Publications by authors named "Stephan Ihrler"

Benign lymphoepithelial tumors of salivary glands had been restricted to sebaceous and non-sebaceous (NSLA) lymphadenomas. However, salivary neoplasms recapitulating carcinoma showing thymus-like elements (CASTLE) have been the subject of recent case reports. We reviewed clinicopathological, immunohistochemical, and molecular findings in 20 salivary gland tumors with thymus-like phenotype (18 histologically benign and two with malignant component).

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Salivary gland tumors are diagnostically challenging due to major diversity of benign and malignant tumors with enormous intra-tumorous and inter-tumorous heterogeneity and, hence, frequently overlapping histologic features. DNA methylation has greatly enhanced tumor classification in several organs and led to the identification of previously unrecognized entities. In a recent study on DNA methylation of salivary gland tumors, we had identified a group of unclassifiable tumors.

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Aims: Mucosal melanoma of the head and neck (MM-H&N) is an aggressive disease known for its frequent residual tumours/relapses (RT/R) at the surgical site, as well as eventual metastases. Our understanding of the MM-H&N mutational landscape, together with the correlation of specific mutations with clinical-pathological features, is significantly less comprehensive compared to that of cutaneous melanoma. Additionally, the mutational status of consecutive samples collected from single patients has not been investigated, which limits our ability to characterise the prognosis and treatment options for this patient subset.

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The pathology of reactive, dysplastic, and neoplastic sinonasal seromucinous glands is complex, and their contribution to tumorigenesis of sinonasal carcinomas remains controversial. In our practice, we have observed the presence of respiratory epithelial adenomatoid hamartomas (REAH) and seromucinous hamartomas (SH) associated with adenoid cystic carcinomas (AdCC) in a subset of cases. In many of these cases, genuine atypical features and dysplastic characteristics of the glands were noted at the interface of SH and AdCC.

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Article Synopsis
  • Adenoid cystic carcinomas (AdCC) of salivary gland origin are primarily defined by the presence of specific gene fusions, notably MYB::NFIB and MYBL1::NFIB, with sinonasal AdCC being particularly aggressive and lacking effective treatments.
  • Researchers conducted an extensive analysis of 88 sinonasal AdCC cases using various techniques like NGS and FISH to identify gene fusions and mutations, finding that the majority harbored canonical fusions while some had noncanonical ones, with a few tumors showing no fusions at all.
  • Mutational analysis revealed that about 68% of AdCCs tested (21 out of 31) had mutations in key oncogenes, highlighting potential areas for targeted
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TFE3 rearrangements characterize histogenetically, topographically, and biologically diverse neoplasms. Besides being a universal defining feature in alveolar soft part sarcoma (ASPS) and clear cell stromal tumor of the lung, TFE3 fusions have been reported in subsets of renal cell carcinoma, perivascular epithelioid cell tumor (PEComa), epithelioid hemangioendothelioma and ossifying fibromyxoid tumors. TFE3 -related neoplasms are rare in the head and neck and may pose diagnostic challenges.

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Basal cell carcinoma is the most common malignant tumor in the fair-skinned population and its incidence continues to rise. An update of the S2k guideline with the participation of all specialist societies familiar with the clinical picture and previous literature research is of great importance for the quality of care for affected patients. In addition to epidemiology, diagnostics and histology are discussed.

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Sclerosing mucoepidermoid carcinoma (SMEC) of the salivary glands is a rare variant of low-grade mucoepidermoid carcinoma with scanty cellular atypia characterized by marked fibrosis/sclerosis and a rich inflammatory infiltrate. Herein, we report 25 unpublished cases of SMEC, two of them with prominent eosinophilia (2/25; 8%) and three with abundant IgG4-positive plasma cells (3/25; 12%). In our series of salivary SMEC, molecular analysis using fluorescence in situ hybridization (FISH) and/or next-generation sequencing (NGS) provided evidence of MAML2 gene rearrangement in 18 cases of the 21 analyzable cases tested (86%), while this gene locus was intact in 3 cases (14%).

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Article Synopsis
  • Tumors of salivary glands vary widely and can overlap, making them challenging to diagnose, despite advances in molecular testing.
  • A study examined 363 cases of 20 different salivary gland tumors and found distinct DNA methylation patterns that help classify these tumors, achieving high accuracy with a machine learning algorithm.
  • The research identified specific epigenetic signatures, distinguishing certain tumor types, and suggested that DNA methylation could aid in diagnosing and potentially uncovering new tumor classes in the future.
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Actinic keratosis (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline "actinic keratosis and cutaneous squamous cell carcinoma" was updated and expanded by the topics cutaneous squamous cell carcinoma in situ (Bowen's disease) and actinic cheilitis.

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Article Synopsis
  • * Some new classifications are seen as provisional, while there’s ongoing debate over terms like "intraductal carcinoma."
  • * Advances in molecular findings, particularly gene fusions, are increasingly relevant for diagnostics, with new tumour types being defined by specific genetic markers.
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There is a widespread impression among clinicians and pathologists that the histomorphological diagnosis of minor salivary gland tumours is more difficult and more frequently misdiagnosed than that of major glands. This is based on subjective clinical impression; scientific proof of and potential reasons for this difference are lacking. We identified 14 putative clinical, histopathological and combined clinical-histological reasons and four consequences, which together could explain the perceived greater difficulty of diagnosing minor gland tumours.

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Article Synopsis
  • - The study investigates the unclear development and clonal relationships of salivary carcinosarcoma (SCS), exploring whether it arises from preexisting pleomorphic adenoma (PA) or develops independently.
  • - An extensive analysis of 16 SCS cases, combined with literature from 111 cases, revealed that SCS almost always originates from PA, demonstrating a complex progression of adenoma to carcinoma to sarcoma through two histogenetic pathways.
  • - The authors suggest that SCS represents a rare and aggressive variant of carcinoma ex PA and propose a new terminology, "sarcomatoid carcinoma ex PA with/without heterologous elements," to better describe its characteristics.
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Microsecretory adenocarcinoma (MSA) of the salivary glands is a recently described entity. Due to lack of reported metastases, in 30 cases described until now, the designation as low-grade cancer was so far solely based on demonstration of local tumor invasion and in a single case with perineural invasion. We herein describe the first documented case with local recurrence and hematogenous metastases.

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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 PLAG1 mapped to 8q12 and HMGA2 mapped to 12q13-15 in most cases. Multiple fusion partners have been identified including CTNNB1, FGFR1, LIFR, CHCHD7 and TCEA for PLAG1 fusions and NFIB, WIF1 and FHIT for HMGA2 fusions.

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Aims: There is a widespread perception among clinicians and pathologists that the histomorphological assessment of minor salivary gland (MinSG) tumours is more difficult and hampered by more misdiagnoses than that of major salivary gland tumours. This is based on a vague, subjective clinical impression, lacking scientific proof. The aim of the present study was to identify and statistically verify potential reasons that could explain this difference.

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Microsecretory adenocarcinoma (MSA) is a recently described salivary gland tumor with a characteristic histologic and immunophenotypic profile and recurrent MEF2C-SS18 fusions. Because only six cases of MSA have been published, its complete clinicopathologic spectrum is unclear, and its biologic behavior has not been documented. Here, we present an updated and expanded experience of 24 MSA cases.

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The majority of salivary gland carcinomas are characterized by recurrent gene fusions that proved highly valuable diagnostically, but only rarely of therapeutic impact. Most of these fusion-positive carcinomas belong to the low-grade or intermediate-grade biological category. To date, only 5 cases of salivary gland carcinomas carrying an oncogenic ALK fusion have been reported in 4 recent studies, but their phenotypic spectrum and their nosological classification remain uncharacterized.

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In October 2020, the lay press, but also some medical journals and websites reported the putative discovery of a new salivary gland in the nasopharynx based on prostate-specific membrane antigen positron emission tomography computed tomography (PSMA-PET/CT) examinations. As an interdisciplinary group from the fields of anatomy, pathology, nuclear medicine and otorhinolaryngology, we come to the view that an accumulation of minor salivary glands has been described here. Minor salivary glands in the nasopharynx and in the peritubar region have been described at least since 1866.

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