Pleuropulmonary blastoma (PPB) and other DICER1-associated high-grade malignancies are morphologically, genetically and epigenetically related - A comparative study of 4 PPBs and 6 sarcomas
Hiemcke-Jiwa, L S; van Belle, S; Eijkelenboom, A; Merks, J H M; van Noesel, M M; Kaal, Suzanne E.J.; Pijnenborg, J M A; Bulten, J; Tops, B B J; van de Ven, C P; van Gorp, J M; de Krijger, R R; Cheesman, E; Kelsey, A M; Kester, L A; Nijmegen, Radboud
(2022) Annals of Diagnostic Pathology, volume 60
(Article)
Abstract
DICER1-related tumors occur hereditary or sporadically, with high-grade malignancies sharing clinicopathological and (epi)genetic features. We compared 4 pleuropulmonary blastomas (PPBs) and 6 sarcomas by mutation analysis, whole transcriptome sequencing and methylation profiling. 9/10 patients were female. PPB patients were 0-4 years. 3/4 were alive; 2 without disease. One patient died
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of metastatic disease (median follow-up, 16 months). Sarcoma patients were 16-56 years. Locations included: uterine cervix/corpus (3/1), soft tissue back/shoulder (1) and paravertebral (1). 5/6 patients were alive; 2 developed metastases: intracranial (1) and lung and kidney (1) (median follow-up, 17 months). The deceased patient previously had a PPB and a Sertoli-Leydig cell tumor. Histologically, tumors showed atypical primitive-looking cells with incomplete rhabdomyoblastic differentiation and cartilage (n = 5). Immunohistochemistry demonstrated desmin- (n = 9/10), myogenin- (n = 6/10) and keratin positivity (n = 1/1). Eight cases harbored biallelic DICER1 mutations with confirmed germline mutations in 4 cases. Two cases showed a monoallelic mutation. By RNA expression- and methylation profiling, distinct clustering of our cases was seen demonstrating a close relationship on (epi)genetic level and similarities to embryonal rhabdomyosarcoma. In conclusion, this study shows overlapping morphological, immunohistochemical and (epi)genetic features of PPBs and DICER1-associated high-grade sarcomas, arguing that these neoplasms form a spectrum with a broad clinicopathological range.
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Keywords: DICER1, Methylation profiling, Mutation analysis, Pleuropulmonary blastoma, Rhabdomyosarcoma, Sarcoma, Whole transcriptome sequencing, Pathology and Forensic Medicine, Journal Article
ISSN: 1092-9134
Publisher: W.B. Saunders Ltd
Note: Funding Information: We would like to sincerely thank Professor A. von Deimling, Department of Neuropathology, University Hospital Heidelberg, Germany, for his help with interpreting the methylation profiling data and for providing Fig. 5. Publisher Copyright: © 2022
(Peer reviewed)