Pleomorphic Parotid Adenoma in a Child Affected with Cri du Chat Syndrome: Clinical, Cytogenetic, and Molecular Analysis

Int J Mol Sci. 2024 Oct 3;25(19):10664. doi: 10.3390/ijms251910664.

Abstract

Salivary gland pleomorphic adenoma (SGPA) is the most common type of benign epithelial tumor; it is observed more commonly in females (with a female-to-male ratio of 1.43:1), and the age at diagnosis ranges between 40 and 59 years, with only 2% of cases diagnosed before age 18. Cri du Chat (CdC) is a rare syndrome caused by deletions of various sizes in the short arm of chromosome 5. Tumors in CdC patients are extremely rare: in Danish, Spanish, Australian, and Japanese groups of cases, no tumors have been reported, while a few cases have been described among 321 CdC patients collected in Italy and Germany. These cases all involve tumors that appear at a young age. We here report the case of a parotid pleomorphic adenoma in an 8-year-old boy with CdC. Exome analysis did not identify variants certainly significant for the development of SGPA. A CGH array, analyzed both in peripheral blood and tumor samples, failed to recognize anomalies previously associated with SGPA but identified a de novo duplication in 7p15.2, which contains part of a gene, SKAP2, in which the increased copy number is associated with the development of a different type of tumor such as pancreatic duct adenocarcinoma. The assumption that the duplication in 7p15.2 is relevant for the development of SGPA in our patient implies that CGH array studies must be included early in life in routine work-ups of CdC to identify CNVs with possible pathogenic roles for tumor development. This is particularly also relevant in relation to the severely impaired possibility for patients with CdC to report discomfort or pain related to tumor development. Constitutional CNVs in addition to the deletion in 5p should also be extensively studied to verify if their presence in some patients could explain why, in these cases, tumors develop at an age younger than expected.

Keywords: Cri du Chat syndrome; array CGH; molecular analysis; parotid pleomorphic adenoma.

Publication types

  • Case Reports

MeSH terms

  • Adenoma, Pleomorphic* / diagnosis
  • Adenoma, Pleomorphic* / genetics
  • Adenoma, Pleomorphic* / pathology
  • Child
  • Chromosomes, Human, Pair 7 / genetics
  • Cri-du-Chat Syndrome* / diagnosis
  • Cri-du-Chat Syndrome* / genetics
  • Cytogenetic Analysis
  • Humans
  • Male
  • Parotid Neoplasms* / diagnosis
  • Parotid Neoplasms* / genetics
  • Parotid Neoplasms* / pathology
  • Salivary Gland Neoplasms

Supplementary concepts

  • Salivary Gland Adenoma, Pleomorphic

Grants and funding

No specific funding was available for this work; all activities were carried out using personal funding of the Authors available for their routine work. In addition, this work was partially supported by grants from the Italian Ministry of Education, University and Research (MIUR) to the Department of Molecular Medicine of the University of Pavia under the initiative “Dipartimenti di Eccellenza (2018–2022)”.