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Amyloidosis of the Urethra
0022-534 7/89 /1411-0052$2.00/0 Vol. 141, January Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright© 1989 by The Williams & Wilkins Co.
AMYLOIDOSIS OF THE URETHRA THOMAS J. STILLWELL, JOSEPH W. SEGURA*
AND
GEORGE M. FARROW
From the Department of Urology and Section of Surgical Pathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
ABSTRACT
Primary, localized amyloidosis of the urethra is rare. The patient usually presents with hematuria and the appearance of urethral carcinoma. However, the disease is benign and it is treated effectively with local removal. We report our experience with 5 cases. (J. Ural., 141: 52-53, 1989) Amyloidosis is an unusual benign disease wherein tissues accumulate deposits of eosinophilic, extracellular, fibrils of protein material. A clinical classification of amyloidosis and amyloid deposits was outlined by Glenner and Page.' Systemic amyloidosis includes amyloid deposits related to plasma cell dyscrasias, heredofamilial diseases and secondary amyloidosis related to chronic inflammatory or neoplastic conditions (osteomyelitis, rheumatoid arthritis, chronic granulomatous disease or neoplasms, such as Hodgkin's lymphoma). Organ involvement often includes the kidney, tongue, liver, gastrointestinal tract and heart. Localized amyloid deposition is confined to a single organ system and usually has no predisposing etiology. Occasionally, local deposits are related to neoplastic masses of a metastasizing tumor.' Localized amyloid disease of the urethra is rare with about 20 previously reported cases. 2 - 10 To the urologist it is important because the patient often presents with hematuria and on examination the disease masquerades as a urethral malignancy. However, the process is benign and rarely requires more than local excision.
row studies and rectal biopsy. Patients were followed for 1 to 8 years after diagnosis and no patient had a local recurrence or systemic progression of the disease. DISCUSSION
Localized amyloid deposits in the urethra appear to occur only in men within a wide age range (25 to 82 years), with a predilection for the older age groups (more than 50 years). 6 • 8 • 9 As in our 5 patients, they are frequently misdiagnosed as urethral malignancy. Patients with bladder amyloidosis usually present with a similar pre-biopsy diagnosis." Hematuria has been a common finding in urethral amyloid
CLINICAL MATERIAL
During the last 40 years, 5 cases of amyloidosis of the urethra were seen at our clinic (see table). All patients were men 35 to 75 years old. All had primary localized amyloid deposits in the urethra without evidence of systemic amyloidosis, or a history of a predisposing chronic inflammatory or neoplastic disease. Histological diagnosis was made by special stains of either methyl violet, Congo red or thioflavin T (fig. 1). To attempt to identify cause for amyloid development (secondary amyloidosis) and to document a lack of systemic involvement, patients underwent a general medical evaluation and special testing, including serum and urine immunoelectrophoresis, bone marFIG. 1. Penile urethral amyloidosis. Urethral lining demonstrates thick squamous metaplasia deep to which is intense subendothelial deposit of amyloid filling entire submucosal space. H & E, reduced from X64.
Accepted for publication May 12, 1988. * Requests for reprints: Department of Urology, Mayo Clinic, 200 First St., S.W., Rochester, Minnesota 55905.
Amyloidosis of the male urethra Pt. 1 Age (yrs.) Symptoms Duration (mos.) Urethroscopy Location Ca suspected Urinalysis
Pt. 2
Pt. 3
Pt. 4
Pyuria, microhematuria
12 Ragged mucosa Penile urethra Yes Microhematuria
36 Ragged mucosa Penile urethra Yes Pyuria, microhe-
Biopsy and removal
Biopsy and removal
Biopsy and removal
Biopsy, neodymium:YAG laser
62 Frequency,urgency
Biopsy and dilation
120 Shaggy mucosa Prostatic urethra Yes
61 Painless gross hematuria, hematosper-
Pt. 5
35 Painless gross hematuria, hematospermia 3 Nodule Bulbous urethra Yes Neg.
48 Hematuria, yellow urethral discharge 24 Ragged mucosa Penile urethra Yes Pyuria
75 Dysuria, urethral pain
mia
maturia
Treatment
52
I\
53
AMYLOIDOSIS OF URETHRA
deposits. 6 •7 Symptoms also can include urethral discharge or pain, hematospermia or obstructive voiding complaints. An indurated urethral segment may be palpated. 6 - 8 A retrograde urethrogram may show an intraurethral filling defect or a stricture. Endoscopically, the lesions are ragged, ulcerated and often hard and fixed. They can partially occlude the urethral lumen. Given the older age group of men, and the aforementioned symptoms and clinical findings, a mimicking of urethral carcinoma is not surprising. The diagnosis is made with adequate biopsy and appropriate staining of the specimen. With light microscopy amyloid stains black with iodine and shows an apple-green birefringence with Congo red under polarized light (fig. 2). Amyloid protein fibrils are identified by electron microscopy. Amyloid may represent a tissue deposit of the variable portion of immunoglobulin light chains coming from an isolated clone of plasma cells. 1 • 12 Given the histological diagnosis of amyloid, if there are clinical suspicions of systemic amyloidosis, or the presence of a predisposing disease or familial condition' an attempt should be made to exclude the presence of systemic disease or other organ involvement. Screening studies might include serum and urine immunoelectrophoresis for special proteins, chest radiograph, electrocardiogram, bone marrow biopsy and proctoscopy with
FIG. 2. Bulbous urethra amyloidosis. Aggregates of amyloid stained with Congo red will show apple-green birefringence when visualized under polarized light. Congo red, reduced from X64.
rectal biopsy. This evaluation probably is unwarranted if the amyloid deposit appears to be a localized condition only. Previously biopsied lesions that occurred in a similar area should be reviewed and examined for undiagnosed amyloid. Initially, small deposits of amyloid may have been overlooked in these prior biopsies. After urethral amyloid is diagnosed therapy should be instituted only when aimed at relieving symptoms, such as urethral bleeding, discharge or pain, or at resolving obstructed voiding. Removal or destruction of amyloid deposits usually can be accomplished by transurethral biopsy, resection or laser fulguration. Other treatments for larger amyloid masses have included open urethral resection and reconstruction. 6 •8 • 13 In most cases localized urethral amyloid does not recur after removal and the development of systemic amyloidosis has not been reported. Thus, the prognosis for this benign process is excellent. REFERENCES
1. Glenner, G. G. and Page, D. L.: Amyloid, amyloidosis, and amyloidogenesis. Int. Rev. Exp. Path., 15: 1, 1976. 2. Ullmann, A. S., Fine, G. and Johnson, A. J.: Localized amyloidosis (amyloid tumor) of the urethra. J. Urol., 92: 42, 1964. 3. Branson, A. D., Kiser, W. S., Gifford, R. W., Jr. and Tung, K. S. K.: Localized amyloidosis of the urethra: report of a case. J. Urol., 101: 68, 1969. 4. Carris, C. K., McLaughlin, A. P., III and Gittes, R. F.: Amyloidosis of the lower genitourinary tract. J. Urol., 115: 423, 1976. 5. Constantian, H. M. and Wyman, P.: Localized amyloidosis of the urethra: report of a case. J. Urol., 124: 728, 1980. 6. Fujime, M., Tajima, A., Minowada, S., Kobayashi, K., Murahashi, I., Isurugi, K. and Aso, Y.: Localized amyloidosis of urethra: report of two cases. Eur. Urol., 7: 189, 1981. 7. Walzer, Y., Bear, R. A., Colapinto, V., McCallum, R. and Lang, A.: Localized amyloidosis of urethra. Urology, 21: 406, 1983. 8. Kaisary, A. V.: Primary localised amyloidosis of the urethra. Eur. Urol., 11: 209, 1985. 9. Dounis, A., Bourounis, M. and Mitropoulos, D.: Primary localized amyloidosis of the urethra. Eur. Urol., 11: 344, 1985. 10. Rosenbaum, T. P., Nicholas, D. S. and Rundle, J. S. H.: Localised amyloidosis of the urethra. Brit. J. Urol., 60: 183, 1987. 11. Malek, R. S., Greene, L. F. and Farrow, G. M.: Amyloidosis of the urinary bladder. Brit. J. Urol., 43: 189, 1971. 12. Glenner, G. G., Ein, D. and Terry, W. D.: The immunoglobulin origin of amyloid. Amer. J. Med., 52: 141, 1972. 13. Bodner, H., Retsky, M. I. and Brown, G.: Primary amyloidosis of glans penis and urethra: resection and reconstruction. J. Urol., 125: 586, 1981.
THE JOURNAL OF UROLOGY
Copyright© 1989 by The Williams & Wilkins Co.
AMYLOIDOSIS OF THE URETHRA THOMAS J. STILLWELL, JOSEPH W. SEGURA*
AND
GEORGE M. FARROW
From the Department of Urology and Section of Surgical Pathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota
ABSTRACT
Primary, localized amyloidosis of the urethra is rare. The patient usually presents with hematuria and the appearance of urethral carcinoma. However, the disease is benign and it is treated effectively with local removal. We report our experience with 5 cases. (J. Ural., 141: 52-53, 1989) Amyloidosis is an unusual benign disease wherein tissues accumulate deposits of eosinophilic, extracellular, fibrils of protein material. A clinical classification of amyloidosis and amyloid deposits was outlined by Glenner and Page.' Systemic amyloidosis includes amyloid deposits related to plasma cell dyscrasias, heredofamilial diseases and secondary amyloidosis related to chronic inflammatory or neoplastic conditions (osteomyelitis, rheumatoid arthritis, chronic granulomatous disease or neoplasms, such as Hodgkin's lymphoma). Organ involvement often includes the kidney, tongue, liver, gastrointestinal tract and heart. Localized amyloid deposition is confined to a single organ system and usually has no predisposing etiology. Occasionally, local deposits are related to neoplastic masses of a metastasizing tumor.' Localized amyloid disease of the urethra is rare with about 20 previously reported cases. 2 - 10 To the urologist it is important because the patient often presents with hematuria and on examination the disease masquerades as a urethral malignancy. However, the process is benign and rarely requires more than local excision.
row studies and rectal biopsy. Patients were followed for 1 to 8 years after diagnosis and no patient had a local recurrence or systemic progression of the disease. DISCUSSION
Localized amyloid deposits in the urethra appear to occur only in men within a wide age range (25 to 82 years), with a predilection for the older age groups (more than 50 years). 6 • 8 • 9 As in our 5 patients, they are frequently misdiagnosed as urethral malignancy. Patients with bladder amyloidosis usually present with a similar pre-biopsy diagnosis." Hematuria has been a common finding in urethral amyloid
CLINICAL MATERIAL
During the last 40 years, 5 cases of amyloidosis of the urethra were seen at our clinic (see table). All patients were men 35 to 75 years old. All had primary localized amyloid deposits in the urethra without evidence of systemic amyloidosis, or a history of a predisposing chronic inflammatory or neoplastic disease. Histological diagnosis was made by special stains of either methyl violet, Congo red or thioflavin T (fig. 1). To attempt to identify cause for amyloid development (secondary amyloidosis) and to document a lack of systemic involvement, patients underwent a general medical evaluation and special testing, including serum and urine immunoelectrophoresis, bone marFIG. 1. Penile urethral amyloidosis. Urethral lining demonstrates thick squamous metaplasia deep to which is intense subendothelial deposit of amyloid filling entire submucosal space. H & E, reduced from X64.
Accepted for publication May 12, 1988. * Requests for reprints: Department of Urology, Mayo Clinic, 200 First St., S.W., Rochester, Minnesota 55905.
Amyloidosis of the male urethra Pt. 1 Age (yrs.) Symptoms Duration (mos.) Urethroscopy Location Ca suspected Urinalysis
Pt. 2
Pt. 3
Pt. 4
Pyuria, microhematuria
12 Ragged mucosa Penile urethra Yes Microhematuria
36 Ragged mucosa Penile urethra Yes Pyuria, microhe-
Biopsy and removal
Biopsy and removal
Biopsy and removal
Biopsy, neodymium:YAG laser
62 Frequency,urgency
Biopsy and dilation
120 Shaggy mucosa Prostatic urethra Yes
61 Painless gross hematuria, hematosper-
Pt. 5
35 Painless gross hematuria, hematospermia 3 Nodule Bulbous urethra Yes Neg.
48 Hematuria, yellow urethral discharge 24 Ragged mucosa Penile urethra Yes Pyuria
75 Dysuria, urethral pain
mia
maturia
Treatment
52
I\
53
AMYLOIDOSIS OF URETHRA
deposits. 6 •7 Symptoms also can include urethral discharge or pain, hematospermia or obstructive voiding complaints. An indurated urethral segment may be palpated. 6 - 8 A retrograde urethrogram may show an intraurethral filling defect or a stricture. Endoscopically, the lesions are ragged, ulcerated and often hard and fixed. They can partially occlude the urethral lumen. Given the older age group of men, and the aforementioned symptoms and clinical findings, a mimicking of urethral carcinoma is not surprising. The diagnosis is made with adequate biopsy and appropriate staining of the specimen. With light microscopy amyloid stains black with iodine and shows an apple-green birefringence with Congo red under polarized light (fig. 2). Amyloid protein fibrils are identified by electron microscopy. Amyloid may represent a tissue deposit of the variable portion of immunoglobulin light chains coming from an isolated clone of plasma cells. 1 • 12 Given the histological diagnosis of amyloid, if there are clinical suspicions of systemic amyloidosis, or the presence of a predisposing disease or familial condition' an attempt should be made to exclude the presence of systemic disease or other organ involvement. Screening studies might include serum and urine immunoelectrophoresis for special proteins, chest radiograph, electrocardiogram, bone marrow biopsy and proctoscopy with
FIG. 2. Bulbous urethra amyloidosis. Aggregates of amyloid stained with Congo red will show apple-green birefringence when visualized under polarized light. Congo red, reduced from X64.
rectal biopsy. This evaluation probably is unwarranted if the amyloid deposit appears to be a localized condition only. Previously biopsied lesions that occurred in a similar area should be reviewed and examined for undiagnosed amyloid. Initially, small deposits of amyloid may have been overlooked in these prior biopsies. After urethral amyloid is diagnosed therapy should be instituted only when aimed at relieving symptoms, such as urethral bleeding, discharge or pain, or at resolving obstructed voiding. Removal or destruction of amyloid deposits usually can be accomplished by transurethral biopsy, resection or laser fulguration. Other treatments for larger amyloid masses have included open urethral resection and reconstruction. 6 •8 • 13 In most cases localized urethral amyloid does not recur after removal and the development of systemic amyloidosis has not been reported. Thus, the prognosis for this benign process is excellent. REFERENCES
1. Glenner, G. G. and Page, D. L.: Amyloid, amyloidosis, and amyloidogenesis. Int. Rev. Exp. Path., 15: 1, 1976. 2. Ullmann, A. S., Fine, G. and Johnson, A. J.: Localized amyloidosis (amyloid tumor) of the urethra. J. Urol., 92: 42, 1964. 3. Branson, A. D., Kiser, W. S., Gifford, R. W., Jr. and Tung, K. S. K.: Localized amyloidosis of the urethra: report of a case. J. Urol., 101: 68, 1969. 4. Carris, C. K., McLaughlin, A. P., III and Gittes, R. F.: Amyloidosis of the lower genitourinary tract. J. Urol., 115: 423, 1976. 5. Constantian, H. M. and Wyman, P.: Localized amyloidosis of the urethra: report of a case. J. Urol., 124: 728, 1980. 6. Fujime, M., Tajima, A., Minowada, S., Kobayashi, K., Murahashi, I., Isurugi, K. and Aso, Y.: Localized amyloidosis of urethra: report of two cases. Eur. Urol., 7: 189, 1981. 7. Walzer, Y., Bear, R. A., Colapinto, V., McCallum, R. and Lang, A.: Localized amyloidosis of urethra. Urology, 21: 406, 1983. 8. Kaisary, A. V.: Primary localised amyloidosis of the urethra. Eur. Urol., 11: 209, 1985. 9. Dounis, A., Bourounis, M. and Mitropoulos, D.: Primary localized amyloidosis of the urethra. Eur. Urol., 11: 344, 1985. 10. Rosenbaum, T. P., Nicholas, D. S. and Rundle, J. S. H.: Localised amyloidosis of the urethra. Brit. J. Urol., 60: 183, 1987. 11. Malek, R. S., Greene, L. F. and Farrow, G. M.: Amyloidosis of the urinary bladder. Brit. J. Urol., 43: 189, 1971. 12. Glenner, G. G., Ein, D. and Terry, W. D.: The immunoglobulin origin of amyloid. Amer. J. Med., 52: 141, 1972. 13. Bodner, H., Retsky, M. I. and Brown, G.: Primary amyloidosis of glans penis and urethra: resection and reconstruction. J. Urol., 125: 586, 1981.