ARTICLE
The sign of Leser-Trélat (SLT) is usually
defined as the abrupt appearance and/or rapid increase in size and number
of multiple seborrheic keratoses (SK) in association with an underlying
cancer. Although these SK may show some characteristic features (distribution
on the trunk, small size, and macular morphology), the most important
criterium in diagnosing SLT is the dynamics of the eruption (acute onset
and rapid growth of the lesions) [1]. Associated malignancies are, in
order of frequency, gastrointestinal adenocarcinomas, hematology cancers,
and breast and lung cancers, although a wide variation of malignances
has been reported [2]. SLT implies a poor prognosis, because the average
survival time after cancer diagnosis is about 11.5 months [1]. The existence
of this entity is still controversial [3]. The literature and clinical
practice bring contradictory data that do not clear up the issue definitely.
In this paper, we report a patient who met the classical features of
SLT, which allowed us to diagnose a rectal adenocarcinoma at a curable
stage.
Case report
A 75-year-old man presented in our department with multiple cutaneous
lesions that had started appearing 3 months before. He described the lesions
as "spots" and they were slightly pruriginous. His past medical history
included benign prostatic hypertrophy and arterial hypertension treated
with enalapril and hydrochlorothiazide. He had undergone appendectomy
thirty years previously. He had no known allergies. His general health
status had not changed during recent months. On examination we observed
a large number of flat tumors sharply demarcated, yellowish to brown in
color, some with a verrucous surface and greasy appearance, mainly located
on the trunk (back, chest and abdomen), but also on the arms and thighs,
clinically very suggestive of SK (Fig.
1). There were isolated, small vascular tumors (senile angiomas)
on the trunk. No other cutaneous lesions were detected. A biopsy specimen
from one of the lesions showed an epidermal tumor composed of basaloid
cells, with acanthosis, papillomatosis, and marked hyperkeratosis. Pseudohorn
cyst formation was frequently observed (Fig.
2). A diagnosis of SLT was made and then a complete anamnesis
and physical examination were accomplished in order to detect an underlying
malignancy, but abnormalities were not observed at this stage. Complete
blood count was normal: hemoglobin 13.5 g/dL (normal range 13-16.5), platelets
360 x 109/L (normal range 150-450 x 109/L),
total white cell count 7.0 x 109/L (normal range 4-10.5
x 109/L), neutrophils 3.9 x 109/L
(normal range 2.1- 4.9 x 109/L), and lymphocytes 2.0
x 109/L (normal range 1.4-2.9 x 109/L).
Serum biochemistry included urea, creatinine, glucose, albumine, uric
acid, bilirrubin, AST, ALT, HDL and LDL cholesterol, triglycerides, and
electrolites (sodium, potassium, and calcium). All of these were normal,
except a moderate hyperglycemia of 117 mg/dL (normal range 74-105 mg/dL).
The urinalysis was normal. Chest radiograph and abdominal ultrasonography
did not reveal any pathological feature. Carcinoembryonic antigen levels
were slightly elevated (6.2 UI/mL, normal range 0-2.5 UI/mL) and tissue
polypeptide specific antigen (TPS) levels were also elevated (187 UI/mL,
normal range 0-80 UI/mL), but the levels of other tumor markers (PSA,
NSE, Ca 19.9, Ca 125, and alpha-fetoprotein) were within normal ranges.
A test for occult blood in feces (modified guaiac method) was positive.
Urologic (physical exploration and endorectal sonography), pulmonary (bronchoscopy),
otorhinolaryngologic (indirect laryngoscopy) and, specially, digestive
investigations (double-contrast upper gastrointestinal radiology, upper
digestive endoscopy, barium contrast enema, and colonoscopy) were carried
out. They revealed that the patient had a moderately differentiated adenocarcinoma
of the rectum (Dukes A stage) (Fig.
3). The patient is asymptomatic after a follow-up of 2 years,
but his SK remain unmodified.
Discussion
SLT consists of the association of the abrupt appearance and/or rapid
increase in size and number of multiple SK and an underlying malignancy.
Although there are a high number of case-reports in the literature, the
existence of this sign is questioned by several authors [3-5]. The detractors
of the existence of the SLT state that SK and cancer are extraordinarily
common in elderly persons, so that it seems that both are determined by
age. Although the average age at onset of SLT is about 60 years, young
patients with SLT have been reported [6, 7], which would invalidate age
as a determining factor for the appearance of both conditions, at least
in these case-reports.
The abundance of case-reports in the literature may argue in favour
of the existence of SLT [1]. In 1996, Swartz [2] counted 86 patients with
this diagnosis. Nevertheless, the analysis of the literature is biased
because the reported articles include only patients with malignancy and
not people with eruptive SK without cancer. In fact, when studies based
on patient series are considered, no evidence of association of SK and
cancer is found [4, 5, 8].
Sixty-five per cent of the patients suffering SLT have concomitantly
other paraneoplastic disorders (the most frequent is acanthosis nigricans,
in one third of cases), which supports the existence of this sign [1].
Moreover, SLT shares some features with florid cutaneous papillomatosis,
an obliged paraneoplastic dermatosis: there are patients with mixed forms,
having both types of lesions (SK and papillomas) and both dermatoses are
associated with acanthosis nigricans and the same type of malignancies
[3, 9-11]. A specific characteristic of the well-defined paraneoplastic
dermatoses that, nonetheless, SLT does not fullfil, is its parallelism
with the course of the malignancy, since it only happens in one third
of case-reports [1, 3].
Paraneoplastic dermatoses characterized by cellular
proliferation, such as acanthosis nigricans and florid cutaneous papillomatosis,
are thought to be due to growth-factors production by malignant cells,
though this has been only documented in some isolated case-reports [12,
13]. The growth hormone has been implied in SLT pathogenesis [12, 14,
15], which goes along with the detection of growth hormone receptor in
SK [16]. Other growth factors implied have been the alpha-transforming
growth factor [13] and the epidermal growth factor [14]. This possible
common pathogenic mechanism mediated by growth factors also supports the
existence of SLT.
Although SK in SLT are usually small and macular, and are located on
the trunk, they do not show any clinical nor pathological feature that
definitively differentiates them from common SK. For this reason, the
most important criterion in diagnosing SLT is the dynamics of the eruption.
However, an exact definition of SLT, especially about the number and/or
the rhythm of appearance of the SK, is lacking [1]. Therefore, the clue
for the diagnosis relies on the history of the eruption provided by the
patient, whose reliability is relative. Rampen and Schwengle [3] have
shown that there is a statistically significant trend towards a shorter
history of SK onset with advancing age, which is attributed to the unreliability
of anamnestic data in elderly persons. Nevertheless, there is no method
to diagnose SLT other than these anamnestic data.
CONCLUSION
In summary, from the available data it is not possible either to demonstrate
or to reject definitively the existence of SLT. Therefore, if a patient
gives us a history of acute onset and/or rapid increase in size and number
of multiple SK, we must carry out studies in order to rule out an underlying
cancer, that may still be at a curable stage. Our case-report is an illustration
of this statement. The rectal adenocarcinoma would not have been detected
so early if the patient had not consulted for the sudden appearance of
his SK, since there had been no symptoms suggestive of that malignancy.
The best way to achieve a definitive conclusion about the existence
or non-existence of SLT would be to study the incidence of malignant neoplasms
in patients with clinical pictures suggestive of SLT, and compare it with
the incidence of cancer among the general population. As SLT is an infrequent
disorder, it would be necessary to investigate patients from many centers,
but the first requirement would be to set convenient diagnostic criteria.
Until this is done, controversy will remain.
Article accepted on 15/2/01
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