Papillary thyroid carcinoma of childhood and adolescence: A 30‐year experience at the istituto nazionale tumori in Milan

Collini, Paola; Massimino, Maura; Leite, Sérgio; Mattavelli, Franco; Seregni, Ettore; Zucchini, Nicola; Spreafico, Filippo; Ferrari, Andrea; Castellani, Maria Rita; Cantù, Giulio; Fossati-Bellani, Franca; Rosaí, Juan

doi:10.1002/pbc.20474

Cited by 57 publications

(68 citation statements)

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“…Follicular variant was noted in 4 of 14 pediatric patients (29%), which is comparable to the 10% to 37% suggested in the literature. [10][11][12][13]16,30 The rate of follicular variant morphology is increasing, according to a recent study, 29 though this may be linked to higher rates of RAS mutations, which were not detected in any of our pediatric patients. Solid variant carcinoma, which has been associated with young age, 18 was not seen in any pediatric patients.…”

Section: Commentmentioning

confidence: 58%

“…The tumors of pediatric patients examined in our study had comparatively more aggressive clinical behavior than those of adults, as is classically seen in other studies. 5,30 This is suggested by significantly increased rates of positive lymph nodes and lymphovascular invasion seen in the younger patient group. However, pediatric patients were more likely to have lymph nodes submitted for pathologic examination (P ¼ .04), suggesting that more extensive operative management was conducted on the pediatric patients.…”

Section: Commentmentioning

confidence: 99%

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Mutation in BRAF and Other Members of the MAPK Pathway in Papillary Thyroid Carcinoma in the Pediatric Population

Gertz

Nikiforov

Rehrauer

et al. 2016

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Papillary thyroid carcinoma (PTC) is an uncommon tumor in the pediatric population. A limited number of studies have examined genetic mutations affecting the mitogen-activated protein kinase (MAPK) pathway in the pediatric population.Objective.-To examine mutations affecting this pathway in PTC in our pediatric population and compare the BRAF V600E mutation rates in pediatric and adult tumors.Design.-Eighty-four patients, including 14 pediatric and 70 adult, with PTC were tested for the BRAF V600E mutation by using real-time polymerase chain reaction and sequencing. Additionally, we examined the rate of RAS point mutations with real-time polymerase chain reaction and rearrangements of RET/PTC1 and RET/PTC3 in the pediatric group with fluorescence in situ hybridization. Clinical and histologic data were compared as well.Results.-Of 77 tumors that had an interpretable result, the BRAF V600E mutant was identified in 4 of 13 pediatric patients (31%) and 43 of 64 adult patients (67%), which was a significant difference (using Fisher exact test, P ¼ .03). One pediatric and 6 adult cases did not reveal an interpretable result with melting curve analysis. One of these cases harbored a rare 3-base pair deletion mutation (c.1799_1801delTGA). Mutations in RAS genes were not seen in any pediatric tumors. One tumor with a RET/PTC1 rearrangement and another with RET/PTC3 were identified in the pediatric population (15%).Conclusions.-The rate of the BRAF V600E mutation in the pediatric population is significantly lower than that seen in the adult population. Mutations in RAS do not contribute significantly to pediatric PTC. This experience from our institution adds to the growing body of knowledge regarding tumor genetics in pediatric PTC.(Arch Pathol Lab Med. 2016;140:134-139; doi: 10.5858/ arpa.2014-0612-OA) P apillary thyroid carcinoma (PTC) is an uncommon tumor in the pediatric population. Despite having an excellent prognosis with long-term mortality rates of less than 1%, 1,2 pediatric patients with PTC tend to present with advanced disease often with increased rates of extrathyroidal tumor extension, lymphovascular invasion, and distant metastases. 1,3-5The distinct clinical nature of papillary thyroid cancer in the pediatric population has prompted interest in the molecular tumorigenesis. The mitogen-activated protein kinase (MAPK) pathway includes components of particular interest, including BRAF, RAS, and RET. Between 37% and 52% of PTCs have been linked to the specific BRAF mutation V600E, and clinical correlations support that this foretells a more aggressive disease course in adults. [6][7][8][9] The incidence of this BRAF mutation in the pediatric population is thought to be lower than in adults with rates of 0% to 37%, 10-15 though 1 recent series 16 revealed a rate of 63%. The rearrangement mutations of RET are also considered a major contributor to PTC tumorigenesis, but rates of this mutation have fluctuated widely in reported series.17 RET/PTC rearrangements have been associated with young age 18 an...

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Section: Commentmentioning

confidence: 58%

Section: Commentmentioning

confidence: 99%

Mutation in BRAF and Other Members of the MAPK Pathway in Papillary Thyroid Carcinoma in the Pediatric Population

Gertz

Nikiforov

Rehrauer

et al. 2016

Archives of Pathology &Amp; Laboratory Medicine

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“…Обусловленный облучением рак щито-видной железы имеет торпидное течение подобно первичному тиреоидному раку у детей. Вторичный тиреоидный рак долгое время после облучения не манифестирует, поэтому данная категория боль-ных должна наблюдаться в течение всей жизни [13,14].…”

Section: Discussionunclassified

Thyroid Dysfunction After Radiotherapy in Children with Hodgkin’s Lymphoma

et al. 2018

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Background.The main approach to Hodgkin’s lymphoma (HL) treatment is the use of cytostatic and consolidation radiation therapy. The combination of both treatment techniques undoubtedly improves the antitumor effect, but also negatively influence on the functioning of the endocrine glands. The most frequent complications are various diseases of the thyroid gland.Objective.Our aim was to determine the relationship between the thyroid disorders and critical dose of neck irradiation in patients with Hodgkin’s lymphoma.Methods.The study included 143 patients aged 2–17 years with HL. In the treatment of all patients, risk-adapted therapy was used: 42 patients were treated according to the DAL-HD protocol, 86 patients — according to the original risk-adjusted SPbHL protocol, and 15 patients included in the unfavorable prognosis group underwent 6 courses of BEACOPP-basic. The next treatment step was consolidation radiation therapy. When the therapy course was completed, patients were diagnosed with structural and/or functional changes in the thyroid gland.Results.The majority of the patients (n =126) received concomitant cervico-supraclavicular radiotherapy involving mediastinal lymph nodes in the total focal dose (SOD) of 15–46 Gy. The mean follow-up period was 7.5 years (range: 0–22). Having performed ROC analysis, we determined the critical dose of radiation leading to the development of thyroid dysfunction — more than 39 Gy; the area under the curve was 0.717±0.108 (CI 0.590–0.822; p =0.0445). The Youden’s Index was 0.3929.Conclusion.Irradiation of the neck and thyroid in total dose of 39 Gy and above is associated with a high risk of developing thyroid dysfunction.

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“…Collini et al reported 13 childhood papillary cancers with relapses after 131 I therapy but there was no description of second primary malignancies [42]. Demidchik et al summarized their results of treatment of 464 childhood Chernobyl thyroid cancers and also reported many cases with relapses and metastases but no second primary malignancies were observed among patients followed-up for one to seventeen years [4,5].…”

Section: Therapy For Childhood Thyroid Cancermentioning

confidence: 99%

Childhood Thyroid Cancers and Radioactive Iodine Therapy: Necessity of Precautious Radiation Health Risk Management

et al. 2007

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Abstract. One of the lessons from Chernobyl's legacy on health impact beyond 20 years is not only how to detect and treat the patients with radiation-associated thyroid cancers but how to follow up those who received radioactive iodine treatment repetitively after surgery in order to monitor any recurrence/worsening and also how to predict the risk of secondary primary cancers for their lifetime period. To evaluate the possibility of second primary tumors after radioactive iodine treatment, we reviewed the reports on risks from both external and internal radiation exposure, especially at high doses during childhood through an internet service of the National Library of Medicine and the National Institutes of Health, PubMed by the end of June, 2007, together with our own experience of Chernobyl childhood thyroid cancers. Children who were internally exposed after Chernobyl accident have a long-term risk of well differentiated thyroid cancers. Once they have disease, ironically radioactive iodine ablation is one of the useful therapies after surgical treatment. Elevated risks of solid cancers and leukemia have been found in radioiodine-treated patients, however, so far precious few reports from Chernobyl thyroid cancer patient were published. To reduce the adverse effects of radioactive iodine therapy on non-target tissues, recombinant human TSH has been applied and proved effective. Period of latency of second primary cancers may be very long. Therefore patients treated with high activities of radioactive iodine, especially children cases, should be carefully followed up during their whole lifespan.

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Papillary thyroid carcinoma of childhood and adolescence: A 30‐year experience at the istituto nazionale tumori in Milan

Cited by 57 publications

References 24 publications

Mutation in BRAF and Other Members of the MAPK Pathway in Papillary Thyroid Carcinoma in the Pediatric Population

Mutation in BRAF and Other Members of the MAPK Pathway in Papillary Thyroid Carcinoma in the Pediatric Population

Thyroid Dysfunction After Radiotherapy in Children with Hodgkin’s Lymphoma

Childhood Thyroid Cancers and Radioactive Iodine Therapy: Necessity of Precautious Radiation Health Risk Management

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