Case Analyses et al
C. C. Chen,
Mucinous Adenocarcinoma of the Renal Pelvis: An
Analysis of 5 Cases
Chao-Chih Chen1, Chien-Long Kuo2, Mao-Sheng Lin1, Hui-Lung Hsieh1,3, Tah-Chong Lin1,
Jungle C.H. Wu1
Departments of 1Urology and 2Pathology, Show-Chwan Memorial Hospital, Changhua, Taiwan
Department of Urology, Chushan Show-Chwan Hospital, Nantou, Taiwan
OBJECTIVES: Mucinous adenocarcinomas are a rare lesion of the renal pelvis. We present our clinical experience
with this disease at Changhua Show-Chwan Memorial Hospital.
MATERIALS AND METHODS: We reviewed the medical records of patients presenting with renal pelvic tumors
from 1987 to 2007, and identified 5 cases of mucinous adenocarcinoma. Clinical data including age, gender, clinical
presentations, laboratory data, concomitant disease, treatment, and outcomes were retrospectively analyzed, and the
histopathological diagnoses were confirmed by a single pathologist.
RESULTS: The incidence of mucinous adenocarcinoma of epithelial tumors of the renal pelvis in our hospital was 1.4%
(5/349). The mean age of these 5 patients, all men, was 69.6 (range, 64~79) years. All patients had renal stones, and 4
patients had hydronephrosis with or without chronic pyelonephritis. Urinalysis confirmed mucin in the urine of 3 pa-
tients (60%). Two of the 5 patients (40%) died of a mucinous adenocarcinoma within 3 years of their diagnosis.
CONCLUSIONS: Early diagnosis of mucinous adenocarcinoma is difficult, and clinical presentations are usually
nonspecific. Mucin in the urine might be a sign of this disease, especially in patients who also have chronic irritation of
the renal pelvis. (JTUA 18:219-24, 2007)
Key words: mucinous adenocarcinoma, mucin, renal pelvis.
INTRODUCTION The pathogenesis of this tumor is not clear. Several
investigators have reported that mucinous adenocarci-
The majority of malignant renal pelvic tumors are noma of the renal pelvis is associated with a long dura-
epithelial in origin. Of these, approximately 90% are tion of irritant conditions of the urothelium, such as
transitional cell carcinomas (TCCs). Adenocarcinomas urolithiasis, inflammation, infection, and hydroneph-
are rare and account for < 1% of renal pelvic neoplasms. rosis.1-15 Since epithelial metaplasia is commonly present
A mucinous adenocarcinoma is a subset of adenocarci- in these conditions, the general consensus is that these
nomas in which cancer cells produce abundant extra- tumors are derived from the metaplastic glandular mu-
cellular mucin. Reports of renal pelvic mucinous adeno- cosa in response to chronic irritation of the uro-
carcinomas in the literature are limited to small series thelium.1,2,7-9,13,14
and isolated case reports. To date, approximately 100 In addition to reviewing the literature on this
cases have been reported in the English medical condition, we present our experience with 5 patients di-
literature. agnosed with mucinous adenocarcinoma of the renal
Early diagnosis of this disease is difficult. Because pelvis in the past 20 years at Show-Chwan Memorial
there are no specific clinical symptoms or laboratory tests Hospital, Taiwan.
for this malignancy, in many cases the diagnosis of re-
nal pelvic mucinous adenocarcinoma is made by the MATERIALS AND METHODS
pathologist, and the tumors are incidentally detected from
nephrectomy specimens of other diseases.1-12 Between 1987 and 2007, 5 patients with renal pel-
vic mucinous adenocarcinoma were diagnosed at Show-
Address reprint requests and correspondence to: Chwan Memorial Hospital. The clinical history, includ-
Dr. Chao-Chih Chen
Department of Urology, Show-Chwan Memorial Hospital, 542 Chung ing the age at diagnosis, gender, clinical presentations,
Shan Rd., Sec. 1, Changhua, Taiwan 500, R.O.C. laboratory data, concomitant diseases, treatment, and
Tel: 886-4-7256166 ext. 1293
E-mail: email@example.com outcomes, were retrospectively reviewed from the medi-
JTUA 2007 18 No. 4 ONV
Mucinous Adenocarcinoma of the Renal Pelvis
cal records. The histopathological diagnoses were re- nying severe pyelonephritis.
viewed and confirmed by a single pathologist, and mu- Patient no. 4 was found to have a renal pelvic tumor
cinous adenocarcinoma was recognized by confirmation during percutaneous nephrolithotomy (PCN-L) surgery
of tall columnar epithelial lining with basally located for a left renal staghorn stone, and a subsequent nephre-
nuclei. Focal pseudostratification and papillary tufting ctomy was performed a few days later.
of epithelial cells were also noted. Evidence of mitosis The tumor of patient no. 3 was incidentally dis-
was rare. In addition to these findings, renal parenchyma covered during PCN-L surgery for a right renal stone.
invasion was noted (Fig. 1), and mucin stains were posi- After histological confirmation and to avoid further
tive (Fig. 2). dialysis, the patient received electrocautery through the
PCN route because of renal insufficiency. Unfortunately,
RESULTS he died of disease 3 years after the operation, at which
time he was discovered to have retroperitoneal invasion.
From 1987 to 2007, 349 cases of urothelial carci- Among the patients who received a nephrectomy, a
noma of the renal pelvis were diagnosed in our hospital. subsequent ureterectomy was not performed. However,
Five of the cases (1.4%) were histologically confirmed none of these patients had tumor recurrence in the re-
as being mucinous adenocarcinoma. The clinical fea- maining ureter or urinary bladder.
tures and characteristics of the patients are shown in Patient no. 1 died of pulmonary metastasis 4 months
Table 1. after the diagnosis. Patient no. 2 died of natural causes 8
All of the patients were male, and the age at diag- years after the diagnosis without tumor recurrence. The
nosis ranged from 64 to 79 (mean, 69.6) years. The main remainder of our patients who underwent a nephrectomy
clinical presentations of patients were gross or micro- were still alive with regular follow-up in our hospital at
scopic hematuria (n = 5) and flank pain (n = 3). It is the time of this writing.
notable that 3 patients (60%) experienced mucin in the
urine, which was detected by urinalysis. However, in all DISCUSSION
of the patients, mucoid material was noted in the dilated
collecting system when the renal pelvis was opened. All Mucinous adenocarcinomas of the renal pelvis are
of the patients had renal stones, and 4 patients (80%) a rare condition, and they are often reported as isolated
had hydronephrosis with or without pyelonephritis. cases. To date, only about 100 cases have been reported
None of the patients was diagnosed preoperatively in the English medical literature. Lesions from muci-
by imaging studies. Three patients were diagnosed from nous adenocarcinoma are usually incidentally detected
the resected surgical specimen. Notably, the operations from surgically resected specimens. One of the predomi-
were conducted to address renal stones with accompa- nant presenting features of this condition is copious,
Fig. 1. High-power microscopic examination of the renal Fig. 2. Tumor cells positive for mucin special stain. (H&E,
pelvis revealing the tall, simple to pseudostratified 400×)
columnar epithelium including goblet cells. Renal pa-
renchymal invasion can be observed. (H&E, 400×)
OOM JTUA 2007 18 No. 4
C. C. Chen, et al
thick, viscid mucous material in the renal pelvis and Because this type of tumor is uncommon, a preop-
calyces.1-6,8-11,13,15 erative diagnosis is rarely made, and most cases are di-
In India, a much higher prevalence (16.7%) of ad- agnosed from resected specimens by a pathologist. The
enocarcinomas of the renal pelvis has been reported.13 symptoms of these patients are often nonspecific, and
The reason for this increased incidence is not clear. In hematuria (gross or microscopic) is the most common
addition, the majority of these renal pelvic adenocarci- sign in the majority of cases. In addition, flank pain and/
nomas were not reported in sufficient detail to provide a or a palpable abdominal mass may also be clinical symp-
basis for further histological subclassification. Terris and toms in late-stage patients.
colleagues suggested that this may result from dietary In most patients, standard imaging studies, includ-
or other environmental factors prevalent in India.15 ing intravenous pyelography (IVP), ultrasonography,
The first major review of this condition was pre- renal scans, and even computed tomographic (CT) scans
sented by Aufderheide and Streitz in 1974, with 28 cases or magnetic resonance imaging (MRI), might not be able
summarized. They found that the majority of the cases to identify these tumors preoperatively. Similarly, no
occurred in patients older than middle age and were usu- specific presentation differentiates mucous adenocarci-
ally associated with a long history of infection, stones, noma from TCCs by clinical symptoms or imaging
or hydronephrosis.4 Similar findings were also demon- modalities.
strated in subsequent reports in the medical literature. Some special features of this infrequently diagnosed
In our series, although small, the mean age at diagnosis tumor may help clinicians. First, a long history of pre-
and the preexisting factors are similar to those of previ- senting symptoms is a common finding: an average 4-
ous reports. year duration of symptoms was found by Murphy and
Although it was reported in the earlier literature that Stevenson.6 This prolonged duration of symptoms was
no difference exists in the prevalence of mucinous ad- also noted by Aufderheide and Streitz.4 Second, this
enocarcinoma between genders,4,5,14 a significantly male condition is often found to be associated with chronic
predominance was found in our series, with all of the irritation from nephrolithiasis, infection, or obstruction.
patients being male. Interestingly, the phenomenon of Urolithiasis was present in the majority of cases reported
male predominance was also noted other literature from earlier. However, in a review by Spires and colleagues
Asian countries (India, Japan, Hong Kong, Malaysia, in 1993, who found that only 31% of cases presented
Singapore, and Taiwan) with a 3:1 male-to-female ratio with stones, most of the cases (92%) showed evidence
(excluding our 5 cases).7-13,15,16 However, the relation- of hydronephrosis.13 In our series, all patients had renal
ship between this ratio and different races is difficult to stones, and 80% had hydronephrosis.
accurately interpret given the small number of cases. Since this tumor is located in the renal pelvis, the
Table 1. Characteristics, clinical presentations, management and outcome
Age (yr)/ Clinical
Case no. Year Gender presentations Associated conditions Management Outcome
1 1988 79/M Microscopic Renal stone, Nephrectomy Died of lung metastasis 4
hematuria hydronephrosis months after surgery
Flank pain Chronic pyelonephritis
Mucin in urine
2 1989 72/M Gross hematuria Renal stone, Nephrectomy Died of natural causes 8
hydronephrosis years after surgery
Flank pain Chronic pyelonephritis
3 1990 64/M Microscopic Renal stone PCN Died of disease 3 years
hematuria electrocautery after surgery with
Mucin in urine Hydronephrosis
4 1996 67/M Microscopic Renal stone Nephrectomy Alive with regular
Flank pain Hydronephrosis
5 2002 69/M Microscopic Renal stone Nephrectomy Alive with regular
Mucin in urine
JTUA 2007 18 No. 4 OON
Mucinous Adenocarcinoma of the Renal Pelvis
tumor cells may exfoliate into the lower urinary tract, Urothelial glandular metaplasia often develops in
and a urine cytologic examination may be used as a di- response to chronic irritation and inflammation, leading
agnostic tool. However, only a small number of cases many investigators to speculate that the metaplasia is a
have been diagnosed by urine cytology.1,12 The reason result of a sequence of changes in the transitional epi-
for this may be that these cases are frequently associ- thelium through successive stages of pyelitis grandulosa,
ated with an obstructive uropathy or even a non-func- pyelitis cystica, and pyelitis grandularis.14 Some authors
tioning kidney, so the urine obtained from the urinary believe that it arises from foci of intestinal metaplasia
bladder might not contain tumor cells. Thus, Yonekawa from chronic irritation.2 Glandular metaplasia of the
and colleagues presented a case of mucinous adenocar- urothelium, which develops as a response to chronic
cinoma arising in the renal pelvis diagnosed by cath- irritation, may progress to dysplasia and an adenocar-
eterized urine cytology, and they indicated that a preop- cinoma. To avoid confusion between mucinous adeno-
erative diagnosis is possible by cytologic findings of carcinomas and metaplasia, Aufderheide and Streitz pro-
catheterized urine together with clinical data.16 posed the following criteria for malignancy: (1) histo-
It is notable that mucous material in the urine was logical evidence of architecture or cellular atypism; (2)
discovered in most of our patients (3/5). This finding microscopic evidence of invasion of the renal pelvic wall
has not been reported in other published literature. In and renal parenchyma, or of nodal or distant metastasis;
general, clear mucous in the urine might not be a and (3) evidence of overt invasion or recurrence, or of
problem, and it is usually found in patients who have nodal or distant metastasis.4 All of our cases fulfilled
urinary tract infections, chronic cystitis, pyelitis, pro- these criteria.
statitis, and bladder reconstruction or contamination. On the other hand, some authors considered that this
Although it is not specific for a mucinous adenocar- tumor may directly develop from transitional cells.
cinoma, it might be an important sign to remind clini- Takehara and colleagues presented a case of an adeno-
cians to keep this disease in mind for the differential carcinoma of the renal pelvis which was not associated
diagnosis, especially in patients with any preexisting with chronic inflammation, and glandular metaplasia was
pathologic conditions as described above. not found in any sections of the resected specimens.
Since the normal mucosa of the renal pelvis does Results of the immunohistochemical examinations in-
not contain glandular epithelium, the mechanism for a dicated that the adenocarcinoma of the renal pelvis in
mucin-secreting tumor to develop in the urothelium is that case may have had a similar biological nature to a
not well understood. As seen with a mucinous adeno- conventional TCC, and the authors hypothesized that it
carcinoma that developed into chronic fistula-in-ano, may have originated by stepwise development from a
most of the published cases were noted to be associated preexisting TCC of the renal pelvis.12
with a prolonged duration of a chronic irritative status Liwnicz postulated that neoplasia of the adenocar-
such as urolithiasis, severe pyelonephritis, obstructive cinoma is merely an advancement via chromosomal
uropathy, and congenital malformations. The patho- transformation from a diploid to polyploid archi-
physiology of a mucinous adenocarcinoma is in part tecture.2 The recent application of molecular biological
believed to be secondary to chronic inflammatory techniques may provide a possible pathogenesis of these
changes. tumors. The p53 gene is known to play an important
Many authors have postulated that these tumors role in regulating the cell cycle, and loss of p53 regula-
originate from metaplastic urothelium, and this hypoth- tion can lead to uncontrolled tumor growth and
esis is supported by both clinical and pathological aggression. In mucinous adenocarcinomas of the colon,
observations.1,2,7-9,13,14 It is known that the urinary tract a lower p53 protein expression and a frequent DNA rep-
epithelium has the potential for metaplasia, usually con- lication error have been reported.18 However, because
verting to squamous epithelium and occasionally to glan- of the limited number of patients studied, these phenom-
dular epithelium. Although with longstanding responses ena have not been reported in mucinous adenocarcino-
to noxious stimuli, metaplasia of the urothelium is usu- mas of the renal pelvis.
ally squamous, but the occurrence of glandular meta- Because this is an uncommon tumor and only lim-
plasia is also recognized. 1 Experimental studies by ited clinical experience exists, standard treatments have
Mostoti in 1954 emphasized the unique ability of the not been subjected to randomized double-blind prospec-
transitional epithelium to respond with glandular meta- tive analyses. However, most authors believe that a radi-
plastic changes to stimuli such as infection or irrita- cal nephrectomy remains the preferred surgical treatment
tion.17 However, this is commonly observed in older pa- and should be performed in any suspected cases because
tients with bladder exstrophy. reports indicate that 1/2 of the recurrences occurred
OOO JTUA 2007 18 No. 4
C. C. Chen, et al
locally at the edge of the retained ureteral tissue. Down- 2 years after surgery.2,3,5-7 In addition, some authors de-
ward seeding and spillage of tumor cells from surgical duced that mucinous adenocarcinomas have a greater
manipulation have also been reported. 2-6 Thus, a propensity for metastasis and behave more aggressively.
nephroureterectomy with ipsilateral bladder cuff exci- We also observed this poor prognosis in our patients: 2
sion has been recommended as the treatment of choice (40%) died of the disease within 3 years of diagnosis.
in these patients by many clinicians, similar to what is Some current studies have reported better outcomes
recommended for a TCC of the upper urinary tract. in patients with mucinous adenocarcinomas of the renal
In fact, nearly all of these cases were undetected pelvis than those previously reported.9-11,13 These recent
preoperatively, and these patients were thought to have analyses reveal that a poor prognosis is related to the
some benign infections or inflammatory conditions, such stage of the disease being treated and to the extent of
as chronic pyelonephritis, abscess, or an infected stone spread, but is not related to the mucinous histology itself.
disease, so subsequently an additional procedure of a Therefore, the key to long-term survival seems to be a
ureterectomy was performed in many cases. It is impor- high index of suspicion.
tant to recognize this tumor intraoperatively to assure
adequacy of resection. Although seldom seen, the possi- CONCLUSIONS
bility of this tumor should be kept in mind when treat-
ing any patient with recurrent infection and hydrone- Mucinous adenocarcinomas of the renal pelvis are
phrosis. Frozen sectioning may be helpful if mucoid ma- often associated with urolithiasis and long-standing in-
terial is encountered during a simple nephrectomy. fection and/or obstruction, and possibly originate from
Hence, special care must be taken in handling cases in- metaplastic urothelium. The presentation of this rare
volving chronic stone and/or infections, especially if tumor is usually late, and the symptoms are nonspecific.
mucoid material is found in the collecting system. Care- Mucinous material in the urine might be a sign to alert
ful manipulation of the kidney is essential to avoid rup- clinicians, especially in patients who also have renal
ture and spillage of the tumor cells. In our patients, no stones, chronic pyelonephritis, and hydronephrosis.
local recurrence was noted despite the lack of a subse-
quent ureterectomy. REFERENCES
Although Takehara and colleagues found that pel-
vic adenocarcinomas have a similar biological nature to 1. Joshi K, Jain K, Mathur S, Mehrotra GC. Mucinous ad-
conventional TCCs and probably originate by the de- enocarcinoma of the renal pelvis. Postgrad Med J 1980;
velopment of preexisting TCCs of the renal pelvis,16 the 56:442-4.
2. Liwnicz BH, Lepow H, Schutte H, Fernadez R, Caberwal
role of adjuvant therapy, such as radiotherapy and D. Mucinous adenocarcinoma of the renal pelvis: dis-
chemotherapy, has not been clearly defined. Since stud- cussion of possible pathogenesis. J Urol 1975;114:306-
ies of cases morphologically similar to mucinous ad- 10.
enocarcinomas of the colon and previous studies have 3. Kutscher HA, Trainer TD, Fagan WT. Mucinous adeno-
shown responsiveness to adjuvant radiotherapy and sys- carcinoma of renal pelvis. Urology 1982;20:94-5.
temic chemotherapy, some authors consider radiotherapy 4. Aufderheide AC, Streitz M. Mucinous adenocarcinoma
to be an additional therapy after surgery with or without of the renal pelvis: report of two cases. Cancer 1974;
chemotherapy.5,19 5. Wan J, Ohl DA, Weatherbee L. Primary mucinous ad-
Ueda and colleagues studied adjuvant chemotherapy enocarcinoma of renal pelvis in solitary pelvic kidney.
for a patient with mucinous adenocarcinoma in a horse- Urology 1993;41:292-4.
shoe kidney; however, the result was disappointing.7 6. Murphy TE, Stevenson JE. Primary adenocarcinoma of
Similarly, there is no strong evidence regarding any the renal pelvis: report of a case. J Urol 1970;104:62-6.
benefits of radiotherapy for these tumors. 7. Ueda T, Okumi M, Ichimaru N, Itoh K, Matsuoka Y,
To date, no adjuvant therapy has been proven to be Fujimoto N. Mucinous adenocarcinoma of the renal pel-
vis in the horseshoe kidney: a case report. Hinyokika
effective for mucinous adenocarcinomas of the renal Kiyo 2002;48:187-9. [in Japanese with English abstract].
pelvis. More cases and clinical experiences are required 8. Yip SKH, Wong MP, Cheung MC, Li JHC. Mucinous
to verify the effectiveness of treatment of this unusual adenocarcinoma of renal pelvis and villous adenoma of
tumor. bladder after a caecal augmentation of bladder. Aust
Unlike TCC of the renal pelvis, mucinous adeno- NZ J Surg 1999;69:247-8.
carcinomas are reported to be more aggressive and usu- 9. Kaur G, Naik VR, Rahman MNG. Mucinous adenocar-
ally have a very poor prognosis. From published reviews, cinoma of the renal pelvis associated with lithiasis and
chronic gout. Singapore Med J 2004;45:125-6.
more than 1/2 of patients with this condition died within
JTUA 2007 18 No. 4 OOP
Mucinous Adenocarcinoma of the Renal Pelvis
10. Chang CP, Yeh KT, Huang SH, Lin J. Primary muci- 15. Terris MK, Anderson RU. Mucinous adenocarcinoma
nous adenocarcinoma of the renal pelvis: a case report of the renal pelvis in natives of India. Urol Int 1997;58:
and literature review. J Urol ROC 1998;9:196-9. 121-3.
11. Huang KH, Lee WC, Chang SC, Lin BH, Chi Hs. Pri- 16. Yonekawa M, Hoshida Y, Hanai J, et al. Catheterized
mary mucinous adenocarcinoma of the renal pelvis: a urine cytology of mucinous carcinoma arising in the re-
case report. JTUA 2004;15:75-7. nal pelvis: a case report. Acta Cytol 2000;44:442-4.
12. Takehara K, Nomata K, Eguchi J, et al. Mucinous ad- 17. Mostofi FK. Potentialities of bladder epithelium. J Urol
enocarcinoma of the renal pelvis associated with tran- 1954;71:705-14.
sitional cell carcinoma in the renal pelvis and the bladder. 18. Hanski C, Tiecke F, Hummel M, et al. Low frequency of
Int J Urol 2004;11:1016-8. p53 gene mutation and protein expression in mucinous
13. Spires SE, Banks ER, Cibull ML, Munch L, Delworth M, colorectal carcinomas. Cancer Lett 1996;103:163-70.
Alexander NJ. Adenocarcinoma of renal pelvis. Arch 19. Mirone V, Prezioso D, Palombini S, Lotti T. Mucinous
Pathol Lab Med 1993;117:1156-60. adenocarcinoma of the renal pelvis. Eur Urol 1984;10:
14. Mavromanolakis E, Samonis G, Cranidis A. Mucinous 284-5.
adenocarcinoma arising in the renal pelvis of an ectopic
pyelic kidney. Oncology 1995;52:331-3.
OOQ JTUA 2007 18 No. 4