Endocrine Abstracts

Objective: To present the rare case of a patient with cutaneous angiosarcoma, multiple benign skin lesions together with multiple thyroid nodules and to discuss his genetic diagnosis.

Case Presentation: A 13^2/12 years-old boy was referred to the Endocrinology department, following chemotherapy and radiotherapy. His medical history was uneventful until the age of 8 years. His mother reported Graves’ disease and his maternal grandmother papillary carcinoma. Starting at the age of 8 years, he gradually developed multiple skin lesions: 1. Hemangioma on the right tibia, 2. Skin lesion on the left posterior chest wall characterized as Kaposi-form hemangioendothelioma that recurred after 1 year. 3. Infiltrating vascular skin neoplasm on the left posterior chest wall, with lymph node involvement, characterized as cutaneous angiosarcoma. The patient received chemotherapy together with radiotherapy. 4. New multiple benign skin lesions (skin fibromas, papillomatous lesions, lymphangioma) appeared during follow-up. The initial clinical assessment was remarkable for macrocephaly (head circumference 1 cm, >97th perc.) as long as obesity (BMI 31.8, >95th percentile), while his height (1.71m) was at the 95th percentile. He was pubertal with testicular size 12ml. Thyroid ultrasound revealed multiple nodules, including a prominent one on the right lobe with dmax:12.9mm, solid, strongly hypo-echogenic, with increased vascularization, wider than taller, without calcifications. Fine needle biopsy (FNB) revealed a hyperplastic nodule, BETHESDA II. Thyroid function was normal whereas anti-TPO, anti-TG were negative. From the age of 14 to the age of 16^10/12 years, two additional FNBs were performed, because during regular follow up, the size of the nodule on the right lobe was increased (dmax: 24mm at the age of 16^10/12 years old). They were both characterized as BETHESDA II. Thyroglobulin progressively increased to 143ng/ml. Genetic testing with WES revealed a variant in PTEN, NM_000314.8:c.389G>A, p.(Arg130GIn), which is characterized as pathogenic.

Conclusions: Pathogenic variants in PTEN are associated with Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome (BRRS), PTEN-related Proteus syndrome (PS), and PTEN-related Proteus-like syndrome. They include a wide range of clinical manifestations, as well as increased risk of cancers mainly breast, thyroid, endometrial and renal. However, cutaneous angiosarcoma is not a typical manifestation of these syndromes. To our knowledge, this is the second case to be reported. Given the patient’s increased risk of thyroid cancer, close follow-up with thyroid US is recommended. Any changes suggestive of malignancy should be appreciated and if results of FNB are suspicious, a total thyroidectomy should be performed.