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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Pediatric Oncology
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1464890
This article is part of the Research Topic New Insights into Cancer Predisposition Syndromes in Pediatric Hematology-Oncology View all 7 articles

Medullary thyroid cancer in MEN 2 pediatric/adolescent carriers of RET mutation: genotype/phenotype correlation and outcome in a retrospective series of 23 patients

Provisionally accepted
Guenda Di Benedetto Guenda Di Benedetto 1Ignazio Barca Ignazio Barca 1Laura De Gregorio Laura De Gregorio 2Claudia Scollo Claudia Scollo 3Fiorenza Gianì Fiorenza Gianì 1Federica Martorana Federica Martorana 4Marco Russo Marco Russo 1Francesco Frasca Francesco Frasca 1Gabriella Pellegriti Gabriella Pellegriti 1,4*Giulia Sapuppo Giulia Sapuppo 1,5*
  • 1 Division of Endocrinology, Department of Clinical and Experimental Medicine, University of Catania, Catania, Sicily, Italy
  • 2 Molecular Biology Service, Multi-diagnostic Health Services Centre, Catania, Italy
  • 3 Endocrinology Service, Department of Internal Medicine, P.O. Maggiore Hospital, Modica, Italy
  • 4 Medical Oncology, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
  • 5 University of Catania, Catania, Italy

The final, formatted version of the article will be published soon.

    Background: Multiple Endocrine Neoplasia type 2 syndrome (MEN2) is a hereditary disease resulting from mutations of the RET protooncogene subclassified into MEN2A (medullary thyroid carcinoma (MTC), pheochromocytoma, primary hyperparathyroidism) and MEN2B (MTC, pheochromocytoma, marfanoid habitus, mucous neuromas, intestinal gangliononeuromatosis). Prophylactic thyroidectomy is recommended in RET-mutated patients. The age at which it should be performed depends on the type and aggressiveness of mutation. Aim of the study: to evaluate the genotype/phenotype correlation and outcome in pediatric/adolescent carriers of MEN 2 RET mutation. Patients and Methods: in a retrospective series of 23 carriers of RET MEN 2 mutation , ≤ 19 years at diagnosis, undergone total thyroidectomy ± lymphadenectomy, were analyzed: 1) specific RET mutation; 2) clinical and histopathological characteristics; 3) genotype/phenotype correlation; 4) outcome at last follow-up. Results: In our series the female gender was more prevalent (F/M ratio 2.8/1) and the median age was 14.9 years (IQR 12.6-17.2). RET mutations were at very high risk in 4.3% of patients (M918T), high risk in 43.5% (C634), moderate risk in 52.2% (47.8% C618, 4.3% C620). All patients underwent surgery: at histology MTC was found in 19/23 (82.6%) patients, C-cell hyperplasia in 2/23 (8.7%) and benign histology in 2/23 (8.7%). Ten patients (52.6%) had a disease event during the follow-up: 2/19 (10.5%) showed biochemical disease, 6/19 (31.6%) lymph node recurrences and 2/19 (10.5%) distant metastases (50% liver, 50% bone). At the last follow-up, 9 MTCs were not cured. One patient died after 9 years of follow-up at 21 years old (M918T RET+). Conclusions: From these data it clearly emerges the importance of genetic counseling and RET screening in all first-degree relatives of patients with proven MEN2. The goal should be to subject patients to surgery for prophylactic and not curative purposes, i.e. before the onset of MTC, given the high risk of persistence or recurrent disease also in pediatric/adolescent patients

    Keywords: pediatric and adolescent MEN 2, childhood medullary thyroid cancer, RET mutation, Response to treatment, Outcome, Persistent disease, thyroid cancer

    Received: 15 Jul 2024; Accepted: 04 Nov 2024.

    Copyright: © 2024 Di Benedetto, Barca, De Gregorio, Scollo, Gianì, Martorana, Russo, Frasca, Pellegriti and Sapuppo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Gabriella Pellegriti, Division of Endocrinology, Department of Clinical and Experimental Medicine, University of Catania, Catania, 95131, Sicily, Italy
    Giulia Sapuppo, University of Catania, Catania, Italy

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