Salivary gland mucoepidermoid carcinoma is a clinically, morphologically and genetically heterogeneous entity: a clinicopathological study of 40 cases with emphasis on grading, histological variants and presence of the t(11;19) translocation

Schwarz, Stephan; Stiegler, Clemens; Müller, Melanie; Ettl, Tobias; Brockhoff, Gero; Zenk, Johannes; Agaimy, Abbas

doi:10.1111/j.1365-2559.2011.03777.x

Cited by 79 publications

(49 citation statements)

References 31 publications

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“…(5,6) CTCR1-MAML2 fusion has been detected in 40-80% of primary salivary gland mucoepidermoid carcinomas, and we and other research groups have shown that the fusion gene is associated with a distinct tumor subset with an indolent clinical course. (7)(8)(9)(10) Fehr et al (2008) report a novel fusion gene, CRTC3-MAML2, (11) and in Nakayama et al (12) we reveal that CRTC3-MAML2 fusion-positive mucoepidermoid carcinoma cases have an excellent prognosis. These findings suggest that both CRTC1-MAML2 and CRTC3-MAML2 fusions may be associated with mucoepidermoid carcinoma cases with favorable clinicopathological tumor features.…”

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confidence: 75%

Clinicopathological significance of MAML2 gene split in mucoepidermoid carcinoma

et al. 2012

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CRTC1-MAML2 and CRTC3-MAML2 fusions have been associated with favorable clinicopathological features of mucoepidermoid carcinomas. However, the significance of the MAML2 gene split has not been fully clarified. In the present study, 95 mucoepidermoid carcinomas (paraffin-embedded materials) were analyzed for CRTC1-MAML2 and CRTC3-MAML2 fusions by RT-PCR and for the MAML2 gene split by FISH. Quantitative RT-PCR for the CRTC1-MAML2 transcript was performed in selected cases. MLL gene involvement, which has been reported in some leukemia cases, was examined by FISH in fusion partner-unknown cases. CRTC1-MAML2 and CRTC3-MAML2 fusions were detected in 37 and 6 cases, respectively. The MAML2 gene split was detected in 62 cases, which included all CRTC1/3-MAML2 fusion-positive cases. The level of CRTC1-MAML2 transcript expression was highly variable, and its clinicopathological impact was unclear. The MLL gene split was not detected. Mucoepidermoid carcinomas negative for CRTC1/3-MAML2 and positive for the MAML2 gene split (n = 19) showed favorable clinicopathological tumor features similar to those positive for CRTC1/3-MAML2 fusions. Compared with negative cases (n = 33), mucoepidermoid carcinomas positive for the MAML2 split (n = 62) were associated with lower patient age, a mild female predilection, a smaller tumor size, less frequent nodal metastasis, a lower clinical stage, a lower histological grade, and longer overall and disease-free survival. The MAML2 gene split emerged as an independent prognostic factor for both overall and disease-free survival in multivariate prognostic analysis. The presence of the MAML2 gene split defines a distinct mucoepidermoid carcinoma subset that is associated clinicopathologically with favorable tumor features. (Cancer Sci 2013; 104: 85-92) M ucoepidermoid carcinomas represent 5% of all salivary gland tumors and 20% of salivary malignancies.(1,2) A subset of these carcinomas has been associated with a recurring chromosomal translocation, t(11;19)(q21;p13), which generates a fusion protein composed of the N-terminal of cAMP response element-binding protein (CREB)-regulated transcription coactivator 1 (CRTC1), also called MECT1, TORC1 or WAMP1, and the C-terminal of mastermind-like gene 2 (MAML2).(3-6) Recent data suggest that CRTC1-MAML2 induced-activation of CREB is critical for cell transformation.(5,6) CTCR1-MAML2 fusion has been detected in 40-80% of primary salivary gland mucoepidermoid carcinomas, and we and other research groups have shown that the fusion gene is associated with a distinct tumor subset with an indolent clinical course. and in Nakayama et al. (12) we reveal that CRTC3-MAML2 fusion-positive mucoepidermoid carcinoma cases have an excellent prognosis. These findings suggest that both CRTC1-MAML2 and CRTC3-MAML2 fusions may be associated with mucoepidermoid carcinoma cases with favorable clinicopathological tumor features. (13) CRTC1/3-MAML2 fusions have been detected using an RT-PCR technique, assuming that exon 1 of CRTC1/3 genes is fused to exons 2-5 of th...

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Clinicopathological significance of MAML2 gene split in mucoepidermoid carcinoma

et al. 2012

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“…Fgf8 and Il6 are of greater importance than Areg or Tnfα. Schwarz et al, 2011). Although the precise etiology of MEC is largely unknown, we have recently shown that cytomegalovirus is an important component of MEC tumorigenesis (Melnick et al, , 2012.…”

Section: Discussionmentioning

confidence: 98%

Cytomegalovirus-induced salivary gland pathology: AREG, FGF8, TNF-α, and IL-6 signal dysregulation and neoplasia

Melnick¹,

Deluca²,

Sedghizadeh

et al. 2013

Experimental and Molecular Pathology

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“…Clear cells have been reported in benign tumors such as PA, myoepithelioma, and oncocytoma, and malignant tumors such as myoepithelial carcinoma, oncocytic carcinoma, MEC, AcCC, PLGA, and AdCC (1). Clear cells are commonly associated with MEC, with sporadic clear cell change reported in up to 30% of cases, but predominant clear cell change is rarer (2,11). AcCC has been shown to feature clear cell in approximately 6% of cases, but with predominant clear cell populations in only 1% (1).…”

Section: Discussionmentioning

confidence: 99%

Clear cell changes in salivary gland neoplasms: A 20-year retrospective study

Woods¹,

Fitzpatrick²,

Cohen³

et al. 2017

Med Oral

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BackgroundClear cells are observed histopathologically in both benign and malignant neoplasms but their presence in salivary gland tumors has not been extensively documented.Material and MethodsWith IRB approval, the archive of the University of Florida College of Dentistry oral pathology biopsy service was retrospectively searched from 1994-2014 for all benign and malignant salivary tumors. Epidemiological data, tumor location and duration, and type of tumor were recorded. A four reviewer panel examined the original slides. Reviewers scaled each case as 0 (no clear cells present), 1 (few to focal clear cells), 2 (less than 50% clear cells), and 3 (greater than 50% clear cells).ResultsA total of 535 cases were included of which 48% of tumors displayed 0 clear cells (257/535), 31.4% (168/535) scored 1, 13.6% (73/535) scored 2, and 7% (37/535) scored 3. Of the 251 (47%) malignant neoplasms, 64% (160/251) demonstrated 0-1 clear cell change, while 36% (91/251) showed a score of 2-3. For the total 284 (53%) benign tumors, 93% (265/535) scored 0-1 and 7% (19/535) scored a 2-3 range. No statistical difference was noted for gender, age, or duration of time present in regards to presence or absence of clear cells. Statistically significant differences in clear cell presence were found between location groups, between benign and malignant diagnosis, and between specific diagnostic groups.ConclusionsThis study demonstrates the frequent presence of increased numbers of clear cells in oral salivary malignancies and highlights salivary gland differential diagnoses when presented with clear cell changes. Key words:Clear cell change, salivary tumors, benign tumors, malignant tumors.

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Salivary gland mucoepidermoid carcinoma is a clinically, morphologically and genetically heterogeneous entity: a clinicopathological study of 40 cases with emphasis on grading, histological variants and presence of the t(11;19) translocation

Abstract: The results underscore the great histological diversity of MEC, the reproducibility of the WHO grading criteria and the value of histological subtypes as an additional prognostic factor.

Cited by 79 publications

References 31 publications

Clinicopathological significance of MAML2 gene split in mucoepidermoid carcinoma

Clinicopathological significance of MAML2 gene split in mucoepidermoid carcinoma

Cytomegalovirus-induced salivary gland pathology: AREG, FGF8, TNF-α, and IL-6 signal dysregulation and neoplasia

Clear cell changes in salivary gland neoplasms: A 20-year retrospective study

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