Introduction: Metachronous mucoepidermoid carcinomas (MMEC) may occur in association with childhood leukemias and lymphomas. We compared molecular abnormalities of MMEC in patients with ALL with the abnormalities found in primary mucoepidermoid carcinomas (MECs) in pediatric cases and young adults. Materials and methods: Immunohistochemical stains for p63 and SOX10, molecular alterations in MAML2 and KMT2A genes detected by FISH and/or next-generation sequencing were studied in 12 pediatric MMECs secondary to ALL and six primary MECs in pediatric patients and young adults. Follow-up information of patients in both groups was obtained. Results: KMT2A rearrangements were detected in pediatric MMECs, and they were associated with remarkable histomorphological changes, including deposits of abundant stromal collagen and intratumoral lymphoid proliferations. No KMT2A rearrangements were found in primary MECs. The prognosis of MMEC in patients with ALL, especially in KMT2A-rearranged cases, was worse than in primary MECs. Kruskal-Wallis test showed a statistically significant difference in overall survival between KMT2A-rearranged MMECs and KMT2A-intact MMECs in cases with ALL (p = 0.027). Conclusion: KMT2A-rearranged MMECs in ALL patients may have inherently more aggressive behavior, even when the histomorphology of MMEC suggests a low-grade malignancy.

• Klíčová slova
• KMT2A gene, MAML2 gene, metachronous mucoepidermoid carcinoma, pediatric leukemia, salivary gland cancer,
• MeSH
• akutní lymfatická leukemie * MeSH
• dítě MeSH
• DNA vazebné proteiny genetika   MeSH
• genová přestavba MeSH
• jaderné proteiny genetika   MeSH
• lidé MeSH
• mladý dospělý MeSH
• mukoepidermoidní karcinom * genetika   patologie   MeSH
• trans-aktivátory genetika   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladý dospělý MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNA vazebné proteiny MeSH
• jaderné proteiny MeSH
• trans-aktivátory MeSH

This review focuses on the heterogenous group of clear cell neoplasms of salivary glands and attempts to identify major differential diagnostic features. Within the head and neck region, clear cells are found most commonly in salivary gland tumors, but may also be seen in tumors of squamous or odontogenic epithelial origin, primary or metastatic carcinomas, benign or malignant melanocytic lesions, or benign or malignant mesenchymal tumors. Clear cells occur fairly commonly among a wide variety of salivary gland neoplasms, but mostly they constitute only a minor component of the tumor cell population. Clear cells represent a major diagnostic feature in two salivary gland neoplasms, epithelial-myoepithelial carcinoma and hyalinizing clear cell carcinoma. In addition, salivary gland neoplasms composed predominantly of clear cells could also include clear cell variants of other salivary neoplasms, such as mucoepidermoid carcinoma and myoepithelial carcinoma, but their tumor type-specific histologic features may only be available in limited nonclear cell areas of the tumor. Diagnosing predominantly clear cell salivary gland tumors is difficult because the immunoprofiles and morphologic features may overlap and the same tumor entity may also have a wide range of other histologic presentations. Many salivary gland tumors are characterized by tumor type-specific genomic alterations, particularly gene fusions of the ETV6 gene in secretory carcinoma, the MYB and MYBL1 genes in adenoid cystic carcinoma, the MAML2 gene in mucoepidermoid carcinoma, the EWSR1 gene in hyalinizing clear cell carcinoma, and others. Thus, along with conventional histopathologic examination and immunoprofiling, molecular and genetic tests may be important in the diagnosis of salivary gland clear cell tumors by demonstrating genetic alterations specific to them.

• MeSH
• karcinom * patologie   MeSH
• lidé MeSH
• mukoepidermoidní karcinom * diagnóza   genetika   patologie   MeSH
• nádorové biomarkery genetika   MeSH
• nádory slinných žláz * diagnóza   genetika   patologie   MeSH
• slinné žlázy patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• nádorové biomarkery MeSH

Oncocytic mucoepidermoid carcinoma (OMEC) is a rare but diagnostically challenging variant of mucoepidermoid carcinoma (MEC). OMEC is notable for differential diagnostic considerations that are raised as a result of overlap with other benign and low-grade oncocytic salivary gland tumors. Diffuse and strong immunoreactivity of p63 protein may be useful in distinguishing OMEC from its mimics. However, focal p63 staining can be present in benign oncytomas. Presence of mucin-containing cells, mucinous cystic formation, and foci of extravasated mucin are considered a hallmark of MEC. True mucocytes may be, however, very few and hardly discernable in OMECs. Recent evidence has shown that most MECs harbor gene fusions involving MAML2. A retrospective review of archived pathology files and the authors' own files was conducted to search for "low-grade/uncertain oncocytic tumor," "oncocytoma," and "oncocytic carcinoma" in the period from 1996 to 2019. The tumors with IHC positivity for p63 and/or p40, and S100 negativity, irrespective of mucicarmine staining, were tested by next-generation sequencing using fusion-detecting panels to detect MAML2 gene rearrangements. Two index cases from consultation practice (A.S. and A.A.) of purely oncocytic low-grade neoplasms without discernible mucinous cells showed a CRTC1-MAML2 fusion using next-generation sequencing, and were reclassified as OMEC. In total, 22 cases of oncocytic tumors, retrieved from the authors' files, and from the Salivary Gland Tumor Registry, harbored the MAML2 gene rearrangements. Presence of mucocytes, the patterns of p63 and SOX10 immunopositivity, and mucicarmine staining were inconsistent findings. Distinguishing OMEC devoid of true mucinous cells from oncocytoma can be very challenging, but it is critical for proper clinical management. Diffuse and strong positivity for p63 and visualization of hidden mucocytes by mucicarmine staining may be misleading and does not always suffice for correct diagnosis. Our experience suggests that ancillary studies for the detection of MAML2 rearrangement may provide useful evidence in difficult cases.

• MeSH
• diagnostické techniky molekulární * MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• fúze genů MeSH
• genová přestavba MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mukoepidermoidní karcinom chemie   genetika   patologie   MeSH
• nádorové biomarkery analýza   genetika   MeSH
• nádory slinných žláz chemie   genetika   patologie   MeSH
• oxyfilní adenom chemie   genetika   patologie   MeSH
• prediktivní hodnota testů MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stupeň nádoru MeSH
• trans-aktivátory genetika   MeSH
• transkripční faktory genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• CRTC1 protein, human MeSH Prohlížeč
• MAML2 protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• trans-aktivátory MeSH
• transkripční faktory MeSH

Mucoepidermoid carcinoma (MEC) with a predominant spindle cell composition occurring in the palatine tonsil is exceedingly rare. We present a case of a 17-year-old boy with an uncommon spindle cell variant of MEC arising in the palatine tonsil. Histologically, the tumor showed a solid, noncystic architecture and was composed of a predominant population of bland spindle to fusiform cells arranged in organoid nests with interspersed goblet cells and focal areas of ductular structures. Reverse transcriptase polymerase chain reaction and fluorescence in situ hybridization (FISH) revealed the presence of a t(11;19) CRTC1-MAML2 gene fusion in this rare variant of MEC. This is the first case report of a spindle cell MEC of the palatine tonsil, with molecular genetic confirmation. It illustrates the importance of awareness and recognition of this uncommon histological variant of MEC, which will help establish appropriate treatment and prognostication.

• Klíčová slova
• CRTC1-MAML2, mucoepidermoid carcinoma, palatine tonsil, salivary gland carcinoma, spindle cell,
• MeSH
• DNA vazebné proteiny genetika   MeSH
• fúzní onkogenní proteiny genetika   MeSH
• jaderné proteiny genetika   MeSH
• krční mandle patologie   MeSH
• lidé MeSH
• mladiství MeSH
• mukoepidermoidní karcinom genetika   patologie   MeSH
• tonzilární nádory genetika   patologie   MeSH
• trans-aktivátory MeSH
• transkripční faktory genetika   MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• přehledy MeSH
• Názvy látek
• CRTC1 protein, human MeSH Prohlížeč
• DNA vazebné proteiny MeSH
• fúzní onkogenní proteiny MeSH
• jaderné proteiny MeSH
• MAML2 protein, human MeSH Prohlížeč
• trans-aktivátory MeSH
• transkripční faktory MeSH

Twenty-one hidradenomas from 20 patients (13 female, 7 male) ranging in age from 18 to 87years (mean, 57.75years; median, 60years) were studied for CRTC1-MAML2 and CRTC3-MAML2 fusions to find out whether there is a correlation between the particular cell type (polyhedral eosinophilic, clear, mucinous, epidermoid, and oncocytic) and presence the above alterations. CRTC1-MAML2 fusions were detected in 10 of the 21 neoplasms (47.6%). Fluorescence in situ hybridization for MAML2 break apart was analyzable in 13 specimens and in all these specimens was positive, including 4 tumors with no demonstrable CRTC1-MAML2 fusion. In none of the cases was a CRTC3-MAML2 fusion detected. No obvious correlation between the cellular composition and presence of t(11,19) translocation was found.

• Klíčová slova
• Cutaneous adnexal tumors, Hidradenoma, MAML2, MECT1, Mucoepidermoid carcinoma,
• MeSH
• DNA vazebné proteiny genetika   MeSH
• dospělí MeSH
• fúzní onkogenní proteiny genetika   MeSH
• hybridizace in situ fluorescenční metody   MeSH
• jaderné proteiny genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mukoepidermoidní karcinom genetika   metabolismus   patologie   MeSH
• nádory kůže genetika   metabolismus   patologie   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• trans-aktivátory MeSH
• transkripční faktory genetika   MeSH
• translokace genetická MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• CRTC1 protein, human MeSH Prohlížeč
• CRTC3 protein, human MeSH Prohlížeč
• DNA vazebné proteiny MeSH
• fúzní onkogenní proteiny MeSH
• jaderné proteiny MeSH
• MAML2 protein, human MeSH Prohlížeč
• trans-aktivátory MeSH
• transkripční faktory MeSH

In recent years the discovery of translocations and the fusion oncogenes that they result in has changed the way diagnoses are made in salivary gland pathology. These genetic aberrations are recurrent; and at the very least serve as powerful diagnostic tools in salivary gland tumors diagnosis and classification. They also show promise as prognostic markers and hopefully as targets of therapy. In this review the 4 carcinomas currently known to harbor translocations will be discussed, namely mucoepidermoid carcinoma, adenoid cystic carcinoma, mammary analogue secretory carcinoma, and hyalinizing clear cell carcinoma. The discovery and implications of each fusion will be highlighted and how they have helped to reshape the current classification of salivary gland tumors.

• Klíčová slova
• salivary gland carcinoma - fusion oncogenes - CRTC1/3-MAML2 - MYB-NFIB - ETV6-NTRK3 - EWSR1-ATF1.,
• MeSH
• adenoidně cystický karcinom diagnóza   genetika   metabolismus   patologie   MeSH
• fúzní onkogenní proteiny genetika   MeSH
• karcinom diagnóza   genetika   metabolismus   patologie   MeSH
• lidé MeSH
• molekulární patologie MeSH
• mukoepidermoidní karcinom diagnóza   genetika   metabolismus   patologie   MeSH
• nádory slinných žláz diagnóza   genetika   metabolismus   patologie   MeSH
• slinné žlázy metabolismus   patologie   MeSH
• translokace genetická * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• fúzní onkogenní proteiny MeSH