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Kim KM, Ahn AR, Hong YT, Chung MJ. Primary small cell thyroid carcinoma combined with poorly differentiated thyroid carcinoma, evidence for a common origin: A case report. Oncol Lett 2023; 25:233. [PMID: 37153036 PMCID: PMC10157610 DOI: 10.3892/ol.2023.13819] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Accepted: 03/01/2023] [Indexed: 05/09/2023] Open
Abstract
Primary small cell thyroid carcinomas are extremely rare and there is still debate about their classification as a distinct disease entity. The present case report reports a small cell carcinoma (SCC) combined with poorly differentiated thyroid carcinoma (PDTC) in a 34 year old man. The tumor consisted of ~80% PDTC and ~20% SCC. The PDTC component was positive for cytokeratin and thyroid transcription factor-1 (TTF-1), and negative for calcitonin, chromogranin and synaptophysin. The SCC component was positive for synaptophysin and CD56, and negative for calcitonin, chromogranin and TTF-1. Seven months after thyroid surgery, two new lung nodules were detected. Histologically and immunohistochemically, the lung tumors were similar to the SCC component of the thyroid carcinoma. The mutational status of cancer-related genes was assessed using targeted next-generation sequencing in both the thyroid and lung, which identified similar genetic alterations. The histogenesis of SCC was evaluated through NGS analysis of the two cancer components.
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Affiliation(s)
- Kyoung Min Kim
- Department of Pathology, Jeonbuk National University Medical School, Jeonbuk National University, Jeonju, Jeollabuk 54896, Republic of Korea
- Research Institute of Clinical Medicine of Jeonbuk National University, Jeonbuk National University, Jeonju, Jeollabuk 54896, Republic of Korea
- Biomedical Research Institute of Jeonbuk National University Hospital, Jeonbuk National University Hospital, Jeonju, Jeollabuk 54896, Republic of Korea
- Research Institute for Endocrine Sciences of Jeonbuk National University, Jeonbuk National University, Jeonju, Jeollabuk 54896, Republic of Korea
| | - Ae Ri Ahn
- Department of Pathology, Jeonbuk National University Medical School, Jeonbuk National University, Jeonju, Jeollabuk 54896, Republic of Korea
| | - Yong Tae Hong
- Department of Otolaryngology-HNS, Jeonbuk National University Medical School, Jeonju, Jeollabuk 54896, Republic of Korea
| | - Myoung Ja Chung
- Department of Pathology, Jeonbuk National University Medical School, Jeonbuk National University, Jeonju, Jeollabuk 54896, Republic of Korea
- Research Institute of Clinical Medicine of Jeonbuk National University, Jeonbuk National University, Jeonju, Jeollabuk 54896, Republic of Korea
- Biomedical Research Institute of Jeonbuk National University Hospital, Jeonbuk National University Hospital, Jeonju, Jeollabuk 54896, Republic of Korea
- Research Institute for Endocrine Sciences of Jeonbuk National University, Jeonbuk National University, Jeonju, Jeollabuk 54896, Republic of Korea
- Correspondence to: Professor Myoung Ja Chung, Department of Pathology, Jeonbuk National University Medical School, San 2-20 Keumam, Dukjin, Jeonju, Jeollabuk 54896, Republic of Korea, E-mail:
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2
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Filotico M, Plutino F. An encapsulated oncoytic neoplasm of follicular origin of thyroid, expressing neuroendocrine markers. A case report and literature review. Pathologica 2022; 113:463-468. [PMID: 34974553 PMCID: PMC8720397 DOI: 10.32074/1591-951x-202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 10/31/2020] [Indexed: 11/30/2022] Open
Abstract
A case is reported of an oncocytic tumor of the thyroid expressing simultaneously follicular and neuroendocrine markers, but not calcitonin. The data reported in the literature and the possible relationships of these lesions with the calcintonin-negative medullary carcinomas were examined.
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Affiliation(s)
| | - Francesca Plutino
- Ospedale Metropolitano Bianchi-Melacrino-Morelli, Reggio Calabria, Italy
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3
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Fernández-Ferreira R, De la Peña-López IR, Zamudio-Coronado KW, Delgado-Soler LA, Torres-Pérez ME, Bourlón-de Los Ríos C, Cortés-González R. Calcitonin-Negative Neuroendocrine Carcinoma of the Thyroid Gland: Case Report and Literature Review. Case Rep Oncol 2021; 14:112-122. [PMID: 33776692 PMCID: PMC7983544 DOI: 10.1159/000510807] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Accepted: 08/07/2020] [Indexed: 11/24/2022] Open
Abstract
Calcitonin-negative neuroendocrine tumor (CNNET) of the thyroid is an extremely rare entity. In some of the previously reported cases within the literature, the terms “atypical medullary thyroid carcinoma,” “calcitonin-free oat cell carcinoma,” and “a distinct clinical entity” were applied to NETs without definitive evidence of calcitonin production. In the English-language literature, not only are there only few reported cases of CNNET, but the criteria for diagnosis in these cases are also controversial. Most of the current published cases were also treated surgically for local disease. We describe a case of NET of the thyroid with calcitonin, chromogranin A and thyroglobulin negativity, synaptophysin and TTF-1 positivity, and a high Ki-67 proliferation index with metastases in the cervical region as well as mediastinal adenopathies. This case was considered an unresectable thyroid carcinoma, and chemotherapy including cisplatin and etoposide was started as neoadjuvant treatment at the department of medical oncology. Total thyroidectomy plus bilateral and central cervical dissection was performed, and the patient underwent 2 cycles of adjuvant radiotherapy. Currently, the patient's <sup>18</sup>F-FDG-PET/CT findings show a complete response 17 months after diagnosis. In conclusion, CNNET of the thyroid is very rare and there is limited evidence regarding treatment in patients with metastases. Chemotherapy including cisplatin and etoposide as well as early aggressive surgical resection appears to positively impact patients' survival.
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Affiliation(s)
- Ricardo Fernández-Ferreira
- Department of Oncology Medicine, Comprehensive Oncology Center "Diana Laura Riojas de Colosio," Medica Sur Clinic & Foundation, Mexico, Mexico
| | - Ildefonso Roberto De la Peña-López
- Department of Oncology Medicine, Comprehensive Oncology Center "Diana Laura Riojas de Colosio," Medica Sur Clinic & Foundation, Mexico, Mexico
| | - Karla Walkiria Zamudio-Coronado
- Department of Endocrinology, Diabetology and Thyroid, National Institute of Medical Sciences and Nutrition "Salvador Zubiran", Mexico, Mexico
| | | | | | - Christianne Bourlón-de Los Ríos
- Department of Oncology Medicine, Comprehensive Oncology Center "Diana Laura Riojas de Colosio," Medica Sur Clinic & Foundation, Mexico, Mexico
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4
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Cai HJ, Wang H, Cao N, Huang B, Kong FL, Lu LR, Huang YY, Wang W. Calcitonin-negative neuroendocrine tumor of the thyroid with metastasis to liver-rare presentation of an unusual tumor: A case report and review of literature. World J Clin Cases 2020; 8:179-187. [PMID: 31970185 PMCID: PMC6962086 DOI: 10.12998/wjcc.v8.i1.179] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Revised: 11/22/2019] [Accepted: 11/30/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Neuroendocrine tumors mainly occur in the stomach, intestine, pancreas, and lung and are rarely detected in the thyroid. Thyroid neuroendocrine tumors, designated medullary thyroid carcinoma, generally present with elevated calcitonin. Calcitonin-negative neuroendocrine tumors of the thyroid are extremely rare.
CASE SUMMARY Here, we present a case report of a 56-year-old female patient with a neck pain complaint. Total thyroidectomy was conducted after comprehensive evaluation, and diagnosis was confirmed as calcitonin-negative neuroendocrine tumor of the thyroid. Two months later, liver metastasis was detected, and transcatheter arterial chemoembolization was subsequently performed to control growth. However, the curative effect was unsatisfactory and multiple intrahepatic metastases occurred after 3 mo.
CONCLUSION Owing to the rarity of this disease, no clear guidelines are available for treatment. In addition to reporting this rare case, we have reviewed and summarized associated medical literature with an aim to provide a comprehensive reference platform for subsequent research.
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Affiliation(s)
- Huai-Jie Cai
- The Fourth Clinical Medicine College, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China
| | - Han Wang
- The Fourth Clinical Medicine College, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China
| | - Nan Cao
- The Fourth Clinical Medicine College, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China
| | - Bin Huang
- The Fourth Clinical Medicine College, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China
| | - Fan-Lei Kong
- Department of Ultrasound, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
| | - Li-Ren Lu
- Department of Ultrasound, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
| | - Ya-Yuan Huang
- Department of Ultrasound, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
| | - Wei Wang
- Department of Ultrasound, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310006, Zhejiang Province, China
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5
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Chorny JA, Orrego JJ, Cameselle-Teijeiro JM. Primary high-grade calcitonin-negative neuroendocrine carcinoma of the thyroid: a very rare cancer. Endocrinol Diabetes Metab Case Rep 2018; 2018:EDM180036. [PMID: 29692901 PMCID: PMC5911662 DOI: 10.1530/edm-18-0036] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2018] [Accepted: 03/27/2018] [Indexed: 01/13/2023] Open
Abstract
Most medullary thyroid carcinomas (MTCs) are low grade and produce calcitonin. There are some calcitonin-negative MTCs that produce only calcitonin gene-related peptide (CGRP). Rarely, MTCs are negative for calcitonin and CGRP peptides, but contain their corresponding mRNAs. Primary thyroid neuroendocrine neoplasms other than MTCs are extremely rare. We describe a primary high-grade neuroendocrine carcinoma that was negative for CGRP and calcitonin at both the protein and mRNA levels. A 42-year-old woman presented with a rapidly enlarging thyroid mass replacing most of the left lobe and isthmus. A computed tomography-guided core-needle biopsy was performed. The tumor was composed of sheets of small-to-medium sized epithelial cells. The cells were immunoreactive for pancytokeratin, synaptophysin, CD56 and thyroid transcription factor-1, but negative for CK7, CK20, CD45, CD99, ERG, chromogranin A, thyroglobulin, calcitonin, CGRP and carcinoembryonic antigen. The Ki-67 proliferation index was ~90%. In situ hybridization was negative for calcitonin mRNA. The patient was initially diagnosed as having a small cell carcinoma. She was treated with cisplatin and etoposide (VP16), followed by radiation therapy. Given the excellent clinical course, the tumor was reviewed and reclassified as a high-grade neuroendocrine carcinoma (non-small-cell type). Heretofore, only a few other similar high-grade neuroendocrine tumors with negative markers of C-cell derivation have been reported. In our case, the patient is cancer free five years after diagnosis, but in the other cases, the outcome was poor. Learning points There are neuroendocrine carcinomas of the thyroid that do not produce calcitonin or calcitonin gene-related peptide.This category of calcitonin-negative neuroendocrine carcinomas is heterogeneous, consisting of low- and high-grade tumors.The high-grade neuroendocrine carcinomas of the thyroid are rare and generally have a poor prognosis. They are divided into small cell and non-small cell or large cell types.
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Affiliation(s)
- Joseph A Chorny
- Department of Pathology, Colorado Permanente Medical Group, Denver, Colorado, USA
| | - John J Orrego
- Department of Endocrinology and Metabolism, Colorado Permanente Medical Group, Denver, Colorado, USA
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6
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Abstract
Neuroendocrine tumors (NETs) of the thyroid are rare; the most common type is medullary thyroid carcinoma (MTC). They are derived from parafollicular cells (C-cells) that usually express calcitonin, chromogranin, and carcinoembryonic antigen. Calcitonin-negative NETs of the thyroid are extremely rare, and the origin of these tumors is unclear. Whereas some believe that these tumors are from follicular cells, recent reports have shown expression of calcitonin gene-related peptide in these tumors, indicating parafollicular C-cell origin. Here, we report a case of calcitonin-negative NET of the thyroid in a 74-year-old woman, with review of the literature.
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Affiliation(s)
- Megan Parmer
- 1 Texas Tech University Health Sciences Center, El Paso, TX, USA
| | - Stacey Milan
- 1 Texas Tech University Health Sciences Center, El Paso, TX, USA
| | - Alireza Torabi
- 1 Texas Tech University Health Sciences Center, El Paso, TX, USA
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Wada H, Matsuda K, Akazawa Y, Yamaguchi Y, Miura S, Ueki N, Kinoshita A, Yoshiura KI, Kondo H, Ito M, Nagayasu T, Nakashima M. Expression of Somatostatin Receptor Type 2A and PTEN in Neuroendocrine Neoplasms Is Associated with Tumor Grade but Not with Site of Origin. Endocr Pathol 2016; 27:179-87. [PMID: 27256098 DOI: 10.1007/s12022-016-9436-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Neuroendocrine neoplasms (NENs) are derived from endocrine cells in various organs and share common morphological features. This study aimed to clarify whether NENs of different organs are comparable at the molecular pathologic level. We retrospectively collected 99 cases of NENs from gastro-entero-pancreatic, lung, and other organs and reclassified these according to identical criteria. Grade, site, and molecular expression profile including NE markers, Ki-67, p53, somatostatin receptor type 2A (SSTR2A), and phosphatase and tensin homolog (PTEN) were compared. PTEN immunoreactivity was also compared with genomic copy number by fluorescence in situ hybridization (FISH) and droplet digital polymerase chain reaction (ddPCR). No significant differences were observed in the immunoreactivities of NE markers, p53, SSTR2A, or PTEN expression in NENs between the different organ sites. PTEN and p53 functional inactivation along with the loss of membranous SSTR2A expression appeared to be commonly involved in high-grade NEN. FISH results were significantly correlated with the level of PTEN immunoreactivity and with the findings of ddPCR analyses. The demonstration that these tumors are comparable at the molecular level will likely contribute to the broadening of therapeutic options such as the use of somatostatin analogues and mTOR inhibitors against NENs regardless of the affected organ, whereas molecular characterization of tumor grade will be useful for determining treatment strategy.
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Affiliation(s)
- Hideo Wada
- Division of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852 8501, Japan
- Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852 8523, Japan
| | - Katsuya Matsuda
- Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852 8523, Japan
| | - Yuko Akazawa
- Department of Gastroenterology and Hepatology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, 852 8501, Japan
| | - Yuka Yamaguchi
- Medical Student Research Programme, Nagasaki University School of Medicine, 1-12-4 Sakamoto, Nagasaki, 852 8523, Japan
| | - Shiro Miura
- Tissue and Histopathology Section, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852 8523, Japan
| | - Nozomi Ueki
- Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852 8523, Japan
| | - Akira Kinoshita
- Department of Human Genetics, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852 8523, Japan
| | - Koh-Ichiro Yoshiura
- Department of Human Genetics, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852 8523, Japan
| | - Hisayoshi Kondo
- Biostatic section, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852 8523, Japan
| | - Masahiro Ito
- Department of Pathology, National Hospital Organization Nagasaki Medical Center, 2-1001-1 Kubara, Nagasaki, 856 8562, Japan
| | - Takeshi Nagayasu
- Division of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852 8501, Japan
| | - Masahiro Nakashima
- Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, 1-12-4 Sakamoto, Nagasaki, 852 8523, Japan.
- Tissue and Histopathology Section, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki, 852 8523, Japan.
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Kim GY, Park CY, Cho CH, Park JS, Jung ED, Jeon EJ. A Calcitonin-Negative Neuroendocrine Tumor Derived from Follicular Lesions of the Thyroid. Endocrinol Metab (Seoul) 2015; 30:221-5. [PMID: 25491784 PMCID: PMC4508268 DOI: 10.3803/enm.2015.30.2.221] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2014] [Revised: 08/26/2014] [Accepted: 09/02/2014] [Indexed: 02/06/2023] Open
Abstract
Neuroendocrine lesions of the thyroid are rare. The most common types are medullary thyroid carcinomas (MTCs) and C-cell hyperplasia. MTCs originate from thyroid parafollicular cells that secrete calcitonin which serves as a serum marker of MTCs. Here, the rare case of a calcitonin-negative neuroendocrine tumor (NET) derived from follicular lesions of the thyroid is described. A 34-year-old man presented at our hospital for the surgical management of an incidental thyroid nodule that was observed on an ultrasound sonography (USG) of the neck. Initially, USG-guided aspiration cytology was performed, and a MTC was suspected. The expressions of thyroglobulin and thyroid transcription factor-1, which are thyroid follicular cell markers, and synaptophysin and chromogranin A, which are neuroendocrine markers, was confirmed following surgical pathology. However, the staining of calcitonin, a marker of MTCs, was not observed. A nonmedullary NET of the thyroid is uncommon, and the distinction between calcitonin-negative NETs and MTCs of the thyroid may be important due to differences in their clinical courses and management.
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Affiliation(s)
- Ga Young Kim
- Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea
| | - Chul Yun Park
- Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea
| | - Chang Ho Cho
- Department of Pathology, Catholic University of Daegu School of Medicine, Daegu, Korea
| | - June Sik Park
- Department of Otolaryngology Head and Neck Surgery, Catholic University of Daegu School of Medicine, Daegu, Korea
| | - Eui Dal Jung
- Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea
| | - Eon Ju Jeon
- Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea.
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