collecting duct carcinoma ( cdc ) of the kidney is an unusual variant of renal cell carcinoma ( rcc ) , accountings for less than 1% of all renal cancers .
cdc arises precisely from the principal cells lining distal collecting ducts of epithelium and distal renal tubules that originates from mesonephros . considering that urothelial carcinoma originating from the ureter , pelvis , or calices also arises from the mesonephros
, cdc might be similar to urothelial carcinoma and its radiologic and pathologic findings differ from those of other rccs .
recent publications have pointed out the histological heterogeneity of this neoplasm and its extensive histological overlapping with high grade papillary tumors and urothelial carcinoma .
accurate diagnosis is important for proper management . in diagnosis of cdc , it is important to distinguish between invasive papillary rcc and urothelial carcinoma .
positive immunohistochemical staining for distal tubules and collecting duct markers is helpful indiscrimination of cdc from the more commonly diagnosed clear cell rcc of proximal nephron origin .
cdc generally expresses broad spectrum keratins and high molecular weight ( hmw ) cytokeratin , which is expressed in the lower nephron and the urothelium .
it also shows positive staining with e - cadherin , epithelial membrane antigen , cke12 , and ck19 .
however , cd10 , c - kit , and a - methylacylcoa racemase ( amacr ) show no staining .
in contrast , papillary rcc showed positive results for cd10 and amacr , and it appears to be different from cdc .
however , this immunohistochemistry is not specific and may be seen in medullary carcinomas and in urothelial carcinoma , including those arising in the renal pelvis .
although the gross and microscopic features of the tumor are well established , diagnostic confusion can still occur .
40% of patients have already developed metastatic lesions , including lymphnodes , lungs , or adrenal glands .
clinical outcome is poor , with 66% of patients dying of the disease within two years after diagnosis .
various treatments have been proposed , including radiation therapy , immunotherapy , and some combinations of chemotherapy , however , results have been unsatisfactory . to date , no standard therapy for cdc has been established .
the aim of this study is to conduct an investigation of the clinicopathologic findings of cdc and to determine their correlation with the disease status and prognosis .
we retrospectively reviewed 35 patients diagnosed with cdc at eight korean medical centers from 1996 to 2009 .
data on gender , age , initial symptoms , and laboratory findings , including complete blood count profile , calcium , and urine analysis , pathological features , treatment , and patient outcome were obtained from patient medical records .
diagnosis of cdc was made by examination of a nephrectomy specimen in 27 cases and by renal biopsy in eight .
tumors were staged according to the 2002 american joint committee on cancer ( ajcc ) tnm stage classification .
this study was approved by the institutional review board ( irb ) from each participating institution .
tumor response after treatment was re - evaluated using the response evaluation criteria in solid tumors ( recist ver .
progression free survival ( pfs ) was estimated from the date treatment began to the date when disease progression was recognized , or the date of the last follow - up visit , or the date of death . overall survival ( os )
was estimated from the date of diagnosis to the date of death from any cause or the last follow - up visit .
the cox regression model was used for multivariate analysis with factors that had been used in univariate ( log rank ) analysis of os and pfs .
p - values less than 0.05 were considered statistically significant and all p - values correspond to two - sided significance tests .
the median age of patients was 56 years ( range , 29 to 82 years ) and 74% of the patients were male .
of 32 symptomatic patients , 16 and 11 experienced pain and gross hematuria . other presenting symptoms included weight loss , microscopic hematuria , and a palpable mass .
seventeen patients had a tumor size of 7 cm or less , and 10 patients had a tumor size of 7 cm or greater .
the median level of hemoglobin and calcium was 12.5 g / dl ( range , 8.9 to 18.3 g / dl ) and 9.30 g / dl ( range , 7.9 to 11.1 g / dl ) , respectively . according to the immunohistochemistry finding ,
cdc expressed cytokeratin in nine patients ( 26% ) , hmw - cytokeratin in 14 ( 40% ) , low molecular weight - cytokeratin in three ( 8.6% ) , and cke12f in one ( 2.9% ) .
it also expressed cd10 in five ( 14.3% ) and vimentin in 11 ( 31.4% ) . at diagnosis , nine , two , four , and 19 patients had tnm stage i , ii , iii , and iv , respectively .
eight patients had two or more metastatic sites of the bone ( 44% ) , lungs ( 39% ) , liver ( 16% ) , and lymph nodes ( 11% ) as the most common sites . with a median follow - up period of 15.8 months ( range , 0.6 to 88.4 months ) , 14 ( 40% )
deaths were reported . during the median follow - up period of 15.8 months , 14 patients died , while nine patients ( 25.7% ) were lost in the follow - up .
twenty seven of the 35 patients underwent nephrectomy for initial treatment ( curative surgery in 17 , and palliative in 10 ) , three patients received chemotherapy , and four patients did not receive any treatment ( fig .
palliative chemotherapy was administered for 22 persons , who were composed of eight of 14 relapsed patients , eight of 10 patients who were in stage iv and underwent palliative surgery , and four patients who did not undergo an operation ( fig .
median pfs and os for all patients were 5.8 months ( 95% confidence interval [ ci ] , 3.5 to 9.2 months ) and 54.4 months ( 95% ci , 0 to 109.2 months ) , respectively ( figs . 2 and 3a ) .
the os of the patients with stages i - iii was 69.9 months ( 95% ci , 54.0 to 85.8 months ) , while that of patients with stage iv was 8.6 months , which showed a statistical significant difference ( p=0.01 ) ( fig .
3b ) . in addition , among patients with stage iv , the os of patients who received a palliative treatment ( immunotherapy , chemotherapy , or targeted therapy ) was 18.4 months , which was higher than the os of patients without treatment of 4.5 months .
the pfs of patients with stages i - iii was 6.9 months ( 95% ci , 1.3 to 12.4 months ) .
recurrence occurred in 14 patients , 82% of the 17 patients who underwent a curative surgery , and their average recurrence period was 5.9 months , with a short pfs and a high relapse rate . using the log - rank method , no relationship was demonstrated between survival end points ( pfs and os ) and explanatory covariates , including patients ' age , gender , and initial calcium level , except for hemoglobin ( p=0.005 and p=0.193 , respectively ) and initial tnm stage ( p=0.022 and p=0.002 , respectively ) .
results of multivariate regression analysis using a cox 's proportional hazards model showed that tnm stage ( i - iii vs. iv ; hazard ratio , 4.58 ; 95% ci , 1.301 to 16.135 ; p=0.018 ) was an independent prognostic factor for survival of cdc ( table 3 ) .
the frequency of cdc is within 1% of the entire rcc and its radiologic and pathologic findings differ from those of other rccs . in 1976 ,
mancilla - jimenez et al .   reported on 34 cases of papillary rcc and postulated a collecting duct origin for three of these tumors based on the findings of atypical hyperplastic changes in adjacent collecting tubules .
this is the first report on cdc based on medical records from eight institutions in korea . in japan ,
a retrospective survey was conducted in order to analyze the nature of cdc . in the study ,
the central pathologists confirmed cdc in 81 of 120 cases diagnosed as cdc at 66 institutions .
it was a large - scale nationwide survey with an advantage of a multi - institutional central review .
on the other hand , in this study , 35 patients were selected from eight different organizations nationwide in korea .
although a pathological central review was not performed , there was significant detailed information on each case with the pattern of cases and treatment outcomes .
thus , based on such information , the results were evaluated with regard to the types of post operational treatment and the drugs used as palliative treatment and the responses .
our results are in agreement with those of previous reports showing that the median age was 56 years ( range , 29 to 82 years ) and that males comprised 74% of the patient population . in our study , cdc expressed cytokeratin , hmw - cytokeratin , and cke12 in many cases , however , it also expressed cd10 and vimentin , which is generally expressed in the upper nephron , and not in the lower nephron .
ninety - one percent of patients had symptoms and the most common presenting symptoms were pain , hematuria , and weight loss . at diagnosis , 19 ( 54% )
patients were tnm stage iv , and the median os period of patients with stage iv was 9.29 months ( 95% ci , 0.0 to 26.78 months ) .
a summary of the clinical data on cdc gathered from published series and case reports is shown in table 4 . due to the rarity of its occurrence , optimal treatment for cdc has not been established . despite past reports on striking responses to cytokines , currently , immunotherapy only has an historical role .
cdc might be distinct from conventional rcc and share embryological origins and biological features with urothelial carcinoma .
therefore , even if trials comparing immunotherapy with chemotherapy have not been conducted , chemotherapy currently represents the most used therapeutic approach .
however , it remains unclear whether this carcinoma should be managed with a treatment similar to that for urothelial cell carcinoma or rcc .
multiple chemotherapeutic and/or immunotherapeutic regimens have been tried for treatment of cdc ( table 4 ) .
these data appear to suggest that chemotherapy and immunotherapy may offer only limited benefits to a selected group of patients . in our study ,
surgical treatment was performed as the initial treatment in 77% of patients . however , recurrence occurred in most patients who underwent surgery and a palliative treatment was administered in 75% of patients .
most patients with advanced or recurrent disease were treated with immunotherapy , chemotherapy , radiation therapy , or targeted therapy .
the most commonly used agents included interferon , gemcitabine , cisplatin / carboplatin , and sunitinib .
it seems that patients with stages i - iii had a high relapse rate with a short pfs of 6.9 months , while seven patients ( 58% ) with stages i - iii survived for a long time with patients in the no evidence of disease state , contributing to the increase of the os , so that there was a discrepancy between the pfs and the os .
most of the long - term survivors were in stages i - iii and those who received palliative treatment after a relapse , and the treatments administered to these patients included target therapy as well as immunotherapy and chemotherapy . due to the small number of patients , the correlation between the prognosis and the treatment could not be known .
however , it can be assumed that palliative treatment takes the role of extending survival . in paticular ,
the current standard therapy against rcc is the targeted therapy , and though it is recognized as a different disease from rcc , there were some cdc patients who were treated with sunitinib , temsirolimus , or other targeted agents , different from the past . according to an analysis of clinical aspects , treatment and prognosis in the records of seven cdc patients diagnosed with rcc in procopio 's study and included in patients treated with the target therapy , five persons showed survival of four months while two patients showed long - term survival of 49 months and 19 months , respectively . in this study of the patients who were recently diagnosed and received a target therapy ,
one patient for whom sunitinib was used finally died , but showed a partial response during treatment .
cdc is an aggressive disease with poor prognosis , however , like some patients in this study who survived for a long period of time , a study on predictive markers by which the outcomes of prognosis and therapy , especially target therapy as well as their clinical features can be predicted is needed .
pfs and os were short , however , there were some long - term survivors , therefore , additional research on the predictive markers of several clinical , pathological differences and their treatments will be needed .
 purposecollecting duct carcinoma ( cdc ) of the kidney is an aggressive disease with a poor prognosis , accountings for less than 1% of all renal cancers . to date , no standard therapy for cdc has been established . 
 the aim of this study is an investigation of clinicopathologic findings of cdc and correlation of the disease status with a prognosis.materials and methodsfrom 1996 to 2009 , 35 patients with cdc were treated at eight medical centers . 
 the diagnosis of cdc was made based on nephrectomy in 27 cases and renal biopsy in eight cases.resultsmedian pfs and os for all patients were 5.8 months ( 95% ci 3.5 to 9.2 ) and 54.4 months ( 95% ci 0 to 109.2 ) , respectively . 
 the os of patients with stages i - iii was 69.9 months ( 95% ci 54.0 to 85.8 ) , while that of patients with stage iv was 8.6 months ( 95% ci 0 to 23.3 ) , which showed a statistically significant difference ( p=0.01 ) . in addition , among patients with stage iv , the os of patients who received a palliative treatment ( immunotherapy , chemotherapy , or targeted therapy ) was 18.4 months , which was higher than the os of patients without treatment of 4.5 months.conclusioncdc is a highly aggressive form of renal cell carcinoma . despite most of the treatments , pfs and os were short , however , there were some long - term survivors , therefore , conduct of additional research on the predictive markers of the several clinical , pathological differences and their treatments will be necessary . 
Introduction
Materials and Methods
Results
Discussion
Conclusion