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Chiara
Fulignati, Pietro Pantaleo, Greta Cipriani, Marianna Turrini,
Rosalia Nicastro, Roberto Mazzanti, Bruno Neri, Department of
Internal Medicine, Centre of Experimental and Clinical Oncology,
University of Florence, School of Medicine, Viale Morgagni, 85,
I-50134 Firenze, Italy
Correspondence to: Bruno Neri, Department of Internal
Medicine, Centre of Experimental and Clinical Oncology, University
of Florence, School of Medicine, Viale Morgagni, 85, I-50134 Firenze,
Italy. brunoneri@unifil.it
Telephone: +39-554-29611
Received: 2004-06-29
Accepted: 2004-08-31
Abstract
We report the case of a patient affected by an extra-nodal
non-Hodgkin lymphoma presenting as a unique, large retroperitoneal
mass with an unusual clinical presentation mimicking gastric peptic
or neoplastic disease. The patient was successfully treated with a
first generation therapy, CHOP modified regimen (cyclophosphamide
600 mg/m2
intravenously on d 1, epirubicin 55 mg/m2
intravenously on d 1, vincristine 1.2 mg/m2
intravenously on d 1, prednisone 60 mg/m2
on d 1-5), and a complete response was achieved. The
(18)F-fluorodeoxyglucose positron emission tomography was used to
assess the therapy outcome. A brief review of literature is
provided.
© 2005 The WJG Press and Elsevier Inc. All rights reserved.
Key words: Lymphoma; Grastric disease
Fulignati C, Pantaleo P, Cipriani G, Turrini M, Nicastro R, Mazzanti
R, Neri B. An uncommon clinical presentation of retroperitoneal
non-Hodgkin lymphoma successfully treated with chemotherapy: A case
report. World J Gastroenterol
2005; 11(20): 3151-3155
http://www.wjgnet.com/1007-9327/11/3151.asp
INTRODUCTION
Non-Hodgkin lymphoma (NHL) causes many deaths worldwide, and its
incidence is increasing[1].
It represents a heterogeneous group of neoplasms originating from
lymphocytes[1-3].
In Western countries, 80% of NHL consists of a neoplastic growth
originating from B lymphocytes[4].
The etiology of this disease is still partially unclear[1].
Some infectious agents have been associated more or less strictly
with the development of a NHL as i.e. the Epstein-Barr virus, the
human herpesvirus 8, and the human T-cell lymphotropic virus type I[1].
Also the Helicobacter pylori chronic infection has been
strictly implicated in the pathogenesis of gastric lymphomas[5].
Several other environmental factors have been linked with the
increasing incidence of NHL with conflicting evidence[6].
Also the disease classification is still complex
and debated. The older classification systems, such as the Kiel
classification and the Working Formulation, were based on NHL
morphology[7].
Only recently, a new system was developed by the International
Lymphoma Study Group, the Revised European and American
Classification of Lymphoid Neoplasms that incorporate all available
information to define the disease such as clinical features,
morphology, immunophenotype as well as genetic features[8].
The stage of the disease is classified according to the Ann Arbor
staging system[6].
Nearly 70% of lymphomas present a generally
multi-localized, single or multiple lymphoadenomegaly without pain,
with involvement in almost 30-40% of latero-cervical lymphnodes. In
30% of patients an extranodal localization is reported in
Waldeyer’s ring, in the stomach and generally in the
gastro-intestinal tract. The retro-peritoneal localization is
extremely rare and its diagnosis is often difficult. It often
requires a time consuming and costly diagnostic workup.
Indolent NHL is generally considered incurable.
Several regimens have been commonly used; however, treatment has
never been shown to extend overall survival[9].
The poly-chemotherapy with CHOP regimen has been
so far considered as the standard first-line treatment for advanced
large B-cell lymphoma but upcoming therapies seem to promise a
relevant improvement in patients’ outcomes[10].
Several efforts have been made also to enhance
the pre- and post-treatment disease assessment. This evaluation
relies mainly on a CT scan performed after three or four
conventional cycles of treatment[11,12].
The current evidence for the ability of (18)F-fluorodeoxyglucose
positron emission tomography (FDG-PET) to detect disease not
suspected from conventional staging is still equivocal, although an
increased number of sites of disease are reported to be found in
many patients by the means of FDG-PET but whether this is an
independent prognostic factor remains to be seen[13,14].
The role of FDG-PET in NHL follow-up has not been
widely investigated but there is some evidence that an early
negative FDG-PET scan after completion of treatment is a strong
predictor for patients who will be cured, and in this group of
patients the follow-up could be minimized. Therapy also, in the case
of aggressive disease, could be tailored[15].
In this article we report the case of an uncommon
clinical presentation of a large B-cell lymphoma in a male patient
treated by a standard CHOP regimen in which a complete remission was
achieved. Besides the uncommon presentation, this article emphasizes
the role and the good sensitivity of FDG-PET in assessing response
to therapy.
CASE REPORT
At the beginning of May 2002, a 56-year-old man, a hard smoker
(30 packs/year) with hypertension, referred to the outpatient
section of the Day-Hospital Unit of the Centre of Experimental and
Clinical Medicine (Department of Internal Medicine, University of
Florence) with recurrent epigastric burning pain following meals.
Anorexia and asthenia associated with a marked loss of weight (a 7
kg reduction in 6 wk) were also present. The patient was referred to
us by the general practitioner since he suspected from the symptom,
the presence of a gastric neoplasia. In the past clinical history of
the patient, no relevant disease was present and he underwent
surgery at the age of 51 because of renal gallstones. No familiar
history of gastric or esophageal cancer was reported.
Physical examination was normal and an accurate
cardiological examination and electrocardiogram ruled out any
cardiological origin of the pain. No alteration was found in the
standard hematochemical determinations, in the hemachrome and in the
differential blood count.
He firstly underwent an ultrasound (US) abdominal
tomography on May 29, 2002 that did not show any relevant finding.
An esophago-gastro-duodenoscopy (EGDS) was
performed just few days later, on June 4, 2002, and a biopsy during
the procedure was performed in a erythematous area of the gastric
antrum. No evidence of esophagitis was present. The
histopathological examination performed on the gastric mucosal
samples showed the presence of a superficial gastritis. Both the
histopathological examination and urea breath test for H pylori
were positive for the presence of this bacterium and the specific
therapy with antibiotics and a proton pump inhibitor was immediately
begun (amoxicillin 1 000 mg along with clarithromicin 500 mg b.i.d.
for a week and omeprazole 40 mg for the 1st
wk and thereafter 20 mg for 3 wk once a day).
A further abdominal US examination performed by a
different examiner from that of the first one did not reveal any
pathological finding. However, despite the therapy, after 2 wk, the
patient reported an increase of the epigastric pain and a posterior
irradiation was associated in that occasion.
On July 19, 2002 an abdominal contrast-enhanced
CT scan demonstrated the presence of a solid mass in the
retroperitoneal space. Its size was 9.5 cm×6.5 cm×12 cm and was
located superiorly between the left hepatic lobe and the stomach.
The gastric corpus was displaced to the left, while the antro-pyloric
region forward. No cleavage limits were observed at the
contrast-enhanced CT scans between the mass, the kidneys and the
pancreas. Some lymphadenopathies were present at pre- and para-aortic
levels (Figure 1). Few days later the patient was referred to the
Surgery Department because of a further increase of the pain. A
port-a-cath catheter was placed in the right subclavian vein and an
intravenous therapy for the pain with morphine chlorhydrate (up to
60 mg/d) and ketorolac salt of trometamol (40 mg/d) was started.
Since it did not appear to be possible to
obtain a sample of the mass percutaneously both under US or CT
guidance, the patient underwent an explorative laparotomy and a
biopsy of the mass that appeared as a solid mass in the
retroperitoneal space was taken. The histopathological examination
revealed the presence of a B large-cell lymphoma. The
immunohistochemical staining was positive for the following
antigens: CD-45, CD-20, Bcl, Bcl-6, and MIB-1. Based on these data
the disease was staged IV according to the Ann Arbor classification[5].
Figure
1 Basal contrast-enhanced abdominal CT scan. The large
retroperitoneal mass is indicated by the white arrow.
On August 29, 2002, the patient was eventually
referred to our Day-Hospital Unit and was started on a treatment
with CHOP modified regimen (cyclophosphamide 600 mg/m2
intravenously on d 1, epirubicin 55 mg/m2
intravenously on d 1, vincristine 1.2 mg/m2
intravenously on d 1, prednisone 60 mg/m2
on d 1-5). He was scheduled to receive seven administrations of this
regimen starting from August 29, 2002 until March 10, 2003. The
patient tolerated the therapy well. No major toxicity, as assessed
by the CTC criteria[16],
was observed during the whole period of the therapy administration.
The general condition improved just after the
administration of the first course of treatment and continued to
improve with the further courses of therapy. The Karnofsky
performance status was 40% before treatment and improved to 100%
after the fourth cycle. The pain was controlled during the treatment
period with the administration of fentanyl via a transdermal device.
The dosage was 75 mg/h
at the beginning and it was reduced to 50 mg/h
and finally to 25 mg/h
during the second course of the treatment and completely
discontinued after the third one. Anorexia and asthenia disappeared
and the patient’s body mass index rose from 20 to 24 in about 6
mo.
A contrast-enhanced CT scan of the abdomen was
performed after the third treatment and it demonstrated a reduction
of the mass with residual disease of about 1 cm localized at celiac
trunk and it was considered as a partial response according to the
SWOG criteria (Figure 2)[17].
The lymphoadenomegalies observed in the prior examination were still
present. After the seventh course of treatment a total-body FDG-PET
was performed and it did not show any pathological finding (Figure
3). However, 4 mo after the completion of the treatment (July 2003),
a contrast-enhanced CT showed a minimal residual disease localized
at the celiac tripod (Figure 4). Finally a further FDG-PET performed
in October 2003 showed the complete remission of the disease (Figure
5).
Two months later the port-a-cath catheter was
removed.
At the moment of writing this case report (April
4, 2004), the patient is alive and no evidence of a relapse of the
disease is observed. His general condition is good and he entered
the follow-up program.
Figure
2 Contrast-enhanced
abdominal CT scan performed. The large retroperitoneal mass is
reduced in size but a residual disease of about 1 cm is localized at
celiac trunk (white arrow).
Figure
3 Total-body
FDG-PET performed after the seventh
course of treatment.
Figure
4 Contrast-enhanced
CT performed 4 mo after the completion of the treatment. A minimal
residual disease is localized at the celiac tripod.
Figure
5 FDG-PET
performed in October 2003: a complete remission of the disease is
showed.
DISCUSSION
A primary and unique retroperitoneal localization of NHL is
quite rare and, according to our knowledge, only case that has been
described yet[18],
and a clinical presentation with an epigastric pain and ulcer-like
dyspepsia mimicking a peptic disease is extremely rare. Abdominal
NHL typically present themselves as a solid mass and they cause
abdominal pain due to compression or infiltration of nerves and its
pain is often referred as a diffuse pain[19].
Abdominal lymphomas often belong to the sclerosant variety of
follicle centre lymphomas[19].
The symptoms presented in this case were very
similar to that of esophagitis and gastric ulcer and the
relationship with meals suggested to the general practitioner, the
presence at least of a peptic-related disease or a gastric neoplasia
since the patient had a previously known risk factor for gastric
cancer (cigarette smoking) and the presence of asthenia, anorexia
and the weight loss prompted the general practitioner to start a
diagnostic workup oriented to gastric cancer. The negative result of
the first abdominal US scan prompted us to perform a further US and
a EGDS. This last examination was negative for gastric cancer and
resulted only with the presence of a mild gastritis associated with H
pylori infection. Even the second US resulted negative.
Therefore, since the data obtained from the first investigations
were in some way contradictory, further assessments were planned.
Contrast-enhanced CT scans identified the mass, but no indication on
the nature was obtained. A laparoscopic examination of the
retroperitoneal space was thereafter planned and performed. So, the
patient underwent several expensive investigations to achieve the
diagnosis. The complexity of this clinical workup is probably due to
the rarity of the disease by itself and also because of the uncommon
clinical presentation. Most probably, the presence of a marked
weight loss is the only symptom that could have oriented the
diagnostic workup towards the suspicion of a neoplastic disease.
Indolent NHL is generally considered incurable.
The CHOP, a first generation chemotherapy regimen, still represents
the standard chemotherapy regimen for NHL treatment[20].
It obtains a complete response in about 45-53% of cases, with a
long-term survival of 30-37%, and few and acceptable side-effects.
The disease localization affects treatment choice, but generally the
correct therapeutic approach to the extra-nodal NHL requires the
integration of chemotherapy, radiotherapy and surgery.
Several regimens have been commonly so far used
in the therapy of nodal and extra-nodal NHL. The response rate to
the treatment is initially greater than 50% but the response and its
duration decrease with subsequent chemotherapy. However, treatment
has never been shown to extend overall survival.
The poly-chemotherapy with CHOP regimen has been
considered as the standard first-line treatment for advanced large
B-cell lymphoma[21]
as no improvement in failure-free survival or overall survival, but
increased toxic effects with newer regimens were shown with the less
complicated and less expensive regimen of CHOP[24].
New strategies are being developed to improve the prognosis of these
patients and the association of the CHOP regimen with rituximab, a
human-mouse chimeric monoclonal anti-CD20 antibody that kills
CD20-positive cells by activation of complement-dependent and
antibody-dependent cell-mediated cytotoxicity, has been recently
proposed[22-24].
In our case the choice of the CHOP regimen was
funded and we obtained a complete remission. The use of the CHOP, a
first generation regimen, should not be discontinued, since there is
no improvement from the use of newer regimens[21].
However, the association of CHOP with mechanism-based drugs such as
rituximab may further improve treatment outcomes especially in
aggressive disease[22].
In this setting it appears clear that a correct
pre- and post-treatment evaluation is mandatory to assess patient
outcome, to evaluate the relapse risk and to establish the prognosis
and in predicting survival and eventually to plan the follow-up[25].
Thus, it seems necessary to use more than one tool to evaluate
disease extension and after the therapy residual disease.
The role of the functional metabolic imaging
through FDG-PET has gained relevance in the staging and evaluation
of response of various solid and hematologic malignancies. FDG-PET
has recently emerged as an useful prognostic tool also in patients
with aggressive lymphomas[13,14,26].
This kind of investigation performed few cycles after the
chemotherapy can predict relapse risk[27,28].
The vast majority of patients with positive FDG-PET scans present
poorer clinical outcomes as compared to patients with negative scans[28].
In patients where FDG-PET showed residual disease after treatment,
relapses were reported in 100% of the cases, whereas a long-term
survival was seen in more than 80% of patients with negative PET
results[28].
Providing that these observations will obtain a
confirmation, by FDG-PET we would be able to customize for the
single patient with aggressive lymphoma, the appropriate treatment
and follow-up. The patient of this case report underwent two FDG-PET
and in both cases the negative result corresponded to a remission of
the disease.
Besides its rarity and complexity, this case
suggests that the use of FDG-PET in assessing the response to
chemotherapy of extra-nodal NHL must be implemented and that FDG-PET
could be the most useful predictive tool in assessing patient
outcome. The use of morphologic tools (contrast-enhanced CT or
magnetic resonance) in association with a functional metabolic
imaging test appears to be mandatory also in the evaluation of
extra-nodal aggressive NHL.
REFERENCES
1
Hennessy BT, Hanrahan EO, Daly PA. Non-Hodgkin
lymphoma: an update. Lancet Oncol 2004; 5: 341-353
2
Rossi D, Gaidano G. Molecular heterogeneity of diffuse
large B-cell lymphoma: implications for disease management
and prognosis. Hematology
2002; 7: 239-252
3
Pileri SA, Zinzani PL, Went P, Pileri A Jr, Bendandi
M. Indolent lymphoma: the pathologist’s viewpoint. Ann Oncol
2004; 15: 12-18
4
Chiu BC, Weisenburger DD. An update of the
epidemiology of non-Hodgkin’s lymphoma. Clin Lymphoma 2003;
4: 161-168
5
Wotherspoon AC. Gastric lymphoma of mucosa-associated
lymphoid tissue and Helicobacter pylori. Annu Rev
Med 1998; 49:
289-299
6 DeVita
VT Jr, Hellman S, Rosenberg SA, eds. Cancer: principles and
practice of oncology, 6th edn. Philadelphia,
PA: Lippincott Williams &
Wilkins 2001
7
Jaffe ES, Harris NL, Diebold J, Muller-Hermelink HK.
World Health Organization classification of neoplastic diseases
of
the hematopoietic and lymphoid
tissues. A progress report. Am J Clin Pathol 1999; 111:
S8-12
8
Armitage JO, Weisenburger DD. New approach to
classifying non-Hodgkin’s lymphomas: clinical features of
the
major histologic subtypes.
Non-Hodgkin’s Lymphoma Classification Project. J Clin Oncol
1998; 16: 2780-2795
9
Marcus R. Current treatment options in aggressive
lymphoma.Leuk Lymphoma 2003; 44: S15-27
10
Fisher RI, Gaynor ER, Dahlberg S, Oken MM, Grogan TM,
Mize EM, Glick JH, Coltman CA Jr, Miller TP. Comparison of
a standard regimen (CHOP) with
three intensive chemotherapy regimens for advanced non-Hodgkin’s
lymphoma. N Engl
J Med 1993; 328:
1002-1006
11
Rankin SC. Assessment of response to therapy using
conventional imaging. Eur J Nucl Med Mol Imaging 2003;
30: S56-64
12
Vinnicombe SJ, Reznek RH. Computerised tomography in
the staging of Hodgkin’s disease and
non-Hodgkin’s lymphoma. Eur
J Nucl Med Mol Imaging 2003; 30: S42-55
13
Otsuka H, Graham M, Kubo A, Nishitani H. Clinical
utility of FDG PET. J Med Invest 2004; 51: 14-19
14
Rohren EM, Turkington TG, Coleman RE. Clinical
applications of PET in oncology. Radiology 2004; 231:
305-332
15
Kasamon YL, Wahl RL, Swinnen LJ. FDG PET and high-dose
therapy for aggressive lymphomas: toward a
risk-adapted strategy. Curr
Opin Oncol 2004; 16: 100-105
16 Arbuck
SG, Ivy SP, Setser A. The Revised Common Toxicity Criteria:
Version 2.0. CTEP Website. Available
from: http://ctep.info.nih.gov
17
Green S, Weiss GR. Southwest oncology group standard
response criteria. Invest. New Drugs 1992; 10: 239-253
18
Waldron JA Jr, Magnifico M, Duray PH, Cadman EC.
Retroperitoneal mass presentations of B-immunoblasti
sarcoma. Cancer 1985; 56:
1733-1741
19
Crump M, Gospodarowicz M, Shepherd FA. Lymphoma of the
gastrointestinal tract. Semin Oncol 1999; 26: 324-337
20
Seymour JF. New treatment approaches to indolent
non-Hodgkin’s lymphoma. Semin Oncol 2004; 31: 27-32
21
Fisher RI, Shah P. Current trends in large cell
lymphoma. Leukemia 2003; 17: 1948-1960
22
Coiffier B. Effective immunochemotherapy for
aggressive non-Hodgkin’s lymphoma. Semin Oncol 2004; 31:
7-11
23
Davis TA, Grillo-Lopez AJ, White CA. Rituximab
anti-CD20 monoclonal antibody therapy in non-Hodgkin’s
lymphoma: safety and efficacy
of retreatment. J Clin Oncol 2000; 18: 3135–3143
24
Rastetter W, Molina A, White CA. Rituximab: expanding
role in therapy for lymphomas and autoimmune
diseases. Annu Rev Med
2004; 55: 477-503
25
Wooldridge JE, Link BK. Post-treatment surveillance of
patients with lymphoma treated with curative intent.
Semin Oncol 2003; 30:
375-381
26
Montravers F, McNamara D, Landman-Parker J,
Grahek D, Kerrou K, Younsi N, Wioland M, Leverger G, Talbot JN.
FDG in childhood lymphoma:
clinical utility and impact on management. Eur J Nucl Med Mol
Imaging 2002;
29: 1155-1165
27
Blum RH, Seymour JF, Wirth A, MacManus M, Hicks
RJ. Frequent impact of [18F]fluorodeoxyglucose positron
emission tomography on the
staging and management of patients with indolent non-Hodgkin’s
lymphoma. Clin
Lymphoma 2003;
4: 43-49
28
Schot B, van Imhoff G, Pruim J, Sluiter W, Vaalburg W,
Vellenga E. Predictive value of early
18F-fluoro-deoxyglucose
positron emission tomography in chemosensitive relapsed lymphoma.
Br J Haematol
2003; 123: 282-287
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