Synchronous and metachronous thyroid cancer, breast cancer, and melanoma in a premenopausal patient with Cowden syndrome

Abstract

Cowden syndrome is a rare autosomal dominant genetic disorder characterized by a germline mutation in the phosphatase and tensin homolog gene, leading to multiple hamartomas, neurodevelopmental disorders, and an increased lifetime risk of multiple cancers. Malignancy is the most common cause of mortality in Cowden syndrome, with breast cancer being the most common malignancy encountered in females with the disorder. Screening guidelines for this population should address this risk at an early age. We present a case of metachronous thyroid cancer followed by synchronous breast cancer and melanoma in a young female with Cowden syndrome, highlighting diagnostic imaging, management, and screening considerations.

Keywords: Breast cancer; Cowden syndrome; Melanoma; PTEN; Screening; Thyroid cancer.

Fig. 1

Right toe parakeratosis. Right foot noncontrast MRI T2-weighted (left) and proton density (right) images demonstrated a chronically enlarged fourth toe with hypointense signal on all sequences (arrows), suggestive of infantile digital fibromatosis. Skin punch biopsy demonstrated focal parakeratosis and thickened dermal collagen.

Fig. 2

Right papillary thyroid carcinoma. Thyroid ultrasound demonstrated a hypoechoic right thyroid nodule (arrows) with minimal vascularity and internal echogenic foci consistent with calcifications. Fine needle aspiration biopsy demonstrated papillary thyroid carcinoma.

Fig. 3

Left breast carcinoma and right breast papilloma. Left breast ultrasound demonstrated an irregular hypoechoic palpable mass (A) with associated prominent left axillary lymph nodes (B), subsequently biopsied as IDC with metastatic lymphadenopathy. Left mammogram magnification CC view demonstrated a global asymmetry in the left outer breast (C) with associated fine pleomorphic calcifications (arrow). Right mammogram CC view demonstrated multiple groups of coarse calcifications (asterisks, E), one of which in the right retroareolar region corresponded to an oval hypoechoic mass with internal vascularity on ultrasound (D), subsequently biopsied as a papilloma with ADH. ADH, atypical ductal hyperplasia; IDC, invasive ductal carcinoma.

Fig. 4

PET/CT of left breast carcinoma and right breast papilloma. Whole body maximum intensity projection (A) and fused axial image (B) demonstrated markedly increased FDG uptake in the left outer breast carcinoma (arrows), as well as minimally increased FDG update in the right retroareolar breast papilloma with ADH (asterisks). ADH, atypical ductal hyperplasia.

Fig. 5

Right calf melanoma. Right medial calf clinical photograph demonstrated a suspicious dark brown macule noted on physical exam. Skin shave biopsy demonstrated superficial spreading malignant melanoma.

Fig. 6

Left papillary thyroid carcinoma. Thyroid ultrasound demonstrated a hypoechoic left thyroid nodule with peripheral vascularity. Fine needle aspiration biopsy demonstrated papillary thyroid carcinoma.