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Page 2 of 13 De Gaspari et al. Vessel Plus 2022;6:57 https://dx.doi.org/10.20517/2574-1209.2022.05

[2]
prevalence of up to 32% in autopsy series in older populations . Since cardiac involvement is still the
leading cause of morbidity and mortality in amyloidosis, early diagnosis remains critical for adequate
therapeutical planning closely related to a better prognosis.

The aim of our paper is to review the available pathology literature on the gross and histological findings of
cardiac involvement in amyloidosis, which are of potential value in interpreting laboratory and imaging
data.

HISTORICAL NOTES
The term “amyloid” comes from the Latin amylum and the Greek amylon, meaning starch. This term was
introduced in the medical field by Rudolf Virchow in 1854 to describe the small round deposits in the brain
that stained pale blue on treatment with iodine and violet upon the subsequent addition of sulfuric acid. He
was convinced that those structures were identical to starch and he named them “corpora amylacea” . The
[3]
representatives of the French and British Schools instead considered amyloid to be more closely related to
cellulose and they, respectively, used the name “lardaceous” (based on the bacon-like appearance of the
[4]
tissue) and “waxy” (based on the homogeneity of the material) . Another historical term is the “sago
spleen”, in cases of splenic involvement by amyloid, which can give a nodular appearance similar to sago
starch grains. Only later observations led to the exclusion of starch and cellulose from the materials
composing “amyloid”. The invention of the metachromatic stains in 1875 (particularly methyl violet stain)
allowed for better detection of amyloid and localizing it in the extracellular tissue. The first description of
[5]
amyloid in the cardiac tissue is reportedly the one by Soyka in 1876 who used this new method . A new dye
originally used to stain textile fibers was then discovered and became widely used: Congo red staining .
[6]
This stain was developed by the German chemist Paul Böttiger in 1884 and then sold to the Agfa company,
which named it “Congo” for marketing purposes, reflecting geopolitical events of that time . However, only
[7]
in 1922, the German chemist Bennhold discovered the capacity of Congo red to bind to amyloid,
introducing it in the diagnostic process. Initially, Congo red was not used as a histological stain to obtain
the diagnosis: it was administered to patients with suspected amyloidosis and its level in plasma was
supposed to decrease in patients with amyloid due to systemic tissue binding. In 1959, the first observation
of amyloid by electron microscopy was reported, demonstrating a fibrillar structure that was different from
collagen and similar in different tissues . One of the first and most successful methods to extract amyloid
[8]
from tissue was described in 1962 by Pras and colleagues (the so-called water extraction method), and it
enabled the identification of the β-pleated sheet configuration of amyloid proteins and the discovery of the
[9]
biochemical structure of those proteins .
ETIOLOGY AND PATHOGENESIS
Amyloidosis is considered a rare disease with still few epidemiological studies published. Data on the
epidemiology of CA are based mainly on single-center studies or population registries. Of the 36 thus far
known precursor proteins, fewer than 10 can accumulate in the myocardium and cause significant cardiac
disease [Table 1]. The most common types of CA result from fibrils composed of monoclonal
[10]
immunoglobulin light chains (AL) or transthyretin (TTR), in either its hereditary or acquired form. AL-CA
is the most frequent form with a reported prevalence of 6-10 per million [11-13] . In recent times, an increase in
AL amyloidosis has been observed, uncoupled with a similar rise in incidence. This was supposed to be
explained by early diagnosis and a consequent improvement in overall survival .
[14]
AL amyloidosis
AL amyloidosis (previously known as primary amyloidosis) results from the deposition of immunoglobin
light chains produced by a plasma cell dyscrasia. The clonal plasma cells in the bone marrow produce