Amyloidosis of seminal vesicles and ejaculatory ducts: a histologic analysis of 21 cases among 447 prostatectomy specimens

To investigate the incidence of amyloidosis of seminal vesicles and ejaculatory system including ejaculatory ducts and vasa deferentia, we reviewed the whole mount sections of 447 radical prostatectomy specimens removed for prostatic cancer, including 273 cases from the United States and 174 cases from Korea. Of these, 21 cases (4.7%) showed amyloidosis in seminal vesicles, vasa deferentia, and in ejaculatory ducts. Ten of these (3.7%) cases were from the United States and 11 cases (6.3%) from Korea. The patients' age ranged from 51 to 79 years (mean, 66.1 years). Amyloid deposition was found in 5 patients in the sixth decade (3.4%), 9 patients in the seventh decade (4.7%), and 7 patients in the eighth decade (9.3%). At the seventh decade of life, the Korean patients showed a higher incidence (8.3%) than American patients (2.5%), but other age groups showed no difference. All cases showed bilateral involvement of the seminal vesicles and ejaculatory systems. The deposits of amyloid tended to be nodular and affected the subepithelial region of seminal vesicles, vasa deferentia, and ejaculatory ducts. There was no amyloid deposit around blood vessels or in the prostatic parenchyma. Localized amyloidosis of the ejaculatory system involves not only the seminal vesicles but also the vasa deferentia and the ejaculatory ducts. The vessels or prostatic stroma are not part of this process. Amyloidosis develops subepithelially spreading to include the wall of these organs and appears to be related to advanced age. The incidence of amyloidosis of the ejaculatory system in Korean patients was higher than in US patients.     

Senile Cardiac Amyloidosis: Evidence of Two Different Amyloid Substances in the Ageing Heart

In a material of seventy-two persons over 70 years of age, forty-seven cases of amyloidosis of the heart were found. In thirty-nine cases, deposits occurred only in the atria (isolated artrial amyloidosis, IAA), while in eight cases amyloid also was seen in the ventricles (senile cardiac amyloidosis, SCA). In some of the latter cases, small amyloid deposits occurred in other organs, especially the lungs. Some definite differences existed between the amyloid substance in SCA and IAA. Thus, tryptophan was demonstrated histochemically in SCA but not in IAA, and, furthermore, amyloid fibrils isolated from patients with IAA lacked protein Asca, the fibril subunit protein of senile cardiac amyloid. It is concluded that the ageing heart may be the target of two different forms of amyloid, one only affecting the atria, while the other is more widespread within the heart and sometimes also is found in other organs.     

Senile amyloid deposition

Amyloid deposition in the aged was studied in a wide selection of tissues from 194 necropsies of subjects aged over 65 years, there being no clinical manifestation of amyloidosis. We employed conventional Congo red staining with the aid of a polarising filter for the identification of amyloid. We analysed the deposits histochemically for tryptophan content and reaction to oxidation using the potassium permanganate method in 26 subjects aged over 85 years. Both the frequency of amyloid deposition and the number of organs involved tended to increase with advancing age, and both increased after the ninth decade with little sex difference. Amyloid deposition preferentially occurred in the aorta, heart, lung, prostate and pancreas among the organs examined. Visceral involvement tended to be confined to the vasculature except in the prostate and pancreas. In cases associated with predisposing conditions considered to evoke secondary amyloidosis such as tuberculosis, multiple myeloma, and rheumatoid arthritis more amyloid was found but the distribution of the deposits was similar by organ and intravisceral site to that of cases unassociated with predisposing disorders. In both groups of cases amyloid was found to contain tryptophan, indicative of immunoamyloid and, with a few exceptions, to be resistant to oxidation by potassium permanganate indicating an immunoglobulin AL component. It can be concluded that senile amyloid should be classified as a form of so-called primary amyloidosis because of its widespread distribution, its occurrence independent of predisposing disorders and its chemical composition. Subclinical chronic inflammation of the respiratory, gastrointestinal and urogenital tracts may provide the necessary prolonged immunological stimulus to lead to amyloid deposition in ageing tissues.     

Senile pulmonary amyloidosis

Lung tissue obtained from 340 necropsies of persons aged 80 years and over was investigated for the occurrence of pulmonary amyloid deposits by means of a sensitive fluorescence technique. The incidence of pulmonary amyloidosis was about 2% below the age of 80, nearly 10% in individuals between 80 and 84 years, and more than 20% at and beyond 85 years. Vascular and concomitant alveolar-septal amyloidosis was seen slightly more often than the pure septal form of senile amyloidoisis. The two modes of deposition correspond to two different forms of cardiac amyloidosis, vascular and nodular. On the other hand, the two different modes of pulmonary amyloidosis affect different age groups. It is postulated that the disorder is related to age-linked immunological disturbances and to genetically determined factors.     

Spontaneous age-associated amyloidosis in senescence-accelerated mouse (SAM)

Morphological studies on spontaneous systemic amyloidosis were conducted on 222 senescence-accelerated mice (SAM) (P) and on 150 mice in the senescence-resistant series (R).Among the pathologic findings, amyloidosis showed the highest incidence in both SAM (79.7%) and R (32.7%) Although an extensive deposition of amyloid was evident in some aged mice in the R series, a more severe amyloidosis occurred with a higher incidence in the P series. There was a statistical significance between the incidence of amyloidosis and age, in both the P and R series. There were no differences in organ distribution and mode of amyloid deposition between the P and R series or between the sexes. In about 60% of the amyloid-positive cases in the 28 killed SAM and 7 mice in the R series, there were no signs of inflammation or neoplasm.The morphological features in SAM more closely resembled those seen in cases of murine spontaneous senile amyloidosis than the features seen in cases of experimentally induced amyloidosis. This model is expected to be a valuable tool with which to assess the relationship between amyloid deposition and the aging process or senescence, perhaps even cases of human senile amyloidosis.     

The prevalence of isolated atrial amyloid

The frequency of isolated atrial amyloid (IAA), a form of 'senile' cardiac amyloidosis, was determined in younger age groups. For the detection of amyloid the Sirius red staining technique was used. IAA first appears in the fourth decade; its prevalence increases roughly linearly by 15-20 per cent with each subsequent decade, reaching 95 per cent in the 81-90 years age group. The prevalence is higher in females than in males.     

Heart valve involvement in familial amyloidosis with polyneuropathy

Involvement of the heart is common in the various types of amyloidosis. Little attention has, however, been paid to the presence and significance of amyloid in cardiac valves. We examined the heart valves of twelve autopsy cases with familial amyloidosis with polyneuropathy. All leaflets showed more or less abundant amyloid infiltration with significant valvular aortic stenosis due to degenerative calcification in two cases. In familial amyloidosis with polyneuropathy, amyloid deposits are thus invariably present in the valves, but the valvular function is often preserved. Amyloid may, however, produce hemodynamically significant valvular lesions, and the importance of valvular involvement in the various types of amyloidosis may still be underestimated.     

Seminal vesicle amyloidosis: morphological, histochemical and immunohistochemical observations

Subepithelial deposits of amyloid were detected within the seminal vesicles of 13 males from a total of 143 unselected autopsies (9%). The incidence increased with increasing age. The amyloid was classified using histochemistry, immunohistochemistry and clinical features. Eight cases were categorized as senile vesicle amyloid, two as systemic AA amyloid with secondary involvement of the seminal vesicle, and three as mixed amyloidosis. The morphological appearances of the different categories of seminal vesicle amyloidosis are similar but a different distribution is common. The staining characteristics of senile vesicle amyloid suggest that this is a different amyloid protein, perhaps locally derived within the seminal vesicle.     

β2-Microglobulin Amyloidosis in Hemodialysis Patients An Autopsy Study of Intervertebral Disks and Posterior Longitudinal Ligaments

Ninety-five autopsy cases of chronic renal failure, which had or had not been treated by hemodialysis, were examined histologically and immunohistochemically for evidence of amyloid deposition in the intervertebral disks and posterior longitudinal ligaments of the spine, β₂-Microglobulin (β₂M) amyloid was not present in non-dialyzed patients with chronic renal failure. In cases showing β₂M amyloid deposition, the shortest term of hemodialysis was 2 years and 5 months. The incidence of β₂M amyloidosis tended to increase as the dialysis period was prolonged. An inverse correlation was present between dialysis period and age in 22 cases showing β₂M amyloid deposition (correlation coefficient: –0.43, p<0.05), and β₂M amyloidosis tended to occur earlier in elderly patients than in younger patients. This suggests that elderly patients are more susceptible to &M amyloidosis. β₂M amyloid was absent in all of 8 cases of systemic lupus erythematosus which were treated by dialysis for periods ranging from 2 days to 12 years. In these patients, β₂M amyloidosis may have been prevented by steroids, which had been administered for long periods in all cases. Another amyloid of unknown composition was also frequently present in the intervertebral disks and posterior longitudinal ligaments not only in patients with chronic renal failure but also control patients without chronic renal failure. This amyloid was immunohistologically negative for β₂M, amyloid A protein, light chain kappa or lambda, prealbumin, and apolipoprotein All. Acta Pathol Jpn 40: 820 826, 1990.     

Intervertebral disc amyloidosis: histochemical, immunohistochemical and ultrastructural observations

Intervertebral discs selected at random from autopsies and surgical operations on herniated discs were examined for evidence of amyloid deposition. Amyloid deposits were detected in 53 (81.5%) of 65 autopsy cases. Discs from subjects over 50 years of age revealed a significantly high incidence of amyloid deposition. Among herniated discs, amyloid deposits were documented in 49 (75.4%) of 65 surgical specimens. The incidence of amyloid deposition in intervertebral discs increased with advancing age. Intervertebral disc amyloidosis consisted of amyloid deposits of three morphological types: linear amyloid deposits around the degenerating chondrocytes (perichondrocyte type), and nodular or band-like deposits in the annulus fibrosus (annulus fibrosus type) and nucleus pulposus (nucleus pulposus type). We suspect that the precursor protein of perichondrocyte type amyloid is derived from chondrocytes, and those of annulus fibrosus type and nucleus pulposus types are derived from the blood. The amyloid deposits were resistant to treatment with potassium permanganate. Immunohistochemically, the amyloid deposits reacted with antibody against amyloid P-component, but not with antibodies against AA, A k , Aλ, transthyretin or β₂-microglobulin. Ultrastructurally, the amyloid deposits were composed of 10 nm-wide nonbranching fibrils. The amyloid in herniated discs had the same biochemical and immunohistochemical properties as those found in autopsy cases. The immunohistochemical characteristics of the amyloid deposits suggest that it derives from an, as yet, unknown precursor protein.     

Arterial hypertension in renal amyloidosis (a clinico-morphological analysis)

The incidence of arterial hypertension (AH) in patients with renal amyloidosis varied with its stage. Thus, AH was encountered in 13% of cases with renal amyloidosis at the proteinuric stage, 15% of those at the nephrotic stage, and 53% of those at the azotemic stage. One determinant of AH at the first two of these stages appears to have been damage to the antihypertensive system of the renal medulla, while the increased rate of AH at the azotemic stage was found to be associated with sodium retention in the body. AH in renal amyloidosis is an unfavorable prognostic factor, for it is conducive to amyloid shrinkage of the kidneys and to chronic renal failure.     

State of humoral and cellular immunity in experimental amyloidosis]

On a model of caseine amyloidosis in 52 rabbits it was shown that in the preamyloid phase the humoral immunity was stimulated, but as soon as the first deposits of amyloid appeared, it was inhibited. The cellular immunity was inhibited starting from the 20th day of the experiment. On the 40th day of the experiment the cellular immunity was found to be less inhibited in the animals with initial deposits of amyloid as compared with the animals with no amyloidosis; on the 60--80th day in progressing of amyloidosis differences in the degree of inhibition of the cellular immunity were obliterated. The degree of fixation of IgG in amyloid was directly dependent on its content in the blood serum and on the "age" of amyloid.     

Amyloid of the seminal vesicles. A distinctive and common localized form of senile amyloidosis.

Amyloid deposits were found subepithelially in the seminal vesicles of 34 of 209 consecutively studied men. The incidence increased with age and was found in 21% of men over 75 years. This senile seminal vesicle amyloidosis (SSVA) is a localized disorder, and the amyloid substance has unique histochemical and immunochemical properties not shared with any other amyloid described until now.     

Incidence and characterization of age related amyloid deposits in the human anterior pituitary gland

Summary To identify amyloid deposits in the anterior pituitary gland, we have immunohistochemical, histochemical and alkaline Congo red staining. The anti-human P component reacted positively with these amyloid deposits, while antisera against prealbumin, AA type amyloid fibril protein and various anterior pituitary hormones were negative. A combination of Congo red and anti-human P component staining was most sensitive and reliable for detection of amyloid in the anterior pituitary glands of 300 randomly autopsied patients. Amyloid deposits increased in parallel with the age of the patients, however, they appeared earlier and more frequently than heretofore reported. Deposition of amyloid was seen initially in the 3rd decade and the positivity rate of amyloid deposits was 73% in the 5th decade. The histochemical characteristics of these pituitary amyloid deposits differed from those of cerebral and systemic deposits, particularly those found in the amyloid of senile systemic amyloidosis.This study was supported in part by a grant from the Fundation for Advancement of Clinical Medicine and Ministry of Health and Welfare of Japan     

Clinicopathological importance of deposits of amyloid in the femoral head.

The pattern of amyloid deposits in the femoral head is described in four cases, two of which had deposits of amyloid related to age and two of which had generalised systemic amyloidosis (one of primary amyloidosis, one of multiple myeloma). The deposition of amyloid in the articular cartilage of the femoral head was similar in all four cases. Heavy deposits of synovial amyloid were identified in the case with primary amyloidosis and in one of the cases with amyloidosis related to age. Both cases of generalised systemic amyloidosis showed abundant deposits of amyloid in the bone marrow. Amyloid was not present in the bone marrow of either case with amyloidosis related to age. The importance of these findings is discussed in relation to the pathogenesis of the arthropathy syndrome of a rheumatoid type described in cases of primary amyloidosis and multiple myeloma.     

Beta 2-microglobulin amyloidosis in hemodialysis patients. An autopsy study of intervertebral disks and posterior longitudinal ligaments

Ninety-five autopsy cases of chronic renal failure, which had or had not been treated by hemodialysis, were examined histologically and immunohistochemically for evidence of amyloid deposition in the intervertebral disks and posterior longitudinal ligaments of the spine. beta 2-Microglobulin (beta 2M) amyloid was not present in non-dialyzed patients with chronic renal failure. In cases showing beta 2M amyloid deposition, the shortest term of hemodialysis was 2 years and 5 months. The incidence of beta 2M amyloidosis tended to increase as the dialysis period was prolonged. An inverse correlation was present between dialysis period and age in 22 cases showing beta 2M amyloid deposition (correlation coefficient: -0.43, p less than 0.05), and beta 2M amyloidosis tended to occur earlier in elderly patients than in younger patients. This suggests that elderly patients are more susceptible to beta 2M amyloidosis. beta 2M amyloid was absent in all of 8 cases of systemic lupus erythematosus which were treated by dialysis for periods ranging from 2 days to 12 years. In these patients, beta 2M amyloidosis may have been prevented by steroids, which had been administered for long periods in all cases. Another amyloid of unknown composition was also frequently present in the intervertebral disks and posterior longitudinal ligaments not only in patients with chronic renal failure but also control patients without chronic renal failure. This amyloid was immunohistologically negative for beta 2M, amyloid A protein, light chain kappa or lambda, prealbumin, and apolipoprotein A-II.     

Atrial amyloid deposits in the failing human heart display both atrial and brain natriuretic peptide-like immunoreactivity

Atrial amyloid deposits are common in the ageing human heart and contain alpha-atrial natriuretic peptide (proANP99-126) immunoreactivity. However, atrial myocytes secrete both amino and carboxy terminal fragments of the ANP prohormone (proANP1-126) and also express an homologous, but separate brain natriuretic peptide (BNP). Characteristic amyloid deposits were identified in the atria of 9/22 patients (26-63 years of age) with end-stage heart failure. Amyloid fibrils displayed immunoreactivity for both amino and carboxy terminal fragments of proANP1-126 and for the distinct BNP sequence. As in other endocrine organs, both mature and precursor peptide sequences appear to be constituents of amyloid fibrils. Whilst immunoreactivity for cardiac peptide hormones is co-localized in atrial amyloid deposits, it is uncertain whether the increase in natriuretic peptide expression which accompanies cardiac failure contributes to the incidence of isolated atrial amyloidosis.     

Classification of amyloid deposits in diagnostic cardiac specimens by immunofluorescence

BackgroundAt least 12 distinct forms of amyloidosis are known to involve the heart or great vessels. Patient treatment regimens require proper subtyping of amyloid deposits in small diagnostic cardiac specimens. A growing lack of confidence in immunohistochemical staining for subtyping amyloid has arisen primarily as a result of studies utilizing immunoperoxidase staining of formalin-fixed paraffin-embedded tissue. Immunofluorescence staining on fresh frozen tissue is generally considered superior to immunoperoxidase staining for subtyping amyloid; however, this technique has not previously been reported in a series of cardiac specimens.MethodsAmyloid deposits were subtyped in 17 cardiac specimens and 23 renal specimens using an immunofluorescence panel.ResultsAmyloid deposits were successfully subtyped as AL, AH, or AA amyloid by immunofluorescence in 82% of cardiac specimens and 87% of renal specimens. In all cases, the amyloid classification was in good agreement with available clinical and laboratory assessments. A cross-study analysis of 163 cases of AL amyloidosis reveals probable systemic misdiagnosis of cardiac AL amyloidosis by the immunoperoxidase technique, but not by the immunofluorescence technique.ConclusionsAmyloid deposits can be reliably subtyped in small diagnostic cardiac specimens using immunofluorescence. The practical aspects of implementing an immunofluorescence approach are compared with those of other approaches for subtyping amyloid in the clinical setting.     

Secondary amyloidosis in chronic polyarthritis

Systemic secondary amyloidosis was a post-mortem finding recorded from 24% of patients with classical chronic polyarthritis. In 80 to 100% of all cases, amyloidosis was present in heart, thyroid gland, kidneys, adrenal gland, pancreas, spleen, and gastro-intestinal canal. It was recordable, in 50 to 70% of all cases, from liver, aorta, lungs, and lymph nodes. Nerves, muscles, skin, and synovial membrane were less often affected (10 to 40% of all cases). No amyloidosis was recorded at all from the brain. Amyloid depositions differed greatly in intensity by organs. The most massive deposits were found in the gastrointestinal tract, kidneys, adrenal glands, thyroid gland, and spleen. Amyloid depositions were moderate in heart, pancreas, lungs, and liver. They were extremely low in lymph nodes, muscles, nerves, synovial membrane, and skin. The author assumes amyloid deposition to be associated with increase in arterial or venous concentrations of circulating amyloid precursors. Frequency and intensity of amyloid depositions in different organs may be linked to blood supply to the latter. The higher the minute volume of a given organ, the more strongly pronounced is the amyloidosis in it. In the context of amyloidogenesis, consideration should be given, as well, to locally delimited factors, such as organ motility.     

Glomerular crescents in renal amyloidosis: An epiphenomenon or distinct pathology?

There have been several reports of cases of renal amyloidosis with glomerular crescents. However, it is not clear whether the association is fortuitous or pathogenic related. The present study analyzed 105 cases of renal amyloidosis (61 autopsy cases and 44 biopsy cases) and found glomerular crescents in 14 (13.3%) cases. Among the 14 cases with crescents, a female predominance was noted (male: female, 3: 11) and rheumatoid arthritis was the most common primary disease of amyloidosis. Immunohistochemical analysis demonstrated amyloid protein of AA type in 12 cases. According to the histologic classification, there were 11 cases of mesangial nodular type, which was almost exclusively accompanied by AA amyloid deposition. Of note, the incidence of crescents neither correlated with the extent of amyloid deposition nor the presence of nephrotic syndrome. By contrast, localization of amyloid deposition was closely related to crescent formation. Moreover, electron microscopic observation displayed rupture of the glomerular basement membrane at the site of amyloid deposition. Our results indicated that glomerular crescents were more frequently associated with renal amyloidosis than previously appreciated. Rupture of the fragile glomerular basement membrane by amyloid deposition, as revealed by immunostaining and electron microscopy, may be the mechanism of crescent formation. We suggest that glomerular crescents are a distinct pathology associated with renal amyloidosis, not fortuitous conditions.