Thyroid findings in pediatric and adult patients with PTEN hamartoma tumor syndrome: A retrospective analysis, and literature review

Milani, Donatella; Dolci, Alessia; Muller, Ilaria; Pavesi, Maria Angela; Runza, Letterio; Kuhn, Elisabetta; Natacci, Federica; Peissel, Bernard; Ricci, Maria Teresa; Despini, Luca; Tomasello, Gianluca; Grossi, Francesco; Garrone, Ornella; Gambini, Donatella

doi:10.1007/s12020-023-03313-x

Cited by 7 publications

(4 citation statements)

References 27 publications

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“…Thus, the high rate of MNG development and the risk for thyroid carcinoma indicates the need for regular ultrasound and a long-term follow up in these patients ( 19 ). Although most patients affected by PTHS develop benign nodular goiter ( 3 , 20 , 21 ), our patient underwent total thyroidectomy at the age of seven without previously performing a cytological investigation by fine-needle aspiration. According to recent studies, the direct surgical approach could be justified because fine needle biopsy may not be sufficient to exclude malignancy in patients with more than one suspicious lesion ( 1 ).…”

Section: Discussionmentioning

confidence: 99%

Case Report - Multinodular goiter in a patient with Congenital Hypothyroidism and Bannayan-Riley-Ruvalcaba syndrome: the possible synergic role of TPO and PTEN mutation

Vincenzi,

Petralia,

Abbate

et al. 2023

Front. Endocrinol.

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We report the case of a paediatric female patient affected by Bannayan-Riley-Ruvalcaba syndrome (BRRS) and congenital hypothyroidism (CH) with homozygous mutation of the TPO gene. She underwent total thyroidectomy at the age of seven years because of the development of a multinodular goiter. BRRS patients present an increased risk of benign and malignant thyroid disease since childhood because of inactivating mutation of PTEN, an onco-suppressor gene. Instead, homozygous mutations in the TPO gene can be associated with severe forms of hypothyroidism with goiter; previous studies have described cases of follicular and papillary thyroid cancer in CH patients with TPO mutation despite a perfectly controlled thyroid function with Levothyroxine therapy. To our knowledge, this is the first case that describes the possible synergic role of coexisting mutation of both TPO and PTEN in the development of multinodular goiter underlining the importance of a tailored surveillance program in these patients, especially during childhood.

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Section: Discussionmentioning

confidence: 99%

Case Report - Multinodular goiter in a patient with Congenital Hypothyroidism and Bannayan-Riley-Ruvalcaba syndrome: the possible synergic role of TPO and PTEN mutation

Vincenzi,

Petralia,

Abbate

et al. 2023

Front. Endocrinol.

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“…Multinodular thyroid disease is another common clinical feature identified in patients with PTEN‐altered thyroid nodules, 42,44 and it offers an important clue for FNA cases. Pilarski et al 45 .…”

Section: Discussionmentioning

confidence: 99%

“…Review and comparison of published DICER1 and PTEN FNA cases. THYROID NODULES WITH DICER1 MUTATION OR PTEN ALTERATIONMultinodular thyroid disease is another common clinical feature identified in patients with PTEN-altered thyroid nodules,42,44 and it offers an important clue for FNA cases. Pilarski et al45 and Tan et al46 reported multinodular thyroid disease in 30%-68% of adults and 2%-14% of children with PTEN mutations, and Laury et al40…”

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confidence: 99%

Thyroid nodules with DICER1 mutation or PTEN alteration: A comparative cytologic, clinical, and molecular study of 117 FNA cases

Jitpasutham,

Andrianus,

Gubbiotti

et al. 2024

Cancer Cytopathology

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BackgroundDICER1 mutations and PTEN alterations are increasingly detected by thyroid fine‐needle aspiration (FNA). Both are associated with nodular thyroid disease and cancer. The authors analyzed a large comparative thyroid FNA cohort with DICER1 mutation or PTEN alteration.MethodsA total of 117 thyroid FNAs with DICER1 or PTEN alterations were retrieved from the databases of two academic medical institutions. Demographic, clinical, and radiologic data were collected; FNA slides were analyzed for 29 cytomorphologic features.ResultsOf 117 thyroid FNAs, 36 (30.8%) had DICER1 mutation and 81 (69.2%) showed PTEN alteration. The DICER1 cohort had 33 (91.7%) females and three (8.3%) males (mean, 40.9 years); 61.8% had multinodular disease. FNAs were classified as atypia of undetermined significance (AUS), 23 (63.9%); follicular neoplasm (FN), 12 (33.3%); and malignant, 1 (2.8%). The PTEN subgroup had 66 (81.5%) females and 15 (18.5%) males (mean, 55.2 years) with increased multinodular disease (93.8%, p = .0016). PTEN FNAs had greater cytologic diversity: non‐diagnostic, 2 (2.5%); benign, 5 (6.2%); AUS, 44 (54.3%); FN, 24 (29.6%); and malignant, 6 (7.4%). Both DICER1 and PTEN cases showed a range of resected tumor subtypes. The DICER1 cohort included thyroblastoma, and the PTEN group included anaplastic carcinoma. The cytomorphology of DICER1 and PTEN cases showed overlapping features, especially microfollicular patterns. Minor cytomorphologic differences included papillary patterns in DICER1 (p = .039), and oncocytic changes (p < .0001) in PTEN.ConclusionsDICER1 and PTEN FNAs reveal many cytologic similarities. DICER1 patients are younger, and PTEN patients had multinodular disease. Awareness of these genetic cohorts can identify patients at risk for thyroid cancer.

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“…Nevertheless, the main concern of PHTS patients is the increased risk of malignancies, in particular of female breast cancer (67-85%), followed by thyroid cancer (6-38%), endometrial cancer (2-28%), renal cancer (2-34%), colorectal cancer (9-20%) and melanoma (0-6%) [7]. Neoplasms mostly develop in adults but may also arise in childhood, in particular thyroid cancer [8]. Because the increased risk for any cancer is estimated between 85% and 89%, specific guidelines have been established for cancer surveillance and are periodically updated [7].…”

Section: Introductionmentioning

confidence: 99%

Cerebellar phenotypes in germline PTEN mutation carriers

Gambini,

Ferrero,

Bulfamante

et al. 2024

Neuropathology Appl Neurobio

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PTEN hamartoma tumour syndrome (PHTS) comprises different hereditary conditions caused by germline PTEN mutations, predisposing to the development of multiple hamartomas in many body tissues and also increasing the risk of some types of cancer.Cerebellar involvement in PHTS patients has been long known due to the development of a pathognomonic cerebellar hamartoma (known as dysplastic gangliocytoma of the cerebellum or Lhermitte‐Duclos disease). Recently, a crucial role of the cerebellum has been highlighted in the pathogenesis of autism spectrum disorders, now recognised as a phenotype expressed in a variable percentage of PHTS children. In addition, rare PTEN variants are indeed identified in medulloblastoma as well, even if they are less frequent than other germline gene mutations.The importance of PTEN and its downstream signalling enzymatic pathways, PI3K/AKT/mTOR, has been studied at different levels in both human clinical settings and animal models, not only leading to a better understanding of the pathogenesis of different disorders but, most importantly, to identify potential targets for specific therapies. In particular, PTEN integrity makes an important contribution to the normal development of tissue architecture in the nervous system, including the cerebellum. Thus, in patients with PTEN germline mutations, the cerebellum is an affected organ that is increasingly recognised in different disorders, whereas, in animal models, cerebellar Pten loss causes a variety of functional and histological alterations.In this review, we summarise the range of cerebellar involvement observed in PHTS and its relationships with germline PTEN mutations, along with the phenotypes expressed by murine models with PTEN deficiency in cerebellar tissue.

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Thyroid findings in pediatric and adult patients with PTEN hamartoma tumor syndrome: A retrospective analysis, and literature review

Cited by 7 publications

References 27 publications

Case Report - Multinodular goiter in a patient with Congenital Hypothyroidism and Bannayan-Riley-Ruvalcaba syndrome: the possible synergic role of TPO and PTEN mutation

Case Report - Multinodular goiter in a patient with Congenital Hypothyroidism and Bannayan-Riley-Ruvalcaba syndrome: the possible synergic role of TPO and PTEN mutation

Thyroid nodules with DICER1 mutation or PTEN alteration: A comparative cytologic, clinical, and molecular study of 117 FNA cases

Cerebellar phenotypes in germline PTEN mutation carriers

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