Medüller Tiroid Kanserleri
Özet
Medüller tiroid kanseri (MTK), tiroid bezinin nöroendokrin C hücrelerinden köken alan ve tüm tiroid tümörlerinin %5-8’ini oluşturan, kalsitonin salınımı ile karakteristik nadir bir hastalıktır. Vakaların %75’i sporadik seyir gösterirken, %25’i RET proto-onkogen mutasyonlarına bağlı olarak multipl endokrin neoplazi tip 2 (MEN-2) sendromu kapsamında kalıtsal özellik taşımaktadır. Tanı aşamasında ince iğne aspirasyon biyopsisi, ultrasonografi ve serum tümör belirteçleri olan kalsitonin ve karsinoembriyonik antijen (CEA) düzeyleri kritik rol oynar. Temel tedavi yaklaşımı cerrahi rezeksiyon ve bölgesel lenf nodu diseksiyonudur; çünkü tümör hücreleri iyot konsantre etmediğinden radyoaktif iyot ve TSH baskılama tedavilerinin etkinlik payı bulunmamaktadır. İleri evre veya metastatik hastalık durumlarında cerrahi genellikle palyatif düzeye kaymakta olup, lezyonların agresifliğine ve RET genotip durumuna göre lokal tedaviler veya adjuvan eksternal radyoterapi tercih edilebilir. Son yıllarda klinik kullanıma giren ve etki mekanizmaları Tablo-4'te özetlenen selpercatinib, pralsetinib, vandetanib ve kabozantinib gibi hedefe yönelik tirozin kinaz inhibitörleri, özellikle semptomatik ilerleyen vakalarda sağkalım sürelerini belirgin şekilde uzatarak metastatik MTK yönetiminde paradigma değişimine yol açmıştır.
Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor originating from the parafollicular C-cells of the thyroid gland, accounting for 5-8% of all thyroid malignancies and characterized by calcitonin secretion. While approximately 75% of cases present as sporadic disease, the remaining 25% are hereditary as part of multiple endocrine neoplasia type 2 (MEN-2) syndromes triggered by germline RET proto-oncogene mutations. Diagnosis relies on fine-needle aspiration biopsy, ultrasonography, and serum biomarkers such as calcitonin and carcinoembryonic antigen (CEA). The primary therapeutic management is surgical resection combined with lymph node dissection, whereas radioactive iodine and TSH suppression are ineffective because the tumor cells do not concentrate iodine. In locally advanced or metastatic disease, surgery often shifts to a palliative intent, supplemented by localized interventions or adjuvant external beam radiation therapy depending on progression rates and specific genetic alterations. In recent years, targeted tyrosine kinase inhibitors—including selpercatinib, pralsetinib, vandetanib, and cabozantinib, whose features are summarized in Table-4—have significantly enhanced progression-free and overall survival rates in symptomatic metastatic cases, redefining the clinical standard of care for advanced disease.
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