Work

Recognition of Macrocephaly for Early Detection of Cowden Syndrome With Differentiated Thyroid Cancer and Melanoma

Year: 2026

Type: article

Abstract: Cowden syndrome (CS) is an autosomal dominant genodermatosis associated with mutations in the phosphatase and tensin homolog gene ( PTEN ). Due to its rarity and variable expressivity, CS may escape detection for many years. We report a case of CS in which the patient presented with the follicular variant of papillary thyroid cancer (FVPTC) and no indication of a genetic abnormality until she was found to have a melanoma and macrocephaly. The patient presented at age 31 with a 3.3 cm thyroid nodule and fine needle aspirate (FNA) that showed a Bethesda IV lesion. She underwent left lobectomy, revealing FVPTC. A completion thyroidectomy showed multiple small foci of FVPTC, the largest of which was 8 mm. Initially, there were no apparent pathologic mucocutaneous lesions, intellectual deficits, or family history of CS. At age 39, the patient developed a Stage IA malignant melanoma. She was simultaneously noted to have macrocephaly with a head circumference of 62 cm (>99 percentile). Analysis of 69 genes revealed a pathogenic variant in the PTEN gene. Macrocephaly is seen in 93%–100% of patients with PTEN pathogenic variants. There is an increased risk of melanoma in differentiated thyroid cancer (DTC) of two to fourfold with a 6% absolute risk in CS. We recommend that head circumference be measured in all patients with DTC. Patients with DTC should have a thorough skin examination.

Source: Case Reports in Endocrinology

DOI: 10.1155/crie/5020127

Authors: Michael S. Gordon, Murray B. Gordon

Institutions: Brigham and Women's Hospital, Harvard University, Allegheny General Hospital

Language: English

Topic: Thyroid Cancer Diagnosis and Treatment

Subfield: Endocrinology, Diabetes and Metabolism

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $870