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      Intermixed medullary and papillary thyroid cancer in a patient with renal cell carcinoma

      research-article
      1 , 2 , 3
      Endocrinology, Diabetes & Metabolism Case Reports
      Bioscientifica Ltd
      Adult, Female, White, United States, Kidney, Thyroid, Thyroid, Calcitonin, Medullary thyroid cancer, Papillary thyroid cancer, Renal cell carcinoma*, Dysphagia, Neck pain/discomfort, Thyroid nodule, Thyroid ultrasonography, Fine needle aspiration biopsy, Calcitonin, Histopathology, Carcinoembryonic antigen, Immunostaining, CT scan, Thyroglobulin, Synaptophysin, Whole body scintigraphy*, Immunohistochemistry, Thyroidectomy, Radionuclide therapy, Lymph node dissection, Laparoscopy, Nephrectomy*, Haematoxylin and eosin staining, Papanicolaou staining*, Radioiodine, Urology, Pathology, Unique/unexpected symptoms or presentations of a disease, June, 2020

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          Abstract

          Summary

          We report a rare case of concurrent medullary thyroid cancer (MTC) and papillary thyroid cancer (PTC) with intermixed disease in several of the lymph node (LN) metastases in a patient who was subsequently diagnosed with clear cell renal cell carcinoma (RCC). A 56 year old female presented with dysphagia and was found to have a left thyroid nodule and left superior cervical LN with suspicious sonographic features. Fine needle aspiration biopsy (FNAB) demonstrated PTC in the left thyroid nodule and MTC in the left cervical LN. Histopathology demonstrated multifocal PTC with 3/21 LNs positive for metastatic PTC. One LN in the left lateral neck dissection exhibited features of both MTC and PTC within the same node. In the right lobe, a 0.3 cm focus of MTC with extra-thyroidal extension was noted. Given persistent calcitonin elevation, a follow-up ultrasound displayed an abnormal left level 4 LN. FNAB showed features of both PTC and MTC on the cytopathology itself. The patient underwent repeat central and left radical neck dissection with 3/6 LNs positive for PTC in the central neck and 2/6 LNs positive for intermixed PTC and MTC in the left neck. There was no evidence of distant metastases on computed tomography and whole body scintigraphy, however a 1.9 x 2.5 cm enhancing mass within the right inter-polar kidney was discovered. This lesion was highly suspicious for RCC. Surgical pathology revealed a 2.5 cm clear cell RCC, Fuhrman grade 2/4, with negative surgical margins. She continues to be observed with stable imaging of her triple malignancies.

          Learning points:
          • Mixed medullary-papillary thyroid neoplasm is characterized by the presence of morphological and immunohistochemical features of both medullary and papillary thyroid cancers within the same lesion. Simultaneous occurrence of these carcinomas has been previously reported, but a mixed disease within the same lymph node is an infrequent phenomenon.

          • Prognosis of mixed medullary-papillary thyroid carcinomas is determined by the medullary component. Therefore, when PTC and MTC occur concurrently, the priority should be given to the management of MTC, which involves total thyroidectomy and central lymph node dissection.

          • Patients with thyroid cancer, predominantly PTC, have shown higher than expected rates of RCC. To our knowledge, this is the first report describing the combination of MTC, PTC, and RCC in a single patient.

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          Most cited references8

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          Hereditary and familial thyroid tumours

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            Papillary thyroid carcinoma associated with papillary renal neoplasia: genetic linkage analysis of a distinct heritable tumor syndrome.

            Papillary thyroid carcinoma usually is sporadic, but may occur in a familial form. The complete clinical and pathological phenotype of familial papillary thyroid carcinoma (fPTC) has not been determined, and the susceptibility gene(s) is unknown. We investigated the clinical and pathological characteristics of an unusually large three-generation fPTC kindred to characterize more fully the clinical phenotype. We performed linkage analysis to determine the chromosomal location of a fPTC susceptibility gene. In addition to the known association of fPTC with nodular thyroid disease, we observed the otherwise rare entity of papillary renal neoplasia (PRN) in two kindred members, one affected with PTC and the other an obligate carrier. The multifocality of PRN in one subject adds weight to the likelihood of a true genetic predisposition to PRN. Both genetic linkage and sequence analysis excluded MET, the protooncogene of isolated familial PRN, as the cause of the fPTC/PRN phenotype. A genome-wide screening and an investigation of specific candidate genes demonstrated that the fPTC/PRN phenotype was linked to 1q21. A maximum three-point log of likelihood ratio score of 3.58 was observed for markers D1S2343 and D1S2345 and for markers D1S2343 and D1S305. Critical recombination events limited the region of linkage to approximately 20 cM. A distinct inherited tumor syndrome has been characterized as the familial association of papillary thyroid cancer, nodular thyroid disease, and papillary renal neoplasia. The predisposing gene in a large kindred with this syndrome has been mapped to 1q21.
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              Mixed medullary-follicular thyroid carcinoma. Molecular evidence for a dual origin of tumor components.

              Mixed medullary-follicular carcinomas (MMFCs) are tumors of the thyroid that display morphological and immunohistochemical features of both medullary and follicular neoplasms. The histogenetic origin and possible molecular mechanisms leading to MMFCs are still unclear. To address these questions, we have isolated the two histological components of 12 MMFCs by (laser-based) microdissection, analyzed them for mutations in the RET proto-oncogene and allelic losses of nine loci on six chromosomes, and studied the clonal composition of MMFCs in female patients. Our results provide strong evidence that the follicular and medullary components in MMFCs are not derived from a single progenitor cell, because the seven tumors amenable for analysis consistently exhibited a different pattern of mutations, allelic losses, and clonal composition. We also demonstrate that follicular structures in MMFCs are often oligo/polyclonal and more frequently exhibit hyperplastic than neoplastic histological features, indicating that at least a subset of MMFCs are composed of a medullary thyroid carcinoma containing hyperplastic follicles.

                Author and article information

                Journal
                Endocrinol Diabetes Metab Case Rep
                Endocrinol Diabetes Metab Case Rep
                EDM
                Endocrinology, Diabetes & Metabolism Case Reports
                Bioscientifica Ltd (Bristol )
                2052-0573
                04 June 2020
                2020
                : 2020
                : 20-0025
                Affiliations
                [1 ]Division of Endocrinology and Metabolism , Loyola University Medical Center, Maywood, Illinois, USA
                [2 ]Division of Internal Medicine , Loyola University Medical Center, Maywood, Illinois, USA
                [3 ]Department of Pathology and Laboratory Medicine , Loyola University Medical Center, Maywood, Illinois, USA
                Author notes
                Correspondence should be addressed to S Samarasinghe; Email: ssamarasinghe@ 123456lumc.edu
                Article
                EDM200025
                10.1530/EDM-20-0025
                7354741
                32538376
                6a944ea5-edb8-4fe4-ad07-4c97694a5fc3
                © 2020 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License..

                History
                : 08 April 2020
                : 30 April 2020
                Categories
                Adult
                Female
                White
                United States
                Kidney
                Thyroid
                Thyroid
                Calcitonin
                Medullary Thyroid Cancer
                Papillary Thyroid Cancer
                Renal Cell Carcinoma*
                Dysphagia
                Neck pain/discomfort
                Thyroid nodule
                Thyroid ultrasonography
                Fine needle aspiration biopsy
                Calcitonin
                Histopathology
                Carcinoembryonic antigen
                Immunostaining
                CT scan
                Thyroglobulin
                Synaptophysin
                Whole body scintigraphy*
                Immunohistochemistry
                Thyroidectomy
                Radionuclide therapy
                Lymph node dissection
                Laparoscopy
                Nephrectomy*
                Haematoxylin and eosin staining
                Papanicolaou staining*
                Radioiodine
                Urology
                Pathology
                Unique/Unexpected Symptoms or Presentations of a Disease
                Unique/Unexpected Symptoms or Presentations of a Disease

                adult,female,white,united states,kidney,thyroid,calcitonin,medullary thyroid cancer,papillary thyroid cancer,renal cell carcinoma*,dysphagia,neck pain/discomfort,thyroid nodule,thyroid ultrasonography,fine needle aspiration biopsy,histopathology,carcinoembryonic antigen,immunostaining,ct scan,thyroglobulin,synaptophysin,whole body scintigraphy*,immunohistochemistry,thyroidectomy,radionuclide therapy,lymph node dissection,laparoscopy,nephrectomy*,haematoxylin and eosin staining,papanicolaou staining*,radioiodine,urology,pathology,unique/unexpected symptoms or presentations of a disease,june,2020

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