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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 -
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 -
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 -
International Journal of Molecular... Jun 2022Renal medullary carcinoma (RMC) is a rare renal malignancy that has been associated with sickle hemoglobinopathies. RMC is aggressive, difficult to treat, and occurs... (Review)
Review
Renal medullary carcinoma (RMC) is a rare renal malignancy that has been associated with sickle hemoglobinopathies. RMC is aggressive, difficult to treat, and occurs primarily in adolescents and young adults of African ancestry. This cancer is driven by the loss of SMARCB1, a tumor suppressor seen in a number of primarily rare childhood cancers (e.g., rhabdoid tumor of the kidney and atypical teratoid rhabdoid tumor). Treatment options remain limited due in part to the limited knowledge of RMC biology. However, significant advances have been made in unraveling the biology of RMC, from genomics to therapeutic targets, over the past 5 years. In this review, we will present these advances and discuss what new questions exist in the field.
Topics: Adolescent; Carcinoma, Medullary; Carcinoma, Renal Cell; Child; Humans; Kidney Neoplasms; Neoplasms, Neuroepithelial; Rhabdoid Tumor; Young Adult
PubMed: 35806102
DOI: 10.3390/ijms23137097 -
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 -
Journal of Veterinary Diagnostic... Nov 2022A 12-y-old, castrated male Weimaraner dog was presented for a wellness examination. A 7-cm, firm mass was palpated on the left, ventral, mid-lateral neck. The neck mass...
A 12-y-old, castrated male Weimaraner dog was presented for a wellness examination. A 7-cm, firm mass was palpated on the left, ventral, mid-lateral neck. The neck mass was removed surgically and submitted for histopathology. A thyroid carcinoma was diagnosed based on microscopic examination. Immunohistochemistry for chromogranin-A, calcitonin, and thyroglobulin identified dual immunoreactivity of the latter two, and a final diagnosis was of a well-differentiated, compact, mixed medullary and follicular cell thyroid carcinoma. These neoplasms are rare in humans and have not been reported in dogs, to our knowledge.
Topics: Humans; Dogs; Male; Animals; Thyroglobulin; Calcitonin; Carcinoma, Medullary; Chromogranins; Adenocarcinoma, Follicular; Thyroid Neoplasms; Dog Diseases
PubMed: 36127830
DOI: 10.1177/10406387221126655 -
Cancer Cell May 2020Renal medullary carcinoma (RMC) is a highly lethal malignancy that mainly afflicts young individuals of African descent and is resistant to all targeted agents used to...
Renal medullary carcinoma (RMC) is a highly lethal malignancy that mainly afflicts young individuals of African descent and is resistant to all targeted agents used to treat other renal cell carcinomas. Comprehensive genomic and transcriptomic profiling of untreated primary RMC tissues was performed to elucidate the molecular landscape of these tumors. We found that RMC was characterized by high replication stress and an abundance of focal copy-number alterations associated with activation of the stimulator of the cyclic GMP-AMP synthase interferon genes (cGAS-STING) innate immune pathway. Replication stress conferred a therapeutic vulnerability to drugs targeting DNA-damage repair pathways. Elucidation of these previously unknown RMC hallmarks paves the way to new clinical trials for this rare but highly lethal malignancy.
Topics: Adult; Animals; Apoptosis; Biomarkers, Tumor; Carcinoma, Medullary; Carcinoma, Renal Cell; Cell Proliferation; Chromosome Aberrations; Cohort Studies; DNA Copy Number Variations; DNA Replication; Female; Gene Expression Regulation, Neoplastic; Genomics; High-Throughput Nucleotide Sequencing; Humans; Kidney Neoplasms; Male; Membrane Proteins; Mice; Mice, Nude; Nucleotidyltransferases; Prognosis; Proto-Oncogene Proteins c-myc; SMARCB1 Protein; Tumor Cells, Cultured; Xenograft Model Antitumor Assays
PubMed: 32359397
DOI: 10.1016/j.ccell.2020.04.002 -
Journal of Oncology Practice Jul 2017Although renal medullary carcinoma (RMC) is a rare subtype of kidney cancer, it is particularly devastating in that it is nearly uniformly lethal. No established... (Review)
Review
Although renal medullary carcinoma (RMC) is a rare subtype of kidney cancer, it is particularly devastating in that it is nearly uniformly lethal. No established guidelines exist for the diagnosis and management of RMC. In April 2016, a panel of experts developed clinical guidelines on the basis of a literature review and consensus statements. The goal was to propose recommendations for standardized diagnostic and management approaches and to establish an international clinical registry and biorepository for RMC. Published data are limited to case reports and small retrospective reviews. The RMC Working Group prepared recommendations to inform providers and patients faced with a low level of medical evidence. The diagnosis of RMC should be considered in all patients younger than 50 years with poorly differentiated carcinoma that arises from the renal medulla. These patients should be tested for sickle cell hemoglobinopathies, and if positive, SMARCB1/INI1 loss should be confirmed by immunohistochemistry. The majority of patients with RMC are diagnosed with metastatic disease. Upfront radical nephrectomy should be considered in patients with good performance status and low metastatic burden or after response to systemic therapy. Currently, cytotoxic, platinum-based chemotherapy provides the best, albeit brief, palliative clinical benefit. Vascular endothelial growth factor-directed therapies and mammalian target of rapamycin inhibitors are ineffective in RMC as monotherapy. Therapeutic trials of novel agents are now available for RMC, and every effort should be made to enroll patients in clinical studies.
Topics: Anemia, Sickle Cell; Carcinoma, Medullary; Humans; Kidney Neoplasms; Practice Guidelines as Topic; Registries
PubMed: 28697319
DOI: 10.1200/JOP.2017.020909 -
Journal of Internal Medicine Jul 2009The clinical management of patients with persistent or recurrent medullary thyroid carcinoma (MTC) is still under debate, because these patients either have a long-term... (Review)
Review
The clinical management of patients with persistent or recurrent medullary thyroid carcinoma (MTC) is still under debate, because these patients either have a long-term survival, due to an indolent course of the disease, or develop rapidly progressing disease leading to death from distant metastases. At this moment, it cannot be predicted what will happen within most individual cases. Biomarkers, indicators which can be measured objectively, can be helpful in MTC diagnosis, molecular imaging and treatment, and/or identification of MTC progression. Several MTC biomarkers are already implemented in the daily management of MTC patients. More research is being aimed at the improvement of molecular imaging techniques and the development of molecular systemic therapies. Recent discoveries, like the prognostic value of plasma calcitonin and carcino-embryonic antigen doubling-time and the presence of somatic RET mutations in MTC tissue, may be useful tools in clinical decision making in the future. In this review, we provide an overview of different MTC biomarkers and their applications in the clinical management of MTC patients.
Topics: Biomarkers, Tumor; Carcinoma, Medullary; Humans; Medical Oncology; Positron-Emission Tomography; Prognosis; Thyroid Neoplasms
PubMed: 19522831
DOI: 10.1111/j.1365-2796.2009.02106.x