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Thyroid : Official Journal of the... Jun 2015The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid... (Review)
Review
INTRODUCTION
The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association.
METHODS
The Task Force identified relevant articles using a systematic PubMed search, supplemented with additional published materials, and then created evidence-based recommendations, which were set in categories using criteria adapted from the United States Preventive Services Task Force Agency for Healthcare Research and Quality. The original guidelines provided abundant source material and an excellent organizational structure that served as the basis for the current revised document.
RESULTS
The revised guidelines are focused primarily on the diagnosis and treatment of patients with sporadic medullary thyroid carcinoma (MTC) and hereditary MTC.
CONCLUSIONS
The Task Force developed 67 evidence-based recommendations to assist clinicians in the care of patients with MTC. The Task Force considers the recommendations to represent current, rational, and optimal medical practice.
Topics: Antineoplastic Combined Chemotherapy Protocols; Biopsy, Fine-Needle; Carcinoma, Medullary; Carcinoma, Neuroendocrine; Disease Management; Genetic Testing; Hormone Replacement Therapy; Humans; Multiple Endocrine Neoplasia Type 2a; Multiple Endocrine Neoplasia Type 2b; Proto-Oncogene Proteins c-ret; Radiotherapy; Societies, Medical; Thyroid Neoplasms; Thyroidectomy
PubMed: 25810047
DOI: 10.1089/thy.2014.0335 -
Endocrinology and Metabolism (Seoul,... Jun 2021Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor originating from the parafollicular cells. The diagnostic and therapeutic strategies for the condition... (Review)
Review
Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor originating from the parafollicular cells. The diagnostic and therapeutic strategies for the condition are different from those used for well-differentiated thyroid cancer. Since the 2015 American Thyroid Association guidelines for the diagnosis and treatment of MTC, the latest, including the National Comprehensive Cancer Network and European Association for Medical Oncology guidelines have been updated to reflect several recent advances in the management of MTC. Advances in molecular diagnosis and postoperative risk stratification systems have led to individualized treatment and follow-up strategies. Multi-kinase inhibitors, such as vandetanib and cabozantinib, can prolong disease progression-free survival with favorable adverse effects. In addition, potent selective rearranged during transfection (RET) inhibitors (selpercatinib and pralsetinib) have shown a promising efficacy in recent clinical trials. This review summarizes the management of MTC in recent guidelines focused on sporadic MTC.
Topics: Carcinoma, Neuroendocrine; Humans; Protein Kinase Inhibitors; Thyroid Neoplasms
PubMed: 34154310
DOI: 10.3803/EnM.2021.1082 -
Current Oncology (Toronto, Ont.) Oct 2019Medullary thyroid carcinoma (mtc) is a rare malignancy of the thyroid gland, and raising awareness of the recommended diagnostic workup and pathologic characteristics of... (Review)
Review
BACKGROUND
Medullary thyroid carcinoma (mtc) is a rare malignancy of the thyroid gland, and raising awareness of the recommended diagnostic workup and pathologic characteristics of this malignancy is therefore important.
METHODS
We reviewed the current clinical practice guidelines and recent literature on mtc, and here, we summarize the recommendations for its diagnosis and workup. We also provide an overview of the pathology of mtc.
RESULTS
A neuroendocrine tumour, mtc arises from parafollicular cells ("C cells"), which secrete calcitonin. As part of the multiple endocrine neoplasia (men) type 2 syndromes, mtc can occur sporadically or in a hereditary form. This usually poorly delineated and infiltrative tumour is composed of solid nests of discohesive cells within a fibrous stroma that might also contain amyloid. Suspicious nodules on thyroid ultrasonography should be assessed with fine-needle aspiration (fna). If a diagnosis of mtc is made on fna, patients require baseline measurements of serum calcitonin and carcinoembryonic antigen. Calcitonin levels greater than 500 pg/mL or clinical suspicion for metastatic disease dictate the need for further imaging studies. All patients should undergo dna analysis for mutations to diagnose men type 2 syndromes, and if positive, they should be assessed for possible pheochromocytoma and hyperparathyroidism.
SUMMARY
Although the initial diagnosis of a suspicious thyroid nodule is the same for differentiated thyroid carcinoma and mtc, the remainder of the workup and diagnosis for mtc is distinct.
Topics: Calcitonin; Carcinoembryonic Antigen; Carcinoma, Neuroendocrine; Germ-Line Mutation; Humans; Practice Guidelines as Topic; Proto-Oncogene Proteins c-ret; Thyroid Neoplasms
PubMed: 31708652
DOI: 10.3747/co.26.5539 -
Genes Sep 2019Thyroid cancer is rare in the pediatric population, but thyroid carcinomas occurring in children carry a unique set of clinical, pathologic, and molecular... (Review)
Review
Thyroid cancer is rare in the pediatric population, but thyroid carcinomas occurring in children carry a unique set of clinical, pathologic, and molecular characteristics. In comparison to adults, children more often present with aggressive, advanced stage disease. This is at least in part due to the underlying biologic and molecular differences between pediatric and adult thyroid cancer. Specifically, papillary thyroid carcinoma (which accounts for approximately 90% of pediatric thyroid cancer) has a high rate of gene fusions which influence the histologic subtypes encountered in pediatric thyroid tumors, are associated with more extensive extrathyroidal disease, and offer unique options for targeted medical therapies. Differences are also seen in pediatric follicular thyroid cancer, although there are few studies of non-papillary pediatric thyroid tumors published in the literature due to their rarity, and in medullary carcinoma, which is most frequently diagnosed in the pediatric population in the setting of prophylactic thyroidectomies for known multiple endocrine neoplasia syndromes. The overall shift in the spectrum of histotypes and underlying molecular alterations common in pediatric thyroid cancer is important to recognize as it may directly influence diagnostic test selection and therapeutic recommendations.
Topics: Adolescent; Child; Genetic Testing; Humans; Thyroid Neoplasms
PubMed: 31540418
DOI: 10.3390/genes10090723 -
The Journal of International Medical... Jul 2022Medullary thyroid carcinoma (MTC) is an uncommon malignancy of neuroendocrine origin derived from the parafollicular C cells. Although infrequent, the interest in this... (Review)
Review
Medullary thyroid carcinoma (MTC) is an uncommon malignancy of neuroendocrine origin derived from the parafollicular C cells. Although infrequent, the interest in this cancer exceeds its incidence owing to its distinctive features and its characteristic association with other endocrine tumors. Although the majority of MTCs are sporadic, hereditary varieties occur in isolation or as a part of multiple endocrine neoplasia type 2 syndrome (MEN 2). Currently, complete surgical resection of the tumor and nodal metastases with a curative intent remains the mainstay of therapy. The role of adjuvant therapy is limited, although radiotherapy and newer targeted therapies are routinely used for metastatic disease. The lack of consensus in the available guidance regarding the most appropriate diagnostic, therapeutic and follow-up strategies has caused substantial variability in clinical practice. Therefore, this review summarizes the latest available evidence and guidelines on the management of MTC with an emphasis on diagnosis, surgical treatment and follow-up.
Topics: Carcinoma, Medullary; Carcinoma, Neuroendocrine; Humans; Multiple Endocrine Neoplasia Type 2a; Thyroid Neoplasms
PubMed: 35822284
DOI: 10.1177/03000605221110698 -
Endocrine Reviews Sep 2023A personalized approach to the management of medullary thyroid cancer (MTC) presents several challenges; however, in the past decade significant progress has been made...
A personalized approach to the management of medullary thyroid cancer (MTC) presents several challenges; however, in the past decade significant progress has been made in both diagnostic and treatment modalities. Germline rearranged in transfection (RET) testing in multiple endocrine neoplasia 2 and 3, and somatic RET testing in sporadic MTC have revolutionized the treatment options available to patients. Positron emission tomography imaging with novel radioligands has improved characterization of disease and a new international grading system can predict prognosis. Systemic therapy for persistent and metastatic disease has evolved significantly with targeted kinase therapy especially for those harboring germline or somatic RET variants. Selpercatinib and pralsetinib are highly selective RET kinase inhibitors that have shown improved progression-free survival with better tolerability than outcomes seen in earlier multikinase inhibitor studies. Here we discuss changes in paradigms for MTC patients: from determining RET alteration status upfront to novel techniques for the evaluation of this heterogenous disease. Successes and challenges with kinase inhibitor use will illustrate how managing this rare malignancy continues to evolve.
Topics: Humans; Carcinoma, Medullary; Proto-Oncogene Proteins c-ret; Carcinoma, Neuroendocrine; Thyroid Neoplasms
PubMed: 37204852
DOI: 10.1210/endrev/bnad013 -
Archives of Pathology & Laboratory... Dec 2019Renal medullary carcinoma, also referred to as the seventh sickle cell nephropathy, typically affects young African Americans with sickle cell trait, or, less... (Review)
Review
Renal medullary carcinoma, also referred to as the seventh sickle cell nephropathy, typically affects young African Americans with sickle cell trait, or, less frequently, patients with sickle cell disease. The existence of renal medullary carcinoma without a concomitant hemoglobinopathy is a topic of controversy. The typical patient is a young male of African or Mediterranean descent, with hematuria and/or flank pain. Most patients have metastatic disease at the time of presentation. The tumor is characteristically a poorly circumscribed mass in the medullary region, commonly showing variable amounts of hemorrhage and necrosis. Microscopically, a characteristic reticular or cribriform pattern with a striking desmoplastic stromal response and a robust mixed inflammatory infiltrate is observed. Collecting duct carcinoma, malignant rhabdoid tumor, urothelial carcinoma, and other subtypes of renal cell carcinoma are in the differential diagnosis. Because of the advanced stage of disease at presentation and the aggressive nature of this malignant neoplasm, survival is poor even with chemotherapy; however, isolated reports of prolonged survival have been documented.
Topics: Anemia, Sickle Cell; Carcinoma, Medullary; Carcinoma, Renal Cell; Humans; Sickle Cell Trait
PubMed: 30855171
DOI: 10.5858/arpa.2017-0492-RS -
The New England Journal of Medicine Sep 2016
Review
Topics: Carcinoma; Carcinoma, Medullary; Carcinoma, Papillary; Humans; Mutation; Thyroid Cancer, Papillary; Thyroid Neoplasms
PubMed: 27626519
DOI: 10.1056/NEJMra1501993 -
Nature Communications May 2023Renal medullary carcinoma (RMC) is an aggressive tumour driven by bi-allelic loss of SMARCB1 and tightly associated with sickle cell trait. However, the cell-of-origin...
Renal medullary carcinoma (RMC) is an aggressive tumour driven by bi-allelic loss of SMARCB1 and tightly associated with sickle cell trait. However, the cell-of-origin and oncogenic mechanism remain poorly understood. Using single-cell sequencing of human RMC, we defined transformation of thick ascending limb (TAL) cells into an epithelial-mesenchymal gradient of RMC cells associated with loss of renal epithelial transcription factors TFCP2L1, HOXB9 and MITF and gain of MYC and NFE2L2-associated oncogenic and ferroptosis resistance programs. We describe the molecular basis for this transcriptional switch that is reversed by SMARCB1 re-expression repressing the oncogenic and ferroptosis resistance programs leading to ferroptotic cell death. Ferroptosis resistance links TAL cell survival with the high extracellular medullar iron concentrations associated with sickle cell trait, an environment propitious to the mutagenic events associated with RMC development. This unique environment may explain why RMC is the only SMARCB1-deficient tumour arising from epithelial cells, differentiating RMC from rhabdoid tumours arising from neural crest cells.
Topics: Humans; Kidney Neoplasms; Sickle Cell Trait; Carcinoma, Medullary; Ferroptosis; Carcinoma, Renal Cell; SMARCB1 Protein; Repressor Proteins; Homeodomain Proteins
PubMed: 37236926
DOI: 10.1038/s41467-023-38472-y