October 2020 — Head and Neck & Surgical

A 12 year old boy was diagnosed with a cystic lesion of the mandible associated with an impacted tooth. The cyst was curetted and submitted for histopathologic evaluation.

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Which of the following genes harbors oncogenic driver mutations in this lesion?

  • CTNNB1
  • BRAF
  • KRAS
  • PTCH1

The correct answer is...

The correct answer is KRAS.

Adenomatoid odontogenic tumor is a rare benign epithelial odontogenic neoplasm, which most frequently arises in the anterior mandible of young patients and is commonly associated with an impacted tooth 1. Microscopic examination shows a nodular pattern of growth with spindle-shaped or basaloid neoplastic cells and scattered ductular structures2. Driver mutations in KRAS codon 12 (c.35G>T or c.34G>C) can be identified in approximately 70% of those tumors3.

Because of its prospensity for arising in the mandible of young patients and its variable morphologic features, adenomatoid odontogenic tumor has to be differentiated from ameloblastoma, which frequently has driver mutations in BRAF (most commonly BRAF V600E) or CTNNB14.

PTCH1 alterations have been reported to have a role in the pathogenesis of odontogenic keratocyst, a much more common mandibular cystic lesion featuring squamous lining with a characteristic cuboidal basal cell layer.5


References
1. Philipsen HP, Reichart PA. Adenomatoid odontogenic tumour: facts and figures. Oral Oncol. 1999;35:12531.
2. Wright JM, Kusama K. Adenomatoid odontogenic tumour. In: El-Naggar A, Chan JKC, Grandis JR, Takata T, Slootweg PJ, editors. WHO Classification of Head and Neck Tumours. 4th edn. Lyon, France: IARC; 2017. p. 2212.
3. Coura BP, Bernardes VF, de Sousa SF, et al. KRAS mutations drive adenomatoid odontogenic tumor and are independent of clinicopathological features. Mod Pathol. 2019;32(6):799-806.
4. Brown NA, Rolland D, McHugh JB, et al. Activating FGFR2-RAS-BRAF mutations in ameloblastoma. Clin Cancer Res. 2014;20(21):5517-5526.
5. Diniz MG, Borges ER, Guimarães AL, et al. PTCH1 isoforms in odontogenic keratocysts. Oral Oncol. 2009;45(3):291-295. doi:10.1016/j.oraloncology.2008.05.020.

Photo of Kyriakos Chatzopoulos, M.D. Kyriakos Chatzopoulos, M.D.
Resident, Anatomic and Clinical Pathology
Mayo Clinic
Photo of Michael Rivera, M.D. Michael Rivera, M.D.
Consultant, Anatomic Pathology
Mayo Clinic
Assistant Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science
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