title: Adenoid cystic carcinoma of the lacrimal gland is frequently characterized by MYB rearrangement.
abstract: PurposeAdenoid cystic carcinoma (ACC) represents ~10-15% of salivary neoplasms and almost universally exhibits a lethal clinical course. ACC is also known to occur in the lacrimal gland. ACC is characterized by its heterogeneous morphology and may demonstrate tubular, cribriform, and/or solid architectural patterns. Unfortunately, these histopathological features are not specific to ACC and can be seen in other salivary gland-type neoplasms, introducing a diagnostic dilemma. The discovery of fusion transcripts has revolutionized the diagnosis, surveillance, and treatment of epithelial malignancies. In several anatomic subsites ACC is frequently characterized by a fusion transcript involving genes MYB and NFIB; more specifically, t(6;9)(q22-23;p23-24). This study explores the incidence of MYB rearrangement in cases of lacrimal gland ACC using fluorescent in situ hybridization.Materials and methodsRetrospective clinical and histopathological review of 12 cases of lacrimal gland ACC seen at Mayo Clinic over a 25-year period (1990-2015) was performed. Demographic and clinical data were obtained from medical records. Surgical pathology archival material including H&E slides and immunostains was re-examined. Formalin-fixed paraffin-embedded material was further evaluated using immunohistochemistry when appropriate. Fluorescent in situ hybridization (FISH) using a MYB break-apart probe was applied to all histologically confirmed cases of ACC and benign salivary gland parenchyma.ResultsThe median patient age was 53.6 years (range 12-64) and distributed equally by gender (six male and six female). Rearrangement of MYB was identified using FISH in seven cases (58%). Twenty-five sections of benign salivary gland parenchyma showed no evidence of MYB rearrangement. Primary surgical resection was most common treatment, and 78% of the patient received adjuvant radiation therapy. Median overall survival (OS) was 11 years. Rearrangement of MYB did not affect OS.ConclusionsIn summary, our results indicate that the MYB rearrangement defines a significant subset of lacrimal gland ACCs. Importantly, FISH for MYB rearrangement may be used as a diagnostic tool during pathological examination of lacrimal gland neoplasms. Our results showed no relationship between rearrangement status and clinical outcome. Lastly, the presence of t(6;9) in ACC may provide a platform for molecular-targeting strategies in the future.
authors.affiliation: Mayo Clinic School of Medicine, Mayo Clinic Rochester, MN, USA.
authors.forename: T Y
authors.initials: TY
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, MN, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Keeney
authors.affiliation: Department of Medical Oncology, Mayo Clinic Rochester, MN, USA.
authors.forename: A V
authors.initials: AV
authors.lastname: Chintakuntlawar
authors.affiliation: Medical Genome Facility, Cytogenetics Core Laboratory, Mayo Clinic Rochester, MN, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Knutson
authors.affiliation: Medical Genome Facility, Cytogenetics Core Laboratory, Mayo Clinic Rochester, MN, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kloft-Nelson
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, MN, USA.
authors.forename: P T
authors.initials: PT
authors.lastname: Greipp
authors.affiliation: Department of Ophthalmology, Mayo Clinic Rochester, MN, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Garrity
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, MN, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Salomao
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester, MN, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Garcia
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics; D001706:Biopsy; D003528:Carcinoma, Adenoid Cystic / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D002648:Child; D005134:Eye Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007765:Lacrimal Apparatus / Q000473:pathology*; D007766:Lacrimal Apparatus Diseases / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020626:Oncogene Proteins v-myb / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D020626:Oncogene Proteins v-myb