Adenoid cystic carcinoma of the lacrimal gland is frequently characterized by MYB rearrangement

T. Y. Chen, M. G. Keeney, Ashish Chintakuntlawar, D. L. Knutson, S. Kloft-Nelson, Patricia T Greipp, J. A. Garrity, D. R. Salomao, J. J. Garcia

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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.

Original languageEnglish (US)
Pages (from-to)720-725
Number of pages6
JournalEye (Basingstoke)
Volume31
Issue number5
DOIs
StatePublished - May 1 2017

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Lacrimal Apparatus
Adenoid Cystic Carcinoma
Fluorescence In Situ Hybridization
Salivary Glands
Salivary Gland Neoplasms
Neoplasms
Surgical Pathology
Survival
Paraffin
Formaldehyde
Medical Records
Cohort Studies
Radiotherapy
Immunohistochemistry
Demography
Hybridization
In Situ
Carcinoma
Therapeutics
Genes

ASJC Scopus subject areas

  • Ophthalmology
  • Arts and Humanities(all)

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Adenoid cystic carcinoma of the lacrimal gland is frequently characterized by MYB rearrangement. / Chen, T. Y.; Keeney, M. G.; Chintakuntlawar, Ashish; Knutson, D. L.; Kloft-Nelson, S.; Greipp, Patricia T; Garrity, J. A.; Salomao, D. R.; Garcia, J. J.

In: Eye (Basingstoke), Vol. 31, No. 5, 01.05.2017, p. 720-725.

Research output: Contribution to journalArticle

Chen, TY, Keeney, MG, Chintakuntlawar, A, Knutson, DL, Kloft-Nelson, S, Greipp, PT, Garrity, JA, Salomao, DR & Garcia, JJ 2017, 'Adenoid cystic carcinoma of the lacrimal gland is frequently characterized by MYB rearrangement', Eye (Basingstoke), vol. 31, no. 5, pp. 720-725. https://doi.org/10.1038/eye.2016.307
Chen, T. Y. ; Keeney, M. G. ; Chintakuntlawar, Ashish ; Knutson, D. L. ; Kloft-Nelson, S. ; Greipp, Patricia T ; Garrity, J. A. ; Salomao, D. R. ; Garcia, J. J. / Adenoid cystic carcinoma of the lacrimal gland is frequently characterized by MYB rearrangement. In: Eye (Basingstoke). 2017 ; Vol. 31, No. 5. pp. 720-725.
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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.",
author = "Chen, {T. Y.} and Keeney, {M. G.} and Ashish Chintakuntlawar and Knutson, {D. L.} and S. Kloft-Nelson and Greipp, {Patricia T} and Garrity, {J. A.} and Salomao, {D. R.} and Garcia, {J. J.}",
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T1 - Adenoid cystic carcinoma of the lacrimal gland is frequently characterized by MYB rearrangement

AU - Chen, T. Y.

AU - Keeney, M. G.

AU - Chintakuntlawar, Ashish

AU - Knutson, D. L.

AU - Kloft-Nelson, S.

AU - Greipp, Patricia T

AU - Garrity, J. A.

AU - Salomao, D. R.

AU - Garcia, J. J.

PY - 2017/5/1

Y1 - 2017/5/1

N2 - 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.

AB - 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.

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