Dataset Information

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 Lastly, both the NCI DICER1 study and the International Pleuropulmonary Blastoma/DICER1 Registry were queried for unpublished cases of nasal chondromesenchymal hamartomas.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 We include six unpublished nasal chondromesenchymal hamartoma cases.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We quantify the risk of developing nasal chondromesenchymal hamartomas in our cohort of 236 DICER1-carriers, report six unpublished cases, and provide an updated review of the literature.

SUBMITTER: Vasta LM

PROVIDER: S-EPMC8218780 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PURPOSE:DICER1 syndrome is an autosomal-dominant, pleiotropic tumor-predisposition disorder caused by pathogenic germline variants in DICER1. We sought to quantify risk, hazard rates, and the probability of neoplasm incidence accounting for competing risks ("cumulative incidence") of neoplasms (benign and malignant) and standardized incidence ratios for malignant tumors in individuals with DICER1 pathogenic variation. PATIENTS AND METHODS:We combined data from three large cohorts of patients who carry germline pathogenic variation in DICER1. To reduce ascertainment bias, we distinguished probands from nonprobands. Neoplasm diagnoses were confirmed by review of pathology reports and/or central review of surgical pathology materials. Standardized cancer incidence ratios were determined relative to the SEER program, which does not capture all DICER1-associated neoplasms. For all malignancies and benign tumors ("neoplasms," excluding type Ir pleuropulmonary blastoma and thyroid nodules), we used the Kaplan-Meier method and nonparametric cumulative incidence curves to estimate neoplasm-free survival. RESULTS:We calculated the age at first neoplasm diagnosis (systematically ascertained cancers plus DICER1-associated neoplasms pleuropulmonary blastoma, cystic nephroma, and nasal chondromesenchymal hamartoma) in 102 female and male nonproband DICER1 carriers. By age 10 years, 5.3% (95% CI, 0.6% to 9.7%) of nonproband DICER1 carriers had developed a neoplasm (females, 4.0%; males, 6.6%). By age 50 years, 19.3% (95% CI, 8.4% to 29.0%) of nonprobands had developed a neoplasm (females, 26.5%; males, 10.2%). After age 10 years, female risk was elevated compared with male risk. Standardized cancer incidence ratio analysis of 102 nonproband DICER1 carriers, which represented 3,344 person-years of observation, showed significant cancer excesses overall, particularly of gynecologic and thyroid cancers. CONCLUSION:This work provides the first quantitative analysis of site-specific neoplasm risk and excess malignancy risk in 102 systematically characterized nonproband DICER1 carriers. Our findings inform DICER1 syndrome phenotype, natural history, and genetic counseling.