title: Clinicopathologic and Immunophenotypic Characterization of 25 Cases of Acinic Cell Carcinoma with High-Grade Transformation.
abstract: Acinic cell carcinoma (AiCC) with high-grade transformation is a rare variant of AiCC composed of both a conventional low-grade (LG) AiCC and a separate high-grade (HG) component. We describe here, the clinicopathologic and immunohistochemical features of 25 cases diagnosed between 1990 and 2015. Available tissue was analyzed and compared with a cohort of pure LG AiCC for the morphologic and immunophenotypic profile. Incidence was higher in females (1.8:1) than males with an overall mean age at presentation of 63.2 years. All tumors occurred in the parotid gland including 76% with facial nerve trunk and branches involvement. Most patients were treated with extensive resection and adjuvant therapy. Local recurrence or distant metastasis occurred in most patients, with 72.7% dead with disease (mean 2.9 years) and 3 patients alive with disease (mean 2.4 years). The majority of the tumors were composed of a LG microcystic AiCC and a HG component consisting of invasive lobules of undifferentiated cells with predominantly solid, cribriform, and glandular patterns. Acinic differentiation was still present in HG areas but aggressive features such as perineural invasion (76%), lymphovascular invasion (62%), positive margins (72%), high mitotic rate, atypical mitoses and/or comedonecrosis (86%) were easily identified. Compared to the pure LG AiCC, the cases with HG transformation showed significantly increased expression of cyclin-D1, p53 and Ki-67. Most HG areas of AiCC expressed membranous β-catenin (92%) and were negative for p63 (three cases were focally positive), S100, SMA, androgen, and estrogen receptors. DOG1 expression was present in all LG AiCC tested with retained expression in 91% of cases with HG transformation, supporting acinic differentiation in the HG foci. Recognition of AiCC with high-grade transformation is imperative as more aggressive clinical management is warranted.
authors.affiliation: Department of Pathology, Southern California Permanente Medical Group, Woodland Hills Medical Center, Woodland Hills, CA, USA.
authors.forename: Lester D
authors.initials: LD
authors.lastname: Thompson
authors.affiliation: Department of Pathology, University of Michigan Health System, 2G332 UH, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, USA.
authors.forename: Muhammad N
authors.initials: MN
authors.lastname: Aslam
authors.affiliation: Department of Pathology, University of Michigan Health System, 2G332 UH, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, USA.
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Stall
authors.affiliation: Department of Pathology, University of Michigan Health System, 2G332 UH, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, USA.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Udager
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, Presbyterian University Hospital, Pittsburgh, PA, USA.
authors.forename: Simion
authors.initials: S
authors.lastname: Chiosea
authors.affiliation: Department of Pathology, University of Michigan Health System, 2G332 UH, 1500 E. Medical Center Drive, Ann Arbor, MI, 48109, USA. jonamch@umich.edu.
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: McHugh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D018267:Carcinoma, Acinar Cell / Q000453:epidemiology / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015994:Incidence; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D010307:Parotid Neoplasms / Q000453:epidemiology / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor
keywords: Acinic cell carcinoma; DOG1; Dedifferentiated; High-grade transformation; Salivary gland