma secretor mamario, que incluye una translocación ETV6 y positividad inmunocitoquímica para la proteína S-100, CK7 y mamaglobina, así como negatividad para DOG1. Este es un tumor raro con características poco comunes en comparación con otros tumores de glándulas salivales. El caso referido aquí es el de una paciente de 28 años de edad que se presentó en la sala de emergencias debido a una masa palpable en la región parotídea izquierda. Se sometió a una parotidectomía superficial con un abordaje de mini-lifting, con resección tumoral, seguida de radioterapia. El tumor identificado compartía la mayoría de las características clínicas con otros casos de CSAM descritos en la literatura

GATA3 immunohistochemistry expression in histologic subtypes of primary breast carcinoma and metastatic breast carcinoma cytology.

GATA3 plays a role in cell proliferation and differentiation in many tissues, including breast, and it has been suggested that GATA3 expression correlates with ER expression. However, little is known on GATA3 expression in various subtypes of breast carcinoma, its utilization in cytology, and on how GATA3 performs in comparison with GCDFP-15 and mammaglobin. Eighty-four histology cases of breast carcinoma of various subtypes, including 28 triple-negative breast carcinomas, along with 20 cytology cases of metastatic breast carcinoma and 12 cytology cases of ER-positive metastatic gynecologic malignancies, were stained for GATA3, GCDFP-15, and mammaglobin. In non-triple-negative breast carcinomas (n=56), GATA3 showed 100% sensitivity, higher than GCDFP-15 (42.8%; P<0.0001) and mammaglobin (58.9%; P<0.0001), whereas staining patterns were similar for all the histologic subtypes examined. Staining scores were determined by multiplying the percentage of cancer cells staining with an intensity score of 1+, 2+, or 3+ (range, 0 to 300). In non-triple-negative carcinomas, GATA3 showed a mean score of 273.7, higher than GCDFP-15 (107.5; P<0.0001) and mammaglobin (147.7; P<0.0001). In triple-negative breast carcinomas (n=28), GATA3 showed a sensitivity of 60.7%, greater than GCDFP-15 (17.9%; P=0.0022) and mammaglobin (7.1%; P<0.0001). These results were consistent irrespective of the subtype examined. In breast carcinoma cytology cases, 100% stained with GATA3, higher than GCDFP-15 (20%; P<0.0001) and mammaglobin (45%; P<0.0001). None of the metastatic endometrial or ovarian carcinomas were positive for GATA3. Although GATA3 expression correlates with ER expression in breast, no correlation is observed in gynecologic malignancies. Thus, in working up ER-positive metastatic malignancies GATA3 demonstrates specificity for breast.

Are mammaglobin and GCDFP-15 sensitive markers for diagnosis of metastatic basal-like triple negative breast carcinomas?

OBJECTIVE: There are small studies on expression of mammaglobin and GCDFP-15 for detection of basal-like triple negative breast cancer. This type of cancer has shorter survival and higher mortality rate. There must be reliable markers for detecting this type of tumor especially in metastatic cases with unknown origin. MATERIAL AND METHOD: In this study we assessed 66 paraffin blocks of breast cancers previously diagnosed as triple negative subtype in Mehr hospital (Tehran, Iran) by tissue microarray and immunohistochemistry technique for expression of mammaglobin and GCDFP-15. RESULTS: GCDFP-15 was positive in 12 cases (18.2%) and the other 54 (81.8%) cases remained negative. Mammaglobin was positive only in 6 cases (9.1%) and the remaining 60 (90.9%) cases were negative. CONCLUSION: According to recent studies and our findings, there is no useful immunohistochemical marker for detection of breast source in cases of metastatic triple negative breast cancer with unknown origin and we must try hard to discover more accurate immunohistochemical markers for these highly metastatic breast cancers.

Male breast carcinoma: a clinicopathological and immunohistochemical characterization study.

Male breast carcinoma is a relatively rare disease. This study retrospectively investigated the clinicopathological features of 73 cases of male breast carcinoma in Chinese population, and classified the molecular subtype based on surrogate immunohistochemical definitions. The expression of GCDFP15, MGB, AR and FOXP1 were evaluated. Invasive carcinoma of no special type was the most common histological type in the study group (71.2%, 52/73). The luminal A and B subtypes were the major types of male breast carcinoma (60.9%, 34.8% respectively). AR and FOXP1 are expressed in 84.2% (48/57) and 71.9% (41/57) of the studied cases. Carcinoma of the luminal A subtype expressed GCDFP15 (73.5%, 25/34) and MGB (58.8%, 20/34) more frequently than cases of the luminal B subtypes (34.8%, 8/23 and 43.5%, 10/23, respectively; P = 0.004, P = 0.255, respectively). In conclusion, invasive carcinoma of no special type was the most common histological type in male breast carcinoma among Chinese population. Our study revealed that the luminal A and B subtypes were the major types of male breast carcinoma. AR and FOXP1 are highly expressed in male breast cancer. The luminal A subtype tends to express GCDFP15 and MGB more frequently than the luminal B subtype.

Immunohistochemical characterization of neoplastic cells of breast origin.

BACKGROUND: After skin cancer, breast cancer is the most common malignancy in women. Tumors of unknown origin account for 5-15% of malignant neoplasms, with 1.5% being breast cancer. An immunohistochemical panel with conventional and newer markers, such as mammaglobin, was selected for the detection of neoplastic cells of breast origin. The specific objectives are: 1) to determine the sensitivity and specificity of the panel, with a special emphasis on the inclusion of the mammaglobin marker, and 2) to compare immunohistochemistry performed on whole tissue sections and on tissue micro-array. METHODS: Twenty-nine metastatic breast tumors were included and assumed as tumors of unknown origin. Other 48 biopsies of diverse tissues were selected and assumed as negative controls. Tissue Micro-Array was performed. Immunohistochemistry for mammaglobin, gross cystic disease fluid protein-15, estrogen receptor, progesterone receptor and cytokeratin 7 was done. RESULTS: Mammaglobin positive staining was observed in 10/29 cases, in 13/29 cases for gross cystic disease fluid protein-15, in 20/29 cases for estrogen receptor, in 9/29 cases for progesterone receptor, and in 25/29 cases for cytokeratin 7. Among the negative controls, mammaglobin was positive in 2/48, and gross cystic disease fluid protein-15 in 4/48. CONCLUSIONS: The inclusion of MAG antibody in the immunohistochemical panel for the detection of tumors of unknown origin contributed to the detection of metastasis of breast cancer. The diagnostic strategy with the highest positive predictive value (88%) included hormone receptors and mammaglobin in serial manner.