Analysis of the Lower Incidence of Medullary Thyroid Cancer in China
Thyroid cancer represents one of the most prevalent endocrine malignancies globally, characterized by distinct histological subtypes with varying prognoses. The four primary types include papillary thyroid cancer (PTC, 80%–90% of cases), follicular thyroid cancer (10%–15%), medullary thyroid cancer (MTC, 3%–10%), and anaplastic thyroid cancer (1%–2%). Among these, PTC and follicular thyroid cancer are associated with better survival outcomes compared to the more aggressive MTC and anaplastic subtypes. Over the past two decades, China has witnessed a substantial rise in thyroid cancer diagnoses, mirroring global trends. However, the proportion of MTC cases in China has declined, contrasting with patterns observed in Western nations. This discrepancy raises critical questions about epidemiological, diagnostic, and genetic factors influencing MTC incidence in China.
Epidemiological Trends in Thyroid Cancer
China’s thyroid cancer burden has grown significantly since 2010. According to the National Central Cancer Registry of China, incidence rates increased steadily from 2010 to 2014, while mortality remained stable. By 2015, China accounted for 16% of global thyroid cancer cases and 14% of related deaths. Notably, the rise in diagnoses is primarily driven by PTC, particularly papillary thyroid microcarcinoma (PTMC), defined as tumors ≤1.0 cm in diameter. PTMC now constitutes over 50% of newly diagnosed thyroid cancers in China, often detected incidentally during imaging or autopsies for unrelated conditions. This surge in PTMC diagnoses has inadvertently reduced the relative proportion of MTC cases, contributing to its lower reported incidence.
Clinical and Genetic Profile of Medullary Thyroid Cancer
MTC originates from thyroid C cells and manifests in two forms: sporadic (75%–80% of cases) and hereditary (20%–25%). Hereditary MTC (hMTC) is linked to germline mutations in the RET proto-oncogene, which drive uncontrolled cell proliferation. hMTC subtypes include multiple endocrine neoplasia type 2A (MEN2A) and type 2B (MEN2B), each associated with distinct RET mutations. Early genetic screening for RET mutations in at-risk families is crucial for timely intervention, as hMTC often presents in younger individuals (18–25 years) and progresses silently for decades. Despite this, genetic testing in China faces barriers, including cost constraints, limited accessibility, and patient reluctance to undergo predictive testing.
Diagnostic Challenges and Misclassification
MTC diagnosis remains challenging due to its indolent early course and nonspecific symptoms. Thyroid function tests often yield normal results in early-stage disease, and only a subset of patients exhibit hormonal abnormalities, such as adrenocorticotropic hormone secretion leading to Cushing syndrome. Advanced MTC presents with dysphagia, dyspnea, or dysphasia due to local tumor invasion, with 63% of patients showing lymph node metastases and 5% exhibiting distant metastases at diagnosis. Misdiagnosis is not uncommon; case reports describe MTC misclassified as lung adenocarcinoma or familial dysautonomia, underscoring the need for heightened clinical suspicion and molecular profiling in ambiguous cases.
International and Regional Incidence Disparities
Globally, MTC accounts for 1%–3% of thyroid cancers in the United States and United Kingdom, but its proportion in China has declined markedly. In Guangzhou, MTC cases fell from 2.03% in 2004 to 0.42% in 2013, while PTC prevalence surged. Similarly, a Zhejiang Province study noted a steady rise in PTC diagnoses from 1972 to 2014, paralleled by a decline in MTC. These trends contrast with Western data, suggesting region-specific factors influencing MTC epidemiology.
Factors Contributing to Lower MTC Incidence in China
Three interrelated factors may explain China’s lower MTC incidence:
- Overdiagnosis of PTMC: The widespread use of high-resolution imaging has led to increased detection of small, indolent PTCs, disproportionately inflating the denominator of total thyroid cancer cases. This “overdiagnosis” artifactually reduces the relative share of MTC, even if its absolute incidence remains stable.
- Underutilization of Genetic Screening: RET mutation testing is not universally adopted in China due to financial barriers and limited awareness among physicians. High-risk families often forego genetic counseling, delaying prophylactic thyroidectomy in mutation carriers. This contrasts with Western protocols, where routine RET screening in MEN2 families has reduced MTC mortality.
- Lack of National Epidemiological Data: China lacks large-scale, population-based studies on MTC prevalence, histopathological subtypes, and genetic variants. Current statistics rely on regional registries, which may underestimate true incidence due to incomplete reporting or diagnostic inconsistencies.
Clinical Evaluation and Multidisciplinary Management
The diagnostic pathway for suspected MTC involves calcitonin testing, imaging (ultrasound, CT, or MRI), and fine-needle aspiration with immunohistochemical staining for calcitonin and carcinoembryonic antigen. Genetic testing for RET mutations is recommended for all confirmed MTC cases to identify hereditary forms. Figure 1 outlines a standardized diagnostic algorithm, emphasizing the role of calcitonin as a biomarker and the necessity of RET screening in first-degree relatives.
Effective MTC management requires multidisciplinary collaboration among endocrinologists, surgeons, oncologists, radiologists, and genetic counselors. Early surgical intervention, including total thyroidectomy with lymph node dissection, offers the best chance of cure. For advanced or metastatic disease, tyrosine kinase inhibitors targeting RET mutations (e.g., vandetanib, cabozantinib) have shown efficacy, though access to these therapies in China remains variable.
Implications for Public Health and Clinical Practice
Addressing China’s MTC burden necessitates targeted strategies:
- Enhanced Genetic Screening: Public health initiatives should subsidize RET testing for high-risk populations and integrate genetic counseling into routine care.
- Standardized Diagnostic Protocols: National guidelines could reduce regional disparities in MTC diagnosis and treatment, promoting early detection through calcitonin screening in thyroid nodules.
- Epidemiological Surveillance: Establishing a national MTC registry would improve data accuracy, inform resource allocation, and track outcomes over time.
Conclusion
China’s declining proportion of MTC cases reflects complex interactions between PTMC overdiagnosis, genetic screening gaps, and fragmented epidemiological data. Addressing these challenges requires a multifaceted approach, combining public health initiatives, clinical education, and research investments. By prioritizing early detection, genetic testing, and multidisciplinary care, China can align its MTC outcomes with global standards, ultimately reducing the morbidity and mortality of this rare but aggressive malignancy.
doi.org/10.1097/CM9.0000000000000463
Was this helpful?
0 / 0