Vol. 115, April
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1976 by The Williams & Wilkins Co.
AMYLOIDOSIS OF THE LOWER GENITOURINARY TRACT CRAIG K. CARRIS, A. P. MCLAUGHLIN, III*
AND
RUBEN F. GITTES*
From the Division of Urology, Department of Surgery, University Hospital, University of California School of Medicine, San Diego, California ABSTRACT
I i
Three patients with amyloidosis of the lower genitourinary tract are described. In the cases of primary localized amyloidosis of the urethra and primary systemic amyloidosis involving the prostate the clinical presentation mimicked cancer of the respective sites. In the case of secondary localized amyloidosis of the seminal vesicles chronic perineal pain suggested seminal vesiculitis. Amyloidosis is a rare disease of obscure etiology, characterized by the extracellular deposition of a homogenous eosinophilic fibrillar protein in various tissues. It is of interest to the urologist because its clinical presentation in the lower genitourinary tract almost always masquerades as a tumor of the involved tissue. Primary and secondary amyloidosis can involve the lower genitourinary tract. Primary amyloidosis occurs de novo in the absence of chronic disease. It is classified as 1) the systemic form with deposition in multiple organs or 2) the localized form in which involvement is limited to the affected organ. The secondary form is found in association with chronic granulomatosis disease, rheumatoid arthritis, decubitis ulcers, multiple myeloma and other tumors. 1 Primary localized amyloid of the urethra has been reported only 9 times previously.2 Herein we report the tenth case. Primary amyloidosis of the seminal vesicles occurs slightly more frequently but there have been no reported cases of symptomatic amyloidosis of the seminal vesicles to our knowledge. We report herein a case of chronic perinea! pain associated with localized amyloidosis of the seminal vesicles. Although less unusual we report a case of primary systemic amyloidosis involving the prostate to illustrate the fact that this can be confused clinically with adenocarcinoma of the prostate. CASE REPORTS
Case 1. Amyloidosis of the male urethra (UH 593-032): A 63-year-old physician was seen with a 3-month history of a brownish-red urethral discharge. He was in excellent health and denied other symptoms except for some decreasing force of stream and occasional nocturia. The patient had treated himself with penicillin and erythromycin with no improvement. Physical examination was entirely normal except for an enlarged, benign-feeling prostate. Urinalysis showed no protein, 5 to 10 white cells and 1 to 2 red cells per high power field. Urine culture was negative and an excretory urogram (IVP) was normal except for some thickening of the bladder wall consistent with long-standing benign prostatic hypertrophy. A retrograde urethrogram revealed a discrete lesion at the penoscrotal junction (fig. 1, A). Urethroscopy revealed a semicircular, friable, ulcerated lesion of the urethral wall in the distal bulbous urethra (fig. 2). The lesion was approximately 180 degrees in circumference. Palpation suggested no involvement of the corpus spongiosum. Endoscopic transurethral biopsy proved the lesion to be amyloidosis, although it was believed to be carcinoma clinically. Accepted for publication August 1, 1975. Read at annual meeting of Western Section, American Urological Association, Portland, Oregon, April 13-17, 1975. * Current address: Peter Bent Brigham Hospital, Boston, Massachusetts 02115.
Therefore, the patient was evaluated for any evidence of systemic amyloidosis. There was no history suggestive of chronic inflammatory disease. There was no macroglossia, extensive cardiac examination was normal and there was no organomegaly in the abdomen. Renal and liver function tests, chest x-ray, electrocardiogram, serum and urine protein electrophoresis, and serum immunoelectrophoresis were all normal. The patient declined a bone marrow aspiration. After a repeat urethrogram 5 months later (fig. 1, B) the amyloid deposit was resected transurethrally. Since the lesion was not completely circumferential an area between 12 and 3 o'clock was left intact as the resection was carried down into the corpus spongiosum. There was no evidence of amyloidosis elsewhere in the genitourinary tract. Histological examination of the tissue showed extensive submucosal infiltration of amyloid (fig. 3). Case 2. Amyloidosis of the seminal vesicles (UH 604-238): A 61-year-old male truck driver had obstructive urinary symptoms and perinea! discomfort exacerbated by sitting. There was no history of dysuria or hematuria and the man denied ejaculatory pain. The patient had had a transverse colectomy for adenocarcinoma of the colon 1 year earlier. He had had urethral catheter drainage for several days after the colon operation. There was no history of arthritis or tuberculosis and no evidence for recurrence of the colon tumor. The prostate and rectal examinations were normal. The patient was given antibiotics but the perinea! pain was not relieved. A wide caliber stricture of the bulbous urethra and a prominent median lobe of the prostate with associated mild bladder trabeculation were found. An internal urethrotomy and transurethral resection of the prostate were done but the perinea! pain was not relieved. Prostatic tissue showed benign hyperplasia. Subsequent examination revealed extreme tenderness to palpation of the prostate and seminal vesicles. Urinalysis and renal and liver function tests were normal. Cystoscopy revealed a hyperemic, edematous mucosa in the prostatic urethra. Vasograms were normal except for mild dilatation of the right vas deferens. Culture of the prostatic secretions was negative. The patient was believed to have seminal vesiculitis and was treated with antibiotics but the disabling perinea! pain persisted. He was treated with a total prostatectomy and seminal vesiculectomy. At operation a dilated, tortuous right seminal vesicle was found extending across the midline. Three months postoperatively the perinea! pain was much improved. Microscopic secretions unexpectedly revealed dense infiltration of both seminal vesicles with amyloid causing the frondular pattern to be markedly thickened and distorted (fig. 4). Because amyloidosis of the seminal vesicles was found a diagnostic study was undertaken to determine if there was evidence for systemic amyloidosis. Serum and urine protein electrophoresis, and immunoelectrophoresis were normal, as was the electrocardiogram, bone marrow aspiration and creatinine clearance.
423
424
CARRIS, MCLAUGHLIN AND GITTES
Fm. 3. Dense subendothelial deposition of amyloid in urethra
found. Abnormal laboratory tests included a hemoglobin of9.9 gm. per cent, an elevated erythrocyte sedimentation rate, increased prothrombin and partial thromboplastin times, a blood urea nitrogen of 31 and a creatinine of 2.1. Liver function tests were normal except for a decreased albumin of 3.4 gm. per cent. Acid phosphate was elevated at 1.0 units (normal 0.13 to 0.63), with a prostatic fraction of 0.1 (normal less than 0.15). Urinalysis showed 3-plus proteinuria with 3 to 5 white cells Fm. 1. A, retrograde urethrogram demonstrates lesion in bulbous per high power field. Urine for Bence Jones protein was urethra. B, same lesion 5 months later. negative. Serum protein electrophoresis showed a mildly decreased albumin. Serum immunoelectrophoresis showed normal lgG and lgA but a decreased IgM. Chest x-ray showed mild, generalized cardiomegaly. An IVP showed some scarring of the right kidney believed to be secondary to previous pyelolithotomy. An upper gastrointestinal series and barium enema were normal. Subsequent bone marrow aspiration showed plasma cell hyperplasia. The hard prostate and the elevated total acid phosphatase led to the diagnosis of metastatic cancer of the prostate. Prostatic biopsy demonstrated nodular hyperplasia, and acute and chronic inflammation. The patient returned to his residence in Canada where the persistent leg pain led to a muscle biopsy, which demonstrated amyloidosis. When the information was known to us the prostatic tissue was stained with Congo red and showed classical features of amyloidosis. Since no predisposing cause could be found this patient falls into the category of primary systemic amyloidosis. Fm. 2. Amyloidosis of urethra at endoscopy
Case 3. Amyloidosis of the prostate (UH 520821): A 58-yearold male mechanic was first seen at our hospital in December 1971 for evaluation of fatigue, anemia and right thigh pain. In late 1971 the patient had to stop working because of increasing fatigue. He was noted to be anemic and the prothrombin and partial thromboplastin times were reportedly markedly elevated, although there was no history of alcohol ingestion. History included dilatation of a urethral stricture in 1966 and 1971. There was no history of chronic inflammatory disease. On physical examination a slightly enlarged tongue, mild cardiomegaly, quadriceps tenderness associated with a peripheral neuropathy and indurated right lobe of the prostate were
DISCUSSION
Primary localized amyloidosis of the urethra is extremely rare. All previous cases have occurred in men, ranging in age between 27 and 72 years, with an average of 53. • No case of secondary amyloidosis of the urethra has been reported. Hematuria and symptoms of urethral stricture in combination or alone are the usual manifestations. Often the symptoms as well as the clinical appearance of the lesion suggest a carcinoma of the urethra, as was the case with our patient. It is impossible to make the diagnosis without biopsy and even then the tissue must be stained appropriately or the diagnosis can be missed. Treatment in our case involved judicial transutethral resection of the lesion, which has been adequate although the patient has been followed only 5 months. There is some
425
AMYLOIDOSIS OF LOWER GENITOURINARY TRACT
FIG.
Amyloidosis of seminal vasicle demonstrates thickened, distorted fronds
evidence that patients with primary amyloidosis of the bladder can have spontaneous remissions,' adding support to the conservative resection used here. There is little doubt that our patient had primary localized amyloidosis. There was nothing in the that to a chronic inflammatory process. Neither was there a of previous urethritis, which has been associated with 4 of the previously reported cases. Whether the urethritis had any direct relationship with the subsequent of urethral amyloidosis seems dubious since the urethritis had occurred a minimum of 30 years prior to the development of amyloidosis. It is not unusual to find amyloid deposits in the seminal vesicles at autopsy. The incidence increases with age and is reported to be between 1 and 9 per cent.'· 6 There is no known clinical manifestation of amyloidosis in the seminal although McDonald speculates that the subendothelial deposits in vessels may cause hemorrhage with resultant hematuria in elderly men in whom no other cause is found. In our case the association of chronic perinea! pain with the finding of amyloidosis in the seminal vesicles is unusual. Although the dense amyloid infiltration of the seminal vesicle noted at operation seems to account for the perinea] pain, focal prostatitis was also found and may have contributed to the pain. Our patient had had an adenocarcinoma of the colon removed previously, which may have contributed to the secondary development of amyloidosis albeit in the localized form. The incidence of amyloid deposition in the prostate ranges from 1.5 to 10 per cent in unselected patients undergoing prostatectomy. '· 8 Older patients have a higher incidence. The prostate is involved frequently in the systemic form of amyloidosis. In fact, it has been suggested that the prostate is as likely a site for a biopsy to diagnose systemic amyloidosis as the customarily used rectal biopsy or gingival Our case illustrates the fact that amyloidosis of the prostate can masquerade as cancer of the prostate, especially if systemic amyloidosis is also present. Had the biopsy material in our case been stained with Congo red originally would have been clear earlier. A should request an amyloid stain when of a hard prostate is believed to be benign. Amyloid is a material in tissues and black with iodine. It exhibits green when stained vvith b}ue. It has a fibrillar appearance electron nw.cn~-" a characteristic diffraction
pattern and affinity for Congo red dye. However, the molecular nature of amy!oid has been clarified only recently. Two observations have pointed to the relationship between amyloid and the immune system. Apitz demonstrated that many patients vvith primary amyloidosis had abnormal plasma cells and plasmacytosis of the bone marrow. 9 In addition, the secondary form of amyloidosis has been associated with chronic antigenic stimulation. analyzing the amino acid sequencing of amyloid, Glenner and associates have shown that amyloid usually represents a monoclonal gammopathy with tissue deposition of the variable portion of immunoglobulin light chains. 10 • 11 Furthermore, when the underlying suppurative process causing antigenic stimulation is eradicated some patients with the secondary form have had total resolution of the and the secondary manifestations. 12 Whereas th~immune pathogenesis of amyloid has been reasonwell established it is still an enigma why local deposits should occur in isolated fashion. In view of the immunologic basis of amyloidosis it might be expected that abnormalities of the serum proteins or immunoglobulins would be likely. However, Barth and associates found abnormalities of the immunoglobulins in only 6 of 15 cases of urinary systemic amyloidosis. 13 All 15 cases demonstrated marrow plasmacytosis. Our patient with primary systemic amyloidosis involving the prostate had an abnormal IgM but, otherwise, no abnormalities of serum immunoglobulins. This patient had plasmacytosis of the bone marrow, whereas the patient with localized amyloidosis of the seminal vesicles had a normal marrow and the patient with primary localized amyloidosis of the urethra declined marrow aspiration. Drs. Vital Haynes and Richard Ugoretz gave permission to include their patients in this paper. REFERENCES
1. Symmers, W. S. C.: Primary amyloidosis: a review. J. Clin. Path.,
9: 187, 1956. 2. Gerarni, S., Easley, G. W. and Payan, H.: Primary localized arnyloidosis of the urethra and bladder (amyloidorna). Amer. Surg., 36: 375, 1970. 3. Ullmann, A. S., Fine, G. and Johnson, A. J.: Localized amyloidosis (amyloid tumor) of the urethra. J. Urol., 92: 42, 1964. 4. 8. H., Kelsey, D. and I-:Ioch" VI .. Primary amyloid disease bladder. J Urn!, H2: 463, 1974.
426
CARRIS, MCLAUGHLIN AND GITTES
5. McDonald, J. H. and Heckel, N. J.: Primary amyloidosis of the 10. Glenner, G. G., Terry, W., Harada, M., Isersky, C. and Page, D.: lower genitourinary tract. J. Urol., 75: 122, 1956. Amyloid fibril proteins: proof of homology with immunoglobulin 6. Goldman, H.: Amyloidosis of seminal vesicles and vas deferens. light chains by sequence analyses. Science, 172: 1150, 1971. Primary localized cases. Arch. Path., 75: 94, 1963. 11. Glenner, G. G., Ein, D. and Terry, W. D.: The immunoglobulin origin of amyloid. Amer. J. Med., 52: 141, 1972. 7. Lupovitch, A.: The prostate and amyloidosis. J. Urol., 108: 301, 12. Lowenstein, J. and Gallo, G.: Remission of the nephrotic syndrome 1972. 8. Wilson, S. K., Buchanan, R. D., Stone, W. J. and Rhamy, R. K.: in renal amyloidosis. New Engl. J. Med., 282: 128, 1970. 13. Barth, W. F., Willerson, J. T., Waldmann, T. A. and Decker, J. L.: Amyloid deposition in the prostate. J. Urol., llO: 322, 1973. 9. Apitz, K.: Die Paraproteinosen (iiber die Storung des EiweisstoffPrimary amyloidosis. Clinical, immunochemical and immunoglobulin metabolism studies in fifteen patients. Amer. J. Med., wechsels bie Plasmocyt
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1976 by The Williams & Wilkins Co.
AMYLOIDOSIS OF THE LOWER GENITOURINARY TRACT CRAIG K. CARRIS, A. P. MCLAUGHLIN, III*
AND
RUBEN F. GITTES*
From the Division of Urology, Department of Surgery, University Hospital, University of California School of Medicine, San Diego, California ABSTRACT
I i
Three patients with amyloidosis of the lower genitourinary tract are described. In the cases of primary localized amyloidosis of the urethra and primary systemic amyloidosis involving the prostate the clinical presentation mimicked cancer of the respective sites. In the case of secondary localized amyloidosis of the seminal vesicles chronic perineal pain suggested seminal vesiculitis. Amyloidosis is a rare disease of obscure etiology, characterized by the extracellular deposition of a homogenous eosinophilic fibrillar protein in various tissues. It is of interest to the urologist because its clinical presentation in the lower genitourinary tract almost always masquerades as a tumor of the involved tissue. Primary and secondary amyloidosis can involve the lower genitourinary tract. Primary amyloidosis occurs de novo in the absence of chronic disease. It is classified as 1) the systemic form with deposition in multiple organs or 2) the localized form in which involvement is limited to the affected organ. The secondary form is found in association with chronic granulomatosis disease, rheumatoid arthritis, decubitis ulcers, multiple myeloma and other tumors. 1 Primary localized amyloid of the urethra has been reported only 9 times previously.2 Herein we report the tenth case. Primary amyloidosis of the seminal vesicles occurs slightly more frequently but there have been no reported cases of symptomatic amyloidosis of the seminal vesicles to our knowledge. We report herein a case of chronic perinea! pain associated with localized amyloidosis of the seminal vesicles. Although less unusual we report a case of primary systemic amyloidosis involving the prostate to illustrate the fact that this can be confused clinically with adenocarcinoma of the prostate. CASE REPORTS
Case 1. Amyloidosis of the male urethra (UH 593-032): A 63-year-old physician was seen with a 3-month history of a brownish-red urethral discharge. He was in excellent health and denied other symptoms except for some decreasing force of stream and occasional nocturia. The patient had treated himself with penicillin and erythromycin with no improvement. Physical examination was entirely normal except for an enlarged, benign-feeling prostate. Urinalysis showed no protein, 5 to 10 white cells and 1 to 2 red cells per high power field. Urine culture was negative and an excretory urogram (IVP) was normal except for some thickening of the bladder wall consistent with long-standing benign prostatic hypertrophy. A retrograde urethrogram revealed a discrete lesion at the penoscrotal junction (fig. 1, A). Urethroscopy revealed a semicircular, friable, ulcerated lesion of the urethral wall in the distal bulbous urethra (fig. 2). The lesion was approximately 180 degrees in circumference. Palpation suggested no involvement of the corpus spongiosum. Endoscopic transurethral biopsy proved the lesion to be amyloidosis, although it was believed to be carcinoma clinically. Accepted for publication August 1, 1975. Read at annual meeting of Western Section, American Urological Association, Portland, Oregon, April 13-17, 1975. * Current address: Peter Bent Brigham Hospital, Boston, Massachusetts 02115.
Therefore, the patient was evaluated for any evidence of systemic amyloidosis. There was no history suggestive of chronic inflammatory disease. There was no macroglossia, extensive cardiac examination was normal and there was no organomegaly in the abdomen. Renal and liver function tests, chest x-ray, electrocardiogram, serum and urine protein electrophoresis, and serum immunoelectrophoresis were all normal. The patient declined a bone marrow aspiration. After a repeat urethrogram 5 months later (fig. 1, B) the amyloid deposit was resected transurethrally. Since the lesion was not completely circumferential an area between 12 and 3 o'clock was left intact as the resection was carried down into the corpus spongiosum. There was no evidence of amyloidosis elsewhere in the genitourinary tract. Histological examination of the tissue showed extensive submucosal infiltration of amyloid (fig. 3). Case 2. Amyloidosis of the seminal vesicles (UH 604-238): A 61-year-old male truck driver had obstructive urinary symptoms and perinea! discomfort exacerbated by sitting. There was no history of dysuria or hematuria and the man denied ejaculatory pain. The patient had had a transverse colectomy for adenocarcinoma of the colon 1 year earlier. He had had urethral catheter drainage for several days after the colon operation. There was no history of arthritis or tuberculosis and no evidence for recurrence of the colon tumor. The prostate and rectal examinations were normal. The patient was given antibiotics but the perinea! pain was not relieved. A wide caliber stricture of the bulbous urethra and a prominent median lobe of the prostate with associated mild bladder trabeculation were found. An internal urethrotomy and transurethral resection of the prostate were done but the perinea! pain was not relieved. Prostatic tissue showed benign hyperplasia. Subsequent examination revealed extreme tenderness to palpation of the prostate and seminal vesicles. Urinalysis and renal and liver function tests were normal. Cystoscopy revealed a hyperemic, edematous mucosa in the prostatic urethra. Vasograms were normal except for mild dilatation of the right vas deferens. Culture of the prostatic secretions was negative. The patient was believed to have seminal vesiculitis and was treated with antibiotics but the disabling perinea! pain persisted. He was treated with a total prostatectomy and seminal vesiculectomy. At operation a dilated, tortuous right seminal vesicle was found extending across the midline. Three months postoperatively the perinea! pain was much improved. Microscopic secretions unexpectedly revealed dense infiltration of both seminal vesicles with amyloid causing the frondular pattern to be markedly thickened and distorted (fig. 4). Because amyloidosis of the seminal vesicles was found a diagnostic study was undertaken to determine if there was evidence for systemic amyloidosis. Serum and urine protein electrophoresis, and immunoelectrophoresis were normal, as was the electrocardiogram, bone marrow aspiration and creatinine clearance.
423
424
CARRIS, MCLAUGHLIN AND GITTES
Fm. 3. Dense subendothelial deposition of amyloid in urethra
found. Abnormal laboratory tests included a hemoglobin of9.9 gm. per cent, an elevated erythrocyte sedimentation rate, increased prothrombin and partial thromboplastin times, a blood urea nitrogen of 31 and a creatinine of 2.1. Liver function tests were normal except for a decreased albumin of 3.4 gm. per cent. Acid phosphate was elevated at 1.0 units (normal 0.13 to 0.63), with a prostatic fraction of 0.1 (normal less than 0.15). Urinalysis showed 3-plus proteinuria with 3 to 5 white cells Fm. 1. A, retrograde urethrogram demonstrates lesion in bulbous per high power field. Urine for Bence Jones protein was urethra. B, same lesion 5 months later. negative. Serum protein electrophoresis showed a mildly decreased albumin. Serum immunoelectrophoresis showed normal lgG and lgA but a decreased IgM. Chest x-ray showed mild, generalized cardiomegaly. An IVP showed some scarring of the right kidney believed to be secondary to previous pyelolithotomy. An upper gastrointestinal series and barium enema were normal. Subsequent bone marrow aspiration showed plasma cell hyperplasia. The hard prostate and the elevated total acid phosphatase led to the diagnosis of metastatic cancer of the prostate. Prostatic biopsy demonstrated nodular hyperplasia, and acute and chronic inflammation. The patient returned to his residence in Canada where the persistent leg pain led to a muscle biopsy, which demonstrated amyloidosis. When the information was known to us the prostatic tissue was stained with Congo red and showed classical features of amyloidosis. Since no predisposing cause could be found this patient falls into the category of primary systemic amyloidosis. Fm. 2. Amyloidosis of urethra at endoscopy
Case 3. Amyloidosis of the prostate (UH 520821): A 58-yearold male mechanic was first seen at our hospital in December 1971 for evaluation of fatigue, anemia and right thigh pain. In late 1971 the patient had to stop working because of increasing fatigue. He was noted to be anemic and the prothrombin and partial thromboplastin times were reportedly markedly elevated, although there was no history of alcohol ingestion. History included dilatation of a urethral stricture in 1966 and 1971. There was no history of chronic inflammatory disease. On physical examination a slightly enlarged tongue, mild cardiomegaly, quadriceps tenderness associated with a peripheral neuropathy and indurated right lobe of the prostate were
DISCUSSION
Primary localized amyloidosis of the urethra is extremely rare. All previous cases have occurred in men, ranging in age between 27 and 72 years, with an average of 53. • No case of secondary amyloidosis of the urethra has been reported. Hematuria and symptoms of urethral stricture in combination or alone are the usual manifestations. Often the symptoms as well as the clinical appearance of the lesion suggest a carcinoma of the urethra, as was the case with our patient. It is impossible to make the diagnosis without biopsy and even then the tissue must be stained appropriately or the diagnosis can be missed. Treatment in our case involved judicial transutethral resection of the lesion, which has been adequate although the patient has been followed only 5 months. There is some
425
AMYLOIDOSIS OF LOWER GENITOURINARY TRACT
FIG.
Amyloidosis of seminal vasicle demonstrates thickened, distorted fronds
evidence that patients with primary amyloidosis of the bladder can have spontaneous remissions,' adding support to the conservative resection used here. There is little doubt that our patient had primary localized amyloidosis. There was nothing in the that to a chronic inflammatory process. Neither was there a of previous urethritis, which has been associated with 4 of the previously reported cases. Whether the urethritis had any direct relationship with the subsequent of urethral amyloidosis seems dubious since the urethritis had occurred a minimum of 30 years prior to the development of amyloidosis. It is not unusual to find amyloid deposits in the seminal vesicles at autopsy. The incidence increases with age and is reported to be between 1 and 9 per cent.'· 6 There is no known clinical manifestation of amyloidosis in the seminal although McDonald speculates that the subendothelial deposits in vessels may cause hemorrhage with resultant hematuria in elderly men in whom no other cause is found. In our case the association of chronic perinea! pain with the finding of amyloidosis in the seminal vesicles is unusual. Although the dense amyloid infiltration of the seminal vesicle noted at operation seems to account for the perinea] pain, focal prostatitis was also found and may have contributed to the pain. Our patient had had an adenocarcinoma of the colon removed previously, which may have contributed to the secondary development of amyloidosis albeit in the localized form. The incidence of amyloid deposition in the prostate ranges from 1.5 to 10 per cent in unselected patients undergoing prostatectomy. '· 8 Older patients have a higher incidence. The prostate is involved frequently in the systemic form of amyloidosis. In fact, it has been suggested that the prostate is as likely a site for a biopsy to diagnose systemic amyloidosis as the customarily used rectal biopsy or gingival Our case illustrates the fact that amyloidosis of the prostate can masquerade as cancer of the prostate, especially if systemic amyloidosis is also present. Had the biopsy material in our case been stained with Congo red originally would have been clear earlier. A should request an amyloid stain when of a hard prostate is believed to be benign. Amyloid is a material in tissues and black with iodine. It exhibits green when stained vvith b}ue. It has a fibrillar appearance electron nw.cn~-" a characteristic diffraction
pattern and affinity for Congo red dye. However, the molecular nature of amy!oid has been clarified only recently. Two observations have pointed to the relationship between amyloid and the immune system. Apitz demonstrated that many patients vvith primary amyloidosis had abnormal plasma cells and plasmacytosis of the bone marrow. 9 In addition, the secondary form of amyloidosis has been associated with chronic antigenic stimulation. analyzing the amino acid sequencing of amyloid, Glenner and associates have shown that amyloid usually represents a monoclonal gammopathy with tissue deposition of the variable portion of immunoglobulin light chains. 10 • 11 Furthermore, when the underlying suppurative process causing antigenic stimulation is eradicated some patients with the secondary form have had total resolution of the and the secondary manifestations. 12 Whereas th~immune pathogenesis of amyloid has been reasonwell established it is still an enigma why local deposits should occur in isolated fashion. In view of the immunologic basis of amyloidosis it might be expected that abnormalities of the serum proteins or immunoglobulins would be likely. However, Barth and associates found abnormalities of the immunoglobulins in only 6 of 15 cases of urinary systemic amyloidosis. 13 All 15 cases demonstrated marrow plasmacytosis. Our patient with primary systemic amyloidosis involving the prostate had an abnormal IgM but, otherwise, no abnormalities of serum immunoglobulins. This patient had plasmacytosis of the bone marrow, whereas the patient with localized amyloidosis of the seminal vesicles had a normal marrow and the patient with primary localized amyloidosis of the urethra declined marrow aspiration. Drs. Vital Haynes and Richard Ugoretz gave permission to include their patients in this paper. REFERENCES
1. Symmers, W. S. C.: Primary amyloidosis: a review. J. Clin. Path.,
9: 187, 1956. 2. Gerarni, S., Easley, G. W. and Payan, H.: Primary localized arnyloidosis of the urethra and bladder (amyloidorna). Amer. Surg., 36: 375, 1970. 3. Ullmann, A. S., Fine, G. and Johnson, A. J.: Localized amyloidosis (amyloid tumor) of the urethra. J. Urol., 92: 42, 1964. 4. 8. H., Kelsey, D. and I-:Ioch" VI .. Primary amyloid disease bladder. J Urn!, H2: 463, 1974.
426
CARRIS, MCLAUGHLIN AND GITTES
5. McDonald, J. H. and Heckel, N. J.: Primary amyloidosis of the 10. Glenner, G. G., Terry, W., Harada, M., Isersky, C. and Page, D.: lower genitourinary tract. J. Urol., 75: 122, 1956. Amyloid fibril proteins: proof of homology with immunoglobulin 6. Goldman, H.: Amyloidosis of seminal vesicles and vas deferens. light chains by sequence analyses. Science, 172: 1150, 1971. Primary localized cases. Arch. Path., 75: 94, 1963. 11. Glenner, G. G., Ein, D. and Terry, W. D.: The immunoglobulin origin of amyloid. Amer. J. Med., 52: 141, 1972. 7. Lupovitch, A.: The prostate and amyloidosis. J. Urol., 108: 301, 12. Lowenstein, J. and Gallo, G.: Remission of the nephrotic syndrome 1972. 8. Wilson, S. K., Buchanan, R. D., Stone, W. J. and Rhamy, R. K.: in renal amyloidosis. New Engl. J. Med., 282: 128, 1970. 13. Barth, W. F., Willerson, J. T., Waldmann, T. A. and Decker, J. L.: Amyloid deposition in the prostate. J. Urol., llO: 322, 1973. 9. Apitz, K.: Die Paraproteinosen (iiber die Storung des EiweisstoffPrimary amyloidosis. Clinical, immunochemical and immunoglobulin metabolism studies in fifteen patients. Amer. J. Med., wechsels bie Plasmocyt
