Myxolipoma in the tongue - A clinical case report and review of the literature

In this article, we present our experience with a case of myxolipoma of the tongue

Comprehensive molecular characterization of adenoid cystic carcinoma reveals tumor suppressors as novel drivers and prognostic biomarkers

© 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Adenoid cystic carcinoma (ACC) is a MYB-driven head and neck malignancy with high rates of local recurrence and distant metastasis and poor long-term survival. New effective targeted therapies and clinically useful biomarkers for patient stratification are needed to improve ACC patient survival. Here, we present an integrated copy number and transcriptomic analysis of ACC to identify novel driver genes and prognostic biomarkers. A total of 598 ACCs were studied. Clinical follow-up was available from 366 patients, the largest cohort analyzed to date. Copy number losses of 1p36 (70/492; 14%) and of the tumor suppressor gene PARK2 (6q26) (85/343; 25%) were prognostic biomarkers; patients with concurrent losses (n = 20) had significantly shorter overall survival (OS) than those with one or no deletions (p < 0.0001). Deletion of 1p36 independently predicted short OS in multivariate analysis (p = 0.02). Two pro-apoptotic genes, TP73 and KIF1B, were identified as putative 1p36 tumor suppressor genes whose reduced expression was associated with poor survival and increased resistance to apoptosis. PARK2 expression was markedly reduced in tumors with 6q deletions, and PARK2 knockdown increased spherogenesis and decreased apoptosis, indicating that PARK2 is a tumor suppressor in ACC. Moreover, analysis of the global gene expression pattern in 30 ACCs revealed a transcriptomic signature associated with short OS, multiple copy number alterations including 1p36 deletions, and reduced expression of TP73. Taken together, the results indicate that TP73 and PARK2 are novel putative tumor suppressor genes and potential prognostic biomarkers in ACC. Our studies provide new important insights into the pathogenesis of ACC. The results have important implications for biomarker-driven stratification of patients in clinical trials. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.info:eu-repo/semantics/publishedVersio

MicroRNA profiling of salivary adenoid cystic carcinoma: association of miR-17-92 upregulation with poor outcome.

Salivary adenoid cystic carcinoma (ACC) is a rare relentlessly progressive malignant tumor. The molecular events associated with ACC tumorigenesis are poorly understood. Variable microRNAs (miRNA) have been correlated with tumorigenesis of several solid tumors but not in ACC. To investigate the association of miRNAs with the development and/or progression of ACC, we performed a comparative analysis of primary ACC specimens and matched normal samples and a pooled salivary gland standard and correlated the results with clinicopathologic factors and validated selected miRNAs in a separate set of 30 tumors.MiRNA array platform was used for the identification of target miRNAs and the data was subjected to informatics and statistical interrelations. The results were also collected with the MYB-NFIB fusion status and the clinicopathologic features.Differentially dysregulated miRNAs in ACC were characterized in comparison to normal expression. No significant differences in miRNA expression were found between the MYB-NFIB fusion positive and -negative ACCs. Of the highly dysregulated miRNA in ACC, overexpression of the miR-17 and miR-20a were significantly associated with poor outcome in the screening and validation sets.Our study indicates that the upregulation of miR-17-92 may play a role in the biology of ACC and could be potentially targeted in future therapeutic studies

Rearrangements, Expression, and Clinical Significance of MYB and MYBL1 in Adenoid Cystic Carcinoma: A Multi-Institutional Study

Adenoid cystic carcinoma (ACC) is an aggressive head and neck malignancy characterized by a t (6;9) translocation resulting in an MYB&ndash;NFIB gene fusion or, more rarely, an MYBL1 fusion. The true frequency and clinical significance of these alterations are still unclear. Here, we have used tissue microarrays and analyzed 391 ACCs and 647 non-ACC salivary neoplasms to study the prevalence, expression, and clinical significance of MYB/MYBL1 alterations by FISH and immunohistochemistry. Alterations of MYB or MYBL1 were found in 78% of the cases, of which 62% had MYB alterations and 16% had MYBL1 rearrangements. Overexpression of MYB/MYBL1 oncoproteins was detected in 93% of the cases. MYB split signal, seen in 39% of the cases, was specific for ACC and not encountered in non-ACC salivary tumors. Loss of the 3&prime;-part of MYB was enriched in grade 3 tumors and was a significant independent prognostic biomarker for overall survival in multivariate analyses. We hypothesize that loss of the 3&prime;-part of MYB results from an unbalanced t(6;9) leading to an MYB&ndash;NFIB fusion with concomitant loss of the segment distal to the MYB breakpoint in 6q23.3. Our study provides new knowledge about the prevalence and clinical significance of MYB/MYBL1 alterations and indicates the presence of genes with tumor suppressive functions in 6q23.3-qter that contribute to poor prognosis and short overall survival in ACC

Downregulated miRNAs in salivary adenoid cystic carcinoma in comparison to normal salivary gland.

<p>NA; no information. miRNA(*); miRNA star strand.</p>a<p>Mann-Whitney U test,^bTumor/Normal median ratio <0.5 classified as significant. <b>^c</b>chromosomal location. ^dThese information obtained from miRBase database (<a href="http://www.mirbase.org" target="_blank">http://www.mirbase.org</a>). ^eThe miR-17-92 cluster and its paralogs.</p

MiRNA expression differences in salivary ACCs and normals.

<p>(A) A heat map of the differential miRNA expression in normal salivary tissues and control versus tumor samples. Note the clean distinction between normal tumors. Quantitative RT-PCR validation of miRNA expression, miR-455-3p (B) and miR-375 (C).</p

Correlation between dysregulated miRNAs and clinical outcome in adenoid cystic carcinoma patients.

<p>miRNA(*); miRNA star strand.</p>a<p><i>P</i>-values were calculated by Log rank test and Cox regression analysis. ^bHR; Hazard ratio, CI; confidence interval.</p

Correlations of miRNAs with histologic pattern of adenoid cystic carcinoma.

<p>miRNA(*); miRNA star strand.</p>a<p><i>P</i>-values were calculated using the Mann-Whitney U test and 2-tailed Fisher exact test for solid and non-solid types. ^bS/N ratio; Solid/non-solid median ratio.</p