Diagnostic challenges in systemic amyloidosis: a case report with clinical and laboratorial pitfalls

Currently, there is growing evidence in the literature warning of misdiagnosis involving amyloidosis and chronic inflammatory demyelinating polyneuropathy (CIDP). Although inducing clinical manifestations outside the peripheral nervous system, light chain and transthyretin amyloidosis may initially present with peripheral neuropathy, which can be indistinguishable from CIDP, leading to a delay in the correct diagnosis. Besides, the precise identification of the amyloid subtype is often challenging. This case report exemplifies clinical and laboratory pitfalls in diagnosing amyloidosis and subtyping amyloid, exposing the patient to potentially harmful procedures.

Keywords
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Diagnostic Errors; Amyloidosis, Familial; Light Chain Immunoglobulin Amyloidosis; Paraproteinemias

Authorship

Angelina Maria Martins Lino

Universidade de São Paulo (USP), Hospital das Clínicas, Department of Neurology, Clinical Peripheral Nerve Group, São Paulo, SP, BrasilUniversidade de São PauloBrasilSão Paulo, SP, BrasilUniversidade de São Paulo (USP), Hospital das Clínicas, Department of Neurology, Clinical Peripheral Nerve Group, São Paulo, SP, Brasil

http://orcid.org/0000-0001-7109-8365

Jussara Bianchi Castelli

Universidade de São Paulo (USP), Instituto do Coração, Laboratory of Pathology, São Paulo, SP, BrasilUniversidade de São PauloBrasilSão Paulo, SP, BrasilUniversidade de São Paulo (USP), Instituto do Coração, Laboratory of Pathology, São Paulo, SP, Brasil

Grupo Fleury, Department of Pathology, São Paulo, SP, BrasilGrupo FleuryBrasilSão Paulo, SP, BrasilGrupo Fleury, Department of Pathology, São Paulo, SP, Brasil

http://orcid.org/0000-0002-8414-4161

Roberta Shcolnik Szor

Universidade de São Paulo (USP), Instituto do Câncer do Estado de São Paulo, São Paulo, SP, BrasilUniversidade de São PauloBrasilSão Paulo, SP, BrasilUniversidade de São Paulo (USP), Instituto do Câncer do Estado de São Paulo, São Paulo, SP, Brasil

http://orcid.org/0000-0001-5254-3486

Fabio Fernandes

Universidade de São Paulo (USP), Instituto do Coração, Cardiomiopathy Group, São Paulo, SP, BrasilUniversidade de São PauloBrasilSão Paulo, SP, BrasilUniversidade de São Paulo (USP), Instituto do Coração, Cardiomiopathy Group, São Paulo, SP, Brasil

http://orcid.org/0000-0002-9323-8805

Vera Demarchi Aiello

http://orcid.org/0000-0002-4185-9423

Authors’ contributions: Angelina Maria Martins Lino reviewed the medical records and carried out the nerve microscopic analysis with heavy and light chains immunohistochemistry analysis and semithin sections. Jussara Bianchi Castelli and Vera Demarchi Aiello carried out the immunohistochemistry analysis for TTR. Jussara Bianchi Castelli and Roberta Shcolnik Szor carried out the laser dissection and mass spectroscopic analysis. Fabio Fernandes performed the cardiac evaluation. All authors wright, reviewed and approved the manuscript.

Conflict of interest: Angelina Maria Martins Lino declares speaking fees and funding for scientific meeting expenses (travel, accommodation and registration) from Pfizer Inc and Sanofi/Genzime and speaking fee from Alnylam Pharmaceuticals. Roberta Shcolnik Szor declares speaking fees from Pfizer Inc, and speaking fees and financial support for research from Jansen-Cilag Farmacêutica Ltda. The remaining authors have no conflict of interest to declare.

CorrespondenceAngelina Maria Martins Lino Universidade de São Paulo (USP), Hospital das Clínicas, Faculdade de Medicina, Divisão de Clínica Neurológica Av. Dr. Eneas de Carvalho Aguiar, 255, 5o. andar, sala 5140, CEP 05403-900, São Paulo, SP, Brasil Phone: +55 (11) 2661-6401angelina.lino@hc.fm.usp.br

SCIMAGO INSTITUTIONS RANKINGS

Grupo Fleury, Department of Pathology, São Paulo, SP, BrasilGrupo FleuryBrasilSão Paulo, SP, BrasilGrupo Fleury, Department of Pathology, São Paulo, SP, Brasil

Figures | Tables

Figures (7)
Tables (1)

Thumbnail

Figure 1
Bone scintigraphy with ^99mTc-MDP in May 2016 showing abnormal bone uptake in 5^th, 6^th and 7^th right coastal arches (arrow).

Thumbnail

Figure 2
Normal bone uptake with slight uptake in the myocardium (arrow) at bone scintigraphy with ^99mTc-MIBI in November 2016.

Thumbnail

Figure 3
Normal bone uptake with ^99mTc-MDP in October 2017, showing distension of urinary tract (arrows).

Thumbnail

Figure 4
Optic microscopy of sural nerve biopsy. A – Extracellular eosinophilic deposits in the endoneuro (arrows) (H&E, X200); B – Semithin section (araldite-embedded) showing nerve fascicles with severe loss of thick and thin myelinated fibers and large amyloid deposits in the endoneuro (asterisk) and around endoneural blood vessels (arrows) (Toluidine blue, X200); C – Congo red staining showing deposits in the endoneuro (arrows) and epineuro (arrowhead) (X100) showing endoneural apple-green birefringence under polarized light in D (X200).

Thumbnail

Figure 5
Brown immunolabeling with anti-IgA antibody (A) showing two large positive areas in the endoneuro (asterisk) and around an epineural blood vessel (arrow). Intense non-specific background immunolabeling was seen with anti-lambda (B) and anti-kappa (C) light-chains antibodies [Horseradish peroxidase, X200]. D – Brown immunolabeling with anti-Transthyretin antibody showing large positive amyloid deposits in the epineuro at the same endoneural area showed in 5A (asterisk) [Horseradish peroxidase, X100].

Thumbnail

Figure 6
Strong diffuse uptake in ventricular walls at 99mTc-pyrophosphate scintigraphy in May 2019.

Thumbnail

Figure 7
Mass spectrometry data of the sural nerve. After selecting the amyloid deposit area, tissue microdissection and laser capture, the analysis of the peptide fragments revealed the presence of three proteins: transthyretin as the amyloidogenic protein and two other constituents common to all types of amyloidosis, apolipoprotein E and serum amyloid P-component. The protein recognition occurs when 3 or more peptide fragments of a specific protein are identified in the sample [spectra acquired by Q-Exactive HF-X spectrometer and analised using MaxQuant, version 1.6.15.0].

Thumbnail

Table 1
Nerve conduction study (2016)

Figure 1 Bone scintigraphy with ^99mTc-MDP in May 2016 showing abnormal bone uptake in 5^th, 6^th and 7^th right coastal arches (arrow).

Figure 2 Normal bone uptake with slight uptake in the myocardium (arrow) at bone scintigraphy with ^99mTc-MIBI in November 2016.

Figure 3 Normal bone uptake with ^99mTc-MDP in October 2017, showing distension of urinary tract (arrows).

Figure 4 Optic microscopy of sural nerve biopsy. A – Extracellular eosinophilic deposits in the endoneuro (arrows) (H&E, X200); B – Semithin section (araldite-embedded) showing nerve fascicles with severe loss of thick and thin myelinated fibers and large amyloid deposits in the endoneuro (asterisk) and around endoneural blood vessels (arrows) (Toluidine blue, X200); C – Congo red staining showing deposits in the endoneuro (arrows) and epineuro (arrowhead) (X100) showing endoneural apple-green birefringence under polarized light in D (X200).

Figure 5 Brown immunolabeling with anti-IgA antibody (A) showing two large positive areas in the endoneuro (asterisk) and around an epineural blood vessel (arrow). Intense non-specific background immunolabeling was seen with anti-lambda (B) and anti-kappa (C) light-chains antibodies [Horseradish peroxidase, X200]. D – Brown immunolabeling with anti-Transthyretin antibody showing large positive amyloid deposits in the epineuro at the same endoneural area showed in 5A (asterisk) [Horseradish peroxidase, X100].

Figure 6 Strong diffuse uptake in ventricular walls at 99mTc-pyrophosphate scintigraphy in May 2019.

Figure 7 Mass spectrometry data of the sural nerve. After selecting the amyloid deposit area, tissue microdissection and laser capture, the analysis of the peptide fragments revealed the presence of three proteins: transthyretin as the amyloidogenic protein and two other constituents common to all types of amyloidosis, apolipoprotein E and serum amyloid P-component. The protein recognition occurs when 3 or more peptide fragments of a specific protein are identified in the sample [spectra acquired by Q-Exactive HF-X spectrometer and analised using MaxQuant, version 1.6.15.0].

Table 1 Nerve conduction study (2016)

Nerve	Motor				Sensory
	CMAP (mV) L/R	CV (m/s) L/R	L (ms) L/R	FWL (ms) L/R	SNAP (µV) L/R	CV (m/s) L/R
Median	1.2/1.7	34.1/33.5	5.5/5.8	ND/ND	U/U	U/U
Ulnar	1.7/2.3	32.5/35.1	4.7/4.8	52.2/47.8	U/U	U/U
Peroneal	U/U	U/	U/U
Tibial	U/U	U/	U/U
Femoral	6.0/4.6	5.6/5.8
Sural					U/U	U/U

CMAP: compound muscle action potential; CV: conduction velocity; L: distal latency; FWL: F-wave latency; L: latency; m/s: meter per second; ms: millisecond; mV: milli Volt; µV: microVolt; ND: not done; SNAP: sensory nerve action potential; U: unexcitable nerve

How to cite

copy

Hospital Universitário da Universidade de São Paulo Hospital Universitário da Universidade de São Paulo, Av. Prof. Lineu Prestes, 2565 - Cidade Universitária, 05508-000 - São Paulo - SP - Brasil, (16) 3307-2068, (16) 3307-2068 - São Paulo - SP - Brazil
E-mail: autopsy.hu@gmail.com

Acompanhe os números deste periódico no seu leitor de RSS

Versão para download de PDF

PDF

Inglês

Versões e tradução automática

Versão original do texto

English

Tradução automática

Google Translator
Microsoft Translator

Como citar

RIS

BIBTEX

Outros formatos de citação e exportação:

SciELO - Scientific Electronic Library Online
Rua Dr. Diogo de Faria, 1087 – 9º andar – Vila Clementino 04037-003 São Paulo/SP - Brasil
E-mail: scielo@scielo.org

Leia a Declaração de Acesso Aberto

Métricas

Diagnostic challenges in systemic amyloidosis: a case report with clinical and laboratorial pitfalls

PlumX

Mensagem

[1] Authors’ contributions: Angelina Maria Martins Lino reviewed the medical records and carried out the nerve microscopic analysis with heavy and light chains immunohistochemistry analysis and semithin sections. Jussara Bianchi Castelli and Vera Demarchi Aiello carried out the immunohistochemistry analysis for TTR. Jussara Bianchi Castelli and Roberta Shcolnik Szor carried out the laser dissection and mass spectroscopic analysis. Fabio Fernandes performed the cardiac evaluation. All authors wright, reviewed and approved the manuscript.