No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Identification of amyloid deposits by histochemical methods of Romhanyi: Applied histochemistry. Systemic secondary (AA) amyloidosis in rheumatoid arthritis
... Tissue samples of pancreas were available for histologic evaluation in 111 of 161 patients. Pancreatitis and AAa were diagnosed histologically according to Romhányi [2] by a modified (more sensitive) Congo red staining [3]. The extent of amyloid A deposition was evaluated by semi-quantitative, visual estimation on a 0 to 3 plus scale, based on the number of involved tissue structures in a light microscopic field [4]. ...
Abstract
Objectives The aim of this study was to describe the prevalence and formal pathogenesis of multi (micro) focal liponecrotic pancreatitis (LnP) caused by systemic secondary AA amyloidosis (AAa) in rheumatoid arthritis (RA).
Methods A randomized autopsy population of 161 in-patients with RA was studied. RA was confirmed clinically according to the criteria of the ACR. Tissue samples of pancreas were available for histologic evaluation in 111 of 161 patients. Pancreatitis and AAa were diagnosed histologically [1]. The possible role of AAa in the pathogenesis of LnP was analyzed by Pearson's chi-squared (χ2) test.
Results: AAa complicated RA in 29 (26.12%) of 111 patients. Amyloid A deposition on different tissue structures of pancreas was detected in 25 (86.2 %) of 29 cases. Marked amyloid A deposition was found in the walls of arterioles, small and medium size arteries, and on different tissue structures of the pancreas.
Acute or chronic LnP with or without AAa was present in different stages of the pathological process (necrotic foci with or without inflammatory reaction, and/or consecutive focal accentuated fibrosis) in 15 (13.51%) of 111 patients. Seven (46.66 %) of these 15 were associated with massive AAa. The correlation between LnP and prevalence of AAa was significant (c²=5.7939, p<0.016). Two (33.33%) of 15 LnP showed a special scattered multifocal appearance throughout the pancreas, characterized by necrotic foci of different size and stage of necrobiosis, without or with inflammation, and in association with severe AAa. The pancreatitis was basically not hemorrhagic, differing from hemorrhagic pancreatitis due to arterial erosions. Ductal changes were not present. The histological picture was dominated by more or less pronounced atrophy of pancreatic glands. The link between this special type of LnP and AAa very strong and significant (c²=16.2658, p<0.0005).
Conclusions The close relationship between AAa and LnP suggests a relationship between amyloidosis and the prevalence of pancreatitis, that even may lead to a special multi (mico) focal pancreatitis. Amyloid A deposition in the walls of the pancreatic arterioles, small and medium size arteries (branches of splenic artery, upper and lower gastroduodenal arteries) can lead to local ischemia and to regressive changes in the pancreatic gland. This process is more or less widespread and multifocal, depending on the number of involved vessels. The size of necrobiotic areas is determined by the size of involved bood vessels. Multi (micro) focal necrosis of the pancreas caused by diminished blood supply is followed by reactive inflammation, and later fibrosis, depending on the stages of the pathological process.
AAa is a progressive cumulative process involving more and more blood vessels of different sizes, thus the regressive changes accumulate in the pancreas with time, and exist in different stages at death. Different size and stage of focal necrosis, and the co-existent marked AAa may identify this type of pancreatitis. The progressive and cumulative process of AAa with multi (micro) focal necrosis in the pancreas may cause recurrent abdominal symptoms. This form of pancreatitis may be regarded a special manifestation of AAa or a new vasculogenic entity caused by AAa in RA. Plausible similar changes of pancreas may be expected in other autoimmune diseases complicated with AAa.
Reference: [1] Bély M. Apáthy Ágnes: Clinical pathology of rheumatoid arthritis. 1-440 pp. Akadémiai Kiadó, Budapest 2012 Budapest 2012. http://www.akkrt.hu
Disclosure of Interest: None declared
http://dx.doi.org/10.1136/annrheumdis-2018-eular.1041
... Tissue samples of pancreas were available for histologic evaluation in 111 of 161 patients. Pancreatitis and AAa were diagnosed histologically according to Romhányi [2] by a modified (more sensitive) Congo red staining [3]. The extent of amyloid A deposition was evaluated by semi-quantitative, visual estimation on a 0 to 3 plus scale, based on the number of involved tissue structures in a light microscopic field [4]. ...
Abstract
Objectives The aim of this study was to describe the prevalence and formal pathogenesis of multi (micro) focal liponecrotic pancreatitis (LnP) caused by systemic secondary AA amyloidosis (AAa) in rheumatoid arthritis (RA).
Methods A randomized autopsy population of 161 in-patients with RA was studied. RA was confirmed clinically according to the criteria of the ACR. Tissue samples of pancreas were available for histologic evaluation in 111 of 161 patients. Pancreatitis and AAa were diagnosed histologically [1]. The possible role of AAa in the pathogenesis of LnP was analyzed by Pearson's chi-squared (χ2) test.
Results: AAa complicated RA in 29 (26.12%) of 111 patients. Amyloid A deposition on different tissue structures of pancreas was detected in 25 (86.2 %) of 29 cases. Marked amyloid A deposition was found in the walls of arterioles, small and medium size arteries, and on different tissue structures of the pancreas.
Acute or chronic LnP with or without AAa was present in different stages of the pathological process (necrotic foci with or without inflammatory reaction, and/or consecutive focal accentuated fibrosis) in 15 (13.51%) of 111 patients. Seven (46.66 %) of these 15 were associated with massive AAa. The correlation between LnP and prevalence of AAa was significant (c²=5.7939, p<0.016). Two (33.33%) of 15 LnP showed a special scattered multifocal appearance throughout the pancreas, characterized by necrotic foci of different size and stage of necrobiosis, without or with inflammation, and in association with severe AAa. The pancreatitis was basically not hemorrhagic, differing from hemorrhagic pancreatitis due to arterial erosions. Ductal changes were not present. The histological picture was dominated by more or less pronounced atrophy of pancreatic glands. The link between this special type of LnP and AAa very strong and significant (c²=16.2658, p<0.0005).
Conclusions The close relationship between AAa and LnP suggests a relationship between amyloidosis and the prevalence of pancreatitis, that even may lead to a special multi (mico) focal pancreatitis. Amyloid A deposition in the walls of the pancreatic arterioles, small and medium size arteries (branches of splenic artery, upper and lower gastroduodenal arteries) can lead to local ischemia and to regressive changes in the pancreatic gland. This process is more or less widespread and multifocal, depending on the number of involved vessels. The size of necrobiotic areas is determined by the size of involved bood vessels. Multi (micro) focal necrosis of the pancreas caused by diminished blood supply is followed by reactive inflammation, and later fibrosis, depending on the stages of the pathological process.
AAa is a progressive cumulative process involving more and more blood vessels of different sizes, thus the regressive changes accumulate in the pancreas with time, and exist in different stages at death. Different size and stage of focal necrosis, and the co-existent marked AAa may identify this type of pancreatitis. The progressive and cumulative process of AAa with multi (micro) focal necrosis in the pancreas may cause recurrent abdominal symptoms. This form of pancreatitis may be regarded a special manifestation of AAa or a new vasculogenic entity caused by AAa in RA. Plausible similar changes of pancreas may be expected in other autoimmune diseases complicated with AAa.
Reference: [1] Bély M. Apáthy Ágnes: Clinical pathology of rheumatoid arthritis. 1-440 pp. Akadémiai Kiadó, Budapest 2012 Budapest 2012. http://www.akkrt.hu
Disclosure of Interest: None declared
http://dx.doi.org/10.1136/annrheumdis-2018-eular.1041
... Tissue samples of pancreas were available for histologic evaluation in 111 of 161 patients. Pancreatitis and AAa were diagnosed histologically according to Romhányi [2] by a modified (more sensitive) Congo red staining [3]. The extent of amyloid A deposition was evaluated by semi-quantitative, visual estimation on a 0 to 3 plus scale, based on the number of involved tissue structures in a light microscopic field [4]. ...
Abstract
Objectives: The aim of our study was to determine the prevalence and severity of systemic AA amyloidosis (sAAa), to specify amyloid A deposits in different tissue structures of the kidneys, to outline the development of renal AA amyloidosis (rAAa), and to estimate the role of sAAa and rAAa in mortality.
Methods: At the National Institute of Rheumatology 9475 patients died between 1969 and 1992; among them 161 with RA (females 116, average age: 64.95 years, range 87–16, onset of RA: 50.19, average disease duration: 14.79 years; males 45, average age: 66.29 years, range 88–19, onset of RA: 52.57, average disease duration: 13.46 years at death); who were autopsied.
RA was confirmed clinically according to the criteria of the ACF.
sAAa was specified histologically, based on evaluation of 5 organs (heart, lung, liver, kidney and pancreas) in each of 161 patients. Amyloid A deposition was diagnosed histologically according to Romhányi by a modified (more sensitive) Congo red staining. Amyloid A deposits were identified in serial sections by immunohistochemical and histochemical methods. The prevalence (existence) and severity (extent) of amyloid A deposition were evaluated microscopically with an Olympus BX51 polarizing microscope.
Results: sAAa complicated RA in 34 (21.12 %) of 161 patients; in 127 (78.88 %) of 161 patients amyloid A deposits were not found.
Amyloid A deposits were found in 29 (87.88 %) kidneys of 33 patients with sAAa; kidneys were negative for amyloid in 4 (12.12 %) of 33 cases (in 1 of 34 patients with sAAa tissue blocks of kidneys were not available).
sAAa was lethal in 17 (50.0 % of 34) patients due to massive amyloid A deposition in the kidneys, leading to renal insufficiency and uremia. Cardiac amyloid A deposition led to death in 3 (8.82 % of 34) patients with sAAa (and contributed to the lethal outcome in further 5). Forteen (41.18 % of 34) patients with sAAa died of other causes such as peritonitis, lethal septic infection, etc.
sAAa was clinically diagnosed in 9 (26.47 %) and missed in 25 (73.52 %) of 34 patients, and only cases with massive renal amyloid A deposits were recognized. Cardiac AAa or its pathogenic role in mortality was not diagnosed.
Conclusions: sAAa is one of the main and the most insidious complications of RA affecting the kidneys with high prevalence and severity. sAAa is related to the cardiovascular system, and rAAa is associated with it. sAAa and rAAa may developed in both sexes, and at any time in the course of the disease.
Systemic and renal amyloid A deposition is a progressive and cumulative process, involving in its early stage only a few structures in various organs, and increasingly more in the later stages of the disease.
In sAAa the renal amyloid A deposition starts after a latent stage. This latency may be caused by a not specified local protective mechanism, e.g. great excretion capacity of the kidneys.
Amyloid A deposition starts in the most frequently involved structures of the kidneys with more massive deposits. The chronology of amyloid A deposition allows an indirect assessment of the stage of renal amyloidosis, which may have a prognostic value in everyday surgical pathology.
Half of the patients with sAAa died of uremia caused by massive rAAa and only 9 of these were clinically recognized. Renal amyloid A deposition should be considered a very serious, life-threatening complication of RA.
Disclosure of Interest: None declared
http://dx.doi.org/10.1136/annrheumdis-2018-eular.1289
In Memoriam David Apáthy (1951. október 27.-2023. szeptember 23.)
Egy amerikai magyar önzetlen hozzájárulása orvosi kongresszusaink sikeréhez
Mély megdöbbenéssel értesültünk amerikai-magyar rokonunk Apáthy Dezső (David Apathy, MBA Harvard) váratlan tragikus haláláról.
David Apathy ugyan közgazdász volt, de három nemzetközi magyar orvosi kongresszus sikeréhez járult hozzá, illetve ezek hatékony lebonyolításában (menedzselésében) vett részt.
XVII. Conference of the International Society for Fluoride Research. Budapest, 22-25 June 1989.
XXI World Conference of the International Society for Fluoride Research. Budapest, 25-29 August 1996.
IX. International Symposium on Amyloidosis, Budapest, Hungary,15-21 July 2001.
A megemlékezéa ennek a három orvosi kongresszusnak a történetét eleveníti fel.
Objectives
The
Aim
of our study was to determine the incidence of
S
ystemic
AA a
myloidosis (
SAAa
) in
RA
, to appraise the prevalence and severity of amyloid A deposits in different tissue structures of the kidneys and heart, to outline the development of
R
enal and
C
ardiac
AA a
myloidosis (
RAAa
and
CAAa
), and to estimate the role of
RAAa
and
CAAa
in mortality.
Methods
One hundred sixty one
(
161
) non- selected autopsy patients with rheumatoid arthritis (
RA
) were studied.
RA
was confirmed clinically according to the criteria of the
ACR
[1].
SAAa
was specified histologically, based on evaluation of
5
organs (heart, lung, liver, kidney and pancreas). Amyloid A deposition was diagnosed histologically according to Romhányi by a modified (more sensitive) Congo red staining [2]. Amyloid A deposits were confirmed in serial sections by immunohistochemical and histochemical methods. Results:
SAAa
complicated
RA
in
34
(
21.12
%) of 161 patients; in
127
(
78.88
%) of 161 patients amyloid A deposits were not found. Amyloid A deposits were found in
29
(
87.88
%)
Kidneys
of 33 patients
With sAAa
; kidneys were negative for amyloid in
4
(
12.12
%) of 33 cases (in 1 of 34 patients with
SAAa
tissue blocks of kidneys were not available). Amyloid A deposits were found in
29
(
87.88
%)
Hearts
of 33
With sAAa
; the heart was negative for amyloid in
4
(
12.12
%) of 33 cases (the heart of one patient with
SAAa
was not available). Renal amyloid A deposition led to death in
17
(50.0% of 34) patients
With sAAa
due to massive amyloid A deposition in the kidneys, leading to renal insufficiency and uremia. Cardiac amyloid A deposition led to death in
3
(8.82% of 34) patients
With sAAa
(and contributed to the lethal outcome in further 5).
Forteen
(41.18% of 34) patients with
SAAa
died of other causes such as peritonitis, lethal septic infection, etc.
SAAa
was clinically diagnosed in
9
(26.47%) and missed in
25
(73.52%) of 34 patients, and only cases with massive renal amyloid A deposits were recognized. Cardiac
AAa
or its pathogenic role in mortality was not diagnosed. Conclusion:
SAAa
is one of the main and the most insidious complications of
RA
affecting the kidneys and heart with high prevalence and severity.
SAAa
is related to the cardiovascular system, and
RAAa
or
CAAa
are associated with it.
SAAa
,
RAAa
and
CAAa
may developed in both sexes, and at any time in the course of the disease. Systemic, renal and cardiac amyloid A deposition is a progressive and cumulative process, involving in its early stage only a few structures in some organs, and increasingly more in the later stages of the disease.
In
SAAa
the renal and cardiac amyloid A deposition starts after a latent stage. This latency may be caused by a not specified local protective mechanism, e.g. great excretion capacity of the kidneys, due to motility of the heart or oxygenisation etc. Amyloid A deposition starts in the most frequently involved structures of the kidneys or heart with more massive deposits. The chronology of amyloid A deposition allows an indirect assessment of the stage of renal or cardiac amyloidosis, which may have a prognostic value in everyday surgical pathology.
Half of the patients with
SAAa
died of uremia caused by massive
RAAa
and only 9 of these were clinically recognized. Renal and cardiac amyloid A deposition should be considered a very serious, life-threatening complication of
RA
.
References
[1] Arnett FC, et al: Arthritis Rheum, 1988; 31: 315-324. DOI: 10.1002/art.1780310302 [2] Bély M, Makovitzky J: Acta Histochemica 108, 175-180 (2006). DOI: 10.1016/j.acthis.2006.03.017
Disclosure of Interests
None declared
[SAT0126] SPECTRUM OF AMYLOID DEPOSITS (AMYLOIDOSES) IN RA – A POSTMORTEM CLINICOPATHOLOGIC STUDY OF 161 PATIENTS
M. Bély1, A. Apáthy2. 1Department of Pathology, Hospital of the Order of the Brothers of Saint John of God; 2Department of Rheumatology, St. Margaret Clinic, Budapest, Hungary
Background: Different types of amyloid deposits may exist simultaneously in patients with rheumatoid arthritis (RA).
Objectives: The aim of this study was to determine the types of amyloid deposits, i.e. the spectrum of amyloidosis, in RA.
Methods: A randomized autopsy population of 161 in-patients with RA was studied. The patients died at the National Institute of Rheumatology between 1969 and 1992.
RA was confirmed clinically according to the criteria of ACR. Amyloid deposits in 25 organs [gastrointestinal tract, heart, urogenital organs (kidney, prostate, seminal vesicles, testis and epididymis, uterus and adnexa), spleen, adrenal glands, liver, pancreas, lungs, thyroid gland, aorta, skeletal muscles, synovial membranes, lymph nodes, peripheral nerves, bone (head of femur), skin and brain] were determined histologically.
Results: Different types of amyloid deposits existed simultaneously in the same patient. Systemic secondary AA amyloidosis (AAa) was present in 34 (21.12%), systemic primary myeloma-associated immunoglobulin AL k-chain amyloidosis in 1 (0.62%) of 161, cerebral b protein-related amyloidosis (cerebral amyloid angiopathy – CAA) in 2 (3.77%) of 53*, dystrophic (aging related) linear or globular amyloid deposits localized to the superficial zone of articular cartilage in 9 (16.98%) of 53*, endocrine related prohormone fragments localized to islets of Langerhans (Islet amyloid polypeptide – AIAPP) in 13 (11.71%) of 111*, b2 microglobulin amyloid (Ab2M) localized to the kidney in 1 (0.63%) of 159*, and prostatic in 6 (54.55%) of 11*, or pulmonary corpora amylacea (b2-microglobulin – Ab2M) in 8 (5.75%) of 139* patients were present.
(*Some organs of 161 RA patients were not available for evaluation.)
Conclusions: Only AA amyloidosis may be considered as a true complication of RA, any other types of amyloidosis may be present in RA as an associated phenomenon or complication of associated diseases [1].
The low prevalence of systemic primary AL k-chain amyloidosis has been deceptive in our autopsy population. One recognized reason has been that patients with lymphoproliferative disorders were transferred to an institution specialized in hematology.
It is difficult to estimate the true prevalence of AAa in RA. The prevalence of amyloidosis depends on the specificity and sensitivity of the applied method. Using a less sensitive staining method some positive cases remain undetected. A more specific method potentially detects more cases, and reveals earlier stages. Older methods are less specific in comparison with Congo red staining applied by Puchtler et al. [2]. Congo red staining according to Romhányi is a more specific and sensitive method for detection of amyloid deposits in comparison with Puchtler's Congo red methods [3].
Less extensive postmortem examination (of fewer organs with a different prevalence of AAa) may explain differences of prevalence and incidence as well.
References:
Bély M, Apáthy A: Clinical pathology of rheumatoid arthritis: Cause of death, lethal complications and associated diseases in rheumatoid arthritis. 1-440 pp. Akadémiai Kiadó, Budapest 2012 http://www.akkrt.hu
Puchtler H, Sweat F, Levine M: On the binding of Congo red by amyloid. J Histochem Cytochem, 1962; 10:355-364
Bély M, Makovitzky J: Sensitivity and Specificity of Congo red Staining According to Romhányi - Comparison with Puchtler's or Bennhold's Methods. Acta Histochemica, 2006; 108:175-180
Disclosure of Interest: None declared
DOI: 10.1136/annrheumdis-2015-eular.3690
Citation: Ann Rheum Dis2015;74(Suppl2): 696
Session: Rheumatoid arthritis - comorbidity and clinical aspects
[SAT0126] SPECTRUM OF AMYLOID DEPOSITS (AMYLOIDOSES) IN RA – A POSTMORTEM CLINICOPATHOLOGIC STUDY OF 161 PATIENTS
Authors: M. Bély1, A. Apáthy2
Session Info: Rheumatoid arthritis - comorbidity and clinical aspects
Year: 2015
The histochemical and immunohistochemical differential diagnosis of amyloidosis in surgical pathology in a referral center is presented. Different forms of amyloidosis are considered e.g. systemic generalized amyloidosis: secondary (AA), primary (AL), senile, hemodialysis-associated, hereditary and organ (tissue)-limited (localized) amyloidosis: cerebral, dystrophic (age-related, so-called "senile"), endocrine-related, localized to tumours, focal (concentrated secretion), and isolated plasma cell (solitary plasmacytoma, B-cell) dyscrasia related amyloidosis. The amyloid deposits were identified and characterized histochemically by Congo red staining after performate pre-treatment at 20 degrees C for 1, 3, 5, 10, 15, 20 or 25 sec, and with oxidation induced proteolysis by trypsin digestion at 20 degrees C for 5, 10, or 30 sec, 1, 2, 3, 4, 5, 6 or 10 min and covered with gum-arabic according to Romhányi, and confirmed by streptavidin-biotin-complex/horseradish peroxidase immunohistochemical reactions. The "sensitivity" or "resistance" to pre-treatment of amyloid deposits depends on the type of amyloid, and the length of pre-treatment. Secondary (AA) amyloid is sensitive to KMnO4 oxidation, followed by trypsin digestion (for 1 min), and its green birefringence under polarized light disappears, while primary (AL) (for 1-5 min), senile (for 1-10 min), and most forms of organ (tissue)-limited (localized) amyloid (for 1-10 min) are resistant. Performate pre-treatment is followed by pronounced congophilia. Secondary (AA) is sensitive to performate pre-treatment (for 1 sec), while primary (AL) amyloid (for 1-20 sec), senile (for 1-25 sec), and most forms of organ (tissue)-limited (localized, isolated) amyloid deposits (for 1-25 sec) are resistant, and are constantly positively birefringent. Early identification and differentiation of amyloid deposits is important for the prognosis and for the choice of therapy. The authors conclude that the presented classical histochemical methods are useful as first line screens for the histological identification of amyloidosis.
Amyloidosis is characterized by extracellular deposition of protein fibrils of chemically heterogeneous composition. Early recognition and identification of amyloid deposits allows an early start of therapy, which may entail a better prognosis. Congo red staining according to Romhányi (1971) is a highly specific and sensitive method for early microscopic recognition of amyloidosis. The main and most important types of amyloidosis may be distinguished by classic histochemical methods of performate pretreatment according to Romhányi (1979), or by KMnO4 oxidation according to Wright (1977) followed by Congo red staining and viewed under polarized light. Differences in the speed of breakdown (disintegration) of amyloid deposits according to Bély and Apáthy allow a more precise distinction of various types of amyloid.
The histochemical and immunohistochemical differential diagnosis of amyloidosis in surgical pathology in a referral center is presented. Different forms of amyloidosis are considered e.g. systemic generalized amyloidosis: secondary (AA), primary (AL), senile, hemodialysis-associated, hereditary and organ (tissue)-limited (localized) amyloidosis: cerebral, dystrophic (age-related, so-called "senile"), endocrine-related, localized to tumours, focal (concentrated secretion), and isolated plasma cell (solitary plasmacytoma, B-cell) dyscrasia related amyloidosis. The amyloid deposits were identified and characterized histochemically by Congo red staining after performate pre-treatment at 20 degrees C for 1, 3, 5, 10, 15, 20 or 25 sec, and with oxidation induced proteolysis by trypsin digestion at 20 degrees C for 5, 10, or 30 sec, 1, 2, 3, 4, 5, 6 or 10 min and covered with gum-arabic according to Romhányi, and confirmed by streptavidin-biotin-complex/horseradish peroxidase immunohistochemical reactions. The "sensitivity" or "resistance" to pre-treatment of amyloid deposits depends on the type of amyloid, and the length of pre-treatment. Secondary (AA) amyloid is sensitive to KMnO4 oxidation, followed by trypsin digestion (for 1 min), and its green birefringence under polarized light disappears, while primary (AL) (for 1-5 min), senile (for 1-10 min), and most forms of organ (tissue)-limited (localized) amyloid (for 1-10 min) are resistant. Performate pre-treatment is followed by pronounced congophilia. Secondary (AA) is sensitive to performate pre-treatment (for 1 sec), while primary (AL) amyloid (for 1-20 sec), senile (for 1-25 sec), and most forms of organ (tissue)-limited (localized, isolated) amyloid deposits (for 1-25 sec) are resistant, and are constantly positively birefringent. Early identification and differentiation of amyloid deposits is important for the prognosis and for the choice of therapy. The authors conclude that the presented classical histochemical methods are useful as first line screens for the histological identification of amyloidosis.