Download orbital lymphomas. presentation of nine cases linfomas orbitarios

ORIGINAL ARTICLE
ARCH SOC ESP OFTALMOL 2008; 83: 95-104
ORBITAL LYMPHOMAS. PRESENTATION OF NINE CASES
LINFOMAS ORBITARIOS. PRESENTACIÓN DE NUEVE CASOS
REY-PORCA C1, PÉREZ-ENCINAS M2, GONZALEZ F3
ABSTRACT
RESUMEN
Purpose: To report nine cases of orbital lymphomas.
Methods: We reviewed the clinical records of nine
patients diagnosed with orbital lymphoma and performed a literature search related to this condition.
Results: We present a series of five women and
four males with orbital lymphoma involving the
orbital region. In our cases, most patients presented
concurrent extraorbital lymphoma when the orbital
disease was first noticed (seven out of nine
patients). We found three MALT lymphomas, two
follicular lymphomas, two non-Hodgkin large B
cell lymphomas, one low grade B cell lymphoma,
and one mantle cell lymphoma. Eight patients were
alive and one had died as a consequence of his
lymphoma at the time this report was written.
Conclusions: An increase in the incidence of nonHodgkin orbital lymphomas has been observed over
the last three decades. The most common type in
the orbital region is the MALT lymphoma. The clinical features observed in our series are similar to
those reported in the literature. Since lymphomas
are the most frequent malignant tumours in the
orbit, usually with extraorbital involvement, and
Objetivo: Describir nueve casos de linfomas orbitarios.
Métodos: Revisión de historias clínicas de nueve
pacientes diagnosticados de linfoma orbitario y
consulta de la bibliografía relacionada con esta
patología.
Resultados: Se presenta una serie compuesta por
cinco mujeres y cuatro varones con linfoma en la
región orbitaria. En nuestros casos, la mayoría de
los pacientes presentaron linfoma extraorbitario
concurrente en el momento en el que el proceso
orbitario fue detectado por primera vez (siete de los
nueve pacientes). Tres de los pacientes presentaron
linfoma MALT, dos linfomas foliculares, dos linfomas no Hodgkin de células B grandes, un linfoma
de células B de bajo grado y un linfoma de células
del manto. Ocho pacientes se mantienen vivos y
uno ha fallecido a consecuencia de su linfoma en el
momento de escribir este artículo.
Conclusiones: Se ha observado un incremento de la
incidencia de los linfomas no Hodgkin orbitarios
durante las últimas tres décadas. El tipo más común
en la región orbitaria es el linfoma MALT. La forma
Received: Feb. 5, 2007. Accepted: Jan. 17, 2008.
1 Graduate in Medicine. Ophthalmology Service of the Santiago de Compostela University Hospital Complex. Spain.
2 Ph.D. in Medicine. Hematology Service. Santiago de Compostela University Hospital Complex. Spain.
3 Ph.D. in Medicine. Ophthalmology Service of the Santiago de Compostela University Hospital Complex. And Dept. of Physiology. Medicine
College of Santiago de Compostela University. Spain.
This study was carried out with funding from the BFU2004-01839 project of the Education and Science Ministry and FEDER.
Correspondence:
Francisco González
Departamento de Fisiología. Facultad de Medicina
Universidad de Santiago de Compostela
15782 Santiago de Compostela
Spain
E-mail: [email protected]
REY-PORCA C, et al.
can be successfully treated in many cases, it is
important for the ophthalmologist to be aware of
this condition (Arch Soc Esp Oftalmol 2008; 83:
95-104).
Key words: Orbit, lymphomas, ocular adnexal
lymphoma, orbital tumours, non-Hodgkin orbital
lymphomas.
de presentación clínica que encontramos en nuestra
serie es similar a la que se presenta en otros estudios.
Dado que los linfomas son los tumores malignos
más frecuentes en la órbita, habitualmente tienen
también localización extraorbitaria, y pueden ser
tratados con éxito en muchos casos, es importante
que el oftalmólogo tenga presente esta patología.
Palabras clave: Órbita, linfoma, linfoma de anejos
oculares, tumores orbitarios, linfomas no Hodgkin
orbitarios.
INTRODUCTION
Lymphomas are the most frequent orbital malignant tumors. According to recent publications, these
tumors account for 11% of all orbital tumors (1) and
55% of malign tumors (2). This high prevalence and
the possibility of providing effective treatment for
their healing increases the importance of these neoplasia for the ophthalmologist. In this article we present nine cases of orbitary lymphomas together with
a bibliographic review related to this pathology.
SUBJECTS, MATERIAL AND
METHODS
Nine cases of orbitary lymphomas are presented,
comprising five females and four males. All were
attended in the Ophthalmology Service of our hospital between July 2002 and September 2006. The
bibliographic information was obtained by searching medical literature, mainly the PubMed database (National Library of Medicine, USA) for
analyzing and verifying our findings. The clinical
characteristics and evolution of the cases of this
series are described below.
RESULTS
Case 1
Female, aged 69, who referred right palpebral
ptosis since September 2002 without any other
symptoms (fig. 1A). She came to the internal medicine and neurology practice between 15 and 20
96
days after its appearance. A CAT scan performed
one month later revealed an injury of approximately
1.5 x 1.8 cm in the central area of the upper right
eyelid (fig. 1B). At that point she was referred to
our Ophthalmology Service. The NMR (fig. 1C)
showed an injury of the same size located behind
the septum and above the eyelid elevator muscle.
When surgically accessing the injury, it was noticed
that it infiltrated the tendon of the elevator muscle
and it was removed. The anatomic diagnostic was
of MALT lymphoma. The patient was referred to
the Hematology Service where the extension study
was carried out which determined a single location
in the right orbit. Radiotherapy treatment was indicated and at present the patient is stable without
relapses.
Case 2
Female, aged 60, who was admitted to the internal medicine service in November 2004 for assessing upper right eyelid tumefaction and multiple
cervical adenopathies which had increased in size
in the past seven months, with progressive appearance of asthenia, anorexia, weight loss and night
sweating. A medullar and ganglionary biopsy allowed for the diagnosis of non-Hodgkin mantle cell
lymphoma, stage IVB. The patient was treated with
chemotherapy which produced a partial remission.
In August 2005 a CAT scan was carried out
which revealed a relapse of the palpebral tumor (fig.
2). Accordingly, she was referred to our service in
September 2005. Due to the rapid growth of the
tumor, an additional chemotherapy and immune
therapy was initiated which produced a rapid response. In March 2006 she exhibited a new relapse
ARCH SOC ESP OFTALMOL 2008; 83: 95-104
Orbitary lymphomas. Presentation of 9 cases
Fig. 2: Case 2. The top image (A) shows a palpebral
tumefaction in the right in caused by the tumor, which
can be seen in the lower image (B) showing a CAT scan
with IV contrast (arrow).
Fig. 1: Case 1. The patient exhibited a RE ptosis secondary to a palpebral mass (A). The orbitary CAT scan (B)
with IV contrast and soft tissue window showed a mass
at the level of the right upper eyelid, adjacent to the ocular globe (arrow). Orbitary NMR (C) enhanced in T1
and with paramagnetic contrast showing the location of
the tumor (arrow).
again treated with chemotherapy with a discrete
response. At present the development process of the
tumor continues.
tary masses which moved with palpation, with an
exophthalmos of about 3 mm vis-à-vis the other
eye. The rest of the ophthalmological exploration
was normal. A previous CAT scan carried out in
June 2002 revealed a left retro-ocular mass classified as a probable inflammatory pseudo-tumor. An
orbitary NMR carried out in June 2002 (fig. 3B)
gave rise to the first diagnostic possibility of an
orbitary lymphoma or metastasis and accordingly
the patient was referred to our Ophthalmology Service in July 2002, where a PAAF was carried out,
the result of which was compatible with a nonHodgkin lymphoma. Subsequently, a biopsy confirmed the diagnostic of low positive B lymphoma for
CD20 and Bcl-2 (without specifying the type). The
extension study revealed the absence of additional
tumor locations. Radiotherapy was indicated. To
this date the patient continues in full remission.
Case 3
Male, aged 50, who was attended at another hospital for a discrete exophthalmos in the left eye
which started one month earlier (fig. 3A). His relevant history included infra-orbitary and supra-orbi-
Case 4
Male, aged 53, who attended our ophthalmology
practice in April 2004 due to a soft, compressible
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REY-PORCA C, et al.
the orbits up to the apex without involving bone tissue. The anatomic and pathological diagnostic was
of MALT lymphoma. The patient was referred to
Hematology where a possible cervical involvement
was detected due to PET. Treatment was established
with radiotherapy in the orbit and neck. To date, the
patient continues in remission.
Case 5
Fig. 3: Case 3. The patient exhibited a slight left exophthalmos (A). The NMR image (B) enhanced with contrast
in T1 shows a left retro-ocular infra-orbitary mass.
bulge of approximately 1 cm diameter in the medial
portion of the right upper eyelid (fig. 4). The patient
history did not include relevant data. One month
later the tumoration was removed and its consistency was semi-soft, with pseudo-capsula and multiple lobes, extending through the internal wall of
Male, aged 71, diagnosed in October 2001 with
nasopharyngeal large B-cell lymphoma with involvement of the middle ear, right maxillary sinus,
right cervical adenopathies and possible pleural and
bone marrow involvement as per flow cytometry.
Loco-regional chemo- and radiotherapy treatment
was initiated, with a full response. In March 2004,
the patient exhibited a right inferior eye lid edema ,
which two months later made it difficult for the
patient to open the eye (fig. 5A). The patient did not
exhibit relevant symptoms. An orbital CAT scan
carried out in May 2004 revealed a soft tissue density mass in the lower internal area of the right orbit
(fig. 5B) which, by means of a PAAF, confirmed the
suspected lymphoma relapse. The extension study
revealed infiltration in the bone marrow. The patient
received systemic chemo- and radiotherapy on the
right orbit. Two years later, the patient exhibited a
new relapse in the facial region (an adenopathy
below the right side of the chin) for which he was
given radiotherapy treatment. At present, he
remains without symptoms.
Case 6
Fig. 4: Case 4. In this case, the lymphoma appeared as
a small tumor in the internal parts of the upper eyelid. It
was removed without previous diagnostic.
98
Female, aged 55, who visited our Ophthalmology
Service in January 2002 for a tumoration in the left
lachrymal fossa which produced palpebral ptosis
and inferior displacement of the globe (fig. 6A). An
orbitary CAT confirmed the existence of a mass in
the left lachrymal fossa which was removed in
February 2002. The diagnostic was of low degree
lymphoma B. The patient did not return until September 2003 exhibiting a left pre-auricular tumoration (fig. 6B) for which a biopsy confirmed the
diagnostic of follicular lymphoma. An extension
study determined stage 4. Chemotherapy treatment
was initiated and the patient is at present free of
symptoms.
ARCH SOC ESP OFTALMOL 2008; 83: 95-104
Orbitary lymphomas. Presentation of 9 cases
Fig. 5: Case 5. The image shows the swelling of the
right lower eyelid (A). The cranial CAT without contrast
(B) shows a mass in the internal inferior area of the right
orbit (arrow).
Case 7
Female, aged 64, diagnosed in May 2002 with
pulmonary MALT lymphoma after a trans-bronchial biopsy and an extension study which revealed
a minimum infiltration in the bone marrow with
flow cytometry. She received chemotherapy treatment with partial response. In October 2002 progression at the pulmonary level and infiltration of
the bone marrow was detected. An additional chemotherapy and immune therapy treatment was prescribed, which gave a partial response. In February
2006 a new extension study was performed which
revealed a mass in the medium straight muscle of
the right eye (fig. 7B), for which she was referred to
our Ophthalmology practice. A PAAF did not allow
for a diagnostic and accordingly the tumor was
biopsied. During the intervention a mass compatible with lymphoma was evidenced in the medium
muscle. The diagnosis of the biopsy was of MALT
lymphoma. Chemotherapy treatment was established with partial response. At present, the patient
remains stable.
Fig. 6: Case 6. The patient exhibited a left palpebral
ptosis caused by a tumoration in the lachrymal fossa (A)
and a left pre-auricular tumoration (B).
Case 8
Male, aged 41, without relevant history. In September 2004 he was attended in our ophthalmology
practice for pain in the right jawbone which irradiated towards the orbit, with palpebral ptosis and
4mm exophthalmos in the RE (fig. 8A). A NMR
revealed a tumoration in the right cavernous sinus
which produced a syndrome of the orbitary apex
(fig. 8B). As a biopsy was not feasible, a systemic
study was carried out which revealed a cecal tumor
which, when biopsied, was diagnosed as large Bcell lymphoma. Therefore the mass in the cavernous sinus was taken to be a metastasis of this
tumor. The patient’s condition involved unfavorably
in a short time with peritoneal metastasis, ascitis
and pleural hemorrhage, with demise occurring
three weeks after the first visit.
Case 9
Female, aged 78, who attended our practice in
August 2006 due to exophthalmos and pain in the
right eye which began approximately 1 year earlier
(fig. 9A). An orbitary CAT (fig. 9B) revealed the
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REY-PORCA C, et al.
Fig. 7: Case 7. The patient (A) exhibits and infiltration
at the level of the medium straight muscle of the LE
which is shown in the axial NMR (B) enhanced in T2.
existence of a solid, contrast-capturing dense mass
occupying the lower external quadrant of the right
orbit. A PAAF performed in September 2006 was
compatible with non-Hodgkin lymphoma. Accordingly, the patient was referred to hematology. A
biopsy of a right supra-clavicular adenopathy and
an extension study confirmed the diagnostic of
follicular lymphoma grade 2 stage 4. Chemotherapy and immune therapy treatment was established
leading to a remission of the condition. At present,
the patient remains stable and free of symptoms.
DISCUSSION
The lymphomas affecting the conjunctiva, lachrymal gland, orbit and eyelids are usually low degree
tumors (2). Recent studies show that lymphomas
represent approximately 11% of all tumors of these
structures and 55% of malign tumors in these areas
(1,2). According to our own statistics, lymphomas
constitute one of the most frequent orbitary tumors,
accounting for approximately 15%.
100
Fig. 8: Case 8. The upper photo shows a slight right
exophthalmos (A). The coronal cerebral NMR (B)
enhanced in T1 with IV contrast shows an injury at the
level of the cavernous sinus (arrow) reaching the orbit
apex.
Published series show that the large majority of
orbitary lymphomas (91%) (2) begin with ophthalmological symptoms consisting of pink-colored
conjunctival masses or conjunctival hyperemia in
32% of cases, exophthalmos in 27%, palpable or
orbitary mass in 19%, visual acuity reduction and
ptosis in 6% and diplopia in 2% (2). In our series,
the most frequent clinical presentation was palpebral or orbitary mass (four cases) followed by
exophthalmos (two cases), palpebral ptosis (one
case), ptosis with exophthalmos (one case) and ptosis with palpebral mass (one case). In spite of the
frequency with which the conjunctival seems to be
affected (32% of cases) (2), we did not observe that
in any of our patients.
The mean interval between the onset of symptoms and the diagnostic date is 4 to 6 months (2-5).
In our series we observed that in most cases the
interval was between one and two months. In one
case (case 8), considering the aggressive evolution
of the neoplasia, the diagnostic was established
ARCH SOC ESP OFTALMOL 2008; 83: 95-104
Orbitary lymphomas. Presentation of 9 cases
Fig. 9: Case 9. the top figure (A) shows the right exophthalmos of the patient. The mass in the external lower
quadrant of the right orbit (arrow) is seen in the axial
CAT with IV contrast (B).
approximately 15 days after the first symptoms. In
two cases (cases 2 and 9), due to the patient’s delay
in visiting the practice, the diagnostic was made
with an interval of over one year since the appearance of the symptoms. In one case (case 7) we
were unable to determine the time which elapsed
between the appearance of the symptoms and the
diagnostic because the initial lymphoma diagnostic
had been made six years before he attended our
Ophthalmology Service.
Lymphoid proliferations in the ocular region can
occur at any age, but more frequently in the fifth or
seventh decade of life (2-9) and involve 1.75 females for every male (4-6,10). In our cases the mean
age was of 60 years at diagnostic time, with the
youngest patient being 41 and the oldest 78. These
numbers match the data published in literature. Our
statistics comprise 5 females and 4 males, which
reflects a similar tendency to that shown in larger
series.
Approximately 50% of ocular region lymphomas
are located in the lachrymal gland and other intraorbitary areas, particularly the anterior-superior
orbit (2,9,11,12). The conjunctiva is affected in a
third of patients and in 96% of cases it involves a
low grade tumor (2). Palpebral involvement varies
in different series between 0% and 44%, with the
mean value of published studies being close to 10%
(2). In approximately 10-17% of cases the lymphoma appears bilaterally (3-5), while it appears simultaneously in both orbits in approximately 80% of
bilateral cases and subsequently in 20% of cases
(13). Other publications broaden the bilaterality
percentage ranges from 7 to 24% of cases (2,9).
Between 20 and 40% of patients have extra-orbitary
lymphoma histories when diagnosing orbitary
lymphoma (4,5,14). The lymphomatous diffuse
disease is found mainly in patients with high-degree
non-Hodgkin lymphoma. Twenty-six percent of
low degree lymphoma patients reach stage 4 while
56% of patients with high degree lymphoma reach
said stage (2,9).
In our study the lymphoma was localized inside
the orbit in 3 cases (in the lower external, inferior
and medial areas) in the lachrymal fossa in 1 case,
sharing eyelid and part of the orbit in 3 cases, only
in the eyelid in 1 case and in the cavernous sinus in
1 case. We did not find conjunctival involvement or
bilaterality in any case. In 7 out of the 9 cases there
was a lymphoma with extra-orbitary location. In 1
case (case 6) we found an extra-orbitary disease in
the follow-up because the patient delayed treatment
and follow-up visits. Even though we have very few
cases to consider this as significant, our series exhibits an occurrence of extra-orbitary lymphoma greater than expected.
In their 112-patient statistics on ocular region
lymphomas, Coupland et al (4) found 64% of B-cell
lymphoma in the extra nodal marginal area
(MALT), 10% of centre follicular lymphomas, 9%
of large diffuse B-cell lymphomas, 6% of plasmocytomes, and 5% lymphplasmocytic lymphoma.
On the other hand, in a series of 73 ocular region
lymphoma cases, McKelvie et al (15) found 63% of
MALT lymphomas, 17% of follicular lymphomas,
11% of large diffuse B-cell lymphomas, 3% of
mantle cell lymphomas, 3% of chronic lymphocytic
leukemia of B cells/small lymphocytic lymphoma,
1.5% of peripheral T-cell lymphomas and 1.5% of
Natural killer cell lymphoma.
Nearly all studies agree in that the most common
type of non-Hodgkin orbitary and ocular region
lymphoma is the MALT (4,15,16). In our statistics we
found 3 MALT lymphomas, one low degree B lymp-
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REY-PORCA C, et al.
homa, two large B-cell non-Hodgkin lymphomas, 2
follicular lymphomas and one mantle lymphoma,
which matches the results of other published studies.
Recent publications refer to the possibility of association between MALT lymphomas with infection by
Chlamydia Psittachi (2,16,17). This means that, even
though radiotherapy was the standard treatment for
localized ophthalmological lymphomas, we are witnessing the emergence of other options with likely
therapeutic value such as antibiotic therapy for Psittaci. In addition, CD20 monoclonal antibody therapy
can constitute a promising alternative for external
irradiation and its potential toxicity (2).
In general terms, the findings of our series are
very similar to those described in literature. It is
important for the ophthalmologist to be familiar
with this type or orbitary pathology because on
many occasions we are the first specialists to examine the patients who suffer it. Early detection is
very important because it is a potentially curable
disease. A comprehensive medical history is particularly relevant because, when ophthalmological
symptoms appear, the presence of extra-orbitary
involvement is quite frequent. Recent studies have
observed an increased prevalence of orbitary nonHodgkin lymphomas and therefore it is important to
identify this entity to avoid it going unnoticed (18).
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