Fluorescence in situ hybridization for detection of MAML2 rearrangements in oncocytic mucoepidermoid carcinomas: utility as a diagnostic test

García, Joaquín J.; Hunt, Jennifer L.; Weinreb, Ilan; McHugh, Jonathan B.; Barnes, Eleanor; Cieply, Kathleen; Đačić, Sanja; Seethala, Raja R.

doi:10.1016/j.humpath.2011.02.028

Cited by 100 publications

(99 citation statements)

References 36 publications

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“…Rearrangements of MAML2 have recently been detected in up to 75 % of MECs of salivary glands, and are very specific for this tumor type [23][24][25][26][27]. They preferentially occur in low/intermediate grade MECs with favorable prognosis where they are regarded as an early genetic alteration that drives tumorigenesis [28].…”

Section: Introductionmentioning

confidence: 99%

Glandular Odontogenic Cysts (GOCs) Lack MAML2 Rearrangements: A Finding to Discredit the Putative Nature of GOC as a Precursor to Central Mucoepidermoid Carcinoma

Bishop

Yonescu

Batista

et al. 2014

Head and Neck Pathol

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Glandular odontogenic cyst (GOC) is a cyst of the gnathic bones that is characterized by squamous and glandular differentiation. The histopathologic features of GOC overlap considerably with central mucoepidermoid carcinoma (MEC), suggesting that GOC could be a precursor lesion to, or even a low-grade form of, central MEC. Differentiating the two lesions may be difficult or impossible on a limited biopsy. MAML2 rearrangements have been recently found to be specific for MEC, even those arising in the jaws. An analysis of MAML2 in GOCs could help clarify its relationship with central MEC. Tissue blocks from 21 GOCs and 5 central MECs were retrieved from the surgical pathology archives of The Johns Hopkins Hospital. Each MEC exhibited solid areas and clear-cut stromal invasion. In addition, 4 of the MECs demonstrated cystic areas that were histologically similar to GOC. Breakapart fluorescence in situ hybridization for MAML2 was performed. For the MECs, analysis was performed on both the solid components and the cystic areas that resembled GOC. MAML2 rearrangements were identified in all 5 of the MECs, but in none of the 21 GOCs (100 vs. 0 %; p \ 0.0001, Fisher's Exact). In the MECs, the rearrangement was present in both the solid and GOC-like cystic areas. While central MECs consistently harbor the MAML2 rearrangement, even in low-grade cystic areas that resemble a pre-existing GOC, true GOCs do not. Accordingly, GOC does not appear to represent an early or low-grade form of central MEC, but rather an unrelated lesion. The high sensitivity and specificity of MAML2 rearrangement for MECs points to its utility as a diagnostic adjunct in separating mucinous cystic lesions of the gnathic bones.

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Section: Introductionmentioning

confidence: 99%

Glandular Odontogenic Cysts (GOCs) Lack MAML2 Rearrangements: A Finding to Discredit the Putative Nature of GOC as a Precursor to Central Mucoepidermoid Carcinoma

Bishop

Yonescu

Batista

et al. 2014

Head and Neck Pathol

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“…6,7 The most common genes involved in this translocation are CREB Regulated Transcription Coactivator1 (CRCT1, also known as MECT1, TORC1 or WAMTP1) on chromosome 19p13 and a member of the MasterMind-Like gene family, MAML2, on chromosome 11q21. In salivary gland tumors, MAML2 rearrangement has been identified in 40-75% of mucoepidermoid carcinomas but not in other salivary gland tumors.…”

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confidence: 99%

Histopathologic, immunophenotypic and cytogenetic features of pulmonary mucoepidermoid carcinoma

et al. 2014

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Pulmonary mucoepidermoid carcinoma is an uncommon but distinctive manifestation of mucoepidermoid carcinoma. Pulmonary mucoepidermoid carcinoma occurs in adults and children and can cause diagnostic problems, especially in small biopsies. Few studies have characterized the histologic and immunophenotypic features of pulmonary mucoepidermoid carcinoma. t(11;19)(q21;p13) is considered disease-defining for mucoepidermoid carcinoma; its significance in pulmonary mucoepidermoid carcinoma warrants further study. Forty three pulmonary mucoepidermoid carcinomas were re-reviewed and graded according to the Brandwein grading system for mucoepidermoid carcinoma. Four cases were excluded because of a split opinion between pathology report and re-review. These cases were negative for MAML2 rearrangement by FISH. TTF-1, napsin A, p40 and p63 immunostains were scored: 0 (negative), 1 (1-25% tumor cells), 2 (26-50%), 3 (51-75%) or 4 (>75%). FISH to detect MAML2 rearrangement used a MAML2-11q21 break-apart probe. Thirty nine pulmonary mucoepidermoid carcinoma (4 low, 30 intermediate, 5 high grade) contained mucous, epidermoid and intermediate cells and lacked keratinization and in situ carcinoma of the overlying epithelium. All cases with available gross description (n=22) had a central/endo- or peribronchial location. All 25 cases tested for immunohistochemistry were positive (scores 1-4) for p63; 23 also expressed p40. In six cases, the p63 score was higher than p40. TTF-1 and napsin were uniformly negative in all 25 cases. MAML2 rearrangement was identified by FISH in each of the 24 cases tested (3 low, 19 intermediate, 2 high grade). Clinical history was available in 29 patients (15 men) (median age, 48 years) with follow-up in 24 (median, 8.4 years). Five patients died of unrelated causes; one developed metastatic pulmonary mucoepidermoid carcinoma. In conclusion, features helpful in distinguishing pulmonary mucoepidermoid carcinoma from other lung cancers include its central/endo- or peribronchial location together with the presence of mucous cells, p63 expression, lack of keratinization and MAML2 rearrangement. TTF-1 and napsin are typically not expressed.

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“…3b). Moreover, none of these tumors showed MAML2 rearrangement, typical of a large proportion of conventional and oncocytic MEC [14,15]. This is not surprising as conventional and oncocytic MEC rarely have the dense sclerosis and cord-like growth of tumor cells that HCCC has.…”

Section: Intracellular Mucin Is Not An Exclusion Criterion For Hccc Amentioning

confidence: 93%

What the EWSR1-ATF1 Fusion has Taught Us About Hyalinizing Clear Cell Carcinoma

Tanguay

Weinreb

2013

Head and Neck Pathol

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Hyalinizing clear cell carcinoma (HCCC) is a unique low-grade tumor composed of cords and nests of clear cells in a hyalinized stroma that was first reported by Milchgrub et al. It was recognized as a separate entity from clear cell variants of epithelial-myoepithelial carcinoma, myoepithelial carcinoma and mucoepidermoid carcinoma. HCCC is included in a long list of clear cell-containing tumors of salivary gland, as well as odontogenic tumors and metastases (renal cell carcinoma). Up until now, it has been considered a diagnosis of exclusion, despite its very distinctive appearance, and labeled as ''not otherwise specified'' by the World Health Organization. The emergence of molecular data in salivary gland tumors, including HCCC now allow for a more rigorous appraisal of its spectrum. The EWSR1-ATF1 fusion has proven the concept of a ''mucinous HCCC'' and removes mucin as an exclusion criterion for this tumor. It has also proven a genetic link between clear cell odontogenic carcinoma and HCCC. Molecularly-proven cases have also highlighted variant morphologies and shown that cases with overt squamous differentiation are true HCCC. This gives further weight to the classification of this tumor as squamous or adenosquamous in differentiation and as a specific entity rather than an ''NOS'' tumor.

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Fluorescence in situ hybridization for detection of MAML2 rearrangements in oncocytic mucoepidermoid carcinomas: utility as a diagnostic test

Cited by 100 publications

References 36 publications

Glandular Odontogenic Cysts (GOCs) Lack MAML2 Rearrangements: A Finding to Discredit the Putative Nature of GOC as a Precursor to Central Mucoepidermoid Carcinoma

Glandular Odontogenic Cysts (GOCs) Lack MAML2 Rearrangements: A Finding to Discredit the Putative Nature of GOC as a Precursor to Central Mucoepidermoid Carcinoma

Histopathologic, immunophenotypic and cytogenetic features of pulmonary mucoepidermoid carcinoma

What the EWSR1-ATF1 Fusion has Taught Us About Hyalinizing Clear Cell Carcinoma

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