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Thyroid
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Differentiated thyroid cancer (DTC), specifically papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC), comprises 95% of all thyroid malignancies, of which about 5% are familial. These may be associated with syndromes that are composed of predominately non-thyroidal tumors, including Cowden’s disease (PTEN-hamartoma tumor syndrome), Pendred syndrome, Werner syndrome, Carney complex type 1, and familial adenomatous polyposis/Gardner’s syndrome. Other conditions with less established links to the development of DTC include ataxia-telangiectasia syndrome, McCune Albright syndrome, and Peutz–Jeghers syndrome. There remain some families with preponderance to DTC with no established genotype–phenotype correlation such as PTC with multinodular goiter or PTC with renal cell carcinoma.11
Thyroid cancer
Published in Pallavi Iyer, Herbert Chen, Thyroid and Parathyroid Disorders in Children, 2020
Follicular carcinomas occur less frequently in children and adolescents, occurring with a more equal ratio between males and females compared with papillary thyroid carcinoma. Risk factors worldwide include iodine deficiency and genetic lesions such as PTEN hamartoma tumor syndrome (such as Cowden syndrome). The FNA of these lesions show Bethesda Class 3 or 4 (atypia of undetermined significance/follicular lesion of undetermined significance or follicular neoplasm/suspicious for follicular neoplasm). Based on these findings, in children, a lobectomy or total thyroidectomy should be performed by a high-volume surgeon. The diagnosis can only be made on surgical pathology with findings of vascular invasion or capsular invasion.
Cowden Syndrome
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Besides CWS1 and LDD, mutations in the PTEN gene located at chromosome 10q23.31 are also observed in Bannayan−Riley−Ruvalcaba syndrome (BRRS), PTEN-related Proteus syndrome, and Proteus-like syndrome. As this spectrum of PTEN-related disorders all produce hamartomatous tumors, they are often referred to collectively as PTEN hamartoma tumor syndrome (PHTS), particularly when a PTEN pathogenic variant is present (Table 90.2). Considerable overlapping exists between CWS1 and BRRS in terms of clinical presentations, with both developing hamartomatous polyps of the gastrointestinal tract, other noncancerous tumors, mucocutaneous lesions, and macrocephaly (see Chapter 10 in this book). There is speculation that CS1 and BRRS represent a single condition with variable expression and age-related penetrance. Proteus syndrome shows congenital malformations and hamartomatous overgrowth of multiple tissues, connective tissue nevi, epidermal nevi, and hyperostoses. Proteus-like syndrome demonstrates significant clinical features of proteus syndrome without meeting the diagnostic criteria for the latter [2–5].
Phosphatidylinositol 3-kinase signaling and immune regulation: insights into disease pathogenesis and clinical implications
Published in Expert Review of Clinical Immunology, 2021
Tina Nguyen, Elissa K Deenick, Stuart G Tangye
Currently, rapamycin is the most commonly used PI3K-specific therapeutic agent to treat APDS. Despite this, data regarding its efficacy for various clinical parameters as well as knowledge of the long-term effects of rapamycin use remains limited. The most comprehensive analysis to date involved a cohort of 26 APDS patients, where lympholiferation demonstrated high responsiveness to rapamycin over a treatment period averaging 18 months, while cytopenias and bowel inflammation responded less well [74]. Interestingly, rapamycin therapy in a PTEN hamartoma tumor syndrome patient, harboring a LOF variant in PTEN, was recently shown to improve a range of immunological parameters as well as gastrointestinal symptoms [95]. Only one study has reported on the effectiveness of rapamycin for developmental defects in APDS [44]; however, there is evidence for the efficacy of rapamycin in treating other patients with growth defects and neurological abnormalities caused by dysregulated PI3K signaling [96,97]. As discussed above, the orally administered p110δ-specific inhibitor leniolisib has shown promising results for patients’ immunological parameters [64,76,77], and may be more widely adopted as additional clinical data are collected. Similarly, nemiralisib, the inhaled p110δ-specific inhibitor originally developed for chronic airway disease [98], could offer an alternative for patients who have exaggerated respiratory symptoms although outcomes from this trial in APDS patients have not yet been reported [64,77]. Altogether, upcoming results from clinical studies will be critical in providing further insights into the successes and limitations of current therapies, informing future clinical management of APDS.