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单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,#,概况,Histologic subtypes of,thyroid cancer,Papillary:,approximately 80%of all thyroid malignancies;,Follicular and H,rthle:,approximately 11%;,Medullary:,less than 5%-8%;,Anaplastic:,less than 2%.,概况Histologic subtypes of thyro,Introduction,Medullary thyroid cancer(,MTC,),Sporadic MTC:,approximately 75%;,50%,somatic,RET,mutations,(p.M918T),-predict a poor prognosis,Hereditary MTC:,approximately 25%;,98%,Germline,RET,mutations,MEN 2A,(95%)and,MEN 2B,(5%),Arises from the neural crest-derived,calcitonin-secreting,parafollicular C cells of the thyroid gland,Introduction Medullary thyroid,Introduction,Sporadic MTC:,a solitary and unilateral,or a palpable cervical lymph node,Hereditary MTC:,multicentric and bilateral,the upper to middle parts of the thyroid lobes,Introduction Sporadic MTC:a,Introduction,Involvement of,cervical lymph nodes,is an early and common manifestation in the clinical course of the disease,with 35%to 50%or more,another 10%to 15%,may have,distant metastases,at the time of initial presentation;,Distant metastatic spread of MTC frequently involves the mediastinal nodes,lung,liver(90%),and bones.,Introduction Involvement of ce,p.C611Y,MEN2A,p.C611Y,Molecular Aberrations,(overexpression),RET,mutations,VEGFR-2,MET,EGFR,FGFR,RAS,(sMTC-56%,KRAS,+;12%,HRAS,),(Mutations in,RAS,appear to be mutually exclusive of,RET,abnormalities),Somatic,RET,mutations,Molecular Aberrations(overexp,Molecular,pathways,PI3K/Akt/mTOR,MAPK,JNK,RAS/ERK,Play critical roles in regulating cell proliferation,differentiation,motility,apoptosis,and survival,Molecular pathways PI3K/Akt/,Diagnosis and Monitoring,FNA,US,and CT,MRI or ECT(Ct 500 pg/mL);,DNA analysis for the,RET,germline mutation,ATA-2015,ETA-2013,NCCN-2017 Guidelines recommend,The MTC specimen is positively stained for Ct,chromogranin A,and CEA or Congo Red.,Diagnosis and Monitoring FNA,Diagnosis and Monitoring,Serum-based biomarkers:,calcitonin and CEA(50%),Pre,operative:,CEA(,),Ct(-)-poorly differentiated tumors,Rare;,Ct,100 pg/mL-,-predictive MTC;,Ct 150 pg/mL,CEA 30 ng/L-regional spread;,Ct 3000 pg/mL,CEA 100 ng/L-distant spread.,Predictors of MTC progress,including recurrence and survival,Diagnosis and Monitoring Seru,Diagnosis and Monitoring,Serum-based biomarkers:,calcitonin and CEA,Post,operative:,Ct(,)-the first sign of tumor recurrence;,Ct(-)and sCt(-)-10-year survival rates(SR)of 100%;yearly Ct measurements;,Ct doubling times(DT)1 yr(2yr)-5-and 10-yr SR,of 98%and 95%;,CEA DT 1 yr-5-and 10-yr SR of 100%,；,Ct DT 1 yr(,6mon,)-5-and 10-yr SR,of 36%and 18%,（,25%and 8%,）,;,CEA 3000 pg/mL,CEA 100 ng/L-distant spread.,SR for patients with distant metastases MTC is 51%at 1 yr,26%at 5 yr,and 10%at 10 yr,respectively.,Predictors of MTC progress,including recurrence and survival,in limited patients with rapidly progressive disease minimal benefit,approximately 50%-80%,postoperation,Preoperative:,Prevention-PD/PGD,Prevention-PD/PGD,ATA-2015 Guidelines recommended,Reduced Ct levels in many patients;,Surgical Management of MTC,Surgical Management of MTC,The,minimum extent,of surgery is a total thyroidectomy(TT)with bilateral central neck dissection(Bi,),(,TT+Bi,LND,);,TT with ipsilateral lateral compartment neck dissection;,(Unilateral lateral,LN,+,MTC size 1 cm,),(TT+Bi+UniLND),TT with bilateral lateral compartment neck dissection.,(Bilateral tumors or extensive LN+on the contralateral side),(TT+Bi+BiLND),Surgical Management of MTC Th,甲状腺髓样癌的分子分型及治疗优质课件,Surgical Management of MTC,*,Current recommendations for the timing of,prophylactic thyroidectomy,depends on the risk level of the,RET,mutation in,hereditary MTC(MEN 2),.,Surgical Management of MTC,ATA-2015 Guidelines recommended,ATA-2015 Guidelines recommende,甲状腺髓样癌的分子分型及治疗优质课件,Surgical Management of MTC,ATA-D(HST)-,MEN 2B,1yr,TT+Bi LND,;,ATA-AC(MODH)-,MEN 2A,basal Ct 40 pg/mL,TT,without Bi LND is adequate.,(Ct,60 ng/L,Elisei R,et al,;Ct,70 ng/L,Qi XP,et al),Surgical Management of MTC AT,Female,5.5yr;p.C634Y;bilateral MTC;DFS 6yr,Female,5.5yr;p.C634Y;bilate,Residual and Recurrent Disease,Residual and Recurrent:,approximately 50%-80%,postoperation,Ct 150 pg/ml,higher probability of distant metastatic,disease;,US,CT/MRI;,Residual and Recurrent Disease,Residual and Recurrent Disease,Cytoreductive(,Salvage,)surgery,Reduced Ct levels in many patients;,Normalization of the Ct levels in up to about 1/3 of patients;,The risk of surgical complications,Residual and Recurrent Disease,Predictors of MTC progress,including recurrence and survival,ATA-2015,ETA-2013,NCCN-2017 Guidelines recommend,Two small-molecule TKIs,vandetanib(Apr 2011)and cabozantinib(Nov 2012),are currently available as approved agents for the treatment of advanced or progressive MTC and provide significant increases in progression-free survival(PFS).,other small-molecule kinase inhibitors sunitinib,sorafenib,and pazopanib,Diagnosis and Monitoring,The minimum extent of surgery is a total thyroidectomy(TT)with bilateral c
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