cryptorchidism ( undescended testis ) is the most common congenital malformation in newborn boys , occurring in approximately 3% of full - term infants . in most cases , the undescended testes seen after birth descend normally within a few months , and only 1% of patients with a persisting cryptorchid condition require medical or surgical treatment .
it is well known that undescended testes , if untreated , lead to an increased risk of testicular malignancy , usually seminomas that arise from mutant germ cells .
urry et al .   reported that azoospermia was evident in 13% of patients with unilateral cryptorchidism ; this rate increases to 89% in untreated bilateral cryptorchid patients .
intratubular germ cell neoplasia ( itgcn ) is the most common precursor of testicular malignancy .
dieckmann and skakkebaek   reported that approximately 50% of patients with itgcn will develop an invasive testicular germ cell tumor within five years , and pourkeramati et al .   found that 23.08% of infertile men with intra - abdominal testis had itgcn based on examinations of orchiectomy specimens
furthermore , the incidence of itgcn has markedly increased over the past decade , and hence , it is essential that it is promptly and accurately diagnosed in patients with cryptorchidism . in the present retrospective study , we aimed to determine the incidence of itcgn in postpubertal cryptorchidism , and the usefulness of immunohistochemical staining in its diagnosis .
in addition , we analyzed the degree of spermatogenesis to evaluate the fertility of these patients .
between january 2002 and august 2012 , we performed orchiectomy in 31 postpubertal patients ( aged 12 years or over ) with unilateral cryptorchidism after counseling them about the risk of malignancy , androgenic dysfunction , and male infertility .
cryptorchidism was defined as a condition where testis that was not descended into the scrotum .
this study was approved by the institutional review board of yonsei university wonju college of medicine ( ywmr-12 - 0 - 027 ) .
one pathologist ( m.e . ) reviewed all the slides to confirm the pathologic diagnosis .
the specimens were evaluated for itgcn using immunohistochemical staining with antibodies against placental - like alkaline phosphatase ( plap ) and oct 3/4 , as it is difficult to recognize itgcn based on hematoxylin - eosin ( h&e ) staining alone .
malignancy was defined cytologically as the presence of atypical germ cells that showed a significant increase in size , were clearly pleomorphic , had hyperchromatic nuclei , and were arranged in layers attached to the basal tubular membrane .
none of the cases involved infiltration of the interstitium or showed signs of inflammatory lymphocytic infiltration . to confirm the diagnosis of itgcn
, sections from the testis were stained with oct 3/4 and plap antibodies . in order to assess fertility ,
this involved assessing 100 tubules and recording their heterogeneity by grading them between one and ten using the most advanced germ cell contained in the tubule .
a key assumption is that the progressive degeneration of the tubule invariably features the loss of constituent cells in a defined order beginning with the most mature ( spermatozoa ) , followed by the spermatogonia , and then the sertoli cells .
all tubules were classed from ten ( normal ) to one ( no germ or sertoli cells ) , with the midpoint on the scale represented by tubules that contained spermatocytes as the most advanced cell type .
the mean patient age at the time of surgery was 34 years ( range , 17 - 74 years ) .
the majority of the patients ( 21 of 31 ) presented with an empty scrotum , and the undescended testis was found on subsequent examination .
abdominal cryptorchidism was present in four patients , while inguinal retention was found in 27 patients .
one patient ( 3.2% ) , a 20-year - old man with abdominal cryptorchidism , was confirmed to have itgcn based on immunohistochemical nuclear staining for plap and oct3/4 in the surgical specimen ( fig .
histological assessment of spermatogenesis revealed that the mean johnsen score was 3.42 ( range , 1 - 9 ) .
the most frequent ( 12 of 31 patients ) johnsen score was 2 ( no germ cells present ) .
the majority of patients ( 27 of 31 ) presented with impaired spermatogenesis with a johnsen score of < 5 ( no spermatozoa or spermatids , but many spermatocytes present ) .
there were two patients each with a johnsen score of 6 ( only a few spermatids present ) and 9 ( many spermatozoa present but the spermatogenesis is disorganized ) .
several putative risk factors for testicular malignancy have been identified , although there is generally only limited evidence to support their prognostic value .
concluded that cryptorchidism is the most widely accepted risk factor for testicular cancer , and is associated with a relative risk of between 3.7 and 7.5 times that among the general population .
granados loarca and esau ortega   reported that one of the 25 ( 4% ) postpubertal undescended testis patients they assessed had seminoma , and similarly , ben jeddou et al .  
found that two of 81 patients aged > 14 years with undescended testis had malignant disease . in the present study ,
one of the 34 men with untreated postpubertal undescended testis was diagnosed as having itgcn .
interestingly , the overall incidence of itgcn in intersex states was found to be higher than in the normal group ( 6% , six of 102 cases ) , and was significantly higher in the pubertal age group .
it is important to elucidate the frequency with which itgcn occurs to appropriately monitor the at - risk groups .
periodic testicular self - examination , close follow - up by the physician , and periodic testicular ultrasound are mandatory .
subtle changes in internal testicular architecture , even in the absence of suspicious palpable findings , may warrant a biopsy .
( we attempted to contact the patient who was confirmed to have itgcn to perform physical exam and check paternity but failed . ) several immunohistochemical markers have been used to identify malignant germ cells in adult cases of itgcn , the most common of which include plap and oct 3/4 .
on the basis of multiple findings , it has been hypothesized that itgcn originates early during fetal development .
this is illustrated by the presence of a number of markers common to itgcn and immature germ cells , including plap and oct 3/4 .
plap shows membranous positivity in 90%-100% of seminomas , and oct 4 shows uniform nuclear staining in all seminomas .
given the risk of itgcn or malignancy in postpubertal undescended testis , immunohistochemical staining for plap and oct 3/4 was recommended as part of the diagnostic process , and preventive orchiectomy might be needed after informing patients of the consequences of testicular preservation and the likelihood of their removal in the therapeutic process . in other studies ,
immunohistochemical study underwent in cases with germ cells did not show itgcn on routine h&e staining .
however , in our study , every specimens were evaluated for itgcn using immunohistochemical staining for plap and oct 3/4 , along with routine h&e staining .
ford et al .   reported that spermatogenesis is severely impaired in persistently undescended testis .
pryor et al .   found itgcn in testicular biopsies with low johnson 's criteria scores and atrophic germinal epitheliums , and other studies have also shown that itgcn and invasive testicular tumors occur at a high incidence in patients with undescended testis , which are characterized by atrophic germinal epitheliums . in our study , the specimen that was positive for the germ cell tumor markers also showed a low johnsen score , which is consistent with these other studies .
oct 3/4 and plap have a high sensitivity and specificity for diagnosing itgcn in adults . however , these proteins are present in a very high proportion of germ cells in the testis of normal neonates and young infants with cryptorchidism .
the presence of these markers is generally related to the early stages of fetal germ cell maturation that normally proceeds in the neonate , but requires a longer period in cryptorchid testes due to delayed maturation .
therefore , in contrast to the situation in adolescents and adults , these markers can be unreliable for the detection of itgcn in very young children , and thus , care is needed when interpreting the results of oct 3/4 and plap immunohistochemical staining in these patients .
first , it was retrospective in nature and was based on a review of medical records .
second , there may have been a selection bias , because only patients in a single center were enrolled .
third , paternity was not investigated , and therefore , we could only use the johnsen score to assess fertility .
we suggest that preventive orchiectomy should be performed in cases of postpubertal cryptorchidism because of its malignant potential and subsequent risk of infertility in some patients . before performing preventive orchiectomy
, we should discuss the possibility of androgenic dysfunction and male infertility with the patient .
after surgery , the pathologist should perform immunohistochemical staining for plap and oct 3/4 , which are frequently expressed in testicular malignancy , because itgcn may be overlooked when using h&e staining alone .
 purposeit is well known that testicular germ cell tumors arise with increased frequency in patients with cryptorchidism . 
 in addition , intratubular germ cell neoplasia ( itgcn ) is a precursor lesion to testicular germ cell tumor . 
 approximately 50% of patients with itgcn will develop an invasive of testicular germ cell tumors within 5 years . 
 therefore , we evaluated that the incidence of itgcn in postpubertal cryptorchidism.materials and methodsbetween january 2002 and august 2012 , orchiectomy specimens from 31 postpubertalpatients ( aged 12 or over ) with cryptorchid testis were reviewed . 
 the specimens were evaluated for itgcn using immunohistochemical stains of placental - like alkaline phosphatase and oct 3/4 with routine hematoxylin - eosin stain . 
 additionally , the degree of spermatogenesis was assessed using the johnsen score.resultsmean age was 34 years ( range , 17 to 74 years ) at surgery . 
 all patients were diagnosed as unilateral cryptorchidism . 
 one patient ( 3.2% ) of 20-year - old had itgcn in surgical specimen with all positive markers . 
 histological assessment of spermatogenesis showed that mean johnsen score was 3.42 ( range , 1 to 9 ) . 
 majority of patients ( 27 of 31 ) presented impaired spermatogenesis with low johnsen score lesser than 5.conclusionsconsidering the risk of malignancy and low spermatogenesis , we should perform immunohistochemical stains and discuss preventative orchiectomy for the postpubertal cryptorchidism . 