RARE DISEASE
Rare thyroid carcinoma
Rare thyroid carcinoma
Rare thyroid carcinoma
Drug discovery
4
drugs
With orphan designations
Overview
Rare thyroid carcinomas encompass aggressive, poorly differentiated malignancies such as anaplastic (ATC), medullary (MTC), Hürthle cell, and primary thyroid lymphomas/sarcomas. These tumors represent <5% of thyroid cancers, exhibit rapid progression, and often present with advanced disease. Prognosis varies widely, with ATC having exceptionally poor survival (median ~6 months) and MTC linked to hereditary syndromes in 25% of cases [1][6][16][20].
Population
Anaplastic thyroid cancer (ATC) accounts for 1-2% of thyroid malignancies, primarily affecting individuals >60 years [1][6].
Medullary thyroid cancer (MTC) represents 2-5% of cases, with 25% arising from RET proto-oncogene mutations [1][8].
Higher incidence observed in non-Hispanic white populations and females (3:1 ratio) [2][7].
Burden
Global DALYs increased 29.98% from 1990-2019, with South Asia experiencing the highest mortality [9][19].
ATC contributes disproportionately to thyroid cancer deaths (median survival 6 months; 5-year survival <20%) [1][6].
Treatment costs escalate with advanced disease management, including palliative airway interventions and targeted therapies [1][6][19].
Therapies
ATC: Multimodal approach with surgery (when resectable), combined chemoradiation, and BRAF/MEK inhibitors (dabrafenib/trametinib) for BRAF V600E-mutated tumors [3][6].
MTC: Tyrosine kinase inhibitors (cabozantinib, vandetanib) for metastatic disease; prophylactic thyroidectomy for RET mutation carriers [8][16].
Emerging therapies: Immune checkpoint inhibitors, NTRK/RET inhibitors, and clinical trial enrollment emphasized for advanced cases [3][8][16].
Categories: rare endocrine diseases, rare neoplastic diseases
Research Papers
1,189 drug discovery papers related to Rare thyroid carcinoma, with 4 first-in-class and 10 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
1,189 drug discovery papers related to Rare thyroid carcinoma, with 4 first-in-class and 10 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-10 | Synchronous Papillary Thyroid Carcinoma and an Angiomatoid Fibrous Histiocytoma: A Rare, Interesting Case Report
Angiomatoid fibrous histiocytoma (AFH) is an uncommon fibrohistiocytic neoplasm of intermediate malignant potential that most often arises in the subcutaneous tissues of children and young adults. Involvement of the neck is unusual, and its clinical and radiological appearance may overlap with nodal or soft-tissue malignancy. Papillary thyroid carcinoma is the most common thyroid malignancy and commonly presents with suspicious thyroid nodules or cervical nodal disease. We report a 52-year-old man who presented with a gradually enlarging ulcerated left lateral neck mass and a small suspicious left thyroid nodule. Preoperative imaging showed a discrete thyroid lesion and a much larger necrotic lateral neck mass. Fine-needle aspiration of the thyroid nodule was suspicious for a follicular-patterned neoplasm, and the lateral mass was considered most likely to represent metastatic nodal disease. After multidisciplinary review, the patient underwent total thyroidectomy with excision of the lateral neck mass and neck dissection. Final histopathology demonstrated a 1.4-cm classic papillary thyroid carcinoma, staged pT1b pN0, with negative margins and no nodal metastasis. The lateral mass was a well-circumscribed fibrohistiocytic neoplasm with morphological and immunohistochemical features favoring AFH. The case represents the coincidence of having two different pathologies together when a patient presents with a lateral neck mass and thyroid malignancy. This emphasizes the need for an extensive workup for both pathologies separately, rather than taking a neck mass as a sequel of metastasis from thyroid malignancy. AFH has a high incidence of local recurrence, and a small proportion presents with distal metastases; thus, close follow-up is required. At one year, the patient remained clinically well, with no evidence of neck recurrence, undetectable thyroglobulin, and a stable incidental pulmonary nodule. This case illustrates the importance of tissue diagnosis from anatomically distinct lesions when the size or appearance of a presumed metastatic deposit is disproportionate to the primary tumor.
2026-07-08 | Ectopic ACTH Production in Medullary Thyroid Carcinoma-A Study of Two Cases.
Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor originating from thyroid parafollicular C-cells, accounting for 1-2% of all thyroid cancers. An exceedingly rare manifestation of MTC is ectopic adrenocorticotropic hormone (ACTH) production, causing Cushing's syndrome and complicating management. This report presents two cases of MTC with ectopic ACTH production, highlighting diagnostic challenges, therapeutic strategies, and clinical outcomes. A comprehensive literature review on this rare paraneoplastic syndrome is included and supplements the case findings. Case 1 involves a 49-year-old man presenting with abdominal pain, weight loss, and pulmonary nodules, diagnosed with MTC and ectopic ACTH-related Cushing's syndrome. Surgical resection and targeted therapy with selpercatinib improved cortisol levels but were complicated by adverse drug reactions. Case 2 details a 65-year-old woman with severe hypercortisolism and locally advanced MTC. Selpercatinib successfully reduced hormone levels and achieved partial tumor regression. Both cases underscore the critical role of tyrosine kinase inhibitors (TKIs) in controlling tumor progression, and paraneoplastic hormone production is exemplified in both cases, as treatment initiation was followed by a biochemical response with declining levels of ACTH, cortisol, and calcitonin. Ectopic ACTH production in MTC is a rare but clinically significant entity associated with aggressive disease. Early recognition, comprehensive biochemical and imaging evaluations, and a multidisciplinary approach are pivotal for optimal management. The advent of targeted therapies, such as selpercatinib, has transformed the therapeutic landscape, offering improved control of both tumor burden and hormone excess. This report highlights the importance of integrating genomic insights and precision medicine in addressing these complex cases.
2026-06-29 | Anterior Chest Wall Reconstruction After Total Sternectomy for Solitary Metastasis From Thyroid Carcinoma: A Case Report of a Wire-Only Technique.
Solitary metastasis of papillary thyroid carcinoma in the sternum is rare. The management and reconstruction of such cases pose a challenge. Surgical removal with clear margins provides local control and relieves the symptoms. However, chest wall reconstruction after total sternectomy remains a complex procedure. A 40-year-old man presented with a painful anterior chest wall mass and a thyroid nodule. Positron emission tomography-computed tomography (PET-CT) revealed a solitary hypermetabolic lytic lesion involving the sternum and a Fluorodeoxyglucose (FDG) - a radioactive glucose analog used primarily as a radiotracer in PET scan- avid lesion in the right thyroid lobe. Biopsy confirmed the presence of malignant papillary thyroid cancer. After undergoing multidisciplinary evaluation, the patient underwent a six-session chemotherapy regimen of paclitaxel-carboplatin; restaging showed no evidence of extra-metastatic disease. The patient underwent total thyroidectomy, followed by radical 'en bloc' total sternectomy with resection of the manubrium, sternal body, xiphoid, and medial ends of both clavicles and first to seventh costal cartilages. Utilising a modified Robicsek stainless steel wire-only technique, a 15×10 cm anterior chest wall defect was reconstructed with a semi-rigid neosternum without any prosthetic mesh or muscle flap. The patient was extubated after 6 h, showed no paradoxical respiration or chest wall instability, and achieved primary healing. One month later, the patient showed complete functional recovery. Total sternectomy with modified Robicsek wire-only reconstruction is a safe, effective, and economical technique in patients with isolated sternal metastases from papillary thyroid cancer (PTC). This method is especially beneficial for patients whose prosthetic materials are prohibitively expensive or unavailable.
2026-07-10 | Synchronous Papillary Thyroid Carcinoma and an Angiomatoid Fibrous Histiocytoma: A Rare, Interesting Case Report
Angiomatoid fibrous histiocytoma (AFH) is an uncommon fibrohistiocytic neoplasm of intermediate malignant potential that most often arises in the subcutaneous tissues of children and young adults. Involvement of the neck is unusual, and its clinical and radiological appearance may overlap with nodal or soft-tissue malignancy. Papillary thyroid carcinoma is the most common thyroid malignancy and commonly presents with suspicious thyroid nodules or cervical nodal disease. We report a 52-year-old man who presented with a gradually enlarging ulcerated left lateral neck mass and a small suspicious left thyroid nodule. Preoperative imaging showed a discrete thyroid lesion and a much larger necrotic lateral neck mass. Fine-needle aspiration of the thyroid nodule was suspicious for a follicular-patterned neoplasm, and the lateral mass was considered most likely to represent metastatic nodal disease. After multidisciplinary review, the patient underwent total thyroidectomy with excision of the lateral neck mass and neck dissection. Final histopathology demonstrated a 1.4-cm classic papillary thyroid carcinoma, staged pT1b pN0, with negative margins and no nodal metastasis. The lateral mass was a well-circumscribed fibrohistiocytic neoplasm with morphological and immunohistochemical features favoring AFH. The case represents the coincidence of having two different pathologies together when a patient presents with a lateral neck mass and thyroid malignancy. This emphasizes the need for an extensive workup for both pathologies separately, rather than taking a neck mass as a sequel of metastasis from thyroid malignancy. AFH has a high incidence of local recurrence, and a small proportion presents with distal metastases; thus, close follow-up is required. At one year, the patient remained clinically well, with no evidence of neck recurrence, undetectable thyroglobulin, and a stable incidental pulmonary nodule. This case illustrates the importance of tissue diagnosis from anatomically distinct lesions when the size or appearance of a presumed metastatic deposit is disproportionate to the primary tumor.
2026-07-08 | Ectopic ACTH Production in Medullary Thyroid Carcinoma-A Study of Two Cases.
Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor originating from thyroid parafollicular C-cells, accounting for 1-2% of all thyroid cancers. An exceedingly rare manifestation of MTC is ectopic adrenocorticotropic hormone (ACTH) production, causing Cushing's syndrome and complicating management. This report presents two cases of MTC with ectopic ACTH production, highlighting diagnostic challenges, therapeutic strategies, and clinical outcomes. A comprehensive literature review on this rare paraneoplastic syndrome is included and supplements the case findings. Case 1 involves a 49-year-old man presenting with abdominal pain, weight loss, and pulmonary nodules, diagnosed with MTC and ectopic ACTH-related Cushing's syndrome. Surgical resection and targeted therapy with selpercatinib improved cortisol levels but were complicated by adverse drug reactions. Case 2 details a 65-year-old woman with severe hypercortisolism and locally advanced MTC. Selpercatinib successfully reduced hormone levels and achieved partial tumor regression. Both cases underscore the critical role of tyrosine kinase inhibitors (TKIs) in controlling tumor progression, and paraneoplastic hormone production is exemplified in both cases, as treatment initiation was followed by a biochemical response with declining levels of ACTH, cortisol, and calcitonin. Ectopic ACTH production in MTC is a rare but clinically significant entity associated with aggressive disease. Early recognition, comprehensive biochemical and imaging evaluations, and a multidisciplinary approach are pivotal for optimal management. The advent of targeted therapies, such as selpercatinib, has transformed the therapeutic landscape, offering improved control of both tumor burden and hormone excess. This report highlights the importance of integrating genomic insights and precision medicine in addressing these complex cases.
2026-06-29 | Anterior Chest Wall Reconstruction After Total Sternectomy for Solitary Metastasis From Thyroid Carcinoma: A Case Report of a Wire-Only Technique.
Solitary metastasis of papillary thyroid carcinoma in the sternum is rare. The management and reconstruction of such cases pose a challenge. Surgical removal with clear margins provides local control and relieves the symptoms. However, chest wall reconstruction after total sternectomy remains a complex procedure. A 40-year-old man presented with a painful anterior chest wall mass and a thyroid nodule. Positron emission tomography-computed tomography (PET-CT) revealed a solitary hypermetabolic lytic lesion involving the sternum and a Fluorodeoxyglucose (FDG) - a radioactive glucose analog used primarily as a radiotracer in PET scan- avid lesion in the right thyroid lobe. Biopsy confirmed the presence of malignant papillary thyroid cancer. After undergoing multidisciplinary evaluation, the patient underwent a six-session chemotherapy regimen of paclitaxel-carboplatin; restaging showed no evidence of extra-metastatic disease. The patient underwent total thyroidectomy, followed by radical 'en bloc' total sternectomy with resection of the manubrium, sternal body, xiphoid, and medial ends of both clavicles and first to seventh costal cartilages. Utilising a modified Robicsek stainless steel wire-only technique, a 15×10 cm anterior chest wall defect was reconstructed with a semi-rigid neosternum without any prosthetic mesh or muscle flap. The patient was extubated after 6 h, showed no paradoxical respiration or chest wall instability, and achieved primary healing. One month later, the patient showed complete functional recovery. Total sternectomy with modified Robicsek wire-only reconstruction is a safe, effective, and economical technique in patients with isolated sternal metastases from papillary thyroid cancer (PTC). This method is especially beneficial for patients whose prosthetic materials are prohibitively expensive or unavailable.
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Drug Discovery Landscape
4 orphan drug designations for Rare thyroid carcinoma, including 2 approved therapies.
4 orphan drug designations for Rare thyroid carcinoma, including 2 approved therapies.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
lenvatinib [Lenvima] | small molecules | FDA | 2012-12-27 | 2015-02-13 | Eisai, Inc. |
ribavirin elaidate | small molecules | FDA | 2011-09-02 | — | Translational Therapeutics, Inc. |
cabozantinib [Cabometyx] | small molecules | FDA | 2010-11-29 | 2021-09-17 | Exelixis, Inc. |
N-Methyl-2-[3-[((E)-2-pyridin-2-yl-vinyl)-1H-indazol-6-ylsulfanyl]benzamide | small molecules | FDA | 2007-05-04 | — | Pfizer, Inc. |
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