Open Journal of Urology, 2011, 1, 11-14
doi:10.4236/oju.2011.12004 Published Online May 2011 (http://www.SciRP.org/journal/oju)
The Clinical Association of Autosomal Dominant Polycystic
Kidney Disease and Renal Cell Carcinoma
Wesley Lane1, Evan Lacefield1, Ruc Tran2, Werner de Riese1
Department of Urology, Texas Tech University Health Science Center, Lubbock, Texas, USA1
Department of Pathology, Texas Tech University Health Science Center, Lubbock, Texas, USA2
Received April 21, 2011; revised May 22, 2011; accepted May 29, 2011
Abstract
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is not currently considered to be a risk factor for renal cell
carcinoma (RCC). We present data from our institution demonstrating incidence of RCC with ADPKD above the inci-
dence rate for RCC in the general population, as well as that in patients with end-stage renal disease (ESRD). The dis-
cussion relates our findings in the context of the current literature including recent case reports published in this entity.
Keywords: Autosomal Dominant Polycystic Kidney Disease, Renal Cell Carcinoma, Incidence
1. Introduction
Since Walters and Brasch first described renal cell car-
cinoma occurring in ADPKD in 1934, 50 more cases
have been reported in the literature [1,2]. Most cases of
RCC in ADPKD have been unilateral, however, 12 cases
of bilateral RCC in this patient population have been
reported since the first in 1954 by Borski and Kimbrough
[2,3]. While premalignant changes have been shown to
occur in ADPKD, clinical research has not supported an
association between RCC and ADPKD until Hajj et al.
suggested an increased incidence of RCC in patients with
ADPKD [4-6]. Current literature recognizes that RCC
tends to occur at a younger age, and is more often bilat-
eral in ADPKD patients, however, there is currently no
recognized increased risk of RCC amongst ADPKD pa-
tients compared to the general population [7,8]. This
paper presents cases of RCC in ADPKD from our insti-
tution between 2000 and 2010.
2. Methods and Materials
All institutional cases of either unilateral or bilateral
nephrectomy between 2000 and 2010, 177 cases in total,
were reviewed for the pathologic diagnosis of ADPKD.
Cases resulting from other causes of cystic disease such
as acquired cystic disease, benign cysts, autosomal re-
cessive polycystic kidney disease, tuberous sclerosis, and
Von-Hippel Lindau disease were excluded. Six cases of
ADPKD were identified in this patient cohort (Table 1).
The presence of renal cell carcinoma was reviewed,
yielding two patients who had both ADPKD and RCC,
as well as one with renal papillary adenoma. Figure 1
shows pathologic specimens of ADPKD with RCC.
(a)
(b)
Figure 1. (a) A representative example of a polycystic kid-
ney composed of cysts of different sizes and dy splastic ducts;
H&E staining; (b) Renal cell carcinoma with polymorphic
nuclei removed from tumor cluster located in polycystic
idney via nephrectomy; H & E staining. k

W. LANE ET AL.
12
Table 1. RCC amongst patients with ADPKD.
ey Disease Patients with Autosomal Dominant Polycystic Kidn
Table 1
Age/Sex Date of
Nephrectom
HDa Prior to Carcinoma Diameter
L/R y Indication Nephrectomy RCC Pathology
1 64/F 06/10 KiBilateral Papilmdney Size 2.5 yrs -
lary Adenomas 0.4 cm 0.4 c
2 59/M 05/10
Renal
ass 3r
Cell Carcinomas 1.1, cm 0.
Unle
Unilateral Clear
Cell Carcinoma 3.
Calcification 0b −
Bilateral Clea
− −
3 57/M 05/09
Solid M
on CT yrs 0.552 cm
4
5
41/F
50/F
11/08
06/07
Kidney Size 2 yrs
1.5 yrs
−
−
−
−
−
− Kidney Size
6 51/M 05/07 Kidney Size availab− 5 cm
a. HD –modialysis; b.ed living donlant priy
utosomal dominant polycystic kidney disease was
pe
our review show that 2 of 6 patients with
ented with overt RCC at time of nephrec-
al cell carcinoma is estimated to be
18.4 per 100 000 in men and 9.5 per 100 000 in women
cell type with the remainder having chromophilic, chro-
mophobic, oncocytic, or papillary [11]. Cigarette smok-
have shown that RCC presents in ADPKD
w
He Receivor transpor to nephrectom
A Pubmed search combining renal cell carcinoma and
a
rformed which yielded 47 independent papers. These
papers were reviewed and 50 case reports of RCC in
ADPKD were identified, 12 with bilateral involvement.
3. Results
The data from
ADPKD pres
tomy, 1 with bilateral malignancies. In addition, subject
1 was found to have singular areas of papillary neoplasia
identified in bilateral kidneys; each measuring 0.4 cm.
Microscopic examination of this tissue revealed low-
grade papillary renal cell carcinoma. According to the
current WHO classification system, the only histologic
distinguishing factor between papillary renal cell carci-
noma (PRCC) and papillary adenoma is size. Currently,
the WHO classification system defines papillary ade-
nomas as epithelial lesions with a tubulopapillary archi-
tecture measuring less than 5 mm [9]. Although the ar-
eas of neoplasia in the latter patient meet the specifica-
tions of adenoma according to the WHO classification
system, we include this patient in our study due to bilat-
eral kidney involvement and characteristic histology of
papillary renal cell carcinoma despite a 1 mm size dis-
crepancy between papillary adenoma and papillary renal
cell carcinoma. Specimen from subject 3 demonstrated 2
separated areas of clear cell RCC in the left kidney (1.1
cm and 0.55 cm), and one clear cell RCC in the right
kidney measuring 0.2 cm. Specimen from subject 6
demonstrated a 3.5 cm clear cell RCC in the right kid-
ney.
4. Discussion
The incidence of ren
[10]. Between 70% and 80% of patients with spontane-
ous renal cell carcinoma are diagnosed as having clear
ing, obesity, chronic hemodialysis, and hypertension are
considered risk factors for renal cell carcinoma [12,13].
The incidence of ADPKD is 1 in 6000 [14]. The inci-
dence of end-stage renal disease due to ADPKD is 8.7 per
1 000 000 men and 6.9 per 1 000 000 million women in
the United States [11]. End stage renal disease in patients
with ADPKD account for 10% - 15% of dialysis patients
[15]. Historically, neither epidemiologic nor clinical ret-
rospective studies have established a link between RCC
and ADPKD [4]. The association between RCC and
ADPKD remains controversial, and there is scarce lit-
erature available attempting to establish a link between
these disorders [6]. Current literature states that there is
no increased risk of RCC in patients with ADPKD de-
spite presentation at a younger age and increased inci-
dence of bilateral renal involvement [8]. The preopera-
tive diagnosis of RCC in end-stage renal disease patients
with ADPKD is cumbersome and difficult. Imaging
studies such as ultrasound and computed tomography
often fail due to the cystic degenerative changes of the
kidneys. On the other hand, end-stage renal disease of
any etiology is considered to be a risk factor for devel-
oping RCC. This makes finding a correlation between
RCC and ADPKD difficult as it is often impossible to
determine if a patient developed the malignancy as a
primary result of ADPKD or due to the elevated risk
associated with chronic hemodialysis in end-stage renal
disease [16].
According to our literature search, 50 cases of RCC in
ADPKD have been described in the literature, 12 of
which were bilateral [2]. Table 2 lists 38 of these cases.
These reports
ith several unique characteristics: younger age at pres-
entation, more likely to present with fever, and more
likely to be bilateral, multicentric and sarcomatoid in
type [5]. To date, there has been little evidence that the

W. LANE ET AL.
13
atie
Patient Age/Sex RCC in-
volvement
Year
Diagnosed
HD
(yrs) Citation
Table 2. Literature review: pnts with ADPKD and RCC.
Year
Diagnosed
HD
(yrs) Citation Patient Age/SexRCC in-
volvement
1 69/F [17] 20 39/M [5] Bilateral 1998 16 Unilateral 1977 −
2 58/M Unilateral 2000 10 [17] 21 47/F Unilateral 1977 − [5]
3
4
69/M
59/M
Bilateral 2002
Bilateral
15
17
[17]
[17]
22
23
62/M
29/F
Unilateral 1977
Unilateral
− [5]
− [5] 2004 1978
5 58/M Unilateral 2005 16 [17] 24 39/F Bilateral 1978 − [5]
6 50/M Unilateral 2005 5 [17] 25 31/F Unilateral 1980 − [5]
7 66/F Unilateral 2007 10 [17] 26 67/F Unilateral 1980 − [5]
8 53/M Unilateral 2007 11 [17] 27 46/M Unilateral 1980 − [5]
9 65/M Unilateral 2005 11 [17] 28 40/M Bilateral 1981 − [5]
10 71/M Unilateral 2008 13 [17] 29 65/F Unilateral 1987 − [5]
11 38/M Unilateral 1938 − [5] 30 61/F Bilateral 1987 − [5]
12 64/M Unilateral 1940 − [5] 31 49/F Unilateral 1988 − [5]
13 46/M Unilateral 1943 − [5] 32 59/M Unilateral 1988 − [5]
14 39/M Bilateral 1952 − [5] 33 31/M Unilateral 1994 − [5]
15 37/M Unilateral 1957 − [5] 34 44/F Unilateral 1994 − [5]
16 65/F Unilateral 1962 − [5] 35 62/F Unilateral 1994 − [5]
17 32/F Unilateral 1969 − [5] 36 58/M Bilateral 2004 14 [2]
18 45/F Unilateral 1972 − [5] 37 60/M Bilateral 2004 − [18]
19 44/M Bilateral 1973 − [5] 38 42/F Bilateral 2004 − [18]
cumive ice is ied its with
DP com
rthearchdies aessary to provide a
beter untandihis imant cnical i
and K. K. Chen, “Bilateral
arcinoma in a Patient with Autosomal
Dominant Polycystic Kidney Disease,” Journal of the
ulat
KD
nciden
pared to t
of RCC
he general population [7].
ncreasn p
A
Hajj et al. demonstrated a prevalence rate of RCC of
8.3% in patients with ADPKD and Chronic Renal Fail-
ure. It increased to 12% in their patient population after
1 year of dialysis or kidney transplantation [6]. These
findings along with an incidence of 50% in our patient
population, even in a small study, indicate an increased
risk of RCC in patients with ADPKD. Additionally, the
propensity of these malignancies to present bilaterally
and at a younger age compared to the general population
also suggests an elevated risk in this patient population.
This incidence of RCC is also far above that which is
observed in ESRD patients with secondary acquired
renal cystic disease (ARCD), a well documented risk
factor for the development of RCC. The risk of devel-
oping ARCD increases with time spent on dialysis. For
example, Ishikawa and coworkers found ARCD in 44%
of patients who had been receiving hemodialysis for less
than 3 years but in 79% of those who had been receiving
hemodialysis for a longer time [19]. Overall, eighty per-
cent of patients with end-stage renal failure eventually
develop acquired renal cystic disease, and 1% to 2% of
this subgroup develops RCC over 10 years of follow-up.
If no RCC has developed after 10 years with ARCD, the
risk is considered almost zero [7]. In contrast, at least
two of the three ADPKD patients with RCC in our study
had not been on hemodialysis for more than three years
prior to the diagnosis of RCC, further suggesting a spe-
cific link between ADPKD and RCC in these patients.
Should this link be confirmed, then early bilateral neph-
rectomy in ADPKD patients with end-stage renal disease
should be recommended.
Fu
t
r rese
ders
and stu
ng of t
re nec
port lissue.
5. References
[1] W. Walters and W. F. Brasch, “Surgical Aspects of Poly-
cystic Kidney,” Surgical and Gynacological Obstetrics,
Vol. 58, No. 3, 1934.
[2] Y. L. Chang, H. J. Chung
Renal Cell C
Chinese Medical Association, Vol. 70, No.9, 2007, pp.
403-405. doi:10.1016/S1726-4901(08)70029-7
[3] A. A. Borski and J. C. Kimbrough, “Bilateral Renal Cell
eoplastic
V. E. Torres, B. F. King, H. Zincki and G. M.
l Dominant Polycystic Kidney
Carcinoma in Polycystic Kidney Disease, an Unique
Case,” Journal of Urology, Vol. 71 No. 5, 1954, pp. 677-
681.
[4] J. R. Gregoire, V. E. Torres, K. E. Holley and G. M.
Farrow, “Renal Epithelial Hyperplastic and N
Proliferation in Autosomal Dominant Polycystic Kidney
Disease,” American Journal of Kidney Diseases, Vol. 9
No. 1, 1987, pp. 27-38.
[5] D. S. Keith,
Farrow, “Renal Cell Carcinoma in Autosomal Dominant
Polycystic Kidney Disease,” Journal of the American So-
ciety of Nephrology, Vol. 4, No. 9, 1994, pp. 1661-1669.
[6] P. Hajj, et al., “Prevalence of Renal Cell Carcinoma in
Patients with Autosoma
Disease and Chronic Renal Failure,” Urology, Vol. 74,

14 W. LANE ET AL.
No. 3, 2009, pp. 631-634.
doi:10.1016/j.urology.2009.02.078
[7] A. J. Wein, et al., “Campbell-Walsh Urology,” 9th Edi-
tion, Elsevier Inc., Philidelphia, Vol. 2, pp. 1583-1588
and Vol.4, 2007, pp. 3323.
[8] L. Gomella, “The 5-Minute Urology Consult,” Lippincott
Williams and Wilkins, Philidelphia, PA, 2009.
.07.016
[9] K. L. Wang, et al., “Renal Papillary Adenoma-A Putative
Precursor of Papillary Renal Cell Carcinoma,” Human
Pathology, Vol. 38, No. 2, 2007, pp. 239-246.
doi:10.1016/j.humpath.2006
ancer in
[10] D. K. Espey, et al., “Annual Report to the Nation on the
Status of Cancer, 1975-2004, Featuring C
American Indians and Alaskan Natives,” Cancer, Vol.
110, No. 10, 2007, pp. 2119-2152.
doi:10.1002/cncr.23044
[11] B. I. Rini, S. C. Campbell and B. Escudier “Renal Cell
Carcinoma,” Lancet, Vol. 28, No. 373, 2009, pp.
1119-1132. doi:10.1016/S0140-6736(09)60229-4
[12] R. P. Theis, S. M. Dolwick Grieb, D. Blurr, T. Siddiqui
and N. R. Asal “Smoking, Env
Smoke, and Risk of R
ironmental Tobacco
enal Cell Cancer: A Popula-
d L. J.
tion-Based Case-Control Study,” BMC Cancer, Vol. 8,
No. 387, 2008, pp. 1-11.
[13] Y. Wang, X. Chen, Y. Song, B. Caballero an
Cheskin, “Association between Obesity and Kidney Dis-
ease: A Systematic Review and Meta-Analysis,” Kidney
International, Vol. 73, No. 1, 2008, pp. 19-33.
doi:10.1038/sj.ki.5002586
[14] P. A. Gabow, “Autosomal Dominant Polycystic Kidney
Disease.” New England Journal of Medicine,
No. 5, 1993, pp. 332-342.
Vol. 329,
doi:10.1056/NEJM199307293290508
[15] K. Badani, A. K. Hemal and M. Menon, “Autosomal
Dominant Polycystic Kidney Disease
view of the Disease from Aetiology, Evaluation, Past
and Pain - A Re-
s: A Single Center Experience,” International
Surgical Treatment Options to Current Practice,” Journal
of Postgraduate medicine, Vol. 50, No. 3, 2004, pp.
222-226.
[16] Y. Kojima, S. Takahara, O. Miyake, N. Nonomura, A.
Morimoto and H. Mori, “Renal Cell Carcinoma in Dialy-
sis Patient
Journal of Urology, Vol. 13 No. 8, 2006, pp. 1045-1048.
doi:10.1111/j.1442-2042.2006.01498.x
[17] H. Nishimura, “Renal Cell Carcinoma in Autosomal
Dominant Polycystic Kidney Disease,” American Journal
of Kidney Disease, Vol. 54, No. 1, 2009, pp . 165-168.
doi:10.1053/j.ajkd.2009.01.270
[18] A. Kapoor, et al., “Renal Cell Carcinoma in Autosomal
Dominant Polycystic Kidney Disease,” European Jour
of Radiology Extra, Vol. 51, No.
nal
2, 2004, pp. 87-89.
doi:10.1016/j.ejrex.2004.05.003
[19] I. Ishikawa, et al., “Development of Acquired Cystic
Disease and Adenocarcinoma of the Kidney in Glom
lonephrotic Chronic Hemodialysis Pati
eru-
ents,” Clinical
Nephrolgy, Vol. 14, No. 1, 1980, pp. 1-6.