title: Acinic cell carcinoma with high-grade transformation: a report of 9 cases with immunohistochemical study and analysis of TP53 and HER-2/neu genes.
abstract: High-grade transformation of acinic cell carcinoma (AciCC) (previously referred to as dedifferentiation) is a rare phenomenon characterized by histologic progression of low-grade AciCC to high-grade adenocarcinoma or undifferentiated carcinoma. We report 9 new cases with immunohistochemical analysis and examination of HER-2/neu and p53 genes to further define the profile of this tumor. Histologically, the high-grade component was composed of polymorphic cells with a high mitotic rate arranged in glandular and solid growth patterns with comedonecrosis. The MIB-1 labeling indices were elevated in the high-grade component, as compared with the low grade conventional AciCC. The high-grade component of AciCC was characterized by strong membrane staining for CK18 and beta-catenin, and nuclear staining for cyclin-D1. HER-2/neu, androgen receptor, C-kit, and epidermal growth factor receptor were absent from both low-grade and high-grade components. In contrast, S-100 protein, alpha-1-antitrypsin, and lysozyme were lost only in high-grade foci of transformed AciCC. The median age was 61 years (with range from 43 to 76 y). Lymph node (LN) metastases were found in 5 of 9 cases (56%). Distant metastases to the lungs (n=4), pleura (n=2), brain (n=3), and peritoneum (n=1), and paraaortic, paratracheal, and mediastinal LNs (n=2) were observed. Six of 9 patients (66%) died from tumor dissemination, all with a median overall survival of 4.3 years (range: 1 to 9 y). The high propensity for LN metastases indicates the need for neck dissection at the time of diagnosis.
authors.affiliation: Department of Pathology, Charles University in Prague, Faculty of Medicine, 305 99 Pilsen, Czech Republic. skalova@fnplzen.cz
authors.forename: Alena
authors.initials: A
authors.lastname: Skálová
authors.forename: Radek
authors.initials: R
authors.lastname: Sima
authors.forename: Tomas
authors.initials: T
authors.lastname: Vanecek
authors.forename: Susan
authors.initials: S
authors.lastname: Muller
authors.forename: Marie
authors.initials: M
authors.lastname: Korabecna
authors.forename: Jana
authors.initials: J
authors.lastname: Nemcova
authors.forename: Goran
authors.initials: G
authors.lastname: Elmberger
authors.forename: Ilmo
authors.initials: I
authors.lastname: Leivo
authors.forename: Fabricio
authors.initials: F
authors.lastname: Passador-Santos
authors.forename: Jiri
authors.initials: J
authors.lastname: Walter
authors.forename: Milena
authors.initials: M
authors.lastname: Rousarova
authors.forename: Kristina
authors.initials: K
authors.lastname: Jedlickova
authors.forename: Romuald
authors.initials: R
authors.lastname: Curik
authors.forename: Marie
authors.initials: M
authors.lastname: Geierova
authors.forename: Michal
authors.initials: M
authors.lastname: Michal
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D018267:Carcinoma, Acinar Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D018734:Genes, erbB-2; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D010307:Parotid Neoplasms / Q000235:genetics* / Q000473:pathology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53