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5. Salivary Gland Secretory Carcinoma: Clinicopathologic and Genetic Characteristics of 215 Cases and Proposal for a Grading System

Author

Baněčková, Martina, Thompson, Lester D.R., Hyrcza, Martin D., Vaněček, Tomáš, Agaimy, Abbas, Laco, Jan, Simpson, Roderick H.W., Di Palma, Silvana, Stevens, Todd M., Brcic, Luka, Etebarian, Arghavan, Dimnik, Katarina, Majewska, Hanna, Stárek, Ivo, O’Regan, Esther, Salviato, Tiziana, Helliwell, Tim, Horáková, Markéta, Biernat, Wojciech, Onyuma, Timothy, Michal, Michal, Leivo, Ilmo, and Skalova, Alena

Published
2023
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6. Novel insights into the BAP1-inactivated melanocytic tumor

Author

Donati, Michele, Martinek, Petr, Steiner, Petr, Grossmann, Petr, Vanecek, Tomas, Kastnerova, Liubov, Kolm, Isabel, Baneckova, Martina, Donati, Pietro, Kletskaya, Irina, Kalmykova, Antonina, Feit, Josef, Blasch, Petr, Szilagyi, Diana, Baldi, Alfonso, Persichetti, Paolo, Crescenzi, Anna, Michal, Michal, and Kazakov, Dmitry V.

Published
2022
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7. Adenoid Cystic Carcinoma With Striking Tubular Hypereosinophilia: A Unique Pattern Associated With Nonparotid Location and Both Canonical and Novel EWSR1: MYB and FUS: MYB Fusions

Author

Weinreb, Ilan, Rooper, Lisa M., Dickson, Brendan C., Hahn, Elan, Perez-Ordonez, Bayardo, Smith, Stephen M., Lewis, James S., Jr, Skalova, Alena, Baněčková, Martina, Wakely, Paul E., Jr, Thompson, Lester D.R., Rupp, Niels J., Freiberger, Sandra N., Koduru, Prasad, Gagan, Jeffrey, and Bishop, Justin A.

Published
2023
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10. Sclerosing Polycystic Adenoma of Salivary Glands: A Novel Neoplasm Characterized by PI3K-AKT Pathway Alterations—New Insights Into a Challenging Entity

Author

Skálová, Alena, Baněčková, Martina, Laco, Jan, Di Palma, Silvana, Agaimy, Abbas, Ptáková, Nikola, Costes-Martineau, Valérie, Petersson, Bengt F., van den Hout, Mari F.C.M., de Rezende, Gisele, Klubíčková, Natálie, Koblížek, Miroslav, Koshyk, Olena, Vaneček, Tomáš, and Leivo, Ilmo

Published
2022
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13. Corrigendum to “Immunohistochemical and genetic analysis of respiratory epithelial adenomatoid hamartomas and seromucinous hamartomas: are they precursor lesions to sinonasal low-grade tubulopapillary adenocarcinomas?” Human Pathology (2020) 97, 94–102

Author

Baněčková, Martina, primary, Michal, Michael, additional, Laco, Jan, additional, Leivo, Ilmo, additional, Ptáková, Nikola, additional, Horáková, Markéta, additional, Michal, Michal, additional, and Skálová, Alena, additional

Published
2023
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14. A minority of cases of acinic cell carcinoma of the salivary glands are driven by an NR4A2 rearrangement: the diagnostic utility of the assessment of NR4A2 and NR4A3 alterations in salivary gland tumors

Author

Klubíčková, Natálie, primary, Grossmann, Petr, additional, Šteiner, Petr, additional, Baněčková, Martina, additional, Mosaieby, Elaheh, additional, Koshyk, Olena, additional, Michal, Michal, additional, Leivo, Ilmo, additional, and Skálová, Alena, additional

Published
2022
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15. Recurrent EWSR1::COLCA2 Fusions Define a Novel Sarcoma With Spindle/Round Cell Morphology and Strong Predilection for the Sinonasal Tract

Author

Agaimy, Abbas, primary, Baněčková, Martina, additional, De Almeida, John, additional, Dickson, Brendan C., additional, Dimmler, Arno, additional, Hartmann, Wolfgang, additional, Laé, Marick, additional, Pablik, Jessica, additional, Schubart, Christoph, additional, Skálová, Alena, additional, Stoehr, Robert, additional, Trautmann, Marcel, additional, Wardelmann, Eva, additional, Wassef, Michel, additional, and Weinreb, Ilan, additional

Published
2022
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16. Adenoid Cystic Carcinoma With Striking Tubular Hypereosinophilia: A Unique Pattern Associated With Nonparotid Location and Both Canonical and Novel EWSR1::MYB and FUS::MYB Fusions.

Author

Weinreb, Ilan, Rooper, Lisa M., Dickson, Brendan C., Hahn, Elan, Perez-Ordonez, Bayardo, Smith, Stephen M., Lewis Jr, James S., Skalova, Alena, Baněčková, Martina, Wakely Jr, Paul E., Thompson, Lester D.R., Rupp, Niels J., Freiberger, Sandra N., Koduru, Prasad, Gagan, Jeffrey, and Bishop, Justin A.

Published
2023
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20. Epithelioid Soft Tissue Neoplasm of the Soft Palate with a PTCH1-GLI1 Fusion: A Case Report and Review of the Literature

Author

Klubíčková, Natálie, primary, Kinkor, Zdeněk, additional, Michal, Michael, additional, Baněčková, Martina, additional, Hájková, Veronika, additional, Michálek, Jaroslav, additional, Pink, Richard, additional, Dvořák, Zdeněk, additional, Michal, Michal, additional, Leivo, Ilmo, additional, and Skálová, Alena, additional

Published
2021
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21. Sclerosing Polycystic Adenoma of Salivary Glands

Author

Skálová, Alena, primary, Baněčková, Martina, additional, Laco, Jan, additional, Di Palma, Silvana, additional, Agaimy, Abbas, additional, Ptáková, Nikola, additional, Costes-Martineau, Valérie, additional, Petersson, Bengt F., additional, van den Hout, Mari F.C.M., additional, de Rezende, Gisele, additional, Klubíčková, Natálie, additional, Koblížek, Miroslav, additional, Koshyk, Olena, additional, Vaneček, Tomáš, additional, and Leivo, Ilmo, additional

Published
2021
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24. Immunohistochemical and Molecular Genetic Methods in the Head and Neck Pathology

Author

Baněčková, Martina, Skálová, Alena, Stárek, Ivo, and Laco, Jan

Abstract

Current doctoral thesis is dealing with morphology, immunohistochemistry, molecular genetics and biological behavior of head and neck tumors with a particular emphasis on salivary gland and sinonasal lesions. Dr. Martina Baneckova has focused on this topic during her postgraduate studies at Charles University, Medical Faculty in Pilsen, in the years 2017 - 2020. In her publication activity, the author focused on rare tumors of the head and neck. A total of 9 publications were published over a span of three years are presented in a form of a commentary. Four of them are first-author papers and these are introduced briefly below. The first study entitled "Mammary analog secretory carcinoma of the nasal cavity: Characterization of 2 cases and their distinction from other low-grade sinonasal adenocarcinomas" deals with the relationship of newly described entities, secretory carcinoma (SC) of the nasal cavity and ETV6-rearranged low-grade sinonasal adenocarcinoma (LG SNAC). It is important to distinguish these 2 entities because of different clinical behaviors. Low-grade non-ITAC, including ETV6-rearranged LG SNAC mostly behave in an indolent manner, whereas SC is a malignancy with metastatic potential. It is important to be aware of the possible occurrence of SC in the sinonasal region, as in this area...

Published
2020

27. Molecular Profiling of Clear Cell Myoepithelial Carcinoma of Salivary Glands With EWSR1 Rearrangement Identifies Frequent PLAG1 Gene Fusions But No EWSR1 Fusion Transcripts

Author

Skálová, Alena, primary, Agaimy, Abbas, additional, Vanecek, Tomas, additional, Baněčková, Martina, additional, Laco, Jan, additional, Ptáková, Nikola, additional, Šteiner, Petr, additional, Majewska, Hanna, additional, Biernat, Wojciech, additional, Corcione, Luigi, additional, Eis, Václav, additional, Koshyk, Olena, additional, Vondrák, Jan, additional, Michal, Michal, additional, and Leivo, Ilmo, additional

Published
2020
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29. What is hiding behind S100 protein and SOX10 positive oncocytomas? Oncocytic pleomorphic adenoma and myoepithelioma with novel gene fusions in a subset of cases

Author

Baněčková, Martina, primary, Uro-Coste, Emmanuelle, additional, Ptáková, Nikola, additional, Šteiner, Petr, additional, Stanowska, Olga, additional, Benincasa, Giulio, additional, Colella, Giuseppe, additional, Vondrák, Jan, additional, Michal, Michal, additional, Leivo, Ilmo, additional, and Skálová, Alena, additional

Published
2020
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32. MUC4 is a valuable marker for distinguishing secretory carcinoma of the salivary glands from its mimics.

Author

Taverna, Cecilia, Baněčková, Martina, Lorenzon, Monica, Palomba, Annarita, Franchi, Alessandro, Skalova, Alena, and Agaimy, Abbas

Subjects
*SALIVARY glands, *CARCINOMA, *ADENOCARCINOMA
Abstract

Aims: Secretory carcinoma (SC) (synonym: mammary analogue secretory carcinoma) is a low‐grade salivary gland tumour that occurs in both major and minor salivary glands. SC is known for its wide morphological, architectural and immunohistochemical spectrum, which overlaps with those of several salivary gland neoplasms, including acinic cell carcinoma (AciCC) and intercalated duct‐type intraductal carcinoma (IDC) in major salivary glands, and polymorphous adenocarcinoma (PAC) in minor salivary glands. These tumours share with SC some morphological features and SOX10 immunoreactivity; also, with the exception of AciCC, they all coexpress S100 and mammaglobin. Methods and results: We compared MUC4 and mammaglobin expression in 125 salivary gland carcinomas (54 genetically confirmed SCs, 20 AciCCs, 21 PACs, and 30 IDCs) to evaluate the potential of these two markers to differentiate these entities. Moderate to strong diffuse MUC4 positivity was detected in 49 SCs (90.7%), as compared with none of the IDCs and PACs. In contrast, mammaglobin was frequently expressed in SCs (30 of 36 cases; 83.3%), IDCs (24/28; 85.7%), and PACs (7/19; 36.8%). Two of three high‐grade SCs lost MUC4 expression in the high‐grade tumour component. No significant correlation was found between MUC4 expression and the fusion variant in SC (ETV6–NTRK versus non‐ETV6–NTRK). Conclusion: The results of our study identify MUC4 as a sensitive (90.7%) and specific (100%) marker for SC, with high positive (100%) and negative (93.4%) predictive values. Thus, MUC4 may be used as a surrogate for SC in limited biopsy material and in cases with equivocal morphology. [ABSTRACT FROM AUTHOR]

Published
2021
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33. Angiosarkom sleziny a jater.

Author

Vítovec, Martin, Baněčková, Martina, and Mírka, Hynek

Subjects
*TUMOR classification, *DISEASE progression, *ANGIOSARCOMA, *AUTOPSY, *BLOOD vessels, *SURGICAL excision
Abstract

Angiosarcomas are rare malignancies arising from blood vessels and can occur in different organs. They are often diagnosed at an advanced stage of the disease, in most cases with apparent generalisation. The clinical symptoms are non-specific, diagnosis is difficult and final diagnosis is often determined by a histopathological finding. Patient prognosis remains poor and the main modality of treatment is surgical resection. In our case report, we present a patient with advanced liver infiltration and a spleen lesion with images in almost all modalities available. Unfortunately, the first biopsy was insufficient, and initially there was a wide differential diagnostic. Subsequently, disease progression is seen with typical images of bleeding foci followed by confirmation after repeated biopsy and subsequent autopsy. This is an illustrative example of what a multifocal form of angiosarcoma disability can look like. [ABSTRACT FROM AUTHOR]

Published
2021

35. Nuclear NR4A3 Immunostaining Is a Specific and Sensitive Novel Marker for Acinic Cell Carcinoma of the Salivary Glands

Author

Haller, Florian, primary, Skálová, Alena, additional, Ihrler, Stephan, additional, Märkl, Bruno, additional, Bieg, Matthias, additional, Moskalev, Evgeny A., additional, Erber, Ramona, additional, Blank, Susanne, additional, Winkelmann, Christa, additional, Hebele, Simone, additional, Baněčková, Martina, additional, Wiemann, Stefan, additional, Müller, Sarina, additional, Zenk, Johannes, additional, Eils, Roland, additional, Iro, Heinrich, additional, Hartmann, Arndt, additional, and Agaimy, Abbas, additional

Published
2019
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37. HMGA2-WIF1Rearrangements Characterize a Distinctive Subset of Salivary Pleomorphic Adenomas With Prominent Trabecular (Canalicular Adenoma-like) Morphology

Author

Agaimy, Abbas, Ihrler, Stephan, Baněčková, Martina, Costés Martineau, Valérie, Mantsopoulos, Konstantinos, Hartmann, Arndt, Iro, Heinrich, Stoehr, Robert, and Skálová, Alena

Abstract

Most of salivary gland neoplasms (benign and malignant) are characterized by recurrent gene fusions. Pleomorphic adenoma (PA), the most frequent salivary gland tumor, is driven by chromosomal rearrangements involving PLAG1mapped to 8q12 and HMGA2mapped to 12q13-15 in most cases. Multiple fusion partners have been identified including CTNNB1, FGFR1, LIFR, CHCHD7and TCEAfor PLAG1fusions and NFIB, WIF1and FHITfor HMGA2fusions. To date, no data exist on the morphology of the few reported HMGA2-WIF1-rearranged PAs. We present 28 major salivary gland adenomas displaying distinctive trabecular and canalicular morphology associated with recurrent genotype. Patients were 15 females and 13 males aged 43 to 87 (median: 65). All tumors originated from the parotid. Their size range was 1 to 4 cm (mean: 2.3). Histologically, all tumors showed elongated or columnar cells arranged into bilayered to multilayered communicating and branching strands and trabeculae in a manner similar to canalicular adenoma of minor salivary glands or trabecular myoepithelioma with variable solid confluent intercalated duct-like areas. Fifteen tumors were exclusively canalicular/trabecular while 13 had intermingled or well-demarcated conventional (chondromyxoid) PA component comprising 5 to >50% of the tumor. The monomorphic areas expressed uniformly CK7 (28/28), vimentin (21/21), S100 (24/24), SOX10 (16/17) and variably p63 (8/21) and mammaglobin (6/16) but were negative with p40 (0/24), smooth muscle actin (0/24) and MUC4 (0/16). Targeted RNA sequencing revealed HMGA2fusions in 14/16 (87%) assessable cases. Fusion partner was WIF1(12), RPSAP52(1) and HELB(1). Separate testing of the 2 components in 1 hybrid tumor showed same HMGA2/WIF1fusion. HMGA2 immunohistochemistry was homogeneously positive in all cases including the 2 fusion-negative cases. A control cohort of 12 genuine canalicular adenomas revealed no HMGA2fusions (0/4) and lacked HMGA2 immunoreactivity (0/12). This study highlights a distinctive variant in the spectrum of PA characterized by prominent trabecular and canalicular adenoma-like morphology. Our data confirm that canalicular adenomas in major salivary glands (either monomorphic or part of hybrid tumors) are distinct from canalicular adenoma of minor salivary glands. Their uniform genotype irrespective of presence or absence of a conventional PA component argues for classifying those tumors lacking a conventional PA component as “monomorphic variants of PA” rather than canalicular/basal cell adenomas, intercalated duct adenoma, trabecular myoepithelioma or true hybrid tumors.

Published
2022
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39. Molecular Profiling of Clear Cell Myoepithelial Carcinoma of Salivary Glands With EWSR1Rearrangement Identifies Frequent PLAG1Gene Fusions But No EWSR1Fusion Transcripts

Author

Skálová, Alena, Agaimy, Abbas, Vanecek, Tomas, Baněčková, Martina, Laco, Jan, Ptáková, Nikola, Šteiner, Petr, Majewska, Hanna, Biernat, Wojciech, Corcione, Luigi, Eis, Václav, Koshyk, Olena, Vondrák, Jan, Michal, Michal, and Leivo, Ilmo

Abstract

Myoepithelial carcinoma of salivary glands is an underrecognized and challenging entity with a broad morphologic spectrum, including an EWSR1-rearranged clear cell variant. Myoepithelial carcinoma is generally aggressive with largely unknown genetic features. A retrospective review of Salivary Gland Tumor Registry in Pilsen searching for the key words “clear cell myoepithelial carcinoma,” “hyalinizing clear cell,” and “clear cell malignant myoepithelioma” yielded 94 clear cell myoepithelial carcinomas (CCMCs) for molecular analysis of EWSR1rearrangement using fluorescence in situ hybridization (FISH). Tumors positive for EWSR1gene rearrangement were tested by next-generation sequencing (NGS) using fusion-detecting panels. NGS results were confirmed by reverse-transcription polymerase chain reaction or by FISH. Twenty-six tumors originally diagnosed as CCMC (26/94, 27.6%) revealed split signals for EWSR1by FISH. Six of these tumors (6/26, 23%) displayed amplification of the EWSR1locus. Fifteen cases were analyzable by NGS, whereas 9 were not, and tissue was not available in 2 cases. None of the CCMCs with EWSR1rearrangements detected by FISH had an EWSR1fusion transcript. Fusion transcripts were detected in 6 cases (6/15, 40%), including LIFR-PLAG1and CTNNB1-PLAG1, in 2 cases each, and CHCHD7-PLAG1and EWSR1-ATF1fusions were identified in 1 case each. Seven cases, including those with PLAG1fusion, were positive for PLAG1rearrangement by FISH, with notable exception of CHCHD7-PLAG1, which is an inversion not detectable by FISH. One single case with EWSR1-ATF1fusion in NGS showed ATF1gene rearrangement by FISH and was reclassified as clear cell carcinoma (CCC). In addition, another 4 cases revealed ATF1rearrangement by FISH and were reclassified as CCC as well. Moreover, 12/68 (17%) CCMCs with intact EWSR1gene were selected randomly and analyzed by NGS. PLAG1fusions were found in 5 cases (5/12, 41.6%) with LIFR(2 cases), FGFR1(2 cases), and CTNNB1(1 case) as partner genes. Overall, PLAG1gene rearrangements were detected in 10/38 (26%) tested cases. None of the tumors had SMARCB1 loss by immunohistochemistry as a possible explanation for the EWSR1abnormalities in FISH. Novel findings in our NGS study suggest that EWSR1-FISH positive CCMC is a gene fusion-driven disease with frequent oncogenic PLAG1fusions, including LIFR-PLAG1and CTNNB1-PLAG1in most cases. Productive EWSR1fusions are found only in a minority of EWSR1-ATF1-rearranged cases, which were in part reclassifiable as CCCs. Detectable EWSR1-FISH abnormality in CCMCs without gene fusion perhaps represents a passenger mutation with minor or no oncologic effect.

Published
2021
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40. MAML2- Rearranged Tumors of the Breast: A Diagnostic Dilemma.

Author

Baněčková, Martina, Kazakov, Dmitry V., Skálová, Alena, and Michal, Michal

Subjects
*BREAST tumors, *NIPPLE (Anatomy), *SKIN tumors, *BENIGN tumors
Abstract

In summary, there were 2 cases of clear cell hidradenoma,[6],[7] 1 case of apocrine hidradenoma,[5] and 1 case of hidradenoma with polyhedral eosinophilic and mucinous cells.[4] The p63 marker was variably expressed across the discussed cases of NH. The tumor cell population is diverse including mucinous cells, polyhedral eosinophilic cells, clear cells, oxyphilic, and transitional cells in many different proportions and variations. 2017;49:84-87. 7 Memon RA, Granada CNP, Wei S. Clear cell papillary neoplasm of the breast with MAML2 gene rearrangement: clear cell hidradenoma or low-grade mucoepidermoid carcinoma?. [Extracted from the article]

Published
2021
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41. What is hiding behind S100 protein and SOX10 positive oncocytomas? Oncocytic pleomorphic adenoma and myoepithelioma with novel gene fusions in a subset of cases

Author

Emmanuelle Uro-Coste, Petr Steiner, Giulio Benincasa, Martina Baněčková, Olga Stanowska, Jan Vondrák, Alena Skálová, Ilmo Leivo, Giuseppe Colella, Michal Michal, Nikola Ptáková, Baněčková, Martina, Uro-Coste, Emmanuelle, Ptáková, Nikola, Šteiner, Petr, Stanowska, Olga, Benincasa, Giulio, Colella, Giuseppe, Vondrák, Jan, Michal, Michal, Leivo, Ilmo, and Skálová, Alena

Subjects
0301 basic medicine, Adult, Male, Pathology, medicine.medical_specialty, Myoepithelioma, Adenoma, Pleomorphic, Biology, S100 protein, Pathology and Forensic Medicine, Malignant transformation, Pleomorphic adenoma, 03 medical and health sciences, 0302 clinical medicine, medicine, SOX10, Biomarkers, Tumor, Adenoma, Oxyphilic, Humans, Oncocytoma, Oncogene Fusion, PLAG1, Aged, Retrospective Studies, Aged, 80 and over, medicine.diagnostic_test, SOXE Transcription Factors, S100 Proteins, Middle Aged, medicine.disease, Salivary Gland Neoplasms, Parotid gland, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Immunohistochemistry, Female, Fluorescence in situ hybridization
Abstract

Oncocytomas (OCs) in salivary glands are rare benign tumors composed of mitochondriarich epithelial cells (oncocytes), mostly localized in the parotid gland. The treatment of choice is simple excision. Extensive oncocytic metaplasia of pleomorphic adenoma (PA) and myoepithelioma (ME) can be diagnostically challenging and may camouflage the correct diagnosis. These tumors should be treated more carefully compared with OC, given the risk of frequent recurrences and the possibility of malignant transformation.We have investigated 89 oncocytic lesions from our files, including OC (n = 74) and metaplastic oncocytic variant of PA/ME (n = 15). All OCs were stained for 5100 protein and SOX10. The tumors with immunohistochemical expression of one or both markers were tested by next-generation sequencing (NGS). The NGS results were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and/or fluorescence in situ hybridization (FISH).Ten cases originally diagnosed as OC, and 1 low-grade uncertain oncocytic tumor (11/74) revealed nuclear-cytoplasmic and/or nuclear positivity for S100 protein and/or SOX10, respectively. Fusion transcripts CHCHD7-PLAG1 and GEM-PLAG1 were found in 2 cases (1 fusion in each), and these were confirmed by RT-PCR and PLAG1 break-apart FISH probe, respectively. Another 5 cases were positive for PLAG1 rearrangement by FISH. In the control group of 15 oncocytic PA/ME, 4/15 tested tumors harbored gene fusions including NFT3-PLAG1, CHCHD7-PLAG1, FBX032-PLAG1, and Clorf116-PLAG1 (1 fusion in each case) as detected by NGS. Two fusions were confirmed by RTPCR, 1 case by FISH, and 1 case was not analyzable by FISH.We additionally tested 24 OCs negative for 5100 protein and SOX10 by immunohistochemistry (IHC) and by FISH for rearrangement of PLAG1 gene, but none of them were positive.SOX10 and/or 5100 protein immunopositivity in conjunction with rearrangement of the PLAG1 gene assisted in reclassification of a subset of oncocytomas as oncocytic variants of PA and ME. Therefore, we recommend to include S100 protein and SOX10 IHC when diagnosing tumors with predominantly oncocytoma-like differentiation. In addition, by NGS, 3 new gene fusions were detected in oncocytic ME, including NTF3-PLAG1, FBX032-PLAG1, and GEM-PLAG1, and a new fusion Clorf116-PLAG1 was detected in oncocytic PA. (C) 2020 Elsevier Inc. All rights reserved.

Published
2020

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