Metastasis of malignant melanoma in the ureter: Possible
algorithms for a therapeutic approach
Georgios Gakis,1Axel S Merseburger,2Karl Sotlar,3Markus A Kuczyk,2Karl-Dietrich Sievert1and Arnulf Stenzl1
Departments of1Urology and3Pathology, University Hospital Tuebingen, Eberhard-Karls University, Tuebingen, and2Department of Urology, Hannover Medical
School, Hannover, Germany
Ureterorenoscopy revealed a pigmented solid mass adherent to the mid-ureteral wall. Histomorphological and immunohistochemical examina-
tion of the biopsy specimen demonstrated a malignant neoplasia with HMB45, Melan A and S100 positivity establishing the diagnosis of
metastatic malignant melanoma. Hence, partial ureterectomy was performed with no further evidence of disease at the time of surgical
intervention. Subsequently, multiple metastases in the renal pelvis and ureter led to secondary nephroureterectomy and retroperitoneal
lymphadenectomy with complete excision of the ureteral orifice. Secondary metastatic lesions of the urinary bladder wall were completely
resected followed by dacarbazine-based chemotherapy and resection of retroperitoneal recurrences. Based on this case as well as on recent
published reports, we propose a possible algorithm for the treatment of metastatic melanoma of the upper urinary tract.
We report on the very rare case of a patient with a malignant melanoma in the right ureter initially hospitalized for colic pains.
malignant melanoma, metastasis, nephroureterectomy, ureter, ureterorenoscopy.
Melanoma is a malignant tumor of melanocytes and, less frequently,
of retinal pigment epithelial cells. In Western Europe, the incidence
of malignant melanoma is steadily increasing with 10–12 cases per
100 000 of the population. So far, the localization of metastases
within the ureter originating from malignant melanoma has been
reported very rarely.1Herein, we report on the very rare case of
malignant melanoma rapidly progressing within the upper and lower
Before admission to our clinic a 46-year-old male patient, presented
herein, had a history of malignant melanoma as follows. It was first
diagnosed on the capillitium accompanied by satellite metastases and
subsequently wide-excised in August 2002. Positive retroauricular
sentinel-node biopsy led to a neck-dissection. Adjuvant immuno-
therapy with a-interferon was applied for two years. One year later, due
to a positron emission tomography–positive cervical lymph node con-
glomerate on the left side, the patient underwent resection of the lower
parotis pole with regional lymphadenectomy followed by adjuvant local
radiotherapy (50 Gy). In the latter, a subcutaneous filia was detected
The patient was first admitted to our hospital due to right-sided
flank pain in August 2006. Following administration of spasmoanal-
getic medication a ureterorenoscopy revealed a pigmented solid mass
adherent to the ureteral wall. Histomorphological and immunohis-
tochemical examination of the biopsy specimen revealed a malignant
neoplasia with HMB45, Melan A and S100 positivity (Fig. 1). Thus,
the diagnosis of metastatic malignant melanoma was established.2
According to the German guidelines for the general treatment for
singular metastases of malignant melanoma, partial ureterectomy
with end-to-end anastomosis of the ureter was carried out. Neither the
preoperative staging by MRI nor an intraoperatively performed cys-
toscopy and ureterorenoscopy revealed any indication of further
metastatic lesions at the time of initial surgical intervention. Six
months later, due to hydronephrosis accompanied by right-sided acute
flank pain, ureteroscopy revealed multiple metastases in the ureter.
Subsequently, nephroureterectomy was performed including resection
of the right ureteral orifice on the level of the bladder wall and
regional lymphadenectomy of multiple lymphatic metastases along
the ureter (Figs 2,3). In the following, transurethral resection of meta-
static melanoma lesions within the urinary bladder wall had to be
carried out with currently no further cystoscopic metastatic lesions in
the bladder. Six months after nephroureterectomy, due to progressive
lymphatic, peritoneal and cutaneous metastatic disease, dacarbazine-
based chemotherapy in combination with CTLA-4 antibody (Cyto-
toxic T-Lymphocyte Antigen 4) was carried out. Four months later,
progressive retroperitoneal disease led to transabdominal tumor resec-
tion of iliacal lymph node metastases. Another four months later,
local retroperitoneal tumor recurrence led to retroperitoneal and
Correspondence: Georgios Gakis MD, Department of Urology, University
Hospital Tuebingen, Eberhard-Karls University, Hoppe-Seyler-Strasse 3,
Tuebingen 72076, Germany. Email: firstname.lastname@example.org
Received 28 March 2008; accepted 24 November 2008.
stain revealing the presence of pigmented tumor cells.
Polypoid metastatic melanoma of the ureter: hematoxylin–eosin
International Journal of Urology (2009) 16, 407–409doi: 10.1111/j.1442-2042.2008.02238.x
© 2009 The Japanese Urological Association
interaortocaval lymphadenectomy. As of October 2008, no further
specific therapy has been conducted and the patient is now in a good
Metastases of malignant melanoma in the urinary tract are extremely
rare.1Distant metastases are usually localized in the liver and cere-
brum. Several prognostic factors that predict a higher likelihood for
the development of distant metastatic spread have been identified.
These include a vertical tumor depth >1.5 mm, an exulceration of the
primary tumor, a positive sentinel node biopsy, male sex and a lesion
primarily localized on the capillitium or in the region of the upper
extremity.3Treatment options for advanced malignant melanomas are
based on surgical procedures, chemo-immunotherapy and radiation
therapy. Surgical approaches preferably include wide excision with
maintenance of adequate margins.4They aim at a reduction of tumor
recurrences at the site of the original lesion. Before the development
of further metastatic lesions, melanomas often spread into lymph
nodes in the region of the primary lesion. The technique of sentinel
node biopsy has been established to reduce complications associated
with lymphadenectomy. If a lymph node is histologically positive,
radical lymph node dissection is performed.5Systemic strategies in
metastatic melanoma include a-interferon and interleukin-2-based
immunotherapy as well as various chemotherapeutic agents, such as
dacarbazine, which have also been conducted in our patients due to
progressive systemic disease.6Radiation therapy is often performed
for patients with locally or regionally advanced disease after primary
surgical treatment or unresectable distant metastases.7In this context,
the case of a 17-year-old patient with a metastasis of malignant mela-
noma in the renal pelvis has been described in the literature. Primary
lesion was localized on the capillitium. Following partial resection of
the renal pelvic wall (R0-resection), only six weeks later, secondary
nephroureterectomy had to be carried out due to multiple metastases
in the ureter and renal pelvis.8
In conclusion, tumor manipulation in the form of ureteroscopy or
placement of a double-j catheter may lead to a distribution of malignant
melanoma cells within the ureter. Secondary, herein, melanoma may
progress rapidly within the upper urinary tract following partial ureter-
ectomy for the treatment of a solitary lesion.
Due to the rare manifestation of malignant melanoma in the
urinary tract, an established therapeutic adjuvant strategy for the
treatment of these patients is not available. However, according to
the experience with the treatment of metastatic melanoma in general,
patients are supposed to derive the largest clinical benefit from radical
resection of metastatic lesions. According to German guidelines for
the treatment of distant metastases of malignant melanoma, surgical
treatment is the therapeutic method of first choice, if primary
R0-resection is possible.9Patients may also derive benefit from sur-
gical treatment in the case of local tumor progression in order to
avoid local problems.10
metastases in the renal pelvis.
Nephroureterectomy gross specimen with multiple melanoma
right side with multiple melanoma metastases (←) in the renal pelvis and
ureter six months after partial resection of the ureter.
Magnetic resonance renography showing hydronephrosis on the
pos. LA or vertical
RTx ± CTx
Stenting of UUT
Upper Urinary Tract Melanoma
melanoma in the upper urinary tract. CTx, chemotherapy; LA, lym-
phadenectomy; NUx, nephroureterectomy; RTx, radiation therapy; TD,
tumor depth of primary cutaneous lesion; UUT, upper urinary tract.
Possible algorithm for the treatment of metastases of malignant
G GAKIS ET AL.
© 2009 The Japanese Urological Association
Therefore, in our opinion, melanoma in the upper urinary tract
should be treated with primary nephroureterectomy and regional
lymphadenectomy. Inthe case
positive lymph nodes or depth of primary cutaneous tumor exceeding
1.5 mm, adjuvant dacarbazine-based
performed. Local recurrence should preferably be treated by
local resection combined with dacarbazine-based chemotherapy. In
case of bilateral resectable metastatic lesions, partial ureterectomy
with bilateral regional lymphadenectomy and adjuvant chemotherapy
should be carried out. In case of non-resectable disease, local
radiation therapy and dacarbazine-based chemotherapy can be per-
formed. These suggestions, which are depicted in an algorithm in
Figure 4, are based on our experience and the published reports to
ofpositive surgical margins,
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Malignant melanoma in the ureter
© 2009 The Japanese Urological Association