Hepatic Amyloidosis: Morphologic Differences Between Systemic AL and AA Types FRANCIS S. BUCK, MD, AND MICHAEL N KOSS, MD The liver is almost universally involved in systemic amyloidosis. Patterns of topographic distribution of amyloid within the liver lobule have been recognized, but the reliability of using these for classification of amyloid type is in question. We examined 286 livers from cases of systemic amyloidosis obtained from autopsies at Los Angeles County-University of Southern California Medical Center, classifying them as AL or AA type by means of the potassium permanganate Congo red-staining method along with a specific antiAA antiserum. Prior publications have asserted that deposition of secondary (AA) amyloidosis is limited to the vessels in the portal tract, constituting a “vascular” pattern, and that in primary (AL) amyloidosis the deposits exhibit a “sinusoidal” pattern in that they are seen along hepatic sinusoids as well as in portal vessels. We confirmed that AL amyloid involves the portal vessels as frequently as AA amyloid and that deposition occurred significantly more frequently in the portal stroma, the central vein, and the “sinusoidal” areas. However, we also found a “sinusoidal” pattern in 29 of 78 cases of secondary (AA) amyloidosis; in 14 of these, more than half of the sinusoidal spaces were replaced by amyloid deposits. We also noted that in 23 of the 29 AA amyloidosis cases with “sinusoidal” involvement, a “saga” pattern of distribution of amyloid in the spleen was present. No consistent association of a specific chronic inflammatory disease with “sago” spleen and “sinusoidal” deposits could be documented. We conclude that topographic distribution of amyloid within the liver lobule is not a reliable method of distinguishing AA from AL amyloidosis and that specific staining methods must be used if the physician is to be able to attempt modern therapeutic modalities. HUM PATHOL 22:904907. Copyright 0 1991 by W.B. Saunders Company
The liver has been recognized as a major site of deposition of anlyloid in the disseminated forms of the
disease since its early description by Rokitansky,’ Virchow,” and others. Levine:’ found hepatic involvement in 56% of his 84 patients with amyloidosis, and in his review of the literature he recorded the incidence of hepatic amyloid as varying between 17% and 98%. Attempts have been made by several researchers at differentiating between primary and secondary amyloidosis in the liver on the basis of the topographic patterns of distribution. The results have been conflicting. Several investigators’” postulated in the older literature that amyloid deposition in the liver in primary amyloidosis was largely confined to the blood vessels of the portal area while cases of the secondary type showed inF1-on1 rhe Dep”““““” of P;1tholo~. Los Angeles County-LXversity of Southern California M&Cal Center. University of Southern California SChool of Medicine. Los Angeles. (:A. Accepted for publication November 27. 191)l.
AtLdrrss correspondence and reprint requests to Fr-antis S. Buck, MD. Hex 55. Room 16-4?8 I.AC/lYK Medical Center, 1200 N State St, Los Angeles. CA 9003S.
904
volvement of the hepatic sinusoids as well as the portal vessels. Subsequently, Chopra et al’ and Looi and Sumithran7 have presented evidence that the reverse might be true. Our review of hepatic amyloidosis supports the latter concept, but also suggests many exceptions to the observation by Looi and Sumithran’ that secondary amyloidosis is confined to the portal vessels. MATERIALS
AND METHODS
Our study is based on 456 cases of amyloidosis found among 52,370 patients autopsied at Los Angeles County-University of Southern California Medical Center between January 1949 and July 1982.H In our series, livers were available for review in 407 cases. The overall occurrence of hepatic amyloidosis was 70% in this series. but further analysis showed that the prevalence of hepatic amyloidosis was 97% in both primary (AL) and secondary (AA) amyloidosis while only 4% of the cases identified as senile cardiac (senile systemic) amyloidosis had hepatic amyloid. In our present study. 138 cases were designated as senile cardiac (senile systemic) amyloidosis based on the following: the patient’s age, the heart as the principal organ involved, and confinement of amyloid in other organs to small blood vessels. The absence of organ failure in any organ other than the heart, the lack of involvement of glomerular capillaries, and the absence of amyloid in the red and white pulp of the spleen were other criteria used to support the diagnosis.“,‘” These cases were not included in the present study. III the remaining cases in which sections of liver were available, paraffin blocks of formalin-fixed tissue were studied using the potassium permanganate Congo red-staining method of Wright et al” and a specific antibody against AA amyloid. The method of Wright et al uses potassium permanganate to remove the affinity of AA amyloid for staining with Congo red; Al, amyloid is not affected by such treatment. A specific antibody against AA amyloid was obtained from the Department of Pathology at Yamquchi University School of Medicine through the courtesy of Dr Mutsuo Tak’ahashi (Ube, Yamaguchi, Japan). Details of its preparation are separately described.” The antibody was applied to duplicate sections by the peroxidase-anti-peroxidase method of Sternberger.” Cases in which the amyloid was oxidized bv potassium permanganate and reacted positively to the antibody against AA amyloid were clesignated as AA amyloidosis. Amyloidosis was categorized as AL type when the deposits were resistant to treatment with potassium permanganate and did not stain positively with the antibody to AA amyloid. Using these methods, 78 cases with available liver were identified as AA amyloidosis and 208 cases with available liver were identified as AL amyloidosis. Sections of liver were simultaneously reviewed by the two investigators using both direct light on hematoxylin-eosinstained sections and polarized light on Congo red-stained sections using an Olympus RH2 microscope. In particular, we evaluated the presence of amyloid in the following structures.
HEPATIC AMYLOIDOSIS’
AL AND AA TYPES (Buck & Koss)
I‘l~e term “port;~l vessels” is used to desiguate lhc hepark. a~-ter\~ and portal win in the portal triad. “Portal stroma” refers to thr interstitial tissue or space of the portal triad, “sir~usoid” wkrs to the spaw of Disse bordering the hepatic sillusoids. and “Central vein” refers to the collecting vein of ttw tiqxitic Ia)hulta. In addition, we reviewed the writkri autopsy report, the tlellialc,s~tin-eosin-stained
placed by amyloid. which was associated with advanced arrophy of hepatic parenchymal cells. We also investigated the 29 AA cases that had deposits of‘ sinusoidal amyloid. We were surprised that a majority of the AA cases with extensive sinusoidal amyloid also exhibited a “sago” pattern of distribution of amyloid in the spleen. Table ‘1 shows that 23 of the 20 cases (79.3%) showed a “saga” pattern of. amyloid distribution in the spleen (deposits of amyloid largely limited to the splenic follicles’ $1. The “saga” pattern does not guarantee the presence of hepat ic sinusoidal amyloid, since 15 cases with “saga” spleen had no sinusoidal involvement. We looked for reasons for the increased frequency of hepatic sinusoidal amyloidosis associated with “saga” spleen; in particular, we investigated the possibility that tuberculosis or other chronic. diseases might be implicated (Table 2) and found no significant difference in the frequency or type of chronic diseases between those saga cases with sinusoidal involvement and those without it.
sections on all available
,jrfidns, arid thr t;o~lgo red-stained sections on additionai St‘St;lristical analysis of data was perfol-med using Ire ted orgms. standard f ttb\ta.
RESULTS 111c,omparing the distribution of amyloid in the liver lobule of iL-\ and Al, amyloidosis cases (Table l), we found no significant difference in the prevalence of anryloid in portal vessels (arteries and veins). However, there was a statistically significant increase in prevalence of 41. amyloid over kd amyloid in other areas of the lobule. In the portal stroma there was a fourfold incrcsase, in cc-ntral veins there was a threefold increase, and in the sinusoidal areas (space of Disse) there was a twofold inc:rease. Nevertheless, we encountered sinu$oidal amyloid deposits in 29 of 78 cases of secondarv (A.%) amyloidosis (Figs 1 and 2). In 14 (48%) of the& c-aes. mor(l than SM of the sinusoidal spaces were re-
DISCUSSION Amyloid accumulation in the liver is nearlv a univrrsal characteristic. of systemic am>loidosis. but is seen
FIGURE 2. Portal area and adjacent hepatlc sinusoids In a case of AA amyloidosis. Note the extensive amyloid deposition in the space of Dlsse with associated hepatic cord atrophy and thickening of the hepatic artery wall due to infiltration by amyloid. (Hematoxylin-eosin stain; magnification *200 )
FIGURE 1. Central vein and surrounding hepatic sinusoids showing extensive amyloid deposition in the space of Disse and hepatic corcl atrophy in a case of AA amyloidosis. (Hematoxylineosin stain; magnification \200.)
905
HUMAN PATHOLOGY
TABLE 2.
Volume 22, No. 9 (September
78 Cases of Secondary (AA) Amyloidosis Cases Associated With Sinusoidal Amyloid
No. No. with sago spleen Associated diseases Tuberculosis Rheumatoid arthritis Chronir pyelonephritis Bronchiectasis Carcinomas, various organs
29 23 (79.3%)
CasesWith no Associated Sinusoidal Amyloid 19
15 (30.6%)
10
7
5 2 0 9
7
1 1 3
less frequently in senile cardiac (senile systemic) amyloidosis. Prior to the development of modern specific immunohistochemical methods for the separation of the forms of systemic amyloidosis, it was held by many authorities’-’ that when amyloidosis occurred in the liver, parenchymal “sinusoidal” involvement of the space of Disse was characteristic of secondary (AA) amyloidosis while “vascular” disease” (portal blood vessel involvement) was a feature of primary (AL) amyloidosis. We now recognize that conclusions by these early investigators were marred by their methods of separating primary from secondary amyloidosis, namely, the pattern of organ distribution and the presence or absence of a chronic inflammatory disease. Chopra et al” were the first to suggest that the findings of earlier authorities might be wrong. In their report they designated cases as primary (AL) amyloidosis when there was no evidence of preceding or coexisting disease, and when there was an increase in bone marrow plasma cells and/or M components or free light chains in serum or urine and/or the presence of myeloma. These were compared with cases of secondary “reactive” (AA) amyloidosis, in which evidence of a chronic infectious or inflammatory disease was present. They were able to show that “sinusoidal” parenchymal involvement was characteristic of primary (AL) amyloidosis, and exclusive “vascular” involvement was characteristic of secondary (AA) amyloidosis. However, they concluded that in individual cases significant overlap occurs and the characterization of the form of amyloidosis based on topographic distribution alone might be possible in only a minority of cases. Subsequently, Looi and Sumithran7 examined 3 1 unselected cases with systemic amyloidosis in which there was histologic evidence of liver involvement. They classified their cases into AA and AL types on the basis of immunohistochemistry and permanganate reaction of the amyloid deposits. In their cases, deposition of AA amyloid was limited to the walls of blood vessels in the portal tract, constituting a “vascular” pattern. In AL amyloidosis the deposits exhibited a “sinusoidal” pattern, in which they were seen in the space of Disse along hepatic sinusoids as well as in portal blood vessels and central veins. In our series, using diagnostic techniques similar to those used by Looi and Sumithran, we were able to 906
1991)
confirm that involvement of the sinusoidal parenchyma (space of Disse) is characteristic of AL amyloidosis and showed that involvement of the portal blood vessels does not differ significantly between AL and AA types. However, we found numerous exceptions to the conclusions of Looi and Sumithran’ that AA amyloidosis is limited to the walls of the vessels of the portal tract. In 29 (37.2%) of our 78 cases of AA amyloidosis we found significant sinusoidal parenchymal involvement, which was often very extensive; this appeared to be more likely when the liver involvement was accompanied by the “saga” pattern of distribution of amyloid in the spleen. In looking for possible explanations for the differences between our results and those of Chopra et al, we note that their study was not quite comparable to ours since their cases were classified clinically rather than histochemically. We have no final answer as to why our findings differ from those of Looi and Sumithran, whose methods of classification were similar to those we used, but we suggest that the following may offer a partial explanation. Our study involved a much larger group of patients. Looi and Sumithran studied 3 1 livers and we studied 286 livers containing either AA or AL amyloid. In addition we have previously showr? that there are significant variations in the prevalence of amyloidosis among various ethnic groups and that the prevalence of the types of amyloidosis within ethnic groups varies. Looi and Sumithran indicated that among their 19 cases of systemic AA amyloidosis, eight patients were Orang Asli (Malayan aborigine), six were Chinese, and five were Australian (presumably white). They did not identify the ethnic designation of their patients with systemic AL amyloidosis. In our patient population with systemic AA amyloidosis, 67.5% were white, 3.9% were black, and 28.6% were Hispanic; there were no Orientals or American Indians. Among our patients with systemic AL amyloidosis, 18.6% were white, 5.6% were black, and 75.9% were Hispanic; there were no Orientals or American Indians. We have no explanation for the increase in “sinusoidal” deposition among AA cases with “sago” spleen in terms of the type of chronic underlying disease. Even though Westernlark and Nilsson” noted an association of “saga” spleen with cases of tuberculosis, we were unable to demonstrate a significant difference in the frequency of tuberculosis between cases of AA amyloidosis that did or did not have sinusoidal amyloidosis. One possible explanation is the extended duration of the illness in patients with certain chronic inflammatory diseases, such as tuberculosis and rheumatoid arthritis, but we are unable to prove this from our data. In conclusion, we recognize that involvement of the space of Disse, the so-called “sinusoidal” pattern, by amyloidosis is statistically more common in AI, amyloidosis than it is in AA amyloidosis, but its presence there does not exclude AA amyloidosis. We believe that classifying the type of amyloidosis from biopsy specimens is important because certain types of amyloidosis may be ameliorated by therapy. For example, in secondary amyloidosis, surgical eradication of the predisposing disease’” may slow the progression of amyloid deposition while in familial Mediterranean
HEPATIC
AMYLOIDOSIS:
AL AND
fever colchit ine therapy is effective in the treatment and prevrntion of arnyloidosis.” Therefore, because topographic separation of .41, from A.4 amyloidosis is unreliable in liver biopsies, application of modern histois essential chemical proc‘edures for accurate idrmtification of anlvloid type.
REFERENCIES
907
AA
TYPES (Buck
& Koss)
The liver has been recognized as a major site of deposition of anlyloid in the disseminated forms of the
disease since its early description by Rokitansky,’ Virchow,” and others. Levine:’ found hepatic involvement in 56% of his 84 patients with amyloidosis, and in his review of the literature he recorded the incidence of hepatic amyloid as varying between 17% and 98%. Attempts have been made by several researchers at differentiating between primary and secondary amyloidosis in the liver on the basis of the topographic patterns of distribution. The results have been conflicting. Several investigators’” postulated in the older literature that amyloid deposition in the liver in primary amyloidosis was largely confined to the blood vessels of the portal area while cases of the secondary type showed inF1-on1 rhe Dep”““““” of P;1tholo~. Los Angeles County-LXversity of Southern California M&Cal Center. University of Southern California SChool of Medicine. Los Angeles. (:A. Accepted for publication November 27. 191)l.
AtLdrrss correspondence and reprint requests to Fr-antis S. Buck, MD. Hex 55. Room 16-4?8 I.AC/lYK Medical Center, 1200 N State St, Los Angeles. CA 9003S.
904
volvement of the hepatic sinusoids as well as the portal vessels. Subsequently, Chopra et al’ and Looi and Sumithran7 have presented evidence that the reverse might be true. Our review of hepatic amyloidosis supports the latter concept, but also suggests many exceptions to the observation by Looi and Sumithran’ that secondary amyloidosis is confined to the portal vessels. MATERIALS
AND METHODS
Our study is based on 456 cases of amyloidosis found among 52,370 patients autopsied at Los Angeles County-University of Southern California Medical Center between January 1949 and July 1982.H In our series, livers were available for review in 407 cases. The overall occurrence of hepatic amyloidosis was 70% in this series. but further analysis showed that the prevalence of hepatic amyloidosis was 97% in both primary (AL) and secondary (AA) amyloidosis while only 4% of the cases identified as senile cardiac (senile systemic) amyloidosis had hepatic amyloid. In our present study. 138 cases were designated as senile cardiac (senile systemic) amyloidosis based on the following: the patient’s age, the heart as the principal organ involved, and confinement of amyloid in other organs to small blood vessels. The absence of organ failure in any organ other than the heart, the lack of involvement of glomerular capillaries, and the absence of amyloid in the red and white pulp of the spleen were other criteria used to support the diagnosis.“,‘” These cases were not included in the present study. III the remaining cases in which sections of liver were available, paraffin blocks of formalin-fixed tissue were studied using the potassium permanganate Congo red-staining method of Wright et al” and a specific antibody against AA amyloid. The method of Wright et al uses potassium permanganate to remove the affinity of AA amyloid for staining with Congo red; Al, amyloid is not affected by such treatment. A specific antibody against AA amyloid was obtained from the Department of Pathology at Yamquchi University School of Medicine through the courtesy of Dr Mutsuo Tak’ahashi (Ube, Yamaguchi, Japan). Details of its preparation are separately described.” The antibody was applied to duplicate sections by the peroxidase-anti-peroxidase method of Sternberger.” Cases in which the amyloid was oxidized bv potassium permanganate and reacted positively to the antibody against AA amyloid were clesignated as AA amyloidosis. Amyloidosis was categorized as AL type when the deposits were resistant to treatment with potassium permanganate and did not stain positively with the antibody to AA amyloid. Using these methods, 78 cases with available liver were identified as AA amyloidosis and 208 cases with available liver were identified as AL amyloidosis. Sections of liver were simultaneously reviewed by the two investigators using both direct light on hematoxylin-eosinstained sections and polarized light on Congo red-stained sections using an Olympus RH2 microscope. In particular, we evaluated the presence of amyloid in the following structures.
HEPATIC AMYLOIDOSIS’
AL AND AA TYPES (Buck & Koss)
I‘l~e term “port;~l vessels” is used to desiguate lhc hepark. a~-ter\~ and portal win in the portal triad. “Portal stroma” refers to thr interstitial tissue or space of the portal triad, “sir~usoid” wkrs to the spaw of Disse bordering the hepatic sillusoids. and “Central vein” refers to the collecting vein of ttw tiqxitic Ia)hulta. In addition, we reviewed the writkri autopsy report, the tlellialc,s~tin-eosin-stained
placed by amyloid. which was associated with advanced arrophy of hepatic parenchymal cells. We also investigated the 29 AA cases that had deposits of‘ sinusoidal amyloid. We were surprised that a majority of the AA cases with extensive sinusoidal amyloid also exhibited a “sago” pattern of distribution of amyloid in the spleen. Table ‘1 shows that 23 of the 20 cases (79.3%) showed a “saga” pattern of. amyloid distribution in the spleen (deposits of amyloid largely limited to the splenic follicles’ $1. The “saga” pattern does not guarantee the presence of hepat ic sinusoidal amyloid, since 15 cases with “saga” spleen had no sinusoidal involvement. We looked for reasons for the increased frequency of hepatic sinusoidal amyloidosis associated with “saga” spleen; in particular, we investigated the possibility that tuberculosis or other chronic. diseases might be implicated (Table 2) and found no significant difference in the frequency or type of chronic diseases between those saga cases with sinusoidal involvement and those without it.
sections on all available
,jrfidns, arid thr t;o~lgo red-stained sections on additionai St‘St;lristical analysis of data was perfol-med using Ire ted orgms. standard f ttb\ta.
RESULTS 111c,omparing the distribution of amyloid in the liver lobule of iL-\ and Al, amyloidosis cases (Table l), we found no significant difference in the prevalence of anryloid in portal vessels (arteries and veins). However, there was a statistically significant increase in prevalence of 41. amyloid over kd amyloid in other areas of the lobule. In the portal stroma there was a fourfold incrcsase, in cc-ntral veins there was a threefold increase, and in the sinusoidal areas (space of Disse) there was a twofold inc:rease. Nevertheless, we encountered sinu$oidal amyloid deposits in 29 of 78 cases of secondarv (A.%) amyloidosis (Figs 1 and 2). In 14 (48%) of the& c-aes. mor(l than SM of the sinusoidal spaces were re-
DISCUSSION Amyloid accumulation in the liver is nearlv a univrrsal characteristic. of systemic am>loidosis. but is seen
FIGURE 2. Portal area and adjacent hepatlc sinusoids In a case of AA amyloidosis. Note the extensive amyloid deposition in the space of Dlsse with associated hepatic cord atrophy and thickening of the hepatic artery wall due to infiltration by amyloid. (Hematoxylin-eosin stain; magnification *200 )
FIGURE 1. Central vein and surrounding hepatic sinusoids showing extensive amyloid deposition in the space of Disse and hepatic corcl atrophy in a case of AA amyloidosis. (Hematoxylineosin stain; magnification \200.)
905
HUMAN PATHOLOGY
TABLE 2.
Volume 22, No. 9 (September
78 Cases of Secondary (AA) Amyloidosis Cases Associated With Sinusoidal Amyloid
No. No. with sago spleen Associated diseases Tuberculosis Rheumatoid arthritis Chronir pyelonephritis Bronchiectasis Carcinomas, various organs
29 23 (79.3%)
CasesWith no Associated Sinusoidal Amyloid 19
15 (30.6%)
10
7
5 2 0 9
7
1 1 3
less frequently in senile cardiac (senile systemic) amyloidosis. Prior to the development of modern specific immunohistochemical methods for the separation of the forms of systemic amyloidosis, it was held by many authorities’-’ that when amyloidosis occurred in the liver, parenchymal “sinusoidal” involvement of the space of Disse was characteristic of secondary (AA) amyloidosis while “vascular” disease” (portal blood vessel involvement) was a feature of primary (AL) amyloidosis. We now recognize that conclusions by these early investigators were marred by their methods of separating primary from secondary amyloidosis, namely, the pattern of organ distribution and the presence or absence of a chronic inflammatory disease. Chopra et al” were the first to suggest that the findings of earlier authorities might be wrong. In their report they designated cases as primary (AL) amyloidosis when there was no evidence of preceding or coexisting disease, and when there was an increase in bone marrow plasma cells and/or M components or free light chains in serum or urine and/or the presence of myeloma. These were compared with cases of secondary “reactive” (AA) amyloidosis, in which evidence of a chronic infectious or inflammatory disease was present. They were able to show that “sinusoidal” parenchymal involvement was characteristic of primary (AL) amyloidosis, and exclusive “vascular” involvement was characteristic of secondary (AA) amyloidosis. However, they concluded that in individual cases significant overlap occurs and the characterization of the form of amyloidosis based on topographic distribution alone might be possible in only a minority of cases. Subsequently, Looi and Sumithran7 examined 3 1 unselected cases with systemic amyloidosis in which there was histologic evidence of liver involvement. They classified their cases into AA and AL types on the basis of immunohistochemistry and permanganate reaction of the amyloid deposits. In their cases, deposition of AA amyloid was limited to the walls of blood vessels in the portal tract, constituting a “vascular” pattern. In AL amyloidosis the deposits exhibited a “sinusoidal” pattern, in which they were seen in the space of Disse along hepatic sinusoids as well as in portal blood vessels and central veins. In our series, using diagnostic techniques similar to those used by Looi and Sumithran, we were able to 906
1991)
confirm that involvement of the sinusoidal parenchyma (space of Disse) is characteristic of AL amyloidosis and showed that involvement of the portal blood vessels does not differ significantly between AL and AA types. However, we found numerous exceptions to the conclusions of Looi and Sumithran’ that AA amyloidosis is limited to the walls of the vessels of the portal tract. In 29 (37.2%) of our 78 cases of AA amyloidosis we found significant sinusoidal parenchymal involvement, which was often very extensive; this appeared to be more likely when the liver involvement was accompanied by the “saga” pattern of distribution of amyloid in the spleen. In looking for possible explanations for the differences between our results and those of Chopra et al, we note that their study was not quite comparable to ours since their cases were classified clinically rather than histochemically. We have no final answer as to why our findings differ from those of Looi and Sumithran, whose methods of classification were similar to those we used, but we suggest that the following may offer a partial explanation. Our study involved a much larger group of patients. Looi and Sumithran studied 3 1 livers and we studied 286 livers containing either AA or AL amyloid. In addition we have previously showr? that there are significant variations in the prevalence of amyloidosis among various ethnic groups and that the prevalence of the types of amyloidosis within ethnic groups varies. Looi and Sumithran indicated that among their 19 cases of systemic AA amyloidosis, eight patients were Orang Asli (Malayan aborigine), six were Chinese, and five were Australian (presumably white). They did not identify the ethnic designation of their patients with systemic AL amyloidosis. In our patient population with systemic AA amyloidosis, 67.5% were white, 3.9% were black, and 28.6% were Hispanic; there were no Orientals or American Indians. Among our patients with systemic AL amyloidosis, 18.6% were white, 5.6% were black, and 75.9% were Hispanic; there were no Orientals or American Indians. We have no explanation for the increase in “sinusoidal” deposition among AA cases with “sago” spleen in terms of the type of chronic underlying disease. Even though Westernlark and Nilsson” noted an association of “saga” spleen with cases of tuberculosis, we were unable to demonstrate a significant difference in the frequency of tuberculosis between cases of AA amyloidosis that did or did not have sinusoidal amyloidosis. One possible explanation is the extended duration of the illness in patients with certain chronic inflammatory diseases, such as tuberculosis and rheumatoid arthritis, but we are unable to prove this from our data. In conclusion, we recognize that involvement of the space of Disse, the so-called “sinusoidal” pattern, by amyloidosis is statistically more common in AI, amyloidosis than it is in AA amyloidosis, but its presence there does not exclude AA amyloidosis. We believe that classifying the type of amyloidosis from biopsy specimens is important because certain types of amyloidosis may be ameliorated by therapy. For example, in secondary amyloidosis, surgical eradication of the predisposing disease’” may slow the progression of amyloid deposition while in familial Mediterranean
HEPATIC
AMYLOIDOSIS:
AL AND
fever colchit ine therapy is effective in the treatment and prevrntion of arnyloidosis.” Therefore, because topographic separation of .41, from A.4 amyloidosis is unreliable in liver biopsies, application of modern histois essential chemical proc‘edures for accurate idrmtification of anlvloid type.
REFERENCIES
907
AA
TYPES (Buck
& Koss)
