title: Reevaluation of MAML2 fusion-negative mucoepidermoid carcinoma: a subgroup being actually hyalinizing clear cell carcinoma of the salivary gland with EWSR1 translocation.
abstract: Hyalinizing clear cell carcinoma (HCCC) is a rare salivary gland tumor with a specific EWSR1-ATF1 fusion gene and can have mucin production. Mucoepidermoid carcinoma (MEC) with a clear cell component is its morphologic mimic. Using MAML2 fluorescence in situ hybridization (FISH), a total of 49 MEC cases were separated into MAML2 fusion-positive (32 cases) and MAML2 fusion-negative groups (17 cases). This study used EWSR1 FISH to investigate MAML2 fusion-negative cases to identify previously unrecognized HCCC. Among 17 MAML2 fusion-negative cases, 3 had rearrangement of the EWSR1 gene and were reclassified as HCCC. Including 5 previously diagnosed HCCC cases, these 8 HCCC cases had a male-to-female ratio of 1:7, and most (7/8) tumors arose from oral minor salivary glands in the oral cavity (tongue base and palate). EWSR1-ATF1 fusion was confirmed by FISH in all 8 HCCC cases. The histologic features between genetically confirmed HCCC and MEC were compared. HCCC was significantly associated with minor salivary gland involvement, a discrepancy between low-grade cytology and intermediate- to high-grade histology using the MEC grading system, and absence of both epidermoid cells with abundant cytoplasm and goblet cells lining cysts or forming clusters. Clear cells and a hyalinized stroma were not specific for HCCC. HCCC may be erroneously classified as MEC because clear cells may be a minor histologic component and mucin production is not uncommon. Previously diagnosed MEC cases should be reevaluated, especially those arising from minor salivary glands or without MAML2 fusion. Careful histologic evaluation with supporting molecular testing can facilitate pathologic diagnoses.
authors: Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan; Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei 10002, Taiwan.
authors: Min-Shu
authors: MS
authors: Hsieh
authors: Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan.
authors: Hsuang
authors: H
authors: Wang
authors: Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan.
authors: Yi-Hsuan
authors: YH
authors: Lee
authors: Department of Otolaryngology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan.
authors: Jenq-Yuh
authors: JY
authors: Ko
authors: Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan; Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei 10002, Taiwan. Electronic address: ntuhylc@gmail.com.
authors: Yih-Leong
authors: YL
authors: Chang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D018277:Carcinoma, Mucoepidermoid / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000473:pathology; D002648:Child; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D050939:Gene Fusion; D020022:Genetic Predisposition to Disease; D006801:Humans; D006818:Hyalin / Q000737:chemistry*; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009687:Nuclear Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010641:Phenotype; D011237:Predictive Value of Tests; D012468:Salivary Gland Neoplasms / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000473:pathology; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C560860:EWSR1-ATF1 fusion protein, human; C471297:MAML2 protein, human; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D015534:Trans-Activators; D014157:Transcription Factors
keywords: ATF1; EWSR1; Hyalinizing clear cell carcinoma; MAML2; Mucoepidermoid carcinoma