The Clinical Association of Autosomal Dominant Polycystic Kidney Disease and renal cell Carcinoma

doi:10.4236/oju.2011.12004

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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

E-mail: [email protected]

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.

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

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

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

He Receivor transpor to nephrectom

A Pubmed search combining renal cell carcinoma and

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.

atie

Patient Age/Sex RCC in-

volvement

Year

Diagnosed

(yrs) Citation

Table 2. Literature review: pnts with ADPKD and RCC.

Year

Diagnosed

(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]

69/M

59/M

Bilateral 2002

Bilateral

[17]

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

nciden

pared to t

of RCC

he general population [7].

ncreasn p

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.

r rese

ders

and stu

ng of t

re nec

port lissue.

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