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Branchioma: immunohistochemical and molecular genetic study of 23 cases highlighting frequent loss of retinoblastoma 1 immunoexpression

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Abstract

Branchioma is an uncommon benign neoplasm with an adult male predominance, typically occurring in the lower neck region. Different names have been used for this entity in the past (ectopic hamartomatous thymoma, branchial anlage mixed tumor, thymic anlage tumor, biphenotypic branchioma), but currently, the term branchioma has been widely accepted. Branchioma is composed of endodermal and mesodermal lineage derivatives, in particular epithelial islands, spindle cells, and mature adipose tissue without preexistent thymic tissue or evidence of thymic differentiation. Twenty-three branchiomas were evaluated morphologically. Eighteen cases with sufficient tissue were assessed by immunohistochemistry, next-generation sequencing (NGS) using the Illumina Oncology TS500 panel, and fluorescence in situ hybridization (FISH) using an RB1 dual-color probe. All cases showed a biphasic morphology of epithelial and spindle cells with intermingled fatty tissue. Carcinoma arising in branchioma was detected in three cases. The neoplastic cells showed strong AE1/3 immunolabeling (100%), while the spindle cells expressed CD34, p63, and SMA (100%); AR was detected in 40–100% of nuclei (mean, 47%) in 14 cases. Rb1 showed nuclear loss in ≥ 95% of neoplastic cells in 16 cases (89%), while two cases revealed retained expression in 10–20% of tumor cell nuclei. NGS revealed a variable spectrum of likely pathogenic variants (n = 5) or variants of unknown clinical significance (n = 6). Loss of Rb1 was detected by FISH in two cases. Recent developments support branchioma as a true neoplasm, most likely derived from the rudimental embryological structures of endoderm and mesoderm. Frequent Rb1 loss by immunohistochemistry and heterozygous deletion by FISH is a real pitfall and potential confusion with other Rb1-deficient head and neck neoplasms (i.e., spindle cell lipoma), especially in small biopsy specimens.

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Funding

This study was in part supported by study grant SVV 260652 from the Ministry of Education, Czech Republic, the Cooperatio Program, research area SURG, and the project National Institute for Cancer Research — NICR (Programme EXCELES, ID Project No. LX22NPO5102) — funded by the European Union-Next Generation EU.

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Authors and Affiliations

  1. Department of Pathology, Faculty of Medicine in Pilsen, Charles University, E. Benese 13, 305 99, Pilsen, Czech Republic

    Martina Bradová, Michael Michal Jr., Alena Skálová & Michal Michal

  2. Bioptic Laboratory, Ltd, Pilsen, Czech Republic

    Martina Bradová, Michael Michal Jr., Alena Skálová & Michal Michal

  3. Head and Neck Pathology Consultations, Woodland Hills, CA, USA

    Lester D. R. Thompson

  4. Department of Pathology and Laboratory Medicine, University of Calgary, Calgary Laboratory Services, Foothills Medical Centre, Calgary, AB, Canada

    Martin Hyrcza

  5. Molecular and Genetic Laboratory, Bioptic Laboratory, Ltd, Pilsen, Czech Republic

    Tomáš Vaněček, Petr Grossman & Veronika Hájková

  6. School of Medicine and Pathology Queensland, University of Queensland, Brisbane, Australia

    Touraj Taheri

  7. Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland

    Niels Rupp

  8. Faculty of Medicine, University of Zurich, Zurich, Switzerland

    Niels Rupp

  9. Department of Pathology, Rutgers University New Jersey Medical School, Newark, NJ, USA

    David Suster

  10. School of Medicine and Pathology Queensland, University of Queensland, UQCCR, Herston, Australia

    Sunil Lakhani

  11. Pathology Department, Regional Hospital Kolin, JSC, Kolin, Czech Republic

    Dimitar Hadži Nikolov & Radim Žalud

  12. Institute of Pathology, University Hospital Erlangen, Friedrich‐Alexander University Erlangen‐Nürnberg (FAU), Comprehensive Cancer Center (CCC) Erlangen-EMN, Erlangen, Germany

    Abbas Agaimy

Authors
  1. Martina Bradová
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  2. Lester D. R. Thompson
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  14. Alena Skálová
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  15. Michal Michal
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  16. Abbas Agaimy
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Contributions

MB, AA, MM, AS, and MM: conception and design of the work; acquisition, analysis, and interpretation of data; drafting the MS; and revising it critically for important intellectual content and scientific integrity. TV, PG, and VH performance and interpretation of molecular genetic analysis, revising it critically for important intellectual content and scientific integrity.

LDRT, MH, NR, DS, SL, NH, and RŽ: providing the case, reading and revising the MS critically for important intellectual content and scientific integrity.

All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Martina Bradová.

Ethics declarations

Ethics approval and consent to participate

Sample was used in accordance with ethical guidelines. Informed consent was not required for the study.

Conflict of interest

The authors declare no competing interests.

Additional information

The preliminary results of the study were presented as a poster presentation at the United States and Canadian Academy of Pathology’s 112th Annual Meeting in Los Angeles, USA, March 11–16, 2023, New Orleans, Louisiana.

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Bradová, M., Thompson, L.D.R., Hyrcza, M. et al. Branchioma: immunohistochemical and molecular genetic study of 23 cases highlighting frequent loss of retinoblastoma 1 immunoexpression. Virchows Arch 484, 103–117 (2024). https://doi.org/10.1007/s00428-023-03697-1

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  • DOI: https://doi.org/10.1007/s00428-023-03697-1

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