Invited Letter Fibrolelastoma and Lambl's Excrescences ... - Icr-heart

Invited Letter
Fibrolelastoma and Lambl’s Excrescences: Localization,
Morphology and Pathogenesis, Differential Diagnosis
and Infection
Waldemar Hort, Dieter Horstkotte 1
Institute of Pathology, Heinrich-Heine University Düsseldorf, Germany, 1 Department of Cardiology, Heart and Diabetes
Center North Rhine-Westphalia, Ruhr University Bochum, Bad Oeynhausen, Germany
Multiple infected papillary fibroelastoma (PFE) was
first described by Fuzellier et al., in 2005 (1). Our comment
on this paper includes some considerations on
the pathogenesis, differential diagnosis, and infection
of this lesion.
Incidence, structure, and pathogenesis
To date, PFEs have been found only in the heart, are
very rare and, although always of a benign nature,
may result in severe embolic complications. They represent
the most common tumor of the cardiac valves,
are slow-growing (2), and resemble sea anemones with
a mean diameter of almost 1 cm (3), ranging from 0.2
to 7 cm. These lesions are commonly located on the
central valvular surfaces, on the chordae tendineae
and, in almost 25% of cases, on the non-valvar (preferably
left-sided) endocardium. Most often, the arterial
or ventricular aspect of aortic valves are affected (4).
The papillae are 0.4 to 2 mm thick, avascular, and
covered by hyperplastic endothelium. Their central
cores consist of dense fibers of collagenic connective
tissue with, most often, elastic fibers arranged in a longitudinal
or coiled fashion (5-7). The central connective
tissue is frequently hyaline, hypocellular or acellular,
and sometimes is calcified.
The structure of PFEs is very similar to that of
Lambl’s excrescences (LEs), first described by Lambl
some 150 years ago (8). Lambl found these inconspicuous
small structures exclusively at the closure margins
of the aortic valves, and depicted their papillary structure
(Fig. 1). Only one year later, Luschka described
their location on the pulmonary valves (9). Very
detailed morphological examinations of Lambl’s
excrescences were performed by Sinapius (10), though
these details remained internationally disregarded
Address for correspondence:
Waldemar Hort MD, Institute of Pathology, Heinrich-Heine
University, Moorenstr. 5, 40589 Düsseldorf, Germany
e-mail: waldemar.hort@uni-duesseldorf.de
because they were published in German only. Sinapius
observed LEs also on the tricuspid valves, on the endocardium
of both atria, and up to 72 LEs were found on
one mitral valve. According to Ribbert (11), the normal
length of LEs is 1-5 mm, and rarely more than 3 mm.
Sinapius detected early stages of 50 µm length in very
thin preparations, which had peeled away from the
endocardial surface (10).
Histologically, LEs are avascular, and often acellular
with a hyaline core. Slender, partly longitudinal and
densely arranged elastic fibers may mimic homogeneous
masses, and there may also be circular arrangements
with alternating hyaline and elastic elements,
which is suggestive of batchwise growth (10).
The genesis of LEs and PFEs has not yet been clarified.
Are they tumors of unknown origin, or are they
reactions to traumas or inflammation? Their comparable
histological structure suggests a common origin
(5,12), but in contrast to PFEs, LEs are mainly found at
Figure 1: Lambl’s excrescences of the aortic valve. Original
illustration (from Lambl, 1856).
© Copyright by ICR Publishers 2006

592
the closure margins of the valves and are markedly
smaller than PFEs. Since valvar leaflets collide with
each heartbeat, microlesions or larger ruptures might
develop on the heavily strained closing margins,
including the nodules of Arantius (13), finally resulting
in the formation of LEs and PFEs. This hypothesis is
supported by the high frequency of LEs on the valvar
closing lines and the rarity of PFEs, which are more
commonly found on the mechanically less-affected
valve areas or other parts of the endocardium.
Furthermore, it seems clear that LEs in their exposed
position are unable to attain the size of PFEs.
Pomerance (5) considered that both LE and PFE have
their origin in an endothelial damage (see also reference
(6)), followed by minor fibrin deposition, the
organization of which finally results in papillary structures.
Thoracic radiation and cardiac surgical procedures
also seem to yield a higher frequency, as
observed by Kurup et al. with a mean interval of 18
years between heart surgery and the demonstration of
PFE (14). The opinion that PFEs develop mainly on
pathologically degenerated cardiac valves was not
confirmed with increasing experience (4).
LE and PFE are not rarely accompanied by thrombus
deposits already observed by Lambl (8). These
deposits may lead to a fusion of neighboring, freefloating
papillary parts, or to their inclusion into the
adjacent valvular tissue. Sinapius (10) supposed that
LEs develop from small, mostly fibrinous thrombi,
which he frequently observed on the endothelium in
patients aged over 30 years, though this was contradicted
by others, including Ribbert (11) and Fishbein et
al. (6).
A familial disposition for filiform structures has not
yet been demonstrated, and reports of congenital PFEs
or those occurring during childhood are rare (15).
Whether in the patient described by Fuzellier et al. (1)
an AV node ablation and pacemaker implantation a
few years later increased his predisposition for PFE
development remains speculative.
Five years ago, Grandmougin et al. (16) reported on
a possible chronic viral inflammation with immunohistologically
proven dendritic cells and remnants of
cytomegaloviruses. The idea of a viral genesis seems
reasonable, as has been verified in other papillary
tumors, for example warts of the skin, condylomas,
and laryngeal papillomas. In this regard, further investigations
are required. In HIV patients, only one case of
PFE has been observed to date (17), which is indicative
of an incidental coincidence.
Differential diagnosis: endocarditis and PFE
Protruding structures on cardiac valves are primarily
suspective of (infected) thrombi. In infectious endo-
carditis, they are partly flat and inconspicuous, but frequently
rather prominent, partly hemispherical, and
often tubercular or fissured (18).
A distinguishing feature, however, is the lack of papillary
structures, which is pathognomic for PFE.
Difficulties may result from thrombus deposits on a
PFE, the differentiation of which has recently become
possible using sophisticated imaging techniques
(4,19,20).
Infection or contamination?
As yet, only one case of an infected PFE has been
reported (21). This was covered by a large thrombus
containing Gram-positive cocci. Previously, the patient
was thought to have suffered from endocarditis following
a tooth extraction, with intermittent fever and
positive blood cultures. The patient described by
Fuzellier et al. (1) suffered from hypertrophic obstructive
cardiomyopathy, massive mitral insufficiency, and
increasing dyspnea. Echocardiographically, protruding
masses were detected on the mitral leaflets, mitral
chordae, ventricular septum, and on the aortic valve.
Both leukocyte count (8,900/mm 3 ) and temperature
(37°C) were normal, and all blood cultures were negative.
Nevertheless, a bacterial endocarditis was suspected
and antibiotics were administered.
One month later, the macroscopic surgical diagnosis
was ‘marked infected aspect’ of the mitral valve.
Cultures from surgically removed material contained
Staphylococcus warneri, which occurs very rarely as a
causative organism in infected endocarditis (22-24)
and is often difficult to identify (25). This bacterium is
usually found in small and transient populations on
the human skin (22), and may cause bacteremias that
are often of nosocomial origin and frequently found in
immunosuppressed patients.
From a histopathological viewpoint, the protrusions
were identified as PFEs. Unfortunately, Fuzellier et al.
(1) only reported on the diagnosis of a mitral valve
endocarditis with infected PFEs, and did not describe
what was the basis of the macroscopic surgical diagnosis
of a ‘marked infected aspect’ of the mitral valve,
how many and what types of inflammatory cell were
present in the resected mitral valve tissue, and where
the Gram-positive bacteria were found. It remains
unclear, therefore, as to what type of mitral valve
lesions were present, and whether the pathogens
found were the result of contamination or infection.
Future perspectives
J Heart Valve Dis
Vol. 15. No. 4
July 2006
Each individual observation of a PFE provides the
opportunity of gathering more information about supporting
factors. Pathohistologic and immunohistologic

J Heart Valve Dis
Vol. 15. No. 4
July 2006
investigations may contribute to verify a possible viral
genesis, as well might the systematic examination of
LEs.
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