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Frontiers in Endocrinology 2023An exceptional number of synchronous MTC/PTC in the same thyroid gland is presented. This may be the most numerous case series reported in the literature. Synchronous...
SYNOPSIS FOR TABLE OF CONTENTS
An exceptional number of synchronous MTC/PTC in the same thyroid gland is presented. This may be the most numerous case series reported in the literature. Synchronous PTC/MTC in the same thyroid gland were classified into 4 subtypes and the clinical and pathological aspects as well as the results are presented.
BACKGROUND AND OBJECTIVES
The synchronous occurrence of multiple neoplastic processes in the thyroid gland is unusual. We investigated the clinicopathological features of 30 medullary thyroid carcinomas (MTC) in association with papillary (PTC).
METHOD
Retrospective analysis of operated patients for thyroid tumors. Synchronous PTC/MTC in the same thyroid gland were classified into 4 subtypes: (type I) True mixed MTC/PTC, MTC and PTC closely intermingled. (Type II) Collision MTC/PTC, i.e. tumors that meet at the same site, invade each other and appear as a single mass in the thyroid gland, i.e. MTC and PTC merge. (Type III) Synchronous anatomically separate tumors in the same thyroid lobe, i.e. separated from each other by non-tumorous thyroid parenchyma. (Type IV) Synchronous tumors occurring in separate anatomical lobes or in the isthmus. Clinical and pathological data were reviewed. Location: Department of thyroid surgery, China-Japan Union Hospital, Jilin University. Time frame: 14 years (June 2008-November 2022).
RESULTS
Thirty patients were identified with an overall prevalence of 28621 (0.1%). 17 (56.7%) were male, 13 (43.3%) female, mean age 51.3 ± 11.0 years, mean BMI 23.6 ± 3.6kg/m. Mean duration of symptoms was 11.2 ± 18.4 months. Mean calcitonin level was 133.7 ± 196.4 pg/ml. Fine needle aspiration (FNA) was offered in 21 cases: 9 (42.9%) were suspected carcinoma, 9 (42.9%) PTC, 1 (4.8%) MTC, 2 (9.4%) MTC/PTC. Pathology revealed type I 4 (13.3%), type II 2 (6.7%), type III 14 (46.7%), type IV 10 (33.3%). The mean diameter of MTC was 1.6 ± 2.0cm, 18 (60%) were micro-MTC. The mean diameter of PTC was 0.9 ± 1.9 cm, 26 (86.7%) were micro-PTC. In 16 (53.3%) micro-PTC/-MTC occurred in synchronous sequence. Four patients had a recurrence: 2 had to be re-operated due to MTC recurrence, 2 died due to distant metastases (bone, liver).
CONCLUSION
We report an exceptional number of MTC/PTC in the same thyroid gland. This may be the most numerous case series reported in the literature. The clinical and pathological aspects as well as the results are presented.
Topics: Humans; Male; Female; Adult; Middle Aged; Thyroid Cancer, Papillary; Retrospective Studies; Carcinoma, Papillary; Thyroid Neoplasms; Carcinoma, Neuroendocrine; Neoplasms, Multiple Primary
PubMed: 37065753
DOI: 10.3389/fendo.2023.1153248 -
Frontiers in Endocrinology 2022Calcitonin (Ct)-negative medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor. This study aimed to clarify its incidence, clinicopathologic characteristics,...
OBJECTIVE
Calcitonin (Ct)-negative medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor. This study aimed to clarify its incidence, clinicopathologic characteristics, management, and treatment outcome.
METHODS
We retrospectively analyzed data of patients with primary MTC. Patients were divided into two groups according to the preoperative serum Ct level (Ct-negative and Ct-positive). The demographic, pathologic, and molecular characteristics, and treatment outcomes were compared between the two groups. In the Ct-negative group, we analyzed the association between the operation type and treatment outcome.
RESULTS
Of the total 312 patients, 24 were diagnosed with Ct-negative MTC. The rate of lymph node metastasis was significantly higher in the Ct-positive than in the Ct-negative group (47.9% vs. 0%, <0.001). The proportion of patients with Ki-67 ≤10% was significantly higher in the Ct-negative than in the Ct-positive group (87.5% vs. 38.2%, <0.001). Excellent response was achieved by 91.7% and 34.7% of patients in the Ct-negative and Ct-positive groups, respectively (<0.001). In the Ct-negative group, excellent response was achieved by all female patients, but only 50% of male patients.
CONCLUSIONS
Ct-negative MTC is rare and unlikely to develop lymph node metastasis. Unilateral lobectomy tends to provide a satisfactory chance of excellent response; however, this requires further validation.
Topics: Humans; Male; Female; Calcitonin; Carcinoma, Medullary; Lymphatic Metastasis; Retrospective Studies; Thyroid Neoplasms; Calcium-Regulating Hormones and Agents; Peptide Hormones; Neuropeptides
PubMed: 36506082
DOI: 10.3389/fendo.2022.1025629 -
JAMA Oncology Aug 2023Thyroid epithelial malignant neoplasms include differentiated thyroid carcinomas (papillary, follicular, and oncocytic), follicular-derived high-grade thyroid... (Review)
Review
IMPORTANCE
Thyroid epithelial malignant neoplasms include differentiated thyroid carcinomas (papillary, follicular, and oncocytic), follicular-derived high-grade thyroid carcinomas, and anaplastic and medullary thyroid carcinomas, with additional rarer subtypes. The discovery of neurotrophic tyrosine receptor kinase (NTRK) gene fusions has fostered developments in precision oncology, with the approval of tropomyosin receptor kinase inhibitors (larotrectinib and entrectinib) for patients with solid tumors, including advanced thyroid carcinomas, harboring NTRK gene fusions.
OBSERVATIONS
The relative rarity and diagnostic complexity of NTRK gene fusion events in thyroid carcinoma present several challenges for clinicians, including variable access to robust methodologies for comprehensive NTRK fusion testing and poorly defined algorithms of when to test for such molecular alterations. To address these issues in thyroid carcinoma, 3 consensus meetings of expert oncologists and pathologists were convened to discuss diagnostic challenges and propose a rational diagnostic algorithm. Per the proposed diagnostic algorithm, NTRK gene fusion testing should be considered as part of the initial workup for patients with unresectable, advanced, or high-risk disease as well as following the development of radioiodine-refractory or metastatic disease; testing by DNA or RNA next-generation sequencing is recommended. Detecting the presence of NTRK gene fusions is important to identify patients eligible to receive tropomyosin receptor kinase inhibitor therapy.
CONCLUSIONS AND RELEVANCE
This review provides practical guidance for optimal integration of gene fusion testing, including NTRK gene fusion testing, to inform the clinical management in patients with thyroid carcinoma.
Topics: Humans; Neoplasms; Receptor, trkA; Tropomyosin; Iodine Radioisotopes; Oncogene Proteins, Fusion; Precision Medicine; Thyroid Neoplasms; Gene Fusion; Protein Kinase Inhibitors
PubMed: 37289450
DOI: 10.1001/jamaoncol.2023.1379 -
Chirurgie (Heidelberg, Germany) May 2023Parafollicular C cells progress via C cell hyperplasia to medullary thyroid cancer (MTC), which can be present even in the first years of life in multiple endocrine... (Review)
Review
Parafollicular C cells progress via C cell hyperplasia to medullary thyroid cancer (MTC), which can be present even in the first years of life in multiple endocrine neoplasia (MEN) type 2A and 2B patients. Basal calcitonin and carcinoembryonic antigen (CEA) are useful tumor markers for the diagnosis and monitoring. The prognosis depends on the stage when the disease is diagnosed and there is a good genotype-phenotype correlation with the RET proto-oncogene, which can be used for estimation of the risk. The risk-stratified prophylactic thyroidectomy plays a decisive role in the prognosis of known gene mutation carriers.
Topics: Humans; Proto-Oncogene Proteins c-ret; Proto-Oncogene Mas; Carcinoma, Medullary; Thyroid Neoplasms
PubMed: 36799965
DOI: 10.1007/s00104-023-01824-x -
Endocrine Pathology Jun 2021This paper will review neuroendocrine lesions of the thyroid and the differential diagnosis with the most significant such tumor of the thyroid, that is, medullary... (Review)
Review
This paper will review neuroendocrine lesions of the thyroid and the differential diagnosis with the most significant such tumor of the thyroid, that is, medullary thyroid carcinoma. A brief overview of the understanding of this tumor's identification as a lesion of C cells and its familial and syndromic associations will be presented. Then, a discussion of the various mimics of medullary carcinoma will be given with an approach to the types of tests that can be done to arrive at a correct diagnostic conclusion. This review will focus on practical "tips" for the practicing pathologist.
Topics: Carcinoma, Neuroendocrine; Humans; Thyroid Neoplasms
PubMed: 33687689
DOI: 10.1007/s12022-021-09672-3 -
Thyroid : Official Journal of the... Oct 2020
Topics: Animals; Carcinoma; Carcinoma, Neuroendocrine; Drug Approval; Glucagon-Like Peptide-1 Receptor; Humans; Incidence; Product Surveillance, Postmarketing; Registries; Thyroid Neoplasms; United States
PubMed: 32316860
DOI: 10.1089/thy.2019.0591 -
The Journal of Clinical Endocrinology... Sep 2023Management of sporadic medullary thyroid microcarcinoma smaller than 1 cm (micro-MTC) is controversial because of conflicting reports of prognosis. As these cancers are...
CONTEXT
Management of sporadic medullary thyroid microcarcinoma smaller than 1 cm (micro-MTC) is controversial because of conflicting reports of prognosis. As these cancers are often diagnosed incidentally, they pose a management challenge when deciding on further treatment and follow-up.
OBJECTIVE
We report the outcomes of surgically managed sporadic micro-MTC in a specialist endocrine surgery and endocrinology unit and identify associations for recurrence and disease-specific survival in this population.
METHODS
Micro-MTCs were identified from a prospectively maintained surgery database, and slides were reviewed to determine pathological grade. The primary end points were recurrence, time to recurrence and disease-specific survival. Prognostic factors assessed included size, grade, lymph node metastasis (LNM), and postoperative calcitonin.
RESULTS
From 1995 to 2022, 64 patients were diagnosed with micro-MTC with 22 excluded because of hereditary disease. The included patients had a median age of 60 years, tumor size of 4 mm, and 28 (67%) were female. The diagnosis was incidental in 36 (86%) with 4 (10%) being high grade, 5 (12%) having LNM and 9 (21%) having elevated postoperative calcitonin. Over a 6.6-year median follow-up, 5 (12%) developed recurrence and 3 (7%) died of MTC. High grade and LNM were associated with 10-year survival estimates of 75% vs 100% for low grade and no LNM (hazard ratio = 831; P < .01). High grade, LNM, and increased calcitonin were associated with recurrence (P < .01). Tumor size and type of surgery were not statistically significantly associated with recurrence or survival. No patients with low grade micro-MTC and normal postoperative calcitonin developed recurrence.
CONCLUSION
Most sporadic micro-MTCs are detected incidentally and are generally associated with good outcomes. Size is not significantly associated with outcomes. Using grade, LNM, and postoperative calcitonin allows for the identification of patients at risk of recurrence to personalize management.
Topics: Humans; Female; Middle Aged; Male; Calcitonin; Thyroid Neoplasms; Thyroidectomy; Lymph Node Excision; Carcinoma, Medullary; Prognosis; Peptide Hormones; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Retrospective Studies
PubMed: 36964913
DOI: 10.1210/clinem/dgad173 -
Journal of Pediatric Endocrinology &... Jan 2022Medullary 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... (Review)
Review
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.
Topics: Carcinoma, Neuroendocrine; Child; Germ-Line Mutation; Humans; Immune Checkpoint Inhibitors; Neck Dissection; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-ret; Thyroid Neoplasms; Thyroidectomy
PubMed: 34592078
DOI: 10.1515/jpem-2021-0502 -
Endocrine Pathology Mar 2021Our understanding of the genomics and epigenomics of medullary thyroid carcinoma (MTC) has advanced since the initial recognition of RET as a driver of MTC tumorigenesis... (Review)
Review
Our understanding of the genomics and epigenomics of medullary thyroid carcinoma (MTC) has advanced since the initial recognition of RET as a driver of MTC tumorigenesis in familial MTC. We now have insight into the frequency and prognostic significance of specific RET mutations in sporadic MTC. For example, the most common RET mutation in sporadic MTC is the RET Met918Thr mutation, the same mutation that underlies MEN2B and a poor prognosticator. This mutation is relatively infrequent in medullary thyroid microcarcinomas but is over-represented in advanced-stage disease. RAS mutations are detected in 70% of sporadic, RET wild-type MTC. Although next-generation and whole-exome sequencing studies have shown that tumors that are wild-type for RET and RAS mutations essentially lack other recurrent mutations, additional pathways and epigenetic alterations have been implicated in MTC tumorigenesis. Increased insight into the clinical course of patients with familial MTC with specific RET mutations has guided treatment recommendations for these patients. Finally, an understanding of the genomics has informed treatment for patients with advanced MTC. In this review, we will examine the genomics and epigenomics of sporadic and familial MTC, along with the prognostic significance of molecular alterations, management of patients with germline RET mutations, and treatment strategies for MTC patients.
Topics: Animals; Carcinoma, Medullary; Carcinoma, Neuroendocrine; Epigenesis, Genetic; Epigenomics; Genomics; Humans; Multiple Endocrine Neoplasia Type 2a; Proto-Oncogene Proteins c-ret; Thyroid Neoplasms
PubMed: 33492588
DOI: 10.1007/s12022-021-09664-3 -
Der Radiologe Nov 2019About 10% of thyroid cancers are medullary thyroid carcinoma (MTC) and can occur sporadically, familially and in the context of type II multiple endocrine neoplasia... (Review)
Review
BACKGROUND
About 10% of thyroid cancers are medullary thyroid carcinoma (MTC) and can occur sporadically, familially and in the context of type II multiple endocrine neoplasia (MEN). Imaging plays a pivotal role in screening family members and in diagnosis.
DIAGNOSTIC METHODS
Diagnosis is based on ultrasound (US), thyroid scintigraphy, serum calcitonin and carcinoembryonic antigen (CEA) as well as fine needle biopsy. High-resolution US is the most important imaging method for locoregional staging, combined with computed tomography (CT) of the mediastinum. Positron emission tomography (PET-CT) using 18-F-DOPA is particularly suited for suspected occult metastases in case of rising tumor markers in serum.
FINDINGS AND COURSE OF DISEASE
Diagnosis is made based on cytologic findings in a hypoechoic, cold thyroid nodule, combined with an elevation of serum calcitonin and CEA. US is the most important imaging modality during routine follow-up. CT is indicated for suspected mediastinal, lung, or liver metastases. CT should be replaced by MRI as early as possible to prevent significant cumulative radiation doses over time.
RECENT CLINICAL DEVELOPMENTS
Although MTC is curable by surgery only, owing to its radio- and chemoresistance, the disease will often progress only slowly, and even patients with metastases will frequently survive 10 years or longer. For more aggressive variants and late symptomatic stages, targeted drugs that have the potential to indicate stabilization or even a partial remission of the disease are under clinical investigation or already approved.
Topics: Calcitonin; Humans; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Thyroid Neoplasms; Tomography, X-Ray Computed; Ultrasonography
PubMed: 31367891
DOI: 10.1007/s00117-019-0575-9