Skip to main content


Log in

Nasal chondromesenchymal hamartomas arise secondary to germline and somatic mutations of DICER1 in the pleuropulmonary blastoma tumor predisposition disorder

  • Original Investigation
  • Published:
Human Genetics Aims and scope Submit manuscript


Nasal chondromesenchymal hamartoma (NCMH) is a rare nasal tumor that typically presents in young children. We previously reported on NCMH occurrence in children with pleuropulmonary blastoma (PPB), a rare pulmonary dysembryonic sarcoma that is the hallmark neoplasm in the PPB-associated DICER1 tumor predisposition disorder. Original pathologic materials from individuals with a PPB, PPB-associated tumor and/or a DICER1 mutation were centrally reviewed by the International PPB Registry. Paraffin-embedded NCMH tumor tissue was available in three cases. Laser-capture microdissection was used to isolate mesenchymal spindle cells and cartilage in one case for Sanger sequencing of DICER1. Nine patients (5F/4M) had PPB and NCMH. NCMH was diagnosed at a median age of 10 years (range 6–21 years). NCMH developed 4.5–13 years after PPB. Presenting NCMH symptoms included chronic sinusitis and nasal congestion. Five patients had bilateral tumors. Local NCMH recurrences required several surgical resections in two patients, but all nine patients were alive at 0–16 years of follow-up. Pathogenic germline DICER1 mutations were found in 6/8 NCMH patients tested. In 2 of the patients with germline DICER1 mutations, somatic DICER1 missense mutations were also identified in their NCMH (E1813D; n = 2). Three additional PPB patients developed other nasal lesions seen in the general population (a Schneiderian papilloma, chronic sinusitis with cysts, and allergic nasal polyps with eosinophils). Two of these patients had germline DICER1 mutations. Pathogenic germline and somatic mutations of DICER1 in NCMH establishes that the genetic etiology of NCMH is similar to PPB, despite the disparate biological potential of these neoplasms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others


  • Bahubeshi A, Bal N, Rio Frio T, Hamel N, Pouchet C, Yilmaz A, Bouron-Dal Soglio D, Williams GM, Tischkowitz M, Priest JR, Foulkes WD (2010) Germline DICER1 mutations and familial cystic nephroma. J Med Genet 47(12):863–866. doi:10.1136/jmg.2010.081216

    Article  PubMed  Google Scholar 

  • Behery RE, Bedrnicek J, Lazenby A, Nelson M, Grove J, Huang D, Smith R, Bridge JA (2012) Translocation t(12;17)(q24.1;q21) as the sole anomaly in a nasal chondromesenchymal hamartoma arising in a patient with pleuropulmonary blastoma. Pediatr Dev Pathol 15(3):249–253. doi:10.2350/11-11-1121-CR.1

    Article  PubMed  Google Scholar 

  • Cho YC, Sung IY, Son JH, Ord R (2013) Nasal chondromesenchymal hamartoma: report of a case presenting with intraoral signs. J Oral Maxillofac Surg 71(1):72–76. doi:10.1016/j.joms.2012.03.020

    Article  PubMed  Google Scholar 

  • de Kock L, Plourde F, Carter MT, Hamel N, Srivastava A, Meyn MS, Arseneau J, Soglio DB, Foulkes WD (2013) Germ-line and somatic DICER1 mutations in a pleuropulmonary blastoma. Pediatr Blood Cancer. doi:10.1002/pbc.24692

    Google Scholar 

  • Doros L, Yang J, Dehner L, Rossi CT, Skiver K, Jarzembowski JA, Messinger Y, Schultz KA, Williams G, Andre N, Hill DA (2012) DICER1 mutations in embryonal rhabdomyosarcomas from children with and without familial PPB-tumor predisposition syndrome. Pediatr Blood Cancer 59(3):558–560. doi:10.1002/pbc.24020

    Article  PubMed  PubMed Central  Google Scholar 

  • Doros L, Rossi C, Yang J, Field A, Williams G, Messinger Y, Schultz KA, Cajaiba M, Perlman E, Cathro H, LeGallo R, LaFortune K, Chikwava K, Faria P, Geller J, Dome J, Mullen E, Gratias E, Dehner LP, Hill DA (2014) DICER1 mutations in childhood cystic nephroma and its relationship to DICER1-renal sarcoma. Mod Pathol. doi:10.1038/modpathol.2013.242 (Epub ahead of print)

    PubMed  PubMed Central  Google Scholar 

  • Foulkes WD, Bahubeshi A, Hamel N, Pasini B, Asioli S, Baynam G, Choong CS, Charles A, Frieder RP, Dishop MK, Graf N, Ekim M, Bouron-Dal Soglio D, Arseneau J, Young RH, Sabbaghian N, Srivastava A, Tischkowitz MD, Priest JR (2011) Extending the phenotypes associated with DICER1 mutations. Hum Mutat 32(12):1381–1384. doi:10.1002/humu.21600

    Article  PubMed  CAS  Google Scholar 

  • Greci V, Mortellaro CM, Olivero D, Cocci A, Hawkins EC (2011) Inflammatory polyps of the nasal turbinates of cats: an argument for designation as feline mesenchymal nasal hamartoma. J Feline Med Surg 13(4):213–219. doi:10.1016/j.jfms.2010.07.009

    Article  PubMed  Google Scholar 

  • Heravi-Moussavi A, Anglesio MS, Cheng SW, Senz J, Yang W, Prentice L, Fejes AP, Chow C, Tone A, Kalloger SE, Hamel N, Roth A, Ha G, Wan AN, Maines-Bandiera S, Salamanca C, Pasini B, Clarke BA, Lee AF, Lee CH, Zhao C, Young RH, Aparicio SA, Sorensen PH, Woo MM, Boyd N, Jones SJ, Hirst M, Marra MA, Gilks B, Shah SP, Foulkes WD, Morin GB, Huntsman DG (2012) Recurrent somatic DICER1 mutations in nonepithelial ovarian cancers. N Engl J Med 366(3):234–242. doi:10.1056/NEJMoa1102903

    Article  PubMed  CAS  Google Scholar 

  • Hill DA, Jarzembowski JA, Priest JR, Williams G, Schoettler P, Dehner LP (2008) Type I pleuropulmonary blastoma: pathology and biology study of 51 cases from the international pleuropulmonary blastoma registry. Am J Surg Pathol 32(2):282–295. doi:10.1097/PAS.0b013e3181484165

    Article  PubMed  Google Scholar 

  • Hill DA, Ivanovich J, Priest JR, Gurnett CA, Dehner LP, Desruisseau D, Jarzembowski JA, Wikenheiser-Brokamp KA, Suarez BK, Whelan AJ, Williams G, Bracamontes D, Messinger Y, Goodfellow PJ (2009) DICER1 mutations in familial pleuropulmonary blastoma. Science 325(5943):965. doi:10.1126/science.1174334

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Johnson C, Nagaraj U, Esguerra J, Wasdahl D, Wurzbach D (2007) Nasal chondromesenchymal hamartoma: radiographic and histopathologic analysis of a rare pediatric tumor. Pediatr Radiol 37(1):101–104. doi:10.1007/s00247-006-0352-6

    Article  PubMed  Google Scholar 

  • Kim B, Park SH, Min HS, Rhee JS, Wang KC (2004) Nasal chondromesenchymal hamartoma of infancy clinically mimicking meningoencephalocele. Pediatr Neurosurg 40(3):136–140. doi:10.1159/000079857

    Article  PubMed  CAS  Google Scholar 

  • Li GY, Fan B, Jiao YY (2013a) Endonasal endoscopy for removing nasal chondromesenchymal hamartoma extending from the lacrimal sac region. Can J Ophthalmol 48(2):e22–e23. doi:10.1016/j.jcjo.2012.10.007

    Article  PubMed  Google Scholar 

  • Li Y, Yang QX, Tian XT, Li B, Li Z (2013b) Malignant transformation of nasal chondromesenchymal hamartoma in adult: a case report and review of the literature. Histol Histopathol 28(3):337–344

    PubMed  Google Scholar 

  • Manivel JC, Priest JR, Watterson J, Steiner M, Woods WG, Wick MR, Dehner LP (1988) Pleuropulmonary blastoma. The so-called pulmonary blastoma of childhood. Cancer 62(8):1516–1526

    Article  PubMed  CAS  Google Scholar 

  • Mattos JL, Early SV (2011) Nasal chondromesenchymal hamartoma: a case report and literature review. Int J Pediatr Otorhinolaryngol Extra 6:215–219

    Article  Google Scholar 

  • McDermott MB, Ponder TB, Dehner LP (1998) Nasal chondromesenchymal hamartoma: an upper respiratory tract analogue of the chest wall mesenchymal hamartoma. Am J Surg Pathol 22(4):425–433

    Article  PubMed  CAS  Google Scholar 

  • Messinger YH, Williams GM, Priest JR, Harris A, Doros LA, Schultz KAP, Dehner LP, Hill DA (2012) Outcome of 116 cases of pleuropulmonary blastoma type I and type Ir (regressed): a report from the International PPB Registry (IPPBR). J Clin Oncol 30S:9522

    Google Scholar 

  • Priest JR, McDermott MB, Bhatia S, Watterson J, Manivel JC, Dehner LP (1997) Pleuropulmonary blastoma: a clinicopathologic study of 50 cases. Cancer 80(1):147–161

    Article  PubMed  CAS  Google Scholar 

  • Priest JR, Hill DA, Williams GM, Moertel CL, Messinger Y, Finkelstein MJ, Dehner LP, International Pleuropulmonary Blastoma R (2006) Type I pleuropulmonary blastoma: a report from the International Pleuropulmonary Blastoma Registry. J Clin Oncol 24(27):4492–4498. doi:10.1200/JCO.2005.05.3595

    Article  PubMed  Google Scholar 

  • Priest JR, Williams GM, Mize WA, Dehner LP, McDermott MB (2010) Nasal chondromesenchymal hamartoma in children with pleuropulmonary blastoma—a report from the International Pleuropulmonary Blastoma Registry. Int J Pediatr Otorhinolaryngol 74(11):1240–1244. doi:10.1016/j.ijporl.2010.07.022

    Article  PubMed  Google Scholar 

  • Pugh TJ, Yu W, Yang J, Field AL, Ambrogio L, Carter SL, Cibulskis K, Giannikopoulos P, Kiezun A, Kim J, McKenna A, Nickerson E, Getz G, Hoffher S, Messinger YH, Dehner LP, Roberts CW, Rodriguez-Galindo C, Williams GM, Rossi CT, Meyerson M, Hill DA (2014) Exome sequencing of pleuropulmonary blastoma reveals frequent biallelic loss of TP53 and two hits in DICER1 resulting in retention of 5p-derived miRNA hairpin loop sequences. Oncogene. doi:10.1038/onc.2014.150

    PubMed  Google Scholar 

  • Rio Frio T, Bahubeshi A, Kanellopoulou C, Hamel N, Niedziela M, Sabbaghian N, Pouchet C, Gilbert L, O’Brien PK, Serfas K, Broderick P, Houlston RS, Lesueur F, Bonora E, Muljo S, Schimke RN, Bouron-Dal Soglio D, Arseneau J, Schultz KA, Priest JR, Nguyen VH, Harach HR, Livingston DM, Foulkes WD, Tischkowitz M (2011) DICER1 mutations in familial multinodular goiter with and without ovarian Sertoli–Leydig cell tumors. JAMA 305(1):68–77. doi:10.1001/jama.2010.1910

    Article  PubMed  CAS  Google Scholar 

  • Sabbaghian N, Hamel N, Srivastava A, Albrecht S, Priest JR, Foulkes WD (2012) Germline DICER1 mutation and associated loss of heterozygosity in a pineoblastoma. J Med Genet 49(7):417–419. doi:10.1136/jmedgenet-2012-100898

    Article  PubMed  CAS  Google Scholar 

  • Slade I, Bacchelli C, Davies H, Murray A, Abbaszadeh F, Hanks S, Barfoot R, Burke A, Chisholm J, Hewitt M, Jenkinson H, King D, Morland B, Pizer B, Prescott K, Saggar A, Side L, Traunecker H, Vaidya S, Ward P, Futreal PA, Vujanic G, Nicholson AG, Sebire N, Turnbull C, Priest JR, Pritchard-Jones K, Houlston R, Stiller C, Stratton MR, Douglas J, Rahman N (2011) DICER1 syndrome: clarifying the diagnosis, clinical features and management implications of a pleiotropic tumour predisposition syndrome. J Med Genet 48(4):273–278. doi:10.1136/jmg.2010.083790

    Article  PubMed  CAS  Google Scholar 

  • Takeshita D, Zenno S, Lee WC, Nagata K, Saigo K, Tanokura M (2007) Homodimeric structure and double-stranded RNA cleavage activity of the C-terminal RNase III domain of human Dicer. J Mol Biol 374(1):106–120. doi:10.1016/j.jmb.2007.08.069

    Article  PubMed  CAS  Google Scholar 

  • Uzomefuna V, Glynn F, Russell J, McDermott M (2012) Nasal chondromesenchymal hamartoma with no nasal symptoms. BMJ Case Rep. doi:10.1136/bcr.11.2011.5148

    PubMed  Google Scholar 

  • Williams GM, Priest JR, Finkelstein MJ, Harris A, Doros LA, Kratz C, Schultz KAP, Hill DA, Dehner LP, Messinger YM (2012) Effect of radiation on outcome of types II and III PPB: a report from the International Pleuropulmonary Blastoma Registry. J Clin Oncol 30S:9521

    Google Scholar 

  • Witkowski L, Mattina J, Schonberger S, Murray MJ, Huntsman DG, Reis-Filho JS, McCluggage WG, Nicholson JC, Coleman N, Calaminus G, Schneider DT, Arseneau J, Stewart CJ, Foulkes WD (2013) DICER1 hotspot mutations in non-epithelial gonadal tumours. Br J Cancer 109(10):2744–2750. doi:10.1038/bjc.2013.637

    Article  PubMed  CAS  Google Scholar 

  • Wu MK, Sabbaghian N, Xu B, Addidou-Kalucki S, Bernard C, Zou D, Reeve AE, Eccles MR, Cole C, Choong CS, Charles A, Tan TY, Iglesias DM, Goodyer PR, Foulkes WD (2013) Biallelic DICER1 mutations occur in Wilms tumours. J Pathol 230(2):154–164. doi:10.1002/path.4196

    Article  PubMed  CAS  Google Scholar 

  • Yao-Lee A, Ryan M, Rajaram V (2011) Nasal chondromesenchymal hamartoma: correlation of typical MR. CT and pathological findings. Pediatr Radiol 41(5):675–677. doi:10.1007/s00247-011-2034-2

    Article  PubMed  Google Scholar 

Download references


This work was supported by the Division of Cancer Epidemiology and Genetics (DCEG) of the National Cancer Institute’s Intramural Research Program. This research was supported by the Intramural Research Program of the NIH and the National Cancer Institute. D.A.H. is supported by National Cancer Institute R01CA143167.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

The experiments reported in this manuscript comply with the current laws of the United States.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Douglas R. Stewart.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Stewart, D.R., Messinger, Y., Williams, G.M. et al. Nasal chondromesenchymal hamartomas arise secondary to germline and somatic mutations of DICER1 in the pleuropulmonary blastoma tumor predisposition disorder. Hum Genet 133, 1443–1450 (2014).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: