Abstract
DICER1 germline mutations are associated with an inherited cancer syndrome, most commonly presenting with pleuropulmonary blastoma (PPB), ovarian sex cord tumors, thyroid cysts/goitre, and cystic nephroma. We describe the occurrence of a Hodgkin lymphoma (HL) of the T cell phenotype in a family with DICER1 syndrome. The patient presented with PPB Type I and HL. Immunohistochemical staining of the Hodgkin and Reed-Sternberg cells revealed CD30, TGP, CD2, CD3, CD15, and IRF4 positivity and weekly positivity of PAX5. T cell receptor repertoire analysis suggested HL of T cell origin, which is in contrast to common B cell-derived HL. The mother had been diagnosed with thyroid cysts, one sister had died from a primitive neuroectodermal tumor, and a brother had died from PPB Type III. Two mutational events were revealed in all affected family members; a single bp deletion, c.5299delC, leading to a frameshift and premature stop in exon 24 and a heterozygous variant (c.4616C>T; p.Thr1539Met) located in exon 23 of the DICER1 gene. This variant is predicted to be benign by in silico analysis.
Conclusion: Future studies looking for DICER1 mutations in HL cases of the T cell phenotype will be important to confirm its association with constitutional DICER1 syndrome.
What is Known: • DICER1 germline mutations are associated with an inherited cancer syndrome, most commonly pleuropulmonary blastoma, ovarian sex cord tumors, thyroid cysts/goitre, and cystic nephroma. • Hodgkin lymphoma is one of the most frequent types of malignant lymphomas and typically arises sporadically. T cell-derived Hodgkin lymphomas are exceptionally rare. |
What is New: • DICER1 syndrome may have an even broader phenotypic spectrum and seems to be associated with rare forms of T cell Hodgkin lymphoma. |
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Abbreviations
- cHD:
-
Classical Hodgkin disease
- (c)HL:
-
(classical) Hodgkin lymphoma
- HRS:
-
Hodgkin and Reed-Sternberg cells
- PNET:
-
Primitive neuroectodermal tumor
- PPB:
-
Pleuropulmonary blastoma
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Acknowledgments
The authors wish to thank Dr. M. Gombert and Msc. S. Ginzel for running the next generation sequencing analysis and the internal SQL database and Mrs. Bianca Killing and Mrs. Katayoun Alemazkour for technical assistance.
Author’s contribution
MK contributed to the concept and design of the analysis and wrote the paper. AH supervised the NGS analysis and critical revised the manuscript of intellectual content. JS and HM performed the pathological analysis. CMK contributed to interpretation of data and revising of intellectual content. AB and AT contributed to the concept, design and execution of the analysis, and revising of intellectual content.
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Arndt Borkhardt and Anja Troeger contributed equally to this work.
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Kuhlen, M., Hönscheid, A., Schemme, J. et al. Hodgkin lymphoma as a novel presentation of familial DICER1 syndrome. Eur J Pediatr 175, 593–597 (2016). https://doi.org/10.1007/s00431-015-2660-z
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DOI: https://doi.org/10.1007/s00431-015-2660-z