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

Abstract

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

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].