testicular germ cell tumors comprise the most common group of solid malignancies in male population of 15 to 35 years old . these tumors account for approximately 95% of all testes cancers .
the incidence of testicular tumors varies in different countries and ethnic groups with the highest reported incidence in scandinavia region ( about 9 in 100,000 males ) .
few reports are present about the incidence and epidemiologic features of testis cancer in the male population of asian and latin american countries , which indicate that testicular germ cell tumors are less common in these regions than most western countries .
a recent study has shown that the incidence of testis cancer is 1.3 in 100,000 male population in iran .
these include positive family or personal history of testis tumor , cryptorchidism and intratubular germ cell neoplasia ( itgcn ) .
earlier studies have claimed that concomitant itgcn is seen in 80%90% of testes affected by germ cell tumors using immunohistochemistry ( ihc ) .
thus , itgcn is also considered as a premalignant lesion and prompt treatment is essential if it is incidentally discovered in testis biopsy .
in addition , in cases of testis sparing surgery , itgcn may be observed in the remnant tissue . in these situations ,
, we aimed to assess the prevalence of itgcn in the patients who have underwent radical orchiectomy due to testicular tumor , as well as its correlations with pathologic features of concomitant testis cancer and patients ' epidemiologic characteristics . to our knowledge , this is the first report on itgcn in association with testicular germ cell tumor in our region , also the first study which is looking for its prognostic role .
this is a descriptive  analytical and cross sectional study which was performed in our center .
the study population was the patients who underwent radical orchiectomy due to testis tumor from 2003 to 2015 .
serum tumor markers had been measured before the surgery and consisted of alpha - fetoprotein ( -fp ) , and beta - human chorionic gonadotropin ( -hcg ) .
cd-117 ( c - kit ) and placental - like alkaline phosphatase were two immuno - reactive agents that were used to identify itgcn via ihc .
data about patients ' age at the time of surgery , predisposing factors ( such as family history , cryptorchidism ) , testis atrophy , and serum tumor marker before surgery were recorded and gathered for further analysis .
pathologic reports were categorized as pure seminoma , mixed germ cell tumors ( mgcts ; defined as containing at least two pathological subtypes of germ cell tumors ) , pure mature teratoma , embryonal carcinoma , yolk sac tumor , lymphoma and benign lesions ( leydig or sertoli cell tumor ) .
data was gathered and analyzed using ibm spss ver . 18.0 ( ibm co. , armonk , ny , usa ) .
independent sample t - test was obtained to assess any relationship between itgcn and quantitative factors . for qualitative factors we used chi - square test and fisher exact test as needed . a p - value less than 0.05 was considered as significant .
the institutional review board of iranian urology and nephrology research center approved the study design .
mean age of the patients was 34.5 years old ( range , 182 years ) .
eighty - four point four percent ( 84.4% ) of patients ( n=151 ) were in the range of 20 to 50 years and 2.2% ( n=4 ) were under 12 months old .
history of testis atrophy ( confirmed by ultrasound study ) was observed in 8 cases ( 4.5% ) .
right and left testicles were involved by tumor in 96 and 83 cases , respectively .
calcification ( diagnosed by ultrasound study ) was observed in 87 patients ( 48.6% ) .
pathologic reports showed that pure classic seminoma and mgcts were the most common histologic types .
considering the pathologic components of all cases ( including those with mgct ) , we found that seminoma was also the most prevalent component .
pathologic features of the patients are demonstrated in table 1 . while primary study of the specimens by light microscopy leaded to diagnosis of itgcn in only 21 patients ( 11.7% ) , further analysis by ihc staining increased this figure to 85 patients ( 47.5% ) .
so , it seems that light microscopy missed about three - fourths ( 75% ) of patients with itgcn .
with exclusion of lymphoma and benign lesions , the prevalence of concomitant itgcn was determined as 49.4% .
there was not a statistically significant difference in mean age , histologic type , histologic components , cryptorchidism , and lymphovascular invasion between the 2 groups ( p=0.151 , p=0.11 , p=0.233 , p=0.413 , and p=0.14 , respectively ) . however , calcif ication of testis parenchyma , as identif ied by ultrasonography , was lower in patients who had concurrent itgcn ( 35% vs. 59% , p=0.001 ) .
the prevalence of itgcn was significantly lower in the patients with stage t1 than those with higher stages ( t2 ) . among the 150 patients with stage t1 , 62 ( 41% ) had itgcn , while 18 out of 29 patients ( 62% ) with stage t2 and t3 had itgcn ( p=0.03 ) .
since patients with pure seminoma do not present with elevated serum tumor markers , any relationship between itgcn and tumor markers was assessed in 98 patients with nonseminoma histology .
fifty - two patients with nonseminoma pathology had concomitant itgcn , of which 44 patients ( 84.6% ) had elevated serum -fp before the surgery , while in the other group , only 24 patients ( 52% ) had elevated serum -fp level . thus , elevated serum -fp level is much common in patients with itgcn ( p<0.001 ) .
prevalence of elevated serum -hcg was 58% and 64% in patients with and without itgcn , respectively ; which did not indicate a significant difference ( p=0.6 ) .
there are several risk factors that contribute to testis cancer , including family or personal history , cryptorchidism , and itgcn .
skakkebaek   have noticed that almost all types of testicular germ cell tumors ( except germ cell tumors in children and spermatocytic seminomas ) originate from itgcn .
the microscopic features of itgcn resemble that of seminoma and ihc is needed for exact diagnosis .
the results of our study shows that light microscopy might underestimate itgcn in patients with testicular germ cell tumors .
it is higher in western countries and scandinavia region , and lower in african americans and asian countries .
the incidence of testicular cancer is about 5.3 cases per 100,000 in the united states , but the highest rate of testis cancer has been reported from scandinavia region as about 9 in 100,000 .
several studies have shown that the incidence of testicular germ cell tumors is increasing . a recent study by basiri et al .  
has shown that the incidence of testis cancer is lower in iran than western countries . in 2009 ,
since itgcn is a major risk factor and precursor to most testicular cancers , we decided to evaluate the prevalence of itgcn and its correlations with other histologic factors in an iranian population who had testis tumor .
earlier studies by skakkebaek   and montironi   indicated that 80%90% of patients who undergo radical orchiectomy have simultaneous itgcn in the adjacent tissue .
another study by klein et al .   have shown that 82% of seminomas and 75% of nonseminomas are associated with itgcn .
although mean age of patients was lower in itgcn group ( 32.6 years old ) , it was not significantly different from the overall group .
. the reason may be that both itgcn and seminomas both originate from primordial germ cells ( gonocytes ) .
current data in the literature supports the idea that microlithiasis is not an independent predisposing factor for testicular cancer , although it may accompany other possible premalignant features . a study by meissner et al .  
concluded that microlithiasis may be accompanied by itgcn , and thus , healthy patients with several risk factors who present with microlithiasis need to undergo routine testicular biopsy to rule out itgcn or testis tumor .
this study and other previous surveys , evaluated the significance of microlithiasis and its correlation with itgcn in healthy patients who did not have testis cancer at the time .
however , the results of our study indicate that in patients who suffer from testis cancer , microlithiasis does not accompany itgcn . in support of this idea
, a recent literature review revealed that there are 5 conditions in relation to microlithiasis and testicular cancer : down syndrome , mccune - albright syndrome , cryptorchidism , infertility and familial disposition of testicular cancer .
itgcn was much common in patients with higher tumor stage ( i.e. , t2 , t3 ) .
this may indicate that itgcn is related with more aggressive tumors , which is a new finding .
in addition , in patients with nonseminoma germ cell tumors , elevated serum -fp level was closely related to itgcn .
more than 84% of patients with itgcn had high serum levels of -fp before orchiectomy .
this study was the first to evaluate the associations of itgcn with epidemiologic and pathologic factors of testis cancer .
high volume , multi center studies with larger sample size are needed to get more constant and reliable information about itgcn .
the prevalence of concomitant itgcn in the iranian population who undergo radical orchiectomy is lower than most western countries .
itgcn is more common in higher tumor stages and is accompanied with elevated serum -fp levels before the surgery . since the prevalence of itgcn is higher in the regions with high incidence of testis cancer and in high stages of germ cell tumors , presence of itgcn in adjacent tissue may suggest a negative cancer behavior .
 purposeto assess the prevalence of intratubular germ cell neoplasia ( itgcn ) in patients with concurrent testis tumor and its correlation with histologic features and serum tumor markers.materials and methodsfrom 2003 to 2015 , 179 patients underwent radical orchiectomy due to testicular mass . 
 tissue specimens were evaluated by an expert uro - pathologist using immunohistochemistry ( ihc ) staining , in addition to light microscopy , to identify presence of itgcn . 
 patients ' demographic characteristics , histologic subtypes , pathologic stage of tumor and serum tumor markers were gathered and analyzed.resultseighty-five out of 179 patients ( 47.5% ) had concomitant itgcn according to ihc staining . there was not statistically significant difference in histologic type , histologic components , cryptorchidism , and lymphovascular invasion between the 2 groups ( p=0.151 , p=0.11 , p=0.233 , p=0.413 , and p=0.14 , respectively ) . 
 the prevalence of itgcn was significantly higher in patients with stage t2 and t3 of tumor than those with stage t1 . 
 elevated serum alpha feto protein level is much common in patients with itgcn ( p<0.001).conclusionsthe prevalence of concurrent itgcn in our region is lower than previous data from western countries . 
 itgcn is more common in higher tumor stages and is accompanied with elevated serum alpha feto protein levels before surgery . 
 presence of itgcn in adjacent tissue may suggest a negative cancer behavior . 