PAX8 mutation disturbing thyroid follicular growth: a case report

Area of Science:

• Endocrinology
• Genetics
• Histopathology

Background:

• Heterozygous inactivating mutations in the PAX8 gene are a known cause of congenital hypothyroidism.
• Over 30 carriers of PAX8 mutations have been identified, but histological data from affected thyroid tissue were previously unavailable.

Observation:

• A 40-year-old female with a history of children diagnosed with congenital hypothyroidism and a confirmed PAX8 mutation (p.K80_A84dup) was studied.
• The patient, who had normal thyroid function, underwent a hemithyroidectomy for a thyroid nodule, providing thyroid tissue for histological examination.
• Mutation analysis confirmed somatic mosaicism for the PAX8 mutation in the patient.

Findings:

• Histological examination of the resected thyroid revealed a distinct lesion in non-neoplastic tissue characterized by dense thyrocyte aggregates and absent or rudimentary follicles, mimicking late-stage fetal thyroid development.
• Laser capture microdissection confirmed that this fetal-like tissue harbored the PAX8 mutation, while adjacent morphologically normal and adenomatous tissues did not.
• The PAX8 mutation was present in lymphocytes, but at a lower allele level compared to wild-type, consistent with somatic mosaicism.

Implications:

• This study provides the first histological characterization of thyroid tissue affected by PAX8 mutations.
• The findings suggest that thyroid follicular development, particularly in the late fetal stage, is sensitive to PAX8 gene dosage.
• Heterozygous inactivating PAX8 mutations can disrupt normal thyroid development, leading to characteristic histological changes.