its incidence worldwide is 10.1 in every 100,000 men and 2.5 in every 100,000 women .
the highest incidence rate of bladder cancer in europe is seen in the western and southern regions , whereas eastern europe has the lowest incidence rate .
the worldwide mortality rate is 4 in every 100,000 men and 1.1 in every 100,000 women .
the mortality rate of bladder cancer in europe in the past decade was 16% in men and 12% in women .
seventy percent of cases of newly diagnosed disease are superficial disease ; roughly 30% of newly diagnosed cases are muscle - invasive metastatic diseases . although local recurrence is significant despite treatment , the natural progression of non - muscle - invasive bladder cancer tends to remain superficial .
about 5% to 20% of superficial tumors will develop into muscle - invasive disease despite treatment .
the most common areas of distant metastases of urothelial carcinomas are typically the liver , lung , mediastinum , bone , and adrenal gland , respectively .
we present a case of non - muscle - invasive bladder cancer that metastasized into the bone , mediastinum , iliac lymph node , and adrenal and thyroid glands .
an 83-year - old male patient visited the urology department with complaints of macroscopic hematuria at intervals over 9 months .
transurethral resection of the bladder ( tur - b ) was performed on the patient when a 17-mm14-mm mass was found in the ultrasound examination .
repeat tur was applied to the patient 4 weeks later and high - grade urothelial carcinoma with lamina propria invasion was found , whereas muscularis propria invasion did not exist .
positron emission tomography ( pet ) was performed during the second month because the patient had chest pain in the postoperative period , and multiple metastatic bone lesions , metastatic lymphadenopathies on the mediastinum and right external iliac area , a hypermetabolic lesion on the left thyroid lobe , and a hypermetabolic lesion on the left adrenal gland were found .
incisional biopsy performed on the fifth rib of the patient was evaluated as urothelial carcinoma metastasis and radiotherapy was applied to the patient for these lesions ( fig .
a fixed , 3-cm mass was palpated on the left lobe of the thyroid . then
, in the neck computed tomography ( ct ) with contrast , a 40 mm34 mm nodular mass was found on the left lobe of the thyroid gland , which caused left - sided destruction of the thyroid cartilage .
malignant tumor cells were observed in the fine - needle aspiration sample taken from the hypermetabolic lesion on the left lobe of the thyroid .
owing to the patient 's clinical history , primary thyroid carcinomas were considered in the differential diagnosis , because metastatic carcinoma and anaplastic and medullar carcinomas are of first priority .
the immunohistochemical panel included thyroid transcription factor-1 ( ttf-1 ) and thyroglobulin in terms of thyroid tumors ; calcitonin , carcinoembryonic antigen ( cea ) , chromogranin a , and synaptophysin in terms of medullar carcinoma ; and cytokeratins ( ck ) 7 and ck 20 antibodies in terms of urothelial carcinoma .
no reaction was observed with neuroendocrine markers ( synaptophysin and chromogranin ) , calcitonin , thyroglobulin , or ttf-1 in tumoral cells .
the tumor was evaluated as a urothelial carcinoma metastasis owing to the clinical history of the patient , the existence of other metastases , the morphological similarity of the tumor cells with the primary tumor , and ck 20 positivity in some cases immunohistochemically ( fig .
because the general condition of the patient worsened while planning chemotherapy , no systematic chemotherapy was applied .
the prognosis and survival of patients with bladder cancer are associated with stage and grade during diagnosis .
survival rates for 5 years were reported as 94% for grade 1 non - muscle - invasive disease , 40% for grade 3 non - muscle - invasive disease , 72% for stage t2 , and 33% for stage t4 muscle - invasive disease .
contrary to muscle - invasive disease , many superficial bladder cancers can be treated by regular monitoring cystoscopy , urinary cytology , and re - tur together or not with protective therapy , transurethral resection , and adjuvant intravesical treatment . despite these measures ,
about 5% to 20% of non - muscle - invasive tumors will progress to muscle - invasive disease .
high - grade non - muscle - invasive tumors are related to a high risk of muscular invasion and metastasis and end up with a worse prognosis .
also , it is known that metastasis can appear without muscular invasion ; these metastases are found in regional lymph nodes during cystectomy .
cases of distant metastasis of low - grade non - muscle - invasive urothelial carcinoma without regional lymph node metastasis have been reported .
errors in clinical staging of bladder tumors are well known . in some pathological staging cases
, it is estimated that low staging was done at a rate as high as 30% to 40% .
the european organisation for research and treatment of cancer ( eortc ) developed a scoring system and a risk table to estimate short- and long - term risks of recurrence and progression separately . in this scoring system ,
clinical and pathological parameters are tumor number , tumor size , previous recurrence rate , t phase , carcinoma in situ presence , and tumor grade . in our patients ,
possible mean progression rates according to the score are reported as 5% in the first year and 17% in the fifth year . in the eortc study ,
no results are reported for new concepts such as re - tur , early single - dose chemotherapy , and maintenance bacillus calmette guerin treatment , and this has been criticized by authors . in our patient ,
early single - dose chemotherapy and re - tur were applied and both pathology reports suggested a high - grade non - muscle - invasive bladder tumor . although the progression rate of our patient for 1 year was estimated as 5% according to the eortc study , progression developed in the patient before initiating induction treatment of intravesical ct and before symptoms associated with bone metastases developed .
there are publications in the current literature that report that low - grade non - muscle - invasive bladder tumors are detected clinically and the distant lung metastasis can appear without regional lymph node involvement .
rare metastases of urothelial carcinoma into the skin , uterus , and orbita and vaginal and omental involvements have also been reported .
.   showed a small cell carcinoma that metastasized into the thyroid gland , which is a minor variant of bladder urothelial carcinoma .
small - cell carcinoma is rarely originated from the bladder and comprises of 0.48% to 1% of all bladder tumors .
metastases in the thyroid gland are observed in many patients by physical examination or imaging methods during routine monitoring after primary tumor resection . in these patients
, fine - needle aspiration may be useful for evaluating possibilities and limiting unnecessary operation for diagnostic purposes .
the most significant conflict in cytologic comment is the differentiation between primary thyroid anaplastic carcinoma and high - grade metastatic malignity . in the fine - needle aspiration material of the patient ,
differential thyroid carcinomas and medullar carcinomas can be excluded morphologically and immunohistochemically . in the present case ,
no reaction was observed with neuroendocrine markers ( synaptophysin and chromogranin a ) , calcitonin , thyroglobulin , or ttf-1 in tumoral cells .
although a positive reaction immunohistochemically with thyroglobulin supports a primary thyroid malignancy , only 20% to 30% of anaplastic carcinomas display thyroglobulin positivity and negative results do not have meaning . because 20% to 30% of anaplastic carcinomas display thyroglobulin positivity and negative results do not have meaning
the patient 's clinical history is the most essential part in the differential diagnosis of these lesions , and it is emphasized that a thyroid nodule found in a patient with a known cancer should be accepted as metastasis unless proven otherwise . because our patient had a known urothelial carcinoma history , other metastases , a morphological similarity between the tumor cells and the primary tumor , and ck 20 positivity immunohistochemically in some cells , the tumor was evaluated as a urothelial carcinoma metastasis . in conclusion , non - muscle - invasive bladder tumors may present with multiple distant metastases even without muscle invasion .
this presented case showed that bladder tumors can metastasize into the thyroid gland in addition to known distant metastasis areas .
metastasis of a bladder tumor should also be kept in mind in the differential diagnosis in patients who have a bladder tumor history and are found to have a mass on the thyroid gland .
 bladder cancer is the most prevalent malignancy of the urinary tract . 
 about 90% of bladder cancers are urothelial carcinomas . 
 seventy percent of cases newly diagnosed are superficial diseases ; roughly 30% of newly diagnosed cases are muscle - invasive metastatic diseases . 
 bladder urothelial carcinoma primarily metastasizes into regional lymph nodes and then into liver , lung , mediastinum , bone , and adrenal gland . in our case , 
 non - muscle - invasive bladder cancer metastasized into the bone , mediastinum , iliac lymph node , and adrenal and thyroid glands . 
 this is the first reported case in the current literature in which urothelial carcinoma metastasized into the thyroid gland . 
INTRODUCTION
CASE REPORT
DISCUSSION