Nasal chondromesenchymal hamartomas in a cohort with pathogenic germline variation in DICER1

Abstract

Background: Nasal chondromesenchymal hamartomas are benign, rare nasal tumors associated with DICER1 pathogenic germline variation. They can be locally destructive and recurrent if not completely resected. Methodology: In this single-center, case-control study, otorhinolaryngology evaluations and review of systems questionnaires of DICER1-carriers and controls enrolled in the DICER1 Natural History Study at the National Cancer Institute were collected. Review of these medical records were analyzed to determine if DICER1-carriers experienced different sinonasal clinical manifestations compared to controls. Additionally, the number of diagnoses of nasal chondromesenchymal hamartoma cases in the NCI DICER1 study was compared against the total person years of observation of DICER1-carriers in the study to determine the total number of cases per person-years of observation. Lastly, both the NCI DICER1 study and the International Pleuropulmonary Blastoma/DI-CER1 Registry were queried for unpublished cases of nasal chondromesenchymal hamartomas. Results: There were no clinical differences in sinonasal symptomatology between DICER1-carriers and control patients seen in the ENT clinic. We observed of two cases of nasal chondromesenchymal hamartoma in a total of 555 person-years of monitoring DICER1-carriers. We include six unpublished nasal chondromesenchymal hamartoma cases. When combined with a comprehensive literature review, 38% of nasal chondromesenchymal hamartoma cases had at least one additional DICER1-associated tumor and 24% of the NCMH were found in the ethmoid sinus, the most commonly involved paranasal sinus. Conclusions: We quantify the risk of developing nasal chondromesenchymal hamartomas in our cohort of 236 DICER1-carriers, report six unpublished cases, and provide an updated review of the literature.

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

“…DICER1(syndrome)-related lesions are benign, such as cystic nephroma (CN), nodular goiter, nasal chondromesenchymal hamartoma and gastrointestinal hamartomatous polyps, as well as malignant, including genitourinary embryonal rhabdomyosarcoma (ERMS), Sertoli-Leydig cell tumor of the ovary, Müllerian adenosarcoma, Wilms tumor, anaplastic sarcoma of the kidney, pituitary blastoma, pineoblastoma, and well-differentiated thyroid carcinoma. Ocular medulloepithelioma, another DICER-associated tumor, may behave in a benign or malignant fashion [1,3,[5][6][7][8][9][10][11][12][13][14][15][16][17]. Furthermore, development of a malignant tumor in a benign lesion has also been reported, e.g.…”

RREB1::MRTFB fusion‐positive extra‐glossal mesenchymal neoplasms: A series of five cases expanding their anatomic distribution and highlighting significant morphological and phenotypic diversity

“…NCMH is a rare sinonasal lesion with strong association with the DICER1 syndrome 31,32 . The vast majority of affected patients are newborns or young children 31–34 . However, the cases we examined herein were diagnosed at an older age compared to the vast majority of NCMH.…”

“…31,32 The vast majority of affected patients are newborns or young children. [31][32][33][34] However, the cases we examined herein were diagnosed at an older age compared to the vast majority of NCMH. Moreover, the one harboring the RREB1::MRTFB fusion affected an adult.…”

Congenital midline spinal hamartoma in an infant with DICER1 syndrome: A case report

“…In 2014, Stewart et al established the association in a case series in which 6/8 evaluable patients with PPB and NCMH were found to harbor a germline DICER1 mutation; two of these were found to have an acquired somatic DICER1 mutation (12). Further studies supported the association, and NCMH is now a wellestablished DICER1-associated tumor (5,13,14). Recently, Apellaniz-Ruiz described two patients with DICER1 syndrome and mesenchymal hamartoma of the liver (MHL).…”