Pleuropulmonary blastoma-like peritoneal sarcoma: a newly described malignancy associated with biallelic DICER1 pathogenic variation

• Authors: Kris Ann P. Schultz, Children’s Minnesota; Alexander Nelson, Children’s Minnesota; Anne Harris, Children’s Minnesota; Mike Finch, Children’s Minnesota; Amanda Field, ResourcePath; Jason A. Jarzembowski, Medical College of Wisconsin; Mercedes Wilhelm, Children’s Minnesota; William Mize, Children’s Minnesota; Portia Kreiger, Children’s Hospital of Philadelphia; Katrina Conard, Nemours/ Alfred I. duPont Hospital for Children; Andrew Walter, Nemours/ Alfred I. duPont Hospital for Children; Thomas Olson, Emory University; Sarah Mitchell, Emory University; Daniel V. Runco, Indiana University; Allison Bechtel, Nemours Children’s Specialty Care; Darren Klawinski, Nemours Children’s Specialty Care; Scott Bradfield, Nemours Children’s Specialty Care; Katie Gettinger, Washington University in St. Louis; Douglas R. Stewart, National Cancer Institute; Yoav Messinger, Children’s Minnesota; Louis P. Dehner, Children’s Minnesota; D. Ashley Hill, Children’s Minnesota
• Journal Title: MODERN PATHOLOGY
• Volume: Volume 33, Number 10
• Publisher: Springer Nature [academic journals on nature.com] | 2020-10-01, Pages 1922-1929
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1038/s41379-020-0558-4
• Subjects: Health Sciences, Oncology; Biology, Genetics
• Keywords: Pleuropulmonary blastoma; sarcoma; DICER1; tumor predisposition; cancer genetics

Abstract

Since the original description of pathogenic germline DICER1 variation underlying PPB, the spectrum of extrapulmonary neoplasms known to be associated with DICER1 has continued to expand and now includes tumors of the ovary, thyroid, kidney, eye and brain among other sites. This report documents our experience with another manifestation: a primitive sarcoma that resembles PPB and DICER1-associated sarcoma of the kidney. These tumors are distinguished by their unusual location in the peritoneal cavity, associated with visceral and/or parietal mesothelium. A total of seven cases were identified through pathology review in children presenting at a median age of 13 years (range 3 to 14 years). Primary sites of origin included the Fallopian tube (4 cases), serosal surface of the colon (one case), and pelvic sidewall (2 cases). One case had pathologic features of type I PPB, another type Ir (regressed) PPB and the remaining 5 had features of type II or III PPB with a mixed primitive sarcomatous pattern with or without cystic elements. All had a pathogenic DICER1 variation identified in germline and/or tumor DNA. PPB-like peritoneal tumors represent a newly described manifestation of DICER1 pathogenic variation whose pathologic features are also recapitulated in DICER1-related renal sarcoma, cervical embryonal rhabdomyosarcoma, and some Sertoli-Leydig cell tumors with heterologous elements. Tumors arising from the Fallopian tube or elsewhere in the abdomen/pelvis, especially those with heterogeneous rhabdomyosarcomatous and/or cartilaginous differentiation, should prompt consideration of germline and tumor DICER1 testing.