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Raja R Seethala - One of the best experts on this subject based on the ideXlab platform.
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IntraDuctal Carcinoma of Salivary Glands Harboring TRIM27-RET Fusion with Mixed Low Grade and Apocrine Types.
Head and neck pathology, 2019Co-Authors: Rondell P. Graham, Raja R Seethala, Deborah J. ChuteAbstract:IntraDuctal carcinomas (IDCs) of salivary gland are rare neoplasms. Here, we report a case of IDCs harboring TRIM27-RET fusion with mixed low grade and apocrine types. A 79-year-old male presented with slowly-growing left parotid mass for 2.5 years. Histologically, the tumor demonstrated two distinct morphologies; a classic Intercalated Duct and low grade apocrine component. The Intercalated Duct component was positive for S100, SOX10 and vimentin, and negative for DOG-1 and HER2. The apocrine component was positive for androgen receptor (AR) and focally positive for HER2. The tumor harbored a TRIM27-RET fusion by FISH, and was negative for ETV6 and PLAG1 rearrangements. This case is unusual in that it displays two true phenotypically distinct components, which has only rarely been reported. This is the first report of intraDuctal carcinoma with two true phenotypically distinct components composed of low-grade and apocrine types with RET rearrangement and TRIM27-RET fusion.
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DOG1: a novel marker of salivary acinar and Intercalated Duct differentiation
Modern Pathology, 2012Co-Authors: Jacinthe Chênevert, Umamaheswar Duvvuri, Simion Chiosea, Sanja Dacic, Kathleen Cieply, Daniel Shiwarski, Raja R SeethalaAbstract:Anoctamin-1 (ANO1) (DOG1, TMEM16a) is a calcium-activated chloride channel initially described in gastrointestinal stromal tumors, but now known to be expressed in a variety of normal and tumor tissues including salivary tissue in murine models. We herein perform a comprehensive survey of DOG1 expression in 156 cases containing non-neoplastic human salivary tissues and tumors. ANO1 mRNA levels were significantly higher (8-fold increase, P
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dog1 a novel marker of salivary acinar and Intercalated Duct differentiation
Modern Pathology, 2012Co-Authors: Jacinthe Chênevert, Umamaheswar Duvvuri, Sanja Dacic, Kathleen Cieply, Daniel Shiwarski, Simion I. Chiosea, Jean Kim, Raja R SeethalaAbstract:Anoctamin-1 (ANO1) (DOG1, TMEM16a) is a calcium-activated chloride channel initially described in gastrointestinal stromal tumors, but now known to be expressed in a variety of normal and tumor tissues including salivary tissue in murine models. We herein perform a comprehensive survey of DOG1 expression in 156 cases containing non-neoplastic human salivary tissues and tumors. ANO1 mRNA levels were significantly higher (8-fold increase, P<0.0001) in normal parotid tissue (n=6) as compared with squamous mucosa (n=15). By immunohistochemistry, DOG1 showed a diffuse moderate (2+) apical membranous staining pattern in normal serous acini, 1+ apical membranous pattern in mucous acini, and variable 1-2+ apical staining of distal Intercalated Ducts. Myoepithelial cells, striated and excretory Ducts were invariably negative. All acinic cell carcinomas (n=28) were DOG1 positive demonstrating a complex mixture of intense (3+) apical membranous, cytoplasmic and complete membranous staining. Most Ductal tumor types were negative or only showed a subset of positive cases. Within the biphasic tumor category, adenoid cystic carcinomas (18/24 cases) and epithelial-myoepithelial carcinomas (8/15 cases) were frequently positive, often showing a distinctive combined apical Ductal and membranous/cytoplasmic myoepithelial staining profile. Thus, DOG1 staining is a marker of salivary acinar and to a lesser extent Intercalated Duct differentiation. Strong staining can be used to support the diagnosis of acinic cell carcinoma. DOG1 may also be a marker of a 'transformed' myoepithelial phenotype in a subset of biphasic salivary gland malignancies.
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Intercalated Duct lesions of salivary gland a morphologic spectrum from hyperplasia to adenoma
The American Journal of Surgical Pathology, 2009Co-Authors: Ilan Weinreb, Raja R Seethala, Irving Dardick, Runjan Chetty, Jennifer L Hunt, Bayardo PerezordonezAbstract:Intercalated Duct lesions (IDLs) are rare, poorly understood and not well-studied lesions that have been associated with a small number of epithelial-myoepithelial carcinomas (EMC) and basal cell adenomas. To examine the nature of IDLs and their association with salivary gland tumors, we reviewed 34
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Intercalated Duct Lesions of Salivary Gland: A Morphologic Spectrum From Hyperplasia to Adenoma
The American journal of surgical pathology, 2009Co-Authors: Ilan Weinreb, Raja R Seethala, Irving Dardick, Runjan Chetty, Jennifer L Hunt, Bayardo Perez-ordonezAbstract:Intercalated Duct lesions (IDLs) are rare, poorly understood and not well-studied lesions that have been associated with a small number of epithelial-myoepithelial carcinomas (EMC) and basal cell adenomas. To examine the nature of IDLs and their association with salivary gland tumors, we reviewed 34 lesions in 32 patients. The IDLs were stained with CK7, estrogen receptors (ER), progesterone receptors, lysozyme, S100, calponin, and CK14. The patients ranged in age from 19 to 80 years (mean 53.8) with a 1.7:1 female predominance. The majorities of IDLs were parotid lesions (82%), were small and nodular (average size 3.1 mm) and showed 3 architectural patterns: hyperplasia (20), adenoma (9), and hybrid forms (5). In 59% of cases, IDLs were seen in conjunction with another salivary gland tumor, most commonly basal cell adenoma (8 cases), followed by EMC (3 cases). One case showed a combination of Intercalated Duct hyperplasia and basal cell adenoma. The IDLs stained diffusely with CK7 (100%) and S100 (73%) and focally for ER (91%) and lysozyme (100%). Calponin and CK14 highlighted a thin myoepithelial cell layer around all Ducts (100%). Normal Intercalated Ducts were also consistently positive for CK7 and lysozyme, and focally for ER, but were S100 negative. In summary, IDLs have a variety of patterns ranging from hyperplasia to adenoma with hybrid lesions and share morphologic and immunophenotypic features with normal Intercalated Ducts. There is an association with basal cell adenomas and EMC, which lends credence to their role as a putative precursor lesion.
Albina Altemani - One of the best experts on this subject based on the ideXlab platform.
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Lysozyme Expression Can be Useful to Distinguish Mammary Analog Secretory Carcinoma from Acinic Cell Carcinoma of Salivary Glands
Head and Neck Pathology, 2016Co-Authors: Fernanda Viviane Mariano, Victor Angelo Martins Montalli, Camila Andrea Concha Gómez, Juliana Souza Do Nascimento, Harim Tavares Santos, Erika Said Egal, Pablo Agustin Vargas, Oslei Paes Almeida, Albina AltemaniAbstract:Lysozyme is an enzymatic marker of acinar and Intercalated Duct cells of normal salivary glands. The aim of this study was to verify whether lysozyme expression could be useful to distinguish acinic cell carcinoma (ACC) from its main mimic, mammary analog secretory carcinoma (MASC). For comparison, DOG1 expression was analyzed as well. Seventeen cases of ACC, 15 MASC, and 125 other salivary tumors were studied. Lysozyme expression was found in tumor cells as well as in secreted material of MASC (86.6 % of cases) and in Ductal cells of epithelial–myoepithelial carcinoma (EMC-53.8 %), pleomorphic adenoma (PA-29.1 %) and polymorphous low-grade adenocarcinoma (PLGA-23.8 %). However, in ACC, lysozyme was not expressed. Three patterns of DOG1 staining were seen: apical–luminal, cytoplasmic, and mixed cytoplasmic/membranous. The apical–luminal pattern was detected in Ductal cells of ACC (58.8 % of cases), EMC (38.4 %), adenoid-cystic carcinoma (AdCC-35.3 %), PA (8.3 %), and PLGA (4.8 %). These tumors also showed mixed membranous/cytoplasmic staining for DOG1. MASC, mucoepidermoid, and salivary Duct carcinomas exhibited only DOG1 cytoplasmic staining. In conclusion, lysozyme cannot be used as a marker of acinar differentiation in salivary tumors. However, lysozyme expression can be helpful to distinguish MASC from ACC due to its high frequency in the former and absence in ACC. It is likely that in MASC, lysozyme expression may reflect a lactational-like secretory differentiation since lysozyme belongs to breast milk proteins. Regarding DOG1 expression, the apical–luminal pattern is related to acinar and Intercalated Duct differentiation whereas the cytoplasmic staining does not seem to be associated with a specific cellular phenotype.
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tubular variant of basal cell adenoma shares immunophenotypical features with normal Intercalated Ducts and is closely related to Intercalated Duct lesions of salivary gland
Web Science, 2014Co-Authors: Victor Angelo Martins Montalli, Elizabeth Ferreira Martinez, Alfio Jose Tincani, Antonio Santos Martins, Maria Do Carmo Abreu, Catarina De Oliveira Neves, Ana Flavia Costa, Vera Cavalcanti De Araujo, Albina AltemaniAbstract:Aims The morphological criteria for identification of Intercalated Duct lesions (IDLs) of salivary glands have been defined recently. It has been hypothesised that IDL could be a precursor of basal cell adenoma (BCA). BCAs show a variety of histological patterns, and the tubular variant is the one that presents the strongest resemblance with IDLs. The aim of this study was to analyse the morphological and immunohistochemical profiles of IDLs and BCAs classified into tubular and non-tubular subtypes, to determine whether or not IDL and tubular BCA represent distinct entities. Methods and results Eight IDLs, nine tubular BCAs and 19 non-tubular BCAs were studied. All tubular BCAs contained IDL-like areas, which represented 20–70% of the tumour. In non-tubular BCA, IDL-like areas were occasional and small (<5%). One patient presented IDLs, tubular BCAs and IDL/tubular BCA combined lesions. Luminal Ductal cells of IDLs and tubular BCAs exhibited positivity for CK7, lysozyme, S100 and DOG1. In the non-tubular BCA group, few luminal cells exhibited such an immunoprofile; they were mainly CK14-positive. Basal/myoepithelial cells of IDLs, tubular BCAs and non-tubular BCAs were positive for CK14, calponin, α-SMA and p63; they were more numerous in BCA lesions. Conclusions IDL, tubular BCA and non-tubular BCA form a continuum of lesions in which IDLs are related closely to tubular BCA. In both, the immunoprofile of luminal and myoepithelial cells recapitulates the normal Intercalated Duct. The difference between the adenoma-like subset of IDLs and tubular BCA rests mainly on the larger numbers of myoepithelial cells in the latter. Our findings indicate that at least some BCAs can arise via IDLs.
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Tubular Variant Of Basal Cell Adenoma Shares Immunophenotypical Features With Normal Intercalated Ducts And Is Closely Related To Intercalated Duct Lesions Of Salivary Gland.
Histopathology, 2014Co-Authors: Victor Angelo Martins Montalli, Elizabeth Ferreira Martinez, Alfio Jose Tincani, Antonio Santos Martins, Maria Do Carmo Abreu, Catarina De Oliveira Neves, Ana Flavia Costa, Vera Cavalcanti De Araujo, Albina AltemaniAbstract:Aims The morphological criteria for identification of Intercalated Duct lesions (IDLs) of salivary glands have been defined recently. It has been hypothesised that IDL could be a precursor of basal cell adenoma (BCA). BCAs show a variety of histological patterns, and the tubular variant is the one that presents the strongest resemblance with IDLs. The aim of this study was to analyse the morphological and immunohistochemical profiles of IDLs and BCAs classified into tubular and non-tubular subtypes, to determine whether or not IDL and tubular BCA represent distinct entities. Methods and results Eight IDLs, nine tubular BCAs and 19 non-tubular BCAs were studied. All tubular BCAs contained IDL-like areas, which represented 20–70% of the tumour. In non-tubular BCA, IDL-like areas were occasional and small (
Runjan Chetty - One of the best experts on this subject based on the ideXlab platform.
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Intercalated Duct lesions of salivary gland a morphologic spectrum from hyperplasia to adenoma
The American Journal of Surgical Pathology, 2009Co-Authors: Ilan Weinreb, Raja R Seethala, Irving Dardick, Runjan Chetty, Jennifer L Hunt, Bayardo PerezordonezAbstract:Intercalated Duct lesions (IDLs) are rare, poorly understood and not well-studied lesions that have been associated with a small number of epithelial-myoepithelial carcinomas (EMC) and basal cell adenomas. To examine the nature of IDLs and their association with salivary gland tumors, we reviewed 34
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Intercalated Duct Lesions of Salivary Gland: A Morphologic Spectrum From Hyperplasia to Adenoma
The American journal of surgical pathology, 2009Co-Authors: Ilan Weinreb, Raja R Seethala, Irving Dardick, Runjan Chetty, Jennifer L Hunt, Bayardo Perez-ordonezAbstract:Intercalated Duct lesions (IDLs) are rare, poorly understood and not well-studied lesions that have been associated with a small number of epithelial-myoepithelial carcinomas (EMC) and basal cell adenomas. To examine the nature of IDLs and their association with salivary gland tumors, we reviewed 34 lesions in 32 patients. The IDLs were stained with CK7, estrogen receptors (ER), progesterone receptors, lysozyme, S100, calponin, and CK14. The patients ranged in age from 19 to 80 years (mean 53.8) with a 1.7:1 female predominance. The majorities of IDLs were parotid lesions (82%), were small and nodular (average size 3.1 mm) and showed 3 architectural patterns: hyperplasia (20), adenoma (9), and hybrid forms (5). In 59% of cases, IDLs were seen in conjunction with another salivary gland tumor, most commonly basal cell adenoma (8 cases), followed by EMC (3 cases). One case showed a combination of Intercalated Duct hyperplasia and basal cell adenoma. The IDLs stained diffusely with CK7 (100%) and S100 (73%) and focally for ER (91%) and lysozyme (100%). Calponin and CK14 highlighted a thin myoepithelial cell layer around all Ducts (100%). Normal Intercalated Ducts were also consistently positive for CK7 and lysozyme, and focally for ER, but were S100 negative. In summary, IDLs have a variety of patterns ranging from hyperplasia to adenoma with hybrid lesions and share morphologic and immunophenotypic features with normal Intercalated Ducts. There is an association with basal cell adenomas and EMC, which lends credence to their role as a putative precursor lesion.
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Intercalated Duct hyperplasia possible relationship to epithelial myoepithelial carcinoma and hybrid tumours of salivary gland
Histopathology, 2000Co-Authors: Runjan ChettyAbstract:Aims : The aims of this study were to ascertain the incidence of Intercalated Duct hyperplasia in association with cases of epithelial-myoepithelial carcinoma (EMC), and to explore a possible relationship between them and hybrid carcinomas of salivary glands. Methods and results : Seven cases of EMC with sufficient surrounding non-tumour parotid were examined. Three cases contained foci of Intercalated Duct hyperplasia adjacent to the tumour. One of the cases was a hybrid tumour composed of EMC and mucoepidermoid carcinoma. The hyperplastic Intercalated Ducts formed multiple foci within the salivary parenchyma and were composed of bland, uniform Ducts. Cytological atypia was not identified. Conclusions : Intercalated Duct hyperplasia may be a precursor lesion to EMC. Furthermore, it may also explain why EMC is frequently associated with other salivary gland carcinomas, so-called hybrid tumours, as well as sharing histological features with adenoid cystic carcinoma. Recognition of the latter is of particular importance because adenoid cystic carcinoma carries a poor prognosis.
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Intercalated Duct hyperplasia: possible relationship to epithelial-myoepithelial carcinoma and hybrid tumours of salivary gland.
Histopathology, 2000Co-Authors: Runjan ChettyAbstract:The aims of this study were to ascertain the incidence of Intercalated Duct hyperplasia in association with cases of epithelial-myoepithelial carcinoma (EMC), and to explore a possible relationship between them and hybrid carcinomas of salivary glands. Seven cases of EMC with sufficient surrounding non-tumour parotid were examined. Three cases contained foci of Intercalated Duct hyperplasia adjacent to the tumour. One of the cases was a hybrid tumour composed of EMC and mucoepidermoid carcinoma. The hyperplastic Intercalated Ducts formed multiple foci within the salivary parenchyma and were composed of bland, uniform Ducts. Cytological atypia was not identified. Intercalated Duct hyperplasia may be a precursor lesion to EMC. Furthermore, it may also explain why EMC is frequently associated with other salivary gland carcinomas, so-called hybrid tumours, as well as sharing histological features with adenoid cystic carcinoma. Recognition of the latter is of particular importance because adenoid cystic carcinoma carries a poor prognosis.
Justin A Bishop - One of the best experts on this subject based on the ideXlab platform.
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The Myoepithelial Cells of Salivary Intercalated Duct-type IntraDuctal Carcinoma Are Neoplastic: A Study Using Combined Whole-slide Imaging, Immunofluorescence, and RET Fluorescence In Situ Hybridization.
The American journal of surgical pathology, 2020Co-Authors: Justin A Bishop, Jeffrey Gagan, Lisa M. Rooper, Ankur R. Sangoi, Lester D.r. Thompson, Hiroshi InagakiAbstract:IntraDuctal carcinoma (IDC) is a salivary gland tumor currently believed to be analogous to breast Ductal carcinoma in situ, consisting of a complex neoplastic epithelial proliferation surrounded by a continuous layer of myoepithelial cells presumed to be native and non-neoplastic. Recent molecular insights have shown that there are at least 3 different types of IDC: (1) Intercalated Duct-like, with frequent NCOA4-RET fusions; (2) apocrine, with multiple mutations similar to salivary Duct carcinoma; and (3) mixed Intercalated Duct-like and apocrine with frequent RET fusions, especially TRIM27-RET. Recent observations (eg, IDC occurring in lymph nodes) have challenged the notion that the myoepithelial cells of IDC are non-neoplastic. Five IDCs with known RET fusions by RNA sequencing were retrieved from the authors' archives, including 4 Intercalated Duct-like IDCs with NCOA4-RET, and 1 mixed Intercalated Duct-like/apocrine IDC with TRIM27-RET. A panel of immunohistochemistry antibodies (S100 protein, p63 or p40, mammaglobin, smooth muscle actin, calponin, androgen receptor) was tested. To precisely localize RET split-positive cells, each case was subjected to sequential retrieval of whole-slide imaging data of hematoxylin and eosin (HE) staining, immunofluorescence staining for calponin, and fluorescence in situ hybridization (FISH) for RET. Because NCOA4-RET is an inversion difficult to visualize on conventional RET FISH, a novel 3-color FISH technique was utilized to demonstrate it clearly. In all 5 cases, the proliferative Ducts were completely surrounded by a layer of myoepithelial cells that were positive for p63 or p40, smooth muscle actin, and calponin. Using combined HE, calponin immunofluorescence, and RET FISH imaging, the positive signals were unmistakably identified in both calponin-negative Ductal cells and peripheral, calponin-positive myoepithelial cells in all 5 cases. Utilizing combined HE, calponin immunofluorescence, and RET FISH imaging, we demonstrated that IDCs with RET fusions harbored this alteration in both the Ductal and myoepithelial cells. This is compelling evidence that the myoepithelial cells of IDC are not mere bystanders, but are rather a component of the neoplasm itself, similar to other biphasic salivary gland neoplasms like pleomorphic adenoma and epithelial-myoepithelial carcinoma. This finding raises questions about the appropriate terminology, classification, and staging of IDC.
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Salivary IntraDuctal Carcinoma Arising within Intraparotid Lymph Node: A Report of 4 Cases with Identification of a Novel STRN-ALK Fusion
Head and Neck Pathology, 2020Co-Authors: Lisa M. Rooper, Jeffrey Gagan, Ilan Weinreb, Lester D.r. Thompson, Bahram R. Oliai, Justin A BishopAbstract:IntraDuctal carcinoma (IDC) is a rare salivary gland tumor that is considered analogous to Ductal carcinoma in-situ of the breast, demonstrating a complex neoplastic epithelial proliferation surrounded by a continuous layer of presumed non-neoplastic myoepithelial cells. It is subcategorized into Intercalated Duct, apocrine, and hybrid subtypes based on morphologic and immunohistochemical features, with frequent NCOA4-RET and TRIM27-RET fusions, respectively, seen in Intercalated Duct and hybrid tumors. However, as an expanding clinicopathologic spectrum of IDC has been documented, controversy has emerged as to whether this tumor type is best defined by its intraDuctal growth pattern or distinctive molecular and immunophenotypic differentiation. Here, we further explore the nature of IDC by evaluating four cases that arose within intraparotid lymph nodes. These Intercalated-Duct phenotype tumors with diffuse S100 protein expression demonstrated a crowded and complex epithelial proliferation arranged in cystic, cribriform, and micropapillary architecture, surrounded by an intact myoepithelial cell layer, and were completely intranodal. Of two tumors with tissue available for molecular analysis, one demonstrated a NCOA4-RET fusion and one harbored a STRN-ALK fusion that is novel to IDC. Not only does the intranodal presence of IDC present a challenging differential diagnosis, but the complex nature of this proliferation within lymph node tissue raises questions as to whether the myoepithelial component of IDC is actually non-neoplastic in nature. Furthermore, identification of a STRN-ALK fusion expands the genetic spectrum of IDC and adds to evidence of an emerging role for ALK in salivary gland tumors. Further attention to the nature of the myoepithelial cells and documentation of alternate fusion events in IDC may inform continued discussion about its appropriate classification.
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low grade apocrine intraDuctal carcinoma expanding the morphologic and molecular spectrum of an enigmatic salivary gland tumor
Head and Neck Pathology, 2020Co-Authors: Justin A Bishop, Jeffrey Gagan, Jeffrey F Krane, Vickie Y JoAbstract:IntraDuctal carcinoma (IDC) is the current designation for a salivary gland neoplasm previously referred to as "low-grade salivary Duct carcinoma" and "low-grade cribriform cystadenocarcinoma," among others. IDC is conceptually believed to be similar to Ductal carcinoma in-situ of the breast. Although IDC is one entity in the current WHO Classification of Head and Neck Tumors, recent studies have suggested that at least three subtypes exist: a low-grade, Intercalated Duct-like variant with frequent RET rearrangements; a high-grade apocrine variant with complex, salivary Duct carcinoma-like genetics; and a mixed variant. We sought to characterize an unusual form of low-grade, purely apocrine IDC. Three cases of apocrine-type IDC with low-grade histology were retrieved from the authors' consultation files. Immunohistochemistry for androgen receptor, GCDFP-15, S100, smooth muscle actin, and p40 was performed. A custom, targeted next generation sequencing (NGS) panel including 1425 cancer-related genes was also done on all cases. All three cases developed in the parotid glands of men, aged 51, 63, and 73 years (mean, 62 years). All cases consisted of large, rounded macrocysts surrounded by smaller nests which were lined by cells with abundant granular eosinophilic cytoplasm and large round nuclei with prominent nucleoli. Pleomorphism was mild, the mitotic rate was low, and necrosis was absent. No cases had any invasive foci or areas of Intercalated Duct-like morphology. By immunohistochemistry, all cases were diffusely positive for androgen receptor and GCDFP-15, surrounded entirely by an intact layer of small myoepithelial cells positive for S100, smooth muscle actin, and p40. Targeted NGS results were obtained from two cases: both harbored HRAS mutations and copy number losses in TP53, while one case each harbored mutations in PIK3CA, SPEN, and ATM. Fusions were absent in both cases. All three patients were treated by surgery alone, and are currently free of disease (follow up 12-190 months). This study confirms the existence of a low-grade, purely apocrine form of IDC. In its pure form, i.e., without an Intercalated Duct-type component, low-grade apocrine IDC is genetically similar to high-grade salivary Duct carcinoma, with frequent HRAS and PI3K pathway mutations. Despite its molecular similarities to the aggressive salivary Duct carcinoma, low-grade apocrine IDC appears to behave in a very indolent manner, supporting is classification as a non-invasive neoplasm, and underscoring the need to distinguish these tumors from each other.
Victor Angelo Martins Montalli - One of the best experts on this subject based on the ideXlab platform.
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Study of the immunoprofile of basal cell adenoma (emphasizing its relation to Intercalated Duct lesion) and myoepithelial cells influenced by factors in the tumor microenvironment
2017Co-Authors: Victor Angelo Martins MontalliAbstract:Resumo: As lesões salivares tumorais compostas por dupla população celular (epitelial e mioepitelial) são consideradas originárias do Ducto intercalado e estas lesões são subdivididas em diversas entidades que apresentam sobreposição morfológica, com delimitações entre elas nem sempre nítidas. Entre as neoplasias benignas estão o adenoma pleomórfico (AP) e o adenoma de células basais (ACB). Recentemente foi descrita uma nova entidade tumoral benigna, com composição epitelial e mioepitelial, denominada de lesão do Ducto intercalado (LDI). Diante disso, o nosso primeiro objetivo foi analisar os perfis morfológicos e imuno-histoquímicos de LDIs e ACBs classificados em tubulares (ACB-T) e não tubulares (ACB-NT) para verificar se as LDIs e ACB-Ts representam entidades distintas. Ainda, dado o papel crítico da célula mioepitelial na morfogênese das lesões tumorais salivares histogeneticamente relacionadas ao Ducto intercalado, nosso segundo objetivo foi avaliar in vitro a influência de fatores do microambiente tumoral (proteínas da matriz extracelular e fatores de crescimento) sobre a morfologia, viabilidade e proliferação de células mioepiteliais advindas de AP. Para a análise morfológica e imuno-histoquímica, foram estudados oito casos de LDIs, nove ACBs-T e 19 ACBs-NT. Todos os ACB-T continham áreas LDI-like, enquanto nos ACB-NT estas eram raras e escassas. As células luminais das LDIs e ACBs-T exibiram positividade para CK7, lisozima, S100 e DOG1. No grupo ACB-NT, poucas células luminais mostraram tal expressão, sendo principalmente positivas para CK14. As células mioepiteliais das LDIs, ACB-T e ACB-NT foram positivas para CK14, calponina, AML e p63, mas essas eram mais numerosas nos ACBs. No estudo in vitro, a morfologia e diferenciação das células mioepiteliais foram avaliadas qualitativamente por imunofluorescência indireta (expressão da vimentina e AML, respectivamente). As células mioepiteliais exibiram morfologia poliédrica em todas as matrizes, independentemente da suplementação do fator de crescimento. AML foi imunoexpressa de forma heterogênea nas células mioepiteliais, porém houve aumento da expressão desta proteína quando acrescentado o TGF- ?1, independentemente do tipo de matriz usada. TGF- β1 também aumentou significantemente a viabilidade das células mioepiteliais cultivadas na matriz fibronectina. Conclusões: as LDI, ACB-T e ACB-NT formam um continuum de lesões onde as LDIs estão estreitamente relacionadas com o ACB-T, visto que em ambos o imunofenótipo das células luminais e mioepiteliais é semelhante àquele observado nos Ductos intercalados. A principal diferença entre LDI e ACB-T é a quantidade de células mioepiteliais, que é maior no último. Além disso, nossos resultados indicam que pelo menos alguns ACBs podem surgir via LDI. Os estudos em cultura de células sugerem que as diferentes matrizes celulares não influenciam a morfologia e diferenciação da célula mioepitelial. Dentre os fatores de crescimento estudados apenas TGF- β1 associou-se com aumento da expressão de AML (diferenciação celular) e aumentou significantemente a viabilidade celular associado à matriz fibronectina. ;;Abstract:Salivary tumor lesions composed of dual cell population (epithelial and myoepithelial) are considered to originate from the Intercalated Duct. These lesions are subdivided into several entities that share morphological features. Among the benign tumors are pleomorphic adenomas (PA) and basal cell adenoma (BCA). Recently, a new entity was described that is a benign tumor with epithelial and myoepithelial composition, called Intercalated Duct lesion (IDL). Our first objective was to analyze the morphological and immunohistochemical profiles of IDLs and BCAs classified into tubular (T-BCA) and non-tubular subtypes (NT-BCA), to determine whether or not IDL and tubular BCA represent distinct entities. Also, given the critical role of myoepithelial cells in the morphogenesis of the salivary tumor lesions histogenetically related to the Intercalated Duct, our second objective was to evaluate in vitro the influence of tumor microenvironment factors (extracellular matrix proteins and growth factors) on the morphology, viability and proliferation of myoepithelial cells arisen from PA . Eight IDLs, nine tubular BCAs and 19 non-tubular BCAs were studied by immunohistochemical technique. All tubular BCAs contained IDL-like areas, which represented 20-70% of the tumor. In non-tubular BCA, IDL-like areas were occasional and small (
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Lysozyme Expression Can be Useful to Distinguish Mammary Analog Secretory Carcinoma from Acinic Cell Carcinoma of Salivary Glands
Head and Neck Pathology, 2016Co-Authors: Fernanda Viviane Mariano, Victor Angelo Martins Montalli, Camila Andrea Concha Gómez, Juliana Souza Do Nascimento, Harim Tavares Santos, Erika Said Egal, Pablo Agustin Vargas, Oslei Paes Almeida, Albina AltemaniAbstract:Lysozyme is an enzymatic marker of acinar and Intercalated Duct cells of normal salivary glands. The aim of this study was to verify whether lysozyme expression could be useful to distinguish acinic cell carcinoma (ACC) from its main mimic, mammary analog secretory carcinoma (MASC). For comparison, DOG1 expression was analyzed as well. Seventeen cases of ACC, 15 MASC, and 125 other salivary tumors were studied. Lysozyme expression was found in tumor cells as well as in secreted material of MASC (86.6 % of cases) and in Ductal cells of epithelial–myoepithelial carcinoma (EMC-53.8 %), pleomorphic adenoma (PA-29.1 %) and polymorphous low-grade adenocarcinoma (PLGA-23.8 %). However, in ACC, lysozyme was not expressed. Three patterns of DOG1 staining were seen: apical–luminal, cytoplasmic, and mixed cytoplasmic/membranous. The apical–luminal pattern was detected in Ductal cells of ACC (58.8 % of cases), EMC (38.4 %), adenoid-cystic carcinoma (AdCC-35.3 %), PA (8.3 %), and PLGA (4.8 %). These tumors also showed mixed membranous/cytoplasmic staining for DOG1. MASC, mucoepidermoid, and salivary Duct carcinomas exhibited only DOG1 cytoplasmic staining. In conclusion, lysozyme cannot be used as a marker of acinar differentiation in salivary tumors. However, lysozyme expression can be helpful to distinguish MASC from ACC due to its high frequency in the former and absence in ACC. It is likely that in MASC, lysozyme expression may reflect a lactational-like secretory differentiation since lysozyme belongs to breast milk proteins. Regarding DOG1 expression, the apical–luminal pattern is related to acinar and Intercalated Duct differentiation whereas the cytoplasmic staining does not seem to be associated with a specific cellular phenotype.
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tubular variant of basal cell adenoma shares immunophenotypical features with normal Intercalated Ducts and is closely related to Intercalated Duct lesions of salivary gland
Web Science, 2014Co-Authors: Victor Angelo Martins Montalli, Elizabeth Ferreira Martinez, Alfio Jose Tincani, Antonio Santos Martins, Maria Do Carmo Abreu, Catarina De Oliveira Neves, Ana Flavia Costa, Vera Cavalcanti De Araujo, Albina AltemaniAbstract:Aims The morphological criteria for identification of Intercalated Duct lesions (IDLs) of salivary glands have been defined recently. It has been hypothesised that IDL could be a precursor of basal cell adenoma (BCA). BCAs show a variety of histological patterns, and the tubular variant is the one that presents the strongest resemblance with IDLs. The aim of this study was to analyse the morphological and immunohistochemical profiles of IDLs and BCAs classified into tubular and non-tubular subtypes, to determine whether or not IDL and tubular BCA represent distinct entities. Methods and results Eight IDLs, nine tubular BCAs and 19 non-tubular BCAs were studied. All tubular BCAs contained IDL-like areas, which represented 20–70% of the tumour. In non-tubular BCA, IDL-like areas were occasional and small (<5%). One patient presented IDLs, tubular BCAs and IDL/tubular BCA combined lesions. Luminal Ductal cells of IDLs and tubular BCAs exhibited positivity for CK7, lysozyme, S100 and DOG1. In the non-tubular BCA group, few luminal cells exhibited such an immunoprofile; they were mainly CK14-positive. Basal/myoepithelial cells of IDLs, tubular BCAs and non-tubular BCAs were positive for CK14, calponin, α-SMA and p63; they were more numerous in BCA lesions. Conclusions IDL, tubular BCA and non-tubular BCA form a continuum of lesions in which IDLs are related closely to tubular BCA. In both, the immunoprofile of luminal and myoepithelial cells recapitulates the normal Intercalated Duct. The difference between the adenoma-like subset of IDLs and tubular BCA rests mainly on the larger numbers of myoepithelial cells in the latter. Our findings indicate that at least some BCAs can arise via IDLs.
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Tubular Variant Of Basal Cell Adenoma Shares Immunophenotypical Features With Normal Intercalated Ducts And Is Closely Related To Intercalated Duct Lesions Of Salivary Gland.
Histopathology, 2014Co-Authors: Victor Angelo Martins Montalli, Elizabeth Ferreira Martinez, Alfio Jose Tincani, Antonio Santos Martins, Maria Do Carmo Abreu, Catarina De Oliveira Neves, Ana Flavia Costa, Vera Cavalcanti De Araujo, Albina AltemaniAbstract:Aims The morphological criteria for identification of Intercalated Duct lesions (IDLs) of salivary glands have been defined recently. It has been hypothesised that IDL could be a precursor of basal cell adenoma (BCA). BCAs show a variety of histological patterns, and the tubular variant is the one that presents the strongest resemblance with IDLs. The aim of this study was to analyse the morphological and immunohistochemical profiles of IDLs and BCAs classified into tubular and non-tubular subtypes, to determine whether or not IDL and tubular BCA represent distinct entities. Methods and results Eight IDLs, nine tubular BCAs and 19 non-tubular BCAs were studied. All tubular BCAs contained IDL-like areas, which represented 20–70% of the tumour. In non-tubular BCA, IDL-like areas were occasional and small (