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Malignant Melanoma of the Renal Pelvis Presenting as a Primary Tumor
0022-534 7 /88/1404-0812$02.00/0 Vol. 140, October
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright © 1988 by The Williams & Wilkins Co.
MALIGNANT MELANOMA OF THE RENAL PELVIS PRESENTING AS A PRIMARY TUMOR BRADLEY L. FRASIER, BARTON H. WACHS, LUKER. WATSON
AND
JOSEPH P. TOMASULO
From the Division of Urology, Department of Surgery, UCLA School of Medicine, Los Angeles, and Departments of Urology and Pathology, Memorial Medical Center, Long Beach, California
ABSTRACT
We report a case of malignant melanoma of the renal pelvis presenting as a primary tumor and review the relevant literature. (J. Ural., 140: 812-813, 1988) Malignant melanoma of the urinary tract is rare. Most cases are not clinically apparent and they are discovered only at autopsy after death of widespread metastases. 1- 3 Two cases of malignant melanoma presenting as a renal pelvic mass have been reported previously. 4 •5 We report a third case, which may represent the first well documented example of primary malignant melanoma of the renal pelvis. CASE REPORT
D. H., a 37-year-old white man, presented to the emergency room in July 1986 with gross hematuria associated with right flank pain. History was negative for major medical illnesses, previous hematuria, urinary calculi or surgery. He denied any history of suspicious skin lesions or regression of atypical nevi. Physical examination was significant for right flank and costovertebral angle tenderness. Laboratory examination was unremarkable except for an elevated serum uric acid (9.4 mg.jdl.) (normal 3.0 to 7_0) and a full field of red blood cells on urinalysis. An excretory urogram (IVP) revealed a filling defect in the right renal pelvis that was confirmed by a retrograde pyelogram (fig. 1). Ureteral washings and pelvic brushings demonstrated atypical cells but they were not diagnostic for malignancy. Ureteroscopy showed no intraluminal ureteral lesions but attempted pyeloscopy was unsuccessful. An abdominal computerized tomography (CT) scan revealed a rounded, soft tissue density confined to the right renal pelvis and no evidence of visceral metastasis (fig. 2). A bone scan was similarly negative. After a second unsuccessful attempt at visualization of the renal pelvic mass by retrograde pyeloscopy, the patient underwent exploration of the right renal pelvis. A moderately firm, tan and yellow variegated tumor with focal areas of pigmentation and hemorrhage was found. Frozen section of the tumor confirmed the presence of poorly differentiated carcinoma, Accepted for publication January 28, 1988.
initially thought to be transitional cell carcinoma, and a nephroureterectomy was performed. On gross pathological examination the tumor measured 5.0 X 4.0 X 3.0 cm. and it filled the entire renal pelvis (fig. 3). It was adherent to the posterior wall but it did not extend into the renal parenchyma. The remainder of the surgical specimen, including the ureter and vascular structures, was free of tumor. Histological evaluation of the tumor revealed organized nests of cells with large hyperchromatic nuclei and occasional intranuclear invaginations (fig. 4, A). The cytoplasm of the tumor cells was highly eosinophilic and a moderate number of mitotic figures were identified. There were isolated areas in which some tumor cells contained a fine dust-like golden pigment within the cytoplasm. The renal pelvis adjacent to the tumor was lined by normal transitional cell epithelium and it contained abundant pigment-laden macrophages. The tumor invaded the smooth muscle of the renal pelvis but it did not extend into the perinephric fat. Iron stains were negative, as were immunoperoxidase stains for keratin. Immunoperoxidase stains for S-100 protein and melanoma antigens were positive. The FontanaMasson stain was positive for melanin. Ultrastructural analysis revealed tumor cells that were predominantly polygonal in shape with round to oval nuclei and inconspicuous nucleoli. No desmosomal junctions were found but occasional sub-plasmalemmal densities were seen. Mitochondria were present in large numbers. An occasional premelanosome with its characteristic transverse striations was seen, which confirmed the melanocytic derivation of the neoplasm (fig. 4, B). Postoperatively, the patient underwent complete evaluation in search of a primary melanoma site. Meticulous dermatological examination with a Wood's light revealed no evidence of a regressed primary cutaneous lesion. Ophthalmologic examination was negative for an ocular primary tumor. A CT scan of the orbit and brain also was negative. A complete head and neck examination, including triple endoscopy, showed no evidence of tumor. Gastrointestinal studies, including upper and
FIG. 1. A, IVP suggests irregular, partially obstructive filling defect in right renal pelvis. B, retrograde pyelogram demonstrates smooth, rounded filling defect in renal pelvis. 812
813 lower series and pr,oc to,;ig:n1cnctos,~01JY weTe 0
NLHHU"'J'
negative,
The patient was on a bacillus Calmette-Guerin (BCG) and allogeneic melanoma cell vaccination protocol because of its relatively low toxicity and suggested efficacy as an adjuvant immunotherapy regimen in malignant melanoma, 6 Followup metastatic survey, including abdominal CT and chest x-ray, showed no evidence of visceral metastasis at 9 months, The patient experienced a recurrence at surgical incision 1 year after initial presentation, which was treated by wide excision. He was asymptomatic and without evidence of disease at 22month followup. DISCUSSION
The presence of a melanoma in the renal pelvis raises the question of whether this is a primary or secondary tumor. Until now no well documented case of primary malignant melanoma of the renal pelvis has been reported, 1 However, 2 cases have
FIG, 2, Abdominal CT scan shows right renal pelvic soft tissue mass and no other visceral lesions,
FIG, 3, Gross pathological specimen shows tan and yellow, variegated tumor that fills entire renal pelvis. Normal renal parenchyma is free of tumor,
been reported of malignant melanoma involving the renal pelvis in which the primary tumor was not clearly identified, 4 , 5 Agnew reported on a 57-year-old man with hematuria and a filling defect of the left renal pelvis on an IVP.4 Surgical exploration revealed malignant melanoma of the renal pelvis, as well as a metastatic node in the greater omentum. The site of the primary lesion was presumed to be in the diseased right eye, in which acute hemorrhage and blindness had developed 4 years before presentation. Ducassou and associates reported on a 42year-old man who presented with gross, painless hematuria and a left renal pelvic mass on an IVP. 5 The patient underwent left pyelotomy and excision of a malignant melanoma with good surgical margins, Metastatic studies, which did not include a CT scan, were negative except for a hypodense area in the right lobe of the liver on a liver-spleen scan. No primary tumor was found. The authors suggested that the primary site may have been the right eye, which had been lost in a previous accident. Judd reported on a similar patient who presented with hydronephrosis secondary to a left ureteral melanoma, 7 A pathological review of an eye enucleated 6 months previously for complications of glaucoma revealed a melanoma arising from the choroid layer. This patient also was found to have a right upper caliceal tumor at autopsy shortly thereafter. Two possible mechanisms have been proposed to explain the histogenesis of pigment-producing cells in urothelial tissue. 8 • 9 Ainsworth and associates postulated that ectopic melanocytes in the bladder mucosa gave rise to a primary malignant melanoma of the bladder, 8 An alternative theory was offered by Anichkov and Nikonov, who postulated that metaplasia of argyrophil urothelial stem cells may result in differentiation to neoplastic melanocytes. 9 While either theory may be extrapolated to explain primary malignant melanoma of the renal pelvis, we present supportive evidence in favor of the ectopic melanocyte theory. Melanophores, the precursor cells of melanocytes, arise from neural crest cells and migrate in the embryo to ectodermal and mesenchymal tissue. 10 These cells normally come to rest in the skin, mucous membranes, nervous tissue and the choroid layer of the eye, although their migration may be arrested anywhere in the mesenchymeo 8 The ureteral bud, the primordial structure of the ureter and the pelviocaliceal system, begins as a diverticulum off the caudal end of the mesonephric duct near the mesonephric-cloacaljunction. The mesonephric duct is thought to be a vestige of the degenerated pronephros, which derives from the intermediate mesoderm, Metastatic malignant melanoma presenting as a solitary lesion in the genitourinary tract is rare. Melanoma typically metastasizes as multiple small, purple or blue-black mucosal nodules, or as small foci in the renal parenchymao 2 These lesions tend to be asymptomatic but they may become clinically apparent by bleeding or by causing urinary tract obstruction.' Metastatic melanoma to the renal pelvis or ureter is particularly rare. A recent review of the literature by Stein and
FIG, 4, A, microscopic appearance of tumor shows markedly pleomorphic cells with abundant eosinophilic cytoplasm, Nuclei are large and contain occasional intranuclear invaginations. Moderate numbers of mitotic figures are present, H & E, reduced from X400. B, electron micrograph depicts solitary pre-melanosome with striated substructure, Reduced from X140,000,
814
FRASIER AND ASSOCIATES
Kendall revealed less than 25 such reported cases. 1 Similarly, they found a 1 to 6 per cent incidence of renal pelvic or ureteral involvement in published autopsy series of patients dying of malignant melanoma. It is interesting to consider our case as a primary malignant melanoma arising in the renal pelvis. Certainly, plausible hypotheses have been offered to explain the occurrence of a primary lesion in this unusual site. In addition, exhaustive clinical studies with state of the art technology have failed to identify any other source of primary melanoma or synchronous metastasis. It would be truly unusual for a metastatic lesion to grow to such proportions in an uncommon site in the absence of other metastatic tumors. However, given the protean nature of malignant melanoma, anything seems possible. Dr. Louis Recher, Department of Pathology, UCI Medical Center, provided the electron microscopy and Dr. Jean B. deKernion reviewed the manuscript. REFERENCES
1. Stein, B. S. and Kendall, A. R.: Malignant melanoma of the genitourinary tract. J. Urol., 132: 859, 1984.
2. Abeshouse, B. S.: Primary and secondary melanoma of the genitourinary tract. South. Med. J., 51: 994, 1958. 3. Das Gupta, T. and Grabstald, H.: Melanoma of the genitourinary tract. J. Urol., 93: 607, 1965. 4. Agnew, C. H.: Metastatic malignant melanoma of the kidney simulating a primary neoplasm. A case report. Amer. J. Roentgen., 80: 813, 1958. 5. Ducassou, J., Richaud, C., Duvinage, J. F., Hermandowicz, M. and Jacquemier, J.: Apropos d'un cas de melanome du bassinet. J. Urol. Nephrol., 83: 651, 1977. 6. Morton, D. L., Nizze, J. A., Gupta, R. K., Famatiga, E., Hoon, D. S. B. and Irie, R. F.: Active specific immunotherapy of malignant melanoma. Proceedings of Eighth Asian-Pacific Cancer Conference, Seoul, Korea, pp. 152-161, 1987. 7. Judd, R. L.: Melanoma of the ureter: a case report. J. Urol., 87: 805, 1962. 8. Ainsworth, A. M., Clark, W. H., Jr., Mastrangelo, M. and Conger, K. B.: Primary malignant melanoma of the urinary bladder. Cancer, 37: 1928, 1976. 9. Anichkov, N. M. and Nikonov, A. A.: Primary malignant melanomas of the bladder. J. Urol., 128: 813, 1982. 10. Rawles, M. E.: Origin of pigment cells from the neural crest in the mouse embryo. Physiol. Zoo!., 20: 248, 1947.
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright © 1988 by The Williams & Wilkins Co.
MALIGNANT MELANOMA OF THE RENAL PELVIS PRESENTING AS A PRIMARY TUMOR BRADLEY L. FRASIER, BARTON H. WACHS, LUKER. WATSON
AND
JOSEPH P. TOMASULO
From the Division of Urology, Department of Surgery, UCLA School of Medicine, Los Angeles, and Departments of Urology and Pathology, Memorial Medical Center, Long Beach, California
ABSTRACT
We report a case of malignant melanoma of the renal pelvis presenting as a primary tumor and review the relevant literature. (J. Ural., 140: 812-813, 1988) Malignant melanoma of the urinary tract is rare. Most cases are not clinically apparent and they are discovered only at autopsy after death of widespread metastases. 1- 3 Two cases of malignant melanoma presenting as a renal pelvic mass have been reported previously. 4 •5 We report a third case, which may represent the first well documented example of primary malignant melanoma of the renal pelvis. CASE REPORT
D. H., a 37-year-old white man, presented to the emergency room in July 1986 with gross hematuria associated with right flank pain. History was negative for major medical illnesses, previous hematuria, urinary calculi or surgery. He denied any history of suspicious skin lesions or regression of atypical nevi. Physical examination was significant for right flank and costovertebral angle tenderness. Laboratory examination was unremarkable except for an elevated serum uric acid (9.4 mg.jdl.) (normal 3.0 to 7_0) and a full field of red blood cells on urinalysis. An excretory urogram (IVP) revealed a filling defect in the right renal pelvis that was confirmed by a retrograde pyelogram (fig. 1). Ureteral washings and pelvic brushings demonstrated atypical cells but they were not diagnostic for malignancy. Ureteroscopy showed no intraluminal ureteral lesions but attempted pyeloscopy was unsuccessful. An abdominal computerized tomography (CT) scan revealed a rounded, soft tissue density confined to the right renal pelvis and no evidence of visceral metastasis (fig. 2). A bone scan was similarly negative. After a second unsuccessful attempt at visualization of the renal pelvic mass by retrograde pyeloscopy, the patient underwent exploration of the right renal pelvis. A moderately firm, tan and yellow variegated tumor with focal areas of pigmentation and hemorrhage was found. Frozen section of the tumor confirmed the presence of poorly differentiated carcinoma, Accepted for publication January 28, 1988.
initially thought to be transitional cell carcinoma, and a nephroureterectomy was performed. On gross pathological examination the tumor measured 5.0 X 4.0 X 3.0 cm. and it filled the entire renal pelvis (fig. 3). It was adherent to the posterior wall but it did not extend into the renal parenchyma. The remainder of the surgical specimen, including the ureter and vascular structures, was free of tumor. Histological evaluation of the tumor revealed organized nests of cells with large hyperchromatic nuclei and occasional intranuclear invaginations (fig. 4, A). The cytoplasm of the tumor cells was highly eosinophilic and a moderate number of mitotic figures were identified. There were isolated areas in which some tumor cells contained a fine dust-like golden pigment within the cytoplasm. The renal pelvis adjacent to the tumor was lined by normal transitional cell epithelium and it contained abundant pigment-laden macrophages. The tumor invaded the smooth muscle of the renal pelvis but it did not extend into the perinephric fat. Iron stains were negative, as were immunoperoxidase stains for keratin. Immunoperoxidase stains for S-100 protein and melanoma antigens were positive. The FontanaMasson stain was positive for melanin. Ultrastructural analysis revealed tumor cells that were predominantly polygonal in shape with round to oval nuclei and inconspicuous nucleoli. No desmosomal junctions were found but occasional sub-plasmalemmal densities were seen. Mitochondria were present in large numbers. An occasional premelanosome with its characteristic transverse striations was seen, which confirmed the melanocytic derivation of the neoplasm (fig. 4, B). Postoperatively, the patient underwent complete evaluation in search of a primary melanoma site. Meticulous dermatological examination with a Wood's light revealed no evidence of a regressed primary cutaneous lesion. Ophthalmologic examination was negative for an ocular primary tumor. A CT scan of the orbit and brain also was negative. A complete head and neck examination, including triple endoscopy, showed no evidence of tumor. Gastrointestinal studies, including upper and
FIG. 1. A, IVP suggests irregular, partially obstructive filling defect in right renal pelvis. B, retrograde pyelogram demonstrates smooth, rounded filling defect in renal pelvis. 812
813 lower series and pr,oc to,;ig:n1cnctos,~01JY weTe 0
NLHHU"'J'
negative,
The patient was on a bacillus Calmette-Guerin (BCG) and allogeneic melanoma cell vaccination protocol because of its relatively low toxicity and suggested efficacy as an adjuvant immunotherapy regimen in malignant melanoma, 6 Followup metastatic survey, including abdominal CT and chest x-ray, showed no evidence of visceral metastasis at 9 months, The patient experienced a recurrence at surgical incision 1 year after initial presentation, which was treated by wide excision. He was asymptomatic and without evidence of disease at 22month followup. DISCUSSION
The presence of a melanoma in the renal pelvis raises the question of whether this is a primary or secondary tumor. Until now no well documented case of primary malignant melanoma of the renal pelvis has been reported, 1 However, 2 cases have
FIG, 2, Abdominal CT scan shows right renal pelvic soft tissue mass and no other visceral lesions,
FIG, 3, Gross pathological specimen shows tan and yellow, variegated tumor that fills entire renal pelvis. Normal renal parenchyma is free of tumor,
been reported of malignant melanoma involving the renal pelvis in which the primary tumor was not clearly identified, 4 , 5 Agnew reported on a 57-year-old man with hematuria and a filling defect of the left renal pelvis on an IVP.4 Surgical exploration revealed malignant melanoma of the renal pelvis, as well as a metastatic node in the greater omentum. The site of the primary lesion was presumed to be in the diseased right eye, in which acute hemorrhage and blindness had developed 4 years before presentation. Ducassou and associates reported on a 42year-old man who presented with gross, painless hematuria and a left renal pelvic mass on an IVP. 5 The patient underwent left pyelotomy and excision of a malignant melanoma with good surgical margins, Metastatic studies, which did not include a CT scan, were negative except for a hypodense area in the right lobe of the liver on a liver-spleen scan. No primary tumor was found. The authors suggested that the primary site may have been the right eye, which had been lost in a previous accident. Judd reported on a similar patient who presented with hydronephrosis secondary to a left ureteral melanoma, 7 A pathological review of an eye enucleated 6 months previously for complications of glaucoma revealed a melanoma arising from the choroid layer. This patient also was found to have a right upper caliceal tumor at autopsy shortly thereafter. Two possible mechanisms have been proposed to explain the histogenesis of pigment-producing cells in urothelial tissue. 8 • 9 Ainsworth and associates postulated that ectopic melanocytes in the bladder mucosa gave rise to a primary malignant melanoma of the bladder, 8 An alternative theory was offered by Anichkov and Nikonov, who postulated that metaplasia of argyrophil urothelial stem cells may result in differentiation to neoplastic melanocytes. 9 While either theory may be extrapolated to explain primary malignant melanoma of the renal pelvis, we present supportive evidence in favor of the ectopic melanocyte theory. Melanophores, the precursor cells of melanocytes, arise from neural crest cells and migrate in the embryo to ectodermal and mesenchymal tissue. 10 These cells normally come to rest in the skin, mucous membranes, nervous tissue and the choroid layer of the eye, although their migration may be arrested anywhere in the mesenchymeo 8 The ureteral bud, the primordial structure of the ureter and the pelviocaliceal system, begins as a diverticulum off the caudal end of the mesonephric duct near the mesonephric-cloacaljunction. The mesonephric duct is thought to be a vestige of the degenerated pronephros, which derives from the intermediate mesoderm, Metastatic malignant melanoma presenting as a solitary lesion in the genitourinary tract is rare. Melanoma typically metastasizes as multiple small, purple or blue-black mucosal nodules, or as small foci in the renal parenchymao 2 These lesions tend to be asymptomatic but they may become clinically apparent by bleeding or by causing urinary tract obstruction.' Metastatic melanoma to the renal pelvis or ureter is particularly rare. A recent review of the literature by Stein and
FIG, 4, A, microscopic appearance of tumor shows markedly pleomorphic cells with abundant eosinophilic cytoplasm, Nuclei are large and contain occasional intranuclear invaginations. Moderate numbers of mitotic figures are present, H & E, reduced from X400. B, electron micrograph depicts solitary pre-melanosome with striated substructure, Reduced from X140,000,
814
FRASIER AND ASSOCIATES
Kendall revealed less than 25 such reported cases. 1 Similarly, they found a 1 to 6 per cent incidence of renal pelvic or ureteral involvement in published autopsy series of patients dying of malignant melanoma. It is interesting to consider our case as a primary malignant melanoma arising in the renal pelvis. Certainly, plausible hypotheses have been offered to explain the occurrence of a primary lesion in this unusual site. In addition, exhaustive clinical studies with state of the art technology have failed to identify any other source of primary melanoma or synchronous metastasis. It would be truly unusual for a metastatic lesion to grow to such proportions in an uncommon site in the absence of other metastatic tumors. However, given the protean nature of malignant melanoma, anything seems possible. Dr. Louis Recher, Department of Pathology, UCI Medical Center, provided the electron microscopy and Dr. Jean B. deKernion reviewed the manuscript. REFERENCES
1. Stein, B. S. and Kendall, A. R.: Malignant melanoma of the genitourinary tract. J. Urol., 132: 859, 1984.
2. Abeshouse, B. S.: Primary and secondary melanoma of the genitourinary tract. South. Med. J., 51: 994, 1958. 3. Das Gupta, T. and Grabstald, H.: Melanoma of the genitourinary tract. J. Urol., 93: 607, 1965. 4. Agnew, C. H.: Metastatic malignant melanoma of the kidney simulating a primary neoplasm. A case report. Amer. J. Roentgen., 80: 813, 1958. 5. Ducassou, J., Richaud, C., Duvinage, J. F., Hermandowicz, M. and Jacquemier, J.: Apropos d'un cas de melanome du bassinet. J. Urol. Nephrol., 83: 651, 1977. 6. Morton, D. L., Nizze, J. A., Gupta, R. K., Famatiga, E., Hoon, D. S. B. and Irie, R. F.: Active specific immunotherapy of malignant melanoma. Proceedings of Eighth Asian-Pacific Cancer Conference, Seoul, Korea, pp. 152-161, 1987. 7. Judd, R. L.: Melanoma of the ureter: a case report. J. Urol., 87: 805, 1962. 8. Ainsworth, A. M., Clark, W. H., Jr., Mastrangelo, M. and Conger, K. B.: Primary malignant melanoma of the urinary bladder. Cancer, 37: 1928, 1976. 9. Anichkov, N. M. and Nikonov, A. A.: Primary malignant melanomas of the bladder. J. Urol., 128: 813, 1982. 10. Rawles, M. E.: Origin of pigment cells from the neural crest in the mouse embryo. Physiol. Zoo!., 20: 248, 1947.