Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Virchows Archiv
Published in: Virchows Archiv 5/2016

Open Access 01-05-2016 | Original Article

Amyloid in biopsies of the gastrointestinal tract—a retrospective observational study on 542 patients

Authors: Sophie Freudenthaler, Ute Hegenbart, Stefan Schönland, Hans-Michael Behrens, Sandra Krüger, Christoph Röcken

Published in: Virchows Archiv | Issue 5/2016

Login to get access

Abstract

In this retrospective observational study, we investigated the histopathological and demographic characteristics of amyloid in gastrointestinal biopsies. From the Amyloid Registry Kiel, we retrieved all cases with amyloid in biopsies of the stomach, duodenum, small intestine, large intestine, and rectum submitted for tertiary referral between January 2003 and April 2013. Amyloid was identified by Congo red staining in combination with polarization microscopy and classified by immunohistochemistry. The TTR-genotype was assessed in 56 patients. Amyloid type was correlated with demographic patient characteristics. Six hundred sixty-three biopsies from 542 patients were retrieved. Amyloid was found in each biopsy as vascular and/or interstitial amyloid deposits. Biopsies were obtained from the colon [254 biopsies (38.3 %)], stomach, [153 (23.1 %)], rectum [112 (16.9 %)], duodenum [105 (15.8 %)], and jejunum/ileum [39 (5.9 %)]. ALλ amyloid was found in 286 (52.8 %), ATTR in 88 (16.2 %), ALκ in 74 (13.7 %), AA in 58 (10.7 %), and ApoAI amyloid in 4 (0.7 %) patients. The remaining 21 cases were ALys amyloid in 4 (0.7 %), AL n.o.s. in 14 (2.6 %), and mixed type amyloidosis in 3 (0.6 %). The amyloid of 11 (2.0 %) cases remained unclassified. The median age of the patients was 68 years. Men [332 (61.7 %)] were significantly more prevalent than women [206 (38.3 %); p < 0.001]. TTR mutations were found in 24 % of the patients with ATTR amyloidosis. The median age, the histoanatomical distribution (proximal to distal; mucosal to submucosal), and the deposition pattern (vascular/interstitial) varied between different amyloid types. Amyloid in gastrointestinal biopsies mainly affects male elderly patients and shows amyloid-type-specific demographic patient characteristics.
Appendix
Available only for authorised users
Literature
1.
2.
Sipe JD, Benson MD, Buxbaum JN, Ikeda S, Merlini G, Saraiva MJ, Westermark P (2014) Nomenclature 2014: amyloid fibril proteins and clinical classification of the amyloidosis. Amyloid 21:221–224CrossRefPubMed
3.
4.
Kieninger B, Eriksson M, Kandolf R, Schnabel PA, Schönland S, Kristen AV, Hegenbart U, Lohse P, Röcken C (2010) Amyloid in endomyocardial biopsies. Virchows Arch 456:523–532CrossRefPubMed
5.
Röcken C, Ernst J, Hund E, Michels H, Perz J, Saeger W, Sezer O, Spuler S, Willig F, Schmidt HHJ (2006) Interdisziplinäre Leitlinien zur Diagnostik und Therapie der extrazerebralen Amyloidosen. DMW 131:S45–S66CrossRef
6.
Bergesio F, Ciciani AM, Santostefano M, Brugnano R, Manganaro M, Palladini G, Di Palma AM, Gallo M, Tosi PL, Salvadori M (2007) Renal involvement in systemic amyloidosis-an Italian retrospective study on epidemiological and clinical data at diagnosis. Nephrol Dial Transplant 22:1608–1618CrossRefPubMed
7.
Bauerova L, Honsova E, Rysava R, Povysil C (2009) Systemic amyloidoses in renal biopsy samples. Cesk Patol 45:64–68PubMed
8.
Helmchen U, Velden J, Kneissler U, Stahl RAK (2008) Clinical pathology of renal amyloidoses. Nephrologe 3:203–215CrossRef
9.
Hassan W, Al-Sergani H, Mourad W, Tabbaa R (2005) Amyloid heart disease. New frontiers and insights in pathophysiology, diagnosis, and management. Tex Heart Inst J 32:178–184PubMedPubMedCentral
10.
Rahman JE, Helou EF, Gelzer-Bell R, Thompson RE, Kuo C, Rodriguez ER, Hare JM, Baughman KL, Kasper EK (2004) Noninvasive diagnosis of biopsy-proven cardiac amyloidosis. J Am Coll Cardiol 43:410–415CrossRefPubMed
11.
Rapezzi C, Merlini G, Quarta CC, Riva L, Longhi S, Leone O, Salvi F, Ciliberti P, Pastorelli F, Biagini E, Coccolo F, Cooke RM, Bacchi-Reggiani L, Sangiorgi D, Ferlini A, Cavo M, Zamagni E, Fonte ML, Palladini G, Salinaro F, Musca F, Obici L, Branzi A, Perlini S (2009) Systemic cardiac amyloidoses: disease profiles and clinical courses of the 3 main types. Circulation 120:1203–1212CrossRefPubMed
12.
Said SM, Grogg KL, Smyrk TC (2015) Gastric amyloidosis: clinicopathological correlations in 79 cases from a single institution. Hum Pathol 46:491–498CrossRefPubMed
13.
Mahmood S, Bridoux F, Venner CP, Sachchithanantham S, Gilbertson JA, Rowczenio D, Wagner T, Sayed R, Patel K, Fontana M, Whelan CJ, Lachmann HJ, Hawkins PN, Gillmore JD, Wechalekar DM (2015) Natural history and outcomes in localized immunoglobulin light chain (AL) amyloidosis: a long-term observational study. Lancet Haematology 2:e241–e250CrossRefPubMed
14.
15.
Ando Y, Coelho T, Berk JL, Cruz MW, Ericzon BG, Ikeda S, Lewis WD, Obici L, Plante-Bordeneuve V, Rapezzi C, Said G, Salvi F (2013) Guideline of transthyretin-related hereditary amyloidosis for clinicians. Orphanet J Rare Dis 8:31CrossRefPubMedPubMedCentral
16.
Dubrey S, Ackermann E, Gillmore J (2015) The transthyretin amyloidoses: advances in therapy. Postgrad Med J 91:439–448CrossRefPubMed
17.
Plante-Bordeneuve V (2014) Update in the diagnosis and management of transthyretin familial amyloid polyneuropathy. J Neurol 261:1227–1233CrossRefPubMed
18.
Eriksson M, Schönland S, Yumlu S, Hegenbart U, von HH, Gioeva Z, Lohse P, Büttner J, Schmidt H, Röcken C (2009) Hereditary apolipoprotein AI-associated amyloidosis in surgical pathology specimens: identification of three novel mutations in the APOA1 gene. J Mol Diagn 11:257–262
19.
Granel B, Valleix S, Serratrice J, Cherin P, Texeira A, Disdier P, Weiller PJ, Grateau G (2006) Lysozyme amyloidosis: report of 4 cases and a review of the literature. Medicine (Baltimore) 85:66–73CrossRef
20.
Röcken C, Becker K, Fändrich M, Schroeckh V, Stix B, Rath T, Kähne T, Dierkes J, Roessner A, Albert FW (2006) ALys amyloidosis caused by compound heterozygosity in exon 2 (Thr70Asn) and exon 4 (Trp112Arg) of the lysozyme gene. Hum Mutat 27:119–120CrossRefPubMed
21.
Gafni J, Sohar E (1960) Rectal biopsy for the diagnosis of amyloidosis. Amer J Med Sci 240:102/332–106/336CrossRef
22.
Kyle RA, Spencer RJ, Dahlin DC (1966) Value of rectal biopsy in the diagnosis of primary systemic amyloidosis. Amer J Med Sci 251:35/501–540/506CrossRef
23.
Gioeva Z, Urban P, Meliss RR, Haag J, Axmann HD, Siebert F, Becker K, Radtke HG, Röcken C (2013) ATTR amyloid in the carpal tunnel ligament is frequently of wildtype transthyretin origin. Amyloid 20:1–6CrossRefPubMed
24.
Kebbel A, Röcken C (2006) Immunohistochemical classification of amyloid in surgical pathology revisited. Am J Surg Pathol 30:673–683CrossRefPubMed
25.
Kuci H, Ebert MP, Röcken C (2007) Anti-lambda-light chain-peptide antibodies are suitable for the immunohistochemical classification of AL amyloid. Histol Histopathol 22:379–387PubMed
26.
Röcken C, Schwotzer E, Linke RP, Saeger W (1996) The classification of amyloid deposits in clinicopathological practice. Histopathology 29:325–335CrossRefPubMed
27.
Schönland SO, Hegenbart U, Bochtler T, Mangatter A, Hansberg M, Ho AD, Lohse P, Röcken C (2012) Immunohistochemistry in the classification of systemic forms of amyloidosis: a systematic investigation of 117 patients. Blood 119:488–493CrossRefPubMed
28.
Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Statist Soc B 57:289–300
29.
30.
Hokama A, Kishimoto K, Nakamoto M, Kobashigawa C, Hirata T, Kinjo N, Kinjo F, Kato S, Fujita J (2011) Endoscopic and histopathological features of gastrointestinal amyloidosis. World J Gastrointest Endosc 3:157–161CrossRefPubMedPubMedCentral
31.
Kim YJ, Kim HS, Park SY, Park SW, Choi YD, Park CH, Choi SK, Rew JS (2012) Intestinal amyloidosis with intractable diarrhea and intestinal pseudo-obstruction. Korean J Gastroenterol 60:172–176CrossRefPubMed
32.
Yamada M, Hatakeyama S, Tsukagoshi H (1985) Gastrointestinal amyloid deposition in AL (primary or myeloma-associated) and AA (secondary) amyloidosis: diagnostic value of gastric biopsy. Hum Pathol 16:1206–1211CrossRefPubMed
33.
Alcalde-Vargas A, Leo-Carnerero E, Rojas-Mercedes N, Trigo-Salado C, Herrera-Justiniano JM, Marquez-Galan JL (2015) Correlation between location of amyloid deposits and endoscopic and clinical manifestations in symptomatic gastrointestinal amyloidosis. Rev Esp Enferm Dig 107:49–51PubMed
34.
35.
Menke DM, Kyle RA, Fleming CR, Wolfe JT 3rd, Kurtin PJ, Oldenburg WA (1993) Symptomatic gastric amyloidosis in patients with primary systemic amyloidosis. Mayo Clin Proc 68:763–767CrossRefPubMed
36.
Cowan AJ, Skinner M, Seldin DC, Berk JL, Lichtenstein DR, O’Hara CJ, Doros G, Sanchorawala V (2013) Amyloidosis of the gastrointestinal tract: a 13-year, single-center, referral experience. Haematologica 98:141–146CrossRefPubMedPubMedCentral
37.
38.
Lachmann HJ, Booth DR, Booth SE, Bybee A, Gilbertson JA, Gillmore JD, Pepys MB, Hawkins PN (2002) Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosis. N Engl J Med 346:1786–1791CrossRefPubMed
39.
Ikeda S, Hanyu N, Hongo M, Yoshioka J, Oguchi H, Yanagisawa N, Kobayashi T, Tsukagoshi H, Ito N, Yokota T (1987) Hereditary generalized amyloidosis with polyneuropathy. Clinicopathological study of 65 Japanese patients. Brain 110:315–337CrossRefPubMed
40.
Wixner J, Mundayat R, Karayal ON, Anan I, Karling P, Suhr OB, investigators T (2014) THAOS: gastrointestinal manifestations of transthyretin amyloidosis—common complications of a rare disease. Orphanet J Rare Dis 9:61
41.
Holmgren G, Ericzon BG, Groth CG, Steen L, Suhr O, Andersen O, Wallin BG, Seymour A, Richardson S, Hawkins PN, Pepys MB (1993) Clinical improvement and amyloid regression after liver transplantation in hereditary transthyretin amyloidosis. Lancet 341:1113–1116CrossRefPubMed
42.
Eriksson M, Büttner J, Todorov T, Yumlu S, Schönland S, Hegenbart U, Kristen AV, Dengler T, Lohse P, Helmke B, Schmidt H, Röcken C (2009) Prevalence of germline mutations in the TTR gene in a consecutive series of surgical pathology specimens with ATTR amyloid. Am J Surg Pathol 33:58–65CrossRefPubMed
43.
44.
Holmgren G, Wikstrom L, Lundgren HE, Suhr OB (2004) Discordant penetrance of the trait for familial amyloidotic polyneuropathy in two pairs of monozygotic twins. J Intern Med 256:453–456CrossRefPubMed
45.
Kato-Motozaki Y, Ono K, Shima K, Morinaga A, Machiya T, Nozaki I, Shibata-Hamaguchi A, Furukawa Y, Yanase D, Ishida C, Sakajiri K, Yamada M (2008) Epidemiology of familial amyloid polyneuropathy in Japan: identification of a novel endemic focus. J Neurol Sci 270:133–140CrossRefPubMed
46.
Lobato L (2003) Portuguese-type amyloidosis (transthyretin amyloidosis, ATTR V30M). J Nephrol 16:438–442PubMed
47.
Sousa A, Andersson R, Drugge U, Holmgren G, Sandgren O (1993) Familial amyloidotic polyneuropathy in Sweden: geographical distribution, age of onset, and prevalence. Hum Hered 43:288–294CrossRefPubMed
48.
Sousa A, Coelho T, Barros J, Sequeiros J (1995) Genetic epidemiology of familial amyloidotic polyneuropathy (FAP)-type I in Povoa do Varzim and Vila do Conde (north of Portugal). Am J Med Genet 60:512–521CrossRefPubMed
Metadata
Title
Amyloid in biopsies of the gastrointestinal tract—a retrospective observational study on 542 patients
Authors
Sophie Freudenthaler
Ute Hegenbart
Stefan Schönland
Hans-Michael Behrens
Sandra Krüger
Christoph Röcken
Publication date
01-05-2016
Publisher
Springer Berlin Heidelberg
Published in
Virchows Archiv / Issue 5/2016
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-016-1916-y

Other articles of this Issue 5/2016

Virchows Archiv 5/2016 Go to the issue

Review and Perspectives

Assessment of the PD-L1 status by immunohistochemistry: challenges and perspectives for therapeutic strategies in lung cancer patients

Editorial

In this issue

Original Article

Total peroxiredoxin expression is associated with survival in patients with follicular lymphoma

Original Article

Sox10 expression in ovarian epithelial tumors is associated with poor overall survival

Original Article

The X-linked inhibitor of apoptosis protein is an independent prognostic marker for rectal adenocarcinoma after preoperative chemoradiotherapy

Original Article

In prostate cancer needle biopsies, detections of PTEN loss by fluorescence in situ hybridization (FISH) and by immunohistochemistry (IHC) are concordant and show consistent association with upgrading