J Pathol Transl Med.  2023 May;57(3):178-183. 10.4132/jptm.2023.03.04.

Thyroid pathology, a clue to PTEN hamartoma tumor syndrome

• Lee Y
• Oh YL

• KMID: 2542284
• DOI: http://doi.org/10.4132/jptm.2023.03.04

Abstract

Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) is a hereditary disorder caused by germline inactivating mutations in the PTEN tumor suppressor gene. As a type of PHTS, Cowden syndrome is associated with abnormalities of the thyroid, breast, uterus, and gastrointestinal tract. A 52-year-old-woman visited the outpatient clinic of our endocrinology clinic with multiple thyroid nodules and Hashimoto's thyroiditis. Computed tomography imaging revealed a multinodular mass measuring up to 3.5 cm in the left thyroid lobe, causing laryngotracheal airway displacement. The total thyroidectomy specimen revealed multiple follicular adenomas and adenomatous nodules with lymphocytic thyroiditis and lipomatous metaplasia in the background. The patient was suspected of PTHS based on her thyroid pathology, family history, and numerous hamartomatous lesions of the breast, uterus, and skin. Her diagnosis was confirmed through molecular testing. This case demonstrates that pathologists must be well acquainted with thyroid pathology in PHTS.

Keyword

PTEN; Hamartoma tumor syndrome; Thyroid pathology; Cowden

Figure

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  Fig. 1. Radiologic and core needle biopsy images of the thyroid. (A) Thyroid ultrasound image showing multiple hypoechoic solid nodules with well-defined margins. (B) Thyroid computed tomography revealing multinodular masses in the left thyroid lobe displacing the laryngotracheal airway (arrow).

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  Fig. 2. Thyroid gross and histologic findings of Cowden syndrome. (A) Multiple well-circumscribed nodular lesions with suspicious encapsulations (arrow) and yellowish fat components. (B) Follicular adenomas with a monomorphic microfollicular pattern of growth are identified and well-demarcated with a fibrous capsule. (C) Multiple microadenomas with or without a thin fibrous band (arrowheads). (D, E) Adenomatous nodules, small to medium-sized adenomas with a microfollicular pattern, lipomatous metaplasia (arrows), and chronic lymphocytic thyroiditis are intermixed. (F) Multiple adenomatous hyperplasias and a lymphoepithelial cyst (arrow), considered a hamartomatous component, are noted.

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  Fig. 3. Phosphatase and tensin homolog (PTEN) immunohistochemistry. (A) A low-magnification image showing heterogeneous PTEN expression between normal tissue and proliferative lesions (asterisks). (B) The contrast of PTEN expression in the left upper area and PTEN loss in the right lower area. (C) Nuclear and cytoplasmic expression of PTEN identified in several normal areas. (D) Loss of expression of PTEN with positive vascular endothelial cells representing the internal control.

Reference

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