Familial Non-Medullary Thyroid Carcinoma in Pediatric Age: Our Surgical Experience

Abstract Background The purpose of the article was to evaluate the existence of significant clinical, pathological and prognostic differences between familial and sporadic form of pediatric non-medullary thyroid carcinoma, in order to tailor the therapeutic strategy to be adopted for patients with family history. Methods We analyzed the records of 76 pediatric patients that underwent surgery for differentiated thyroid cancer from 2014 to 2019 at the Surgical Pathology Department of the University of Pisa, Italy. Among these, 20 (26,3%) had positive family history (familial non-medullary thyroid carcinoma—FNMTC group) while 56 (73.7%) were affected by sporadic forms (sporadic non-medullary thyroid carcinoma—SNMTC group). Results In our study, the correlation between the FNMTC and the SNMTC group showed no difference in terms of tumor features like multifocality, bilaterality, capsular/extracapsular invasion and the presence of vascular emboli. A statistical significance, on the other hand, was revealed by observation of clinical outcomes, such as distant metastasis (p = 0,022), persistence of disease (p = 0,054) and necessity of radioiodine sessions (p = 0,005). Conclusions These findings suggest that family history may have an independent role on the outcome, expressing its action through an intrinsic more aggressive biological behavior. Therefore, familial non-medullary thyroid carcinoma in children represents a nosological entity that requires an accurate pre-operative evaluation, an adequate surgical strategy and a careful follow up.

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Medullary Thyroid Carcinoma in Multiple Endocrine Neoplasm Type II Syndromes

Tumori Journal ◽

10.1177/030089168507100414 ◽

1985 ◽

Vol 71 (4) ◽

pp. 397-401 ◽

Cited By ~ 1

Author(s):

A.S. Fassina ◽

A. Scapinello ◽

M.R. Pelizzo ◽

P. Dall'Orto ◽

G. Viale ◽

...

Keyword(s):

Family History ◽

Thyroid Gland ◽

Thyroid Carcinoma ◽

Medullary Thyroid Carcinoma ◽

Positive Family History ◽

Biological Behavior ◽

Type Ii ◽

Cell Hyperplasia ◽

Medullary Thyroid ◽

C Cell Hyperplasia

A case of multiple endocrine neoplasm (MEN) type IIa and 2 cases of MEN type IIb are reported. The biological behavior of medullary thyroid carcinoma was more aggressive in the MEN type IIb. C-cell hyperplasia was present in the thyroid gland of the patient with a positive family history.

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Results and Clinical Interpretation of Germline RET Analysis in a Series of Patients with Medullary Thyroid Carcinoma: The Challenge of the Variants of Uncertain Significance

Cancers ◽

10.3390/cancers12113268 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3268

Author(s):

Giovanni Innella ◽

Cesare Rossi ◽

Maria Romagnoli ◽

Andrea Repaci ◽

Davide Bianchi ◽

...

Keyword(s):

Family History ◽

Thyroid Carcinoma ◽

Medullary Thyroid Carcinoma ◽

Cancer Genetics ◽

Positive Family History ◽

Risk Class ◽

Medullary Thyroid ◽

Risk Variants ◽

Uncertain Significance ◽

The Difference

Germline RET variants are responsible for approximately 25% of medullary thyroid carcinoma (MTC) cases. Identification of RET variant carriers allows for the adoption of preventative measures which are dependent on the risk associated with the specific alteration. From 2002 to 2020, at our cancer genetics clinic, RET genetic testing was performed in 163 subjects (102 complete gene analyses and 61 targeted analyses), 72 of whom presented with MTC. A germline RET variant was identified in 31.9% of patients affected by MTC (93.8% of those having positive family history and 14.3% of clinically sporadic cases). Subsequent target testing in relatives allowed us to identify 22 asymptomatic carriers, who could undertake appropriate screening. Overall, patients with germline RET variants differed significantly from those who tested negative by family history (p < 0.001) and mean age at MTC diagnosis (44.45 vs. 56.42 years; p = 0.010), but the difference was not significant when only carriers of moderate risk variants were considered (51.78 vs. 56.42 years; p = 0.281). Out of 12 different variants detected in 49 patients, five (41.7%) were of uncertain significance (VUS). For two of these, p.Ser904Phe and p.Asp631_Leu633delinsGlu, co-segregation and genotype/phenotype analysis, matched with data from the literature, provided evidence supporting their classification in the moderate and the highest/high risk class (with a MEN2B phenotype), respectively.

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All in the family? Analyzing the impact of family history in addition to genotype on medullary thyroid carcinoma aggressiveness in MEN2A patients

Familial Cancer ◽

10.1007/s10689-016-9948-7 ◽

2016 ◽

Vol 16 (2) ◽

pp. 283-289 ◽

Cited By ~ 7

Author(s):

Kristin L. Long ◽

Carol Etzel ◽

Thereasa Rich ◽

Samuel Hyde ◽

Nancy D. Perrier ◽

...

Keyword(s):

Family History ◽

Thyroid Carcinoma ◽

Medullary Thyroid Carcinoma ◽

Medullary Thyroid ◽

The Family ◽

The Impact

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Medullary thyroid carcinoma in children: current state of the art and future perspectives

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2021-0502 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Andreas Kiriakopoulos ◽

Anastasia Dimopoulou ◽

Constantinos Nastos ◽

Dimitra Dimopoulou ◽

Konstantina Dimopoulou ◽

...

Keyword(s):

Lymph Node ◽

Thyroid Carcinoma ◽

Medullary Thyroid Carcinoma ◽

Lymph Node Dissection ◽

Locally Advanced ◽

Biological Behavior ◽

Prophylactic Surgery ◽

Node Dissection ◽

Serum Calcitonin ◽

Medullary Thyroid

Abstract Medullary thyroid carcinoma (MTC) is a distinct type of malignant thyroid tumor in cell origin, biological behavior, and natural history. It accounts for 1.6% of all thyroid cancers and presents either sporadically or as a hereditary disease, the latter occurring as a part of multiple endocrine neoplasia (MEN) 2A and MEN2B syndromes or as a familial MTC disease with no other manifestations. The gene responsible for the hereditary form is the rearranged during transfection (RET) gene, a proto-oncogene located to human chromosome 10. Most pediatric MTC cases have been discovered after genetic testing investigations, leading to the concept of prophylactic surgery in presymptomatic patients. Therefore, the genetic status of the child, along with serum calcitonin levels and ultrasonographic findings, determine the appropriate age for prophylactic surgical intervention. Nevertheless, a diagnosis at an early stage of MTC warrants total thyroidectomy and central lymph node dissection with the addition of lateral/contralateral lymph node dissection depending on the tumor size, ultrasonographic evidence of neck disease, or calcitonin levels. Conversely, locally advanced/unresectable or metastatic MTC is primarily treated with multikinase inhibitors, while more specific RET inhibitors are being tested in clinical trials with promising results.

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Ultrastructure in C cell hyperplasia in asymptomatic patients with hypercalcitoninemia and a family history of medullary thyroid carcinoma

Human Pathology ◽

10.1016/s0046-8177(81)80045-7 ◽

1981 ◽

Vol 12 (7) ◽

pp. 617-622 ◽

Cited By ~ 5

Author(s):

Abdul A. Al Saadi

Keyword(s):

Family History ◽

Thyroid Carcinoma ◽

Medullary Thyroid Carcinoma ◽

Cell Hyperplasia ◽

Medullary Thyroid ◽

C Cell Hyperplasia ◽

C Cell ◽

Asymptomatic Patients ◽

History Of

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OR21-01 Pre-Operative Calcitonin Value as a Predictive Factor of Cancer Related Death in Sporadic Medullary Thyroid Carcinoma

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.487 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Antonio Matrone ◽

Virginia Cappagli ◽

Delio Stefani Donati ◽

Alessandro Prete ◽

Laura Valerio ◽

...

Keyword(s):

Prognostic Factor ◽

Thyroid Carcinoma ◽

Medullary Thyroid Carcinoma ◽

Statistical Significance ◽

Univariate Analysis ◽

Central Compartment ◽

Medullary Thyroid ◽

Negative Prognostic Factor ◽

Lymph Nodes Dissection

Abstract Introduction: Medullary thyroid carcinoma (MTC) is a rare tumor, it originates from the C cells producing calcitonin (CT) and can occur as sporadic or associated to germline RET mutation. The initial treatment is represented by total thyroidectomy associated with central compartment lymph nodes dissection and possible extension to the laterocervical compartment. CT is the main marker of follow-up of MTC, conversely its pre-operative role as diagnostic and prognostic factor is still debated. The aim of the present study was to evaluate several predictive factors of cancer related death in a large series of sporadic MTCs. Patients and Methods: We evaluated 537 consecutive patients surgically treated for sporadic MTC, from 2000 to 2019, and followed at the Operative Unit of Endocrinology 1 of the University of Pisa. We evaluated epidemiological, clinical and pathological data and pre and post-operative CT values, and their correlation with cancer related death. Results: At the end of the follow-up (average 75 months), 300/537 (55.9%) pts were cured, 100/537 (18.6%) pts showed biochemical disease, 88/537 (16.4%) pts showed metastatic disease and 49/537 (9.1 %) pts died for the disease. The factors significantly correlated with the cancer related death to the univariate analysis were the male gender, dimension of the primary tumor> 4 cm, the presence of lymph node metastasis to histology (N1) and/or distant metastasis (M1) at the time of diagnosis, multifocality, minimal extrathyroidal extension (mETE), initial staging, pre-operative CT values> 500 pg/ml and post-operative> 20 pg/ml. At multivariate analysis, statistical significance persisted only for pre- and post-operative CT and for the staging. Conclusions: 1) In our study we observed a significant improvement in the outcome and survival in the medium-long term of sporadic CMT patients, compared to the previous studies. 2) A more advanced staging at the time of diagnosis has been confirmed as a negative prognostic factor and it is evident that an early diagnosis is an essential requirement for improving cancer related death. 3) This is the first study that showed, in a large monocentric series of sporadic MTCs, as pre-operative CT represents a prognostic factor associated with cancer related death, as well as the value of post-operative CT.

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Comparison Between Clinicopathological Characteristics, BRAF V600E and TERT Promoter Mutation of Familial Non-Medullary Thyroid Carcinomas, and Sporadic Case

Frontiers in Oncology ◽

10.3389/fonc.2021.616974 ◽

2021 ◽

Vol 11 ◽

Author(s):

Tian Yang ◽

Longsheng Huang ◽

Chang Chen ◽

Han Luo ◽

Yong Jiang

Keyword(s):

Thyroid Carcinoma ◽

Medullary Thyroid Carcinoma ◽

Nodular Goiter ◽

Sporadic Case ◽

Clinicopathological Characteristics ◽

Braf V600e ◽

Biological Behavior ◽

Promoter Mutation ◽

Medullary Thyroid ◽

Significant Difference

BackgroundIt has been debated whether familial non-medullary thyroid carcinoma (FNMTC) is more aggressive and has a worse prognosis than sporadic non-medullary thyroid carcinoma (SNMTC). Our aim was to compare the invasiveness and prognosis of FNMTC and SNMTC by their biological behavior and molecular changes.Method and MaterialOur group mainly compared 106 patients with FNMTC whom have complete clinicopathological data during 2011–2019 in West China Hospital, Sichuan University, and 212 randomly selected cases with SNMTC were included to compare their biological behavior, recurrence and mortality, and molecular expression of BRAF V600E and TERT promoter. At the same time, FNMTC cases were divided into four subgroups, namely, two affected members group, three or more affected members, parent/offspring group, and sibling group, and they were compared with SNMTC separately to analyze the difference in their invasiveness and prognosis.ResultsWe found that the mean tumor size of FNMTC (0.96 ± 0.53cm) was smaller than that of SNMTC (1.15 ± 0.72 cm) (p = 0.020), while no significant difference in the incidence of other clinicopathological factors, including bilateral growth, capsular invasion, with thyroid nodular goiter or not, multifocality, lymph node metastasis, extrathyroidal extension, iodine 131 treatments, T stage, and American Joint Committee on Cancer (AJCC) stage, was observed between FNMTC and SNMTC (p > 0.05), between each FNMTC subgroup (p > 0.05), and between each FNMTC subgroup and SNMTC (p > 0.05). There was no significant difference in recurrence, mortality, and BRAF V600E and TERT promoter mutation between FNMTC and SNMTC, among which 50/60 (83.33%) of FNMTC patients had BRAF V600E mutation and 1/32 (3.13%) had TERT promoter mutation, while the mutation rates of SNMTC were 93/108 (86.11%) and 3/64 (4.69%) (p > 0.05).ConclusionThere was no significant difference in invasiveness and prognosis between FNMTC and SNMTC by biological behavior, patient survival, and molecular level comparison.

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