the diffuse sclerosing variant of papillary thyroid carcinoma ( dsv - ptc ) , first described by vickery et al . in 1985 , is a histological variant of ptc .
it is characterized by diffuse involvement of one or both thyroid lobules with prominent squamous metaplasia , numerous psammoma bodies , and dense sclerosis in intratumoral areas together with a background of lymphocytic infiltration .
extensive lymphovascular invasion indicates frequent metastasis . because of the early spread of dsv - ptc
dsv - ptc is a major subtype of ptc in young patients , with a higher female predominance ( male : female ratio , 1:7.5 ) .
however , the frequency of dsv - ptc is 0.35.5% among ptc [ 4 , 5 , 6 ] .
we herein report a 15-year - old female patient with estrogen receptor ( er)- and progesterone receptor ( pgr)-positive dsv - ptc with paratracheal lymph node metastasis in whom recurrence in the right cervical lymph nodes was diagnosed 7 years after the first operation .
a 15-year - old female patient with no medical or family history of thyroid tumors consulted an otolaryngological clinic for evaluation of an anterior neck swelling .
a thyroid neoplasm was suspected , and she was referred to kansai medical university takii hospital .
diffuse enlargement of the right thyroid gland with many small calcifications was detected by ultrasonography ( fig .
however , lymph node swelling of the right neck was detected 7 years after the operation and reexcision was performed .
during the treatment course , her serum t3 , t4 , and tsh levels were within the reference ranges and autoantibodies were not detected .
on macroscopic examination , the tumor , which had been located in the right lobe , was 22 mm along its major axis without formation of a dominant mass .
the tumor showed a papillary growth pattern with distinct fibrosis , severe lymphocyte infiltration ( fig .
3c ) ; all characteristics of dsv - ptc were frequently seen . in high - power fields ,
many of the tumor cell nuclei exhibited a ground - glass appearance , frequent grooves , and pseudoinclusions ( fig .
tumor invasion extended outside the capsule and reached the mesenchymal tissue , and lymph node metastasis was notable .
4a , b ) , and the cells were positive for epithelial membrane antigen , cytokeratin 7 , thyroglobulin , e - cadherin , and -catenin .
reduced membranous staining and increased cytoplasmic staining of e - cadherin were notable ( fig .
however , the tumor cells were negative for cytokeratin 20 , bcl-2 , c - kit , wilms tumor antigen 1 , cd56 , chromogranin a , synaptophysin , and androgen receptor . the ki-67 and p53 indices were both <
a 15-year - old female patient with no medical or family history of thyroid tumors consulted an otolaryngological clinic for evaluation of an anterior neck swelling .
a thyroid neoplasm was suspected , and she was referred to kansai medical university takii hospital .
diffuse enlargement of the right thyroid gland with many small calcifications was detected by ultrasonography ( fig .
however , lymph node swelling of the right neck was detected 7 years after the operation and reexcision was performed .
during the treatment course , her serum t3 , t4 , and tsh levels were within the reference ranges and autoantibodies were not detected .
on macroscopic examination , the tumor , which had been located in the right lobe , was 22 mm along its major axis without formation of a dominant mass .
the tumor showed a papillary growth pattern with distinct fibrosis , severe lymphocyte infiltration ( fig .
3c ) ; all characteristics of dsv - ptc were frequently seen . in high - power fields ,
many of the tumor cell nuclei exhibited a ground - glass appearance , frequent grooves , and pseudoinclusions ( fig .
tumor invasion extended outside the capsule and reached the mesenchymal tissue , and lymph node metastasis was notable .
4a , b ) , and the cells were positive for epithelial membrane antigen , cytokeratin 7 , thyroglobulin , e - cadherin , and -catenin .
reduced membranous staining and increased cytoplasmic staining of e - cadherin were notable ( fig .
however , the tumor cells were negative for cytokeratin 20 , bcl-2 , c - kit , wilms tumor antigen 1 , cd56 , chromogranin a , synaptophysin , and androgen receptor .
dsv - ptc is a subtype of ptc and is characterized by diffuse enlargement of the thyroid gland and numerous scattered microcalcifications ( a so - called  snowstorm appearance ) on ultrasonography .
histologically , dsv - ptc is characterized by papillary growth of atypical cells , similar to conventional ptc   with prominent fibrosis , numerous psammoma bodies , frequent squamous metaplasia , and dense infiltration of lymphocytes [ 2 , 3 , 8 , 9 ] .
in addition , dsv - ptc shows a strong tendency for invasion and metastasis , and metastatic lesions have been frequently reported in lymph nodes , lungs , bones , and brain [ 10 , 11 ] .
although lymph node metastasis was seen , multifocal tumor emboli in lymphatic channels at the primary site were unremarkable .
immunohistochemical studies have been performed on dsv - ptc [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ] .
immunohistochemically , p63 expression in foci of squamous metaplasia is the hallmark for distinguishing between dsv - ptc and conventional ptc [ 3 , 12 ] .
ptc cells are positive for thyroid transcription factor-1 , thyroglobulin , and -catenin [ 12 , 18 ] .
in addition , positive localization of e - cadherin is decreased in the cell membrane and relocation to the cytoplasm occurs .
therefore , it is easy to conclude that the decrement in the membrane level of e - cadherin may promote increased potency of invasion and/or metastasis of dsv - ptc . because dsv - ptc is characterized by aggressive growth , it has been thought to be associated with a poor prognosis .
in contrast , although the recurrence - free survival rate of dsv - ptc is lower than that of non - dsv - ptc , there is no difference in the overall survival rate [ 3 , 19 , 20 , 21 ] .
the reason for the dissociation between the clinical course and survival should be further investigated .
dense accumulations of s-100 protein - positive dendritic / langerhans cells , usually in areas of lymphocytic infiltration   and between tumor cells , correlate with a benign clinical course .
thyroid cancer nuclei are sex hormone receptor positive [ 14 , 15 , 16 ] , and er and pgr expression is demonstrated mainly in differentiated thyroid cancer nuclei
. however , overexpression of er and pgr in thyroid cancer suggests their role in carcinogenesis . in small t1-differentiated thyroid cancer ,
er positivity and androgen receptor expression are associated with a more aggressive phenotype . because the present case was er and pgr positive and androgen receptor negative with accumulation of s-100 protein - positive dendritic / langerhans cells , a prognostic prediction based on these markers was complex .
more reliable markers , which are necessary in order to determine prognosis , must be investigated . in the present case , although the macis ( metastases , age , completeness of resection , invasion , size ) score   was 7.85 ( table 2 ) , the 20-year survival rate after surgery was estimated as 56% .
strict follow - up is desired in such cases . in the present tumor , strong infiltration of lymphocytes with a germinal center  
although approximately 30% of patients with dsv - ptc have positive antithyroid antibodies as part of hashimoto 's thyroiditis , autoimmune antibodies were not detected in the present case .
interestingly , hrthle cells are reportedly absent in dsv - ptc , including in the present case [ 2 , 12 ] .
taken together , diagnosis of dsv - ptc seems to be possible using ultrasonography and histological investigation . in conclusion
, we herein reported a case of er- and pgr - positive dsv - ptc .
although survival remains unpredictable , further studies are necessary to identify good markers with which to predict the prognosis of dsv - ptc .
this paper is the first to report er- and pgr - positive dsv - ptc .
the authors declare no potential conflicts of interests with respect to the authorship and/or publication of this article .
 the diffuse sclerosing variant of papillary thyroid carcinoma ( dsv - ptc ) is a relatively rare tumor . 
 we herein report the case of young woman with dsv - ptc who developed cervical lymph node recurrence 7 years after the initial surgery . a 15-year - old female patient with no medical or family history of thyroid tumors developed a thyroid neoplasm in the right lobe . 
 right thyroidectomy and regional lymphadenectomy were performed , and the tumor was diagnosed as dsv - ptc . she was followed up as an outpatient . 
 seven years after the surgery , cervical lymph node recurrence developed . 
 on microscopic examination , the thyroid tumor showed a papillary growth pattern with numerous psammoma bodies and distinct fibrosis . 
 immunohistochemically , the tumor cells were estrogen receptor and progesterone receptor positive with reduced membranous expression of e - cadherin and were intermingled with s-100-positive dendritic / langerhans cells . 
 dsv - ptc is characterized by a strong tendency for invasion and metastasis . 
 thus , accurate diagnosis is clinically important , and a morphological and immunohistochemical understanding of dsv - ptc is necessary . 
Introduction
Case Report
Clinical Findings
Pathological Findings
Discussion
Disclosure Statement
Funding