at 23 years of age , our patient presented with a palpable neck mass with no other underlying disease .
sonographic findings revealed an enlarged isoechoic mass ( 42.52.5 cm ) with peripheral rim - like calcification in the right lobe of the thyroid .
a preoperative diagnosis of papillary thyroid carcinoma was determined and a bilateral total thyroidectomy with ccnd and right internal jugular neck dissection was performed .
the pathologic diagnosis determined that the mass was a diffuse sclerosing variant of papillary thyroid carcinoma confined to the right thyroid parenchyma ( fig .
the tumor metastasized to several lymph nodes on the right side of the neck and the following regional lymph nodes ( 8/30 ) : level ii ( 2/6 ) , level iii ( 2/13 ) , level iv ( 3/10 ) , and perithyroidal ( 1/1 ) .
approximately 30 mci of radioactive iodine ( i ) was used for postoperative adjuvant treatment .
excision of the left surgical site with left modified radical neck dissection and right level ii and iii selective node dissection were performed .
the tumor had again metastasized to several lymph nodes on the left side of the neck and the following regional lymph nodes ( 8/33 ) : right level ii ( 0/3 ) ; left level ii ( 1/9 ) , level iii ( 1/4 ) , and level iv ( 4/15 ) , and perithyroidal ( 2/2 ) .
postoperatively , 200 mci of radioactive iodine ( i ) was administered and a daily dose of 200 g of levothyroxine was prescribed for adjuvant treatment .
even though the patient continued with treatment , the tumor recurred at the left surgical site and the tumor size increased . at 31 years of age
, the patient identified another newly developed , palpable small mass at the right postauricular area , which grew rapidly within a month .
excision of the trachea with right modified radical neck node dissection and left level vi selective neck dissection was performed .
histologic diagnosis of the pretracheal lesion determined that the lesion was an anaplastic thyroid carcinoma with a focal papillary carcinoma component , and the tumor metastasized to the following bilateral lymph nodes ( 8/18 ) : right level ii ( 5/14 ) and level v ( 0/1 ) and left level vi ( 3/3 ) .
after surgery , the patient experienced dysphagia and dyspnea , and despite intensive care for respiratory failure , he died 4 months later .
the right thyroid gland contained a 42.5-cm ill - defined , yellow - tan mass .
histologically , the tumor showed typical papillary thyroid carcinoma features with lymphocytic thyroiditis , squamous morules , and abundant psammoma bodies in the outside of the tumor .
. the histologic findings of the recurred tumor showed a pattern similar to the previous primary thyroid carcinoma .
our review of this tumor histology revealed a focal ( < 5% ) poorly differentiated carcinoma component in the first recurrent papillary thyroid carcinoma of the left surgical site ( fig .
we defined a poorly differentiated carcinoma component as a tumor with 1 ) a focal solid pattern of growth , 2 ) absence of conventional nuclear features of papillary carcinoma , and 3 ) presence of convoluted nuclei.3 the anaplastic carcinoma of the second recurrent tumor revealed typical histologic findings : large pleomorphic , epithelioid , spindle , and multinucleated giant tumor cells , abundant eosinophilic cytoplasm , pleomorphic nuclei , more than two prominent nucleoli , frequent mitosis , and focal tumor necrosis ( fig .
immunohistochemical staining for thyroglobulin , galectin-3 , thyroid transcription factor 1 ( ttf-1 ) , p53 , and ki-67 was performed .
thyroglobulin showed diffuse , granular , cytoplasmic staining in the tumor cells of the initially diagnosed and recurred papillary thyroid carcinoma .
< 1% of the initially diagnosed tumor cells and recurred papillary thyroid carcinoma . in the poorly differentiated tumor carcinoma component of
the first recurrent tumor , thyroglobulin , ttf-1 , and galectin-3 expression was lower than in the other part of the first recurrent tumor , but p53 and ki-67 expression was the same .
thyroglobulin , ttf-1 , and galectin-3 expression were decreased in the anaplastic carcinoma of the second recurrent tumor . however , nuclear p53 and ki-67 expression levels were 70% and 60% to 70% , respectively , of the anaplastic carcinoma component .
the braf gene mutation analysis of each tumor tissue performed by a pyrosequencing method revealed braf gene mutations in all tissues ( fig .
we defined the mutant allele peak of 5% to 95% as the optimal cutoff value.4 the braf v600e ( c.1799t > a ) and a low level of the braf v600v ( c.1800g > a ) mutation were found in the initially diagnosed papillary thyroid carcinoma and poorly differentiated carcinoma component of the recurred papillary thyroid carcinoma , but only the prominent braf v600v ( c.1800g > a ) mutation was found in the anaplastic carcinoma component .
at 23 years of age , our patient presented with a palpable neck mass with no other underlying disease .
sonographic findings revealed an enlarged isoechoic mass ( 42.52.5 cm ) with peripheral rim - like calcification in the right lobe of the thyroid .
a preoperative diagnosis of papillary thyroid carcinoma was determined and a bilateral total thyroidectomy with ccnd and right internal jugular neck dissection was performed .
the pathologic diagnosis determined that the mass was a diffuse sclerosing variant of papillary thyroid carcinoma confined to the right thyroid parenchyma ( fig .
the tumor metastasized to several lymph nodes on the right side of the neck and the following regional lymph nodes ( 8/30 ) : level ii ( 2/6 ) , level iii ( 2/13 ) , level iv ( 3/10 ) , and perithyroidal ( 1/1 ) .
approximately 30 mci of radioactive iodine ( i ) was used for postoperative adjuvant treatment .
excision of the left surgical site with left modified radical neck dissection and right level ii and iii selective node dissection were performed .
the tumor had again metastasized to several lymph nodes on the left side of the neck and the following regional lymph nodes ( 8/33 ) : right level ii ( 0/3 ) ; left level ii ( 1/9 ) , level iii ( 1/4 ) , and level iv ( 4/15 ) , and perithyroidal ( 2/2 ) .
postoperatively , 200 mci of radioactive iodine ( i ) was administered and a daily dose of 200 g of levothyroxine was prescribed for adjuvant treatment .
even though the patient continued with treatment , the tumor recurred at the left surgical site and the tumor size increased . at 31 years of age
, the patient identified another newly developed , palpable small mass at the right postauricular area , which grew rapidly within a month .
excision of the trachea with right modified radical neck node dissection and left level vi selective neck dissection was performed .
histologic diagnosis of the pretracheal lesion determined that the lesion was an anaplastic thyroid carcinoma with a focal papillary carcinoma component , and the tumor metastasized to the following bilateral lymph nodes ( 8/18 ) : right level ii ( 5/14 ) and level v ( 0/1 ) and left level vi ( 3/3 ) .
after surgery , the patient experienced dysphagia and dyspnea , and despite intensive care for respiratory failure , he died 4 months later .
the first surgical specimen was comprised of bilateral thyroid glands and lymph nodes . the right thyroid gland contained a 42.5-cm ill - defined , yellow - tan mass .
histologically , the tumor showed typical papillary thyroid carcinoma features with lymphocytic thyroiditis , squamous morules , and abundant psammoma bodies in the outside of the tumor .
the histologic findings of the recurred tumor showed a pattern similar to the previous primary thyroid carcinoma .
our review of this tumor histology revealed a focal ( < 5% ) poorly differentiated carcinoma component in the first recurrent papillary thyroid carcinoma of the left surgical site ( fig .
we defined a poorly differentiated carcinoma component as a tumor with 1 ) a focal solid pattern of growth , 2 ) absence of conventional nuclear features of papillary carcinoma , and 3 ) presence of convoluted nuclei.3 the anaplastic carcinoma of the second recurrent tumor revealed typical histologic findings : large pleomorphic , epithelioid , spindle , and multinucleated giant tumor cells , abundant eosinophilic cytoplasm , pleomorphic nuclei , more than two prominent nucleoli , frequent mitosis , and focal tumor necrosis ( fig .
immunohistochemical staining for thyroglobulin , galectin-3 , thyroid transcription factor 1 ( ttf-1 ) , p53 , and ki-67 was performed .
thyroglobulin showed diffuse , granular , cytoplasmic staining in the tumor cells of the initially diagnosed and recurred papillary thyroid carcinoma .
< 1% of the initially diagnosed tumor cells and recurred papillary thyroid carcinoma . in the poorly differentiated tumor carcinoma component of
the first recurrent tumor , thyroglobulin , ttf-1 , and galectin-3 expression was lower than in the other part of the first recurrent tumor , but p53 and ki-67 expression was the same .
thyroglobulin , ttf-1 , and galectin-3 expression were decreased in the anaplastic carcinoma of the second recurrent tumor .
however , nuclear p53 and ki-67 expression levels were 70% and 60% to 70% , respectively , of the anaplastic carcinoma component .
the braf gene mutation analysis of each tumor tissue performed by a pyrosequencing method revealed braf gene mutations in all tissues ( fig .
we defined the mutant allele peak of 5% to 95% as the optimal cutoff value.4 the braf v600e ( c.1799t > a ) and a low level of the braf v600v ( c.1800g > a ) mutation were found in the initially diagnosed papillary thyroid carcinoma and poorly differentiated carcinoma component of the recurred papillary thyroid carcinoma , but only the prominent braf v600v ( c.1800g > a ) mutation was found in the anaplastic carcinoma component .
we report a rare case of anaplastic carcinoma in a young patient , analyze the follow - up pathology data related to anaplastic transformation , and discuss the mechanism of anaplastic transformation .
the mean age of diagnosis is 55 to 65 years , with the peak incidence in the sixth to seventh decade of life .
the age of most reported cases was more than 30 years , and only a few reported cases were younger than 30 years.1 most reported cases of anaplastic transformation by dedifferentiation from a wdtc were in the elderly.5 therefore , thorough clinical history of previous thyroid diseases should be determined and the possibility of an anaplastic transformation should be considered when a diagnosis of anaplastic carcinoma is confirmed in an elderly patient .
the mortality rate is > 90% , with a mean survival of 6 months after diagnosis.6 almost all patients complain of a rapidly growing neck mass and symptoms associated with a large mass such as hoarseness , dysphagia , vocal cord paralysis , cervical pain , and dyspnea are the most frequent and important .
the overall 5-year survival ranges from 0% to 14% and the median survival is 4 to 12 months .
the enlarged tumor mass often causes death by obstruction or invasion of a vital structure , similar to the occurrence in our patient.6 anaplastic thyroid carcinoma may arise de novo or , more commonly , through anaplastic transformation ( or dedifferentiation ) of a preexisting papillary or follicular thyroid carcinoma .
the mechanism of this transformation , however , is not well understood.5 in this study , we performed immunohistochemical staining and braf mutation analysis to determine the mechanism of anaplastic transformation in the wdtc , and we found that the well - expressed markers in the wdtc showed loss of expression in the anaplastic carcinoma .
we also confirmed that the markers known to participate in transformation including p53 , ki-67 , and others were not initially expressed but were expressed at the full anaplastic transformation .
todd and wenig7 reported that thyroglobulin and ttf-1 immunoreactivity was completely reduced in recurrent or metastatic thyroid carcinoma and anaplastic thyroid carcinoma , which showed less differentiated histologic features , and these results were identical to the immunostaining results of our case .
ozaki et al.8 reported that high ki-67 expression was found in more malignant tumors , which was also similar to the findings in our case .
many studies have examined the role of the p53 gene in the thyroid as well as other organs , and most of these studies have shown that a loss in p53 gene expression is related to malignant transformation .
furthermore , studies of the thyroid have reported to be related to anaplastic transformation in wdtc.9 the p53-positive staining that appears in the full anaplastic transformation of our case is similar to other reports .
however , additional research is necessary to determine the stage of anaplastic transformation in which the change in p53 and ki-67 expression appears .
mutation of the braf gene represents the most common genetic alteration in papillary thyroid cancer and is found in 45% of these tumors in western countries and up to 90% of these tumors in korea.10 the vast majority of braf alterations in papillary thyroid cancer are braf v600e mutations,10 but braf k601e mutations have been reported in both follicular and solid variants.11 in multifocal thyroid cancer , different tumor nodules have distinct genetic alterations , such as different types of ret / ptc rearrangement or variation in the presence of the braf mutation.12 recently , in korea , kim et al.11 reported braf mutations that appeared in different forms according to the histologic subtype in a multifocal papillary carcinoma . because the conventional papillary carcinoma component in their patient revealed the braf v600e mutation , but the follicular variant component revealed the braf k601e mutation , they determined that the multifocal papillary carcinoma occurred de novo rather than as a result of intrathyroid metastasis , although no clear classification can be determined yet . in our case
, the braf v600e and braf v600v mutations were found in the initially diagnosed papillary thyroid carcinoma and the poorly differentiated carcinoma component of the recurred papillary thyroid carcinoma , but only the braf v600v mutation was found in the anaplastic carcinoma component .
however , there has not been any report of a braf v600v ( c.1800g > a ) mutation in thyroid carcinoma .
we found two reports of a braf v600v mutation in malignant melanoma13 and colorectal cancer,14 but the reports did not attempt to explain the relevance of the braf v600v mutation expression .
we found that the braf mutation type changed during the tumor relapse process , but additional research is necessary to determine whether the alteration of the braf mutation is just an incidental finding or a phenotypic change relevant to the anaplastic transformation . in conclusion
, we evaluated the rare occurrence of anaplastic carcinoma in young patients and did not find p53 or ki-67 expression or decreased thyroglobulin , ttf-1 , and galectin-3 expression in the poorly differentiated tumor cells .
therefore , we considered the possibility that overexpression of p53 and ki-67 contributed to the anaplastic transformation .
additional studies are necessary to ascertain the intermediate steps of anaplastic transformation . if the markers that are well manifested in wdtc are lost even though p53 and ki-67 are not expressed , then we can consider those changes in expression as precursors to anaplastic transformation .
therefore , future studies with thorough and careful histologic examination may allow us to predict the anaplastic transformation of the tumor .
 this study reports a case of anaplastic transformation from a well - differentiated thyroid carcinoma in a young patient . 
 the first recurrent tissue contained poorly differentiated foci that revealed lower thyroglobulin , thyroid transcription factor 1 ( ttf-1 ) , and galectin-3 expression than the well - differentiated area . 
 however there was no increased p53 or ki-67 expression in the poorly differentiated foci , nor in the well - differentiated area . 
 the tissue subsequently relapsed and revealed only anaplastic features , complete loss of thyroglobulin , ttf-1 , and galectin-3 expression and revealed an increase in p53 and ki-67 expression . 
 the braf v600e and braf v600v mutation were found in the initially diagnosed papillary thyroid carcinoma and the poorly differentiated foci of the recurring papillary thyroid carcinoma ; however , only the braf v600v mutation was found in the anaplastic carcinoma . 
 these results suggest that overexpression of p53 and ki-67 contributed to the anaplastic transformation . 
 we also found that the braf type changed during the tumor relapse . 
CASE REPORT
Clinical manifestation
Histopathologic findings
Immunohistochemical staining and 
DISCUSSION