Ann Hematol (2002) 81:228–231
DOI 10.1007/s00277-002-0436-9
C A S E R E P O RT
E. Nadal · A. Martinez · M. Jiménez · À. Ginés
E. Campo · J. Piqué · A. López-Guillermo
Primary follicular lymphoma arising in the ampulla of Vater
Received: 24 October 2001 / Accepted: 7 January 2002 / Published online: 13 March 2002
© Springer-Verlag 2002
Abstract Primary gastrointestinal lymphomas constitute
more than one-third of all extranodal lymphomas, but
among them follicular lymphomas (FL) are infrequent,
accounting for only 1–4%. We report the case of a
55-year-old man diagnosed with a FL of the ampulla of
Vater. He complained of dyspepsia. An upper gastroen-
doscopic study 1 year before showed a slight enlarge-
ment of the papilla with the biopsy initially interpreted
as atypical follicular hyperplasia. The study performed
because of persistence of the symptoms again showed an
enlarged papilla, and the histological examination was
diagnostic of FL (CD10+, bcl-2+). The full staging study
did not show other FL involvement. The patient was
treated with six courses of cyclophosphamide, hydroxy-
daunomycin, vincristine, and prednisone (CHOP), and
the endoscopy as well as the biopsies revealed no abnor-
malities since the third course of chemotherapy. After
2 years of follow-up he remains asymptomatic and the
gastroendoscopic study is normal.
Introduction
The gastrointestinal tract (GI) is the most frequent local-
ization for extranodal lymphomas. The stomach is the
most common site affected, followed by the colorectum
and terminal ileum [1]. A few cases of primary lympho-
ma of the ampulla of Vater have been reported, mostly of
the mucosa-associated lymphoid tissue (MALT) subtype
[2, 3, 4, 5]. Follicular lymphoma (FL) of the ampulla is a
E. Nadal (✉) · M. Jiménez · A. López-Guillermo
Institute of Hematology and Oncology, Hematology Department,
IDIBAPS, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain
e-mail: alopezg@clinic.ub.es
Tel.: +34-93-2275428, Fax: +34-93-2275428
A. Martinez · E. Campo
Hematopathology Department, Hospital Clínic, Villarroel 170,
08036 Barcelona, Spain
À. Ginés · J. Piqué
Institute of Digestive Diseases, Gastroenterology Department,
Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain
very rare entity with only a few cases reported in the
literature [6, 7]. Interestingly, all these cases of primary
lymphoma of the papilla of Vater occurred in female pa-
tients with an average age of 55 years and, as one could
expect, the most common clinical feature was unspecific
dyspepsia, while few of them presented with obstructive
jaundice. Most cases were diagnosed after surgical resec-
tion, since endoscopic biopsies were difficult to assess.
We present a case of a male patient presenting with
a FL of the papilla of Vater who was diagnosed by
endoscopic biopsy and successfully treated with chemo-
therapy.
Case report
A 55-year-old man with no remarkable medical history consulted
our institution because of dyspepsia. The patient presented with no
other symptoms and his physical examination was normal. Blood
counts and serum biochemistry, including LDH and β2-microglob-
ulin levels were normal. An upper gastroendoscopic study showed
slight enlargement of the papilla of Vater. The biopsies performed
demonstrated the presence of an atypical follicular hyperplasia
of the papilla. Helicobacter pylori infection was ruled out by a
Campylobacter-like organism test (CLOtest) and histologic exam-
ination. The patient received symptomatic therapy (ranitidine
150 mg/12 h p.o. for 2 months) and his symptoms were alleviated.
One year later, a new gastroendoscopy was performed due to
the recurrent dyspepsia. This maneuver again showed a prominent
papilla with inflammatory signs around. No evidence of local
lymph node involvement was found. The endoscopic ultrasound
showed enlargement of mucosa and submucosa layers. Biopsy
specimens stained with hematoxylin and eosin showed a nodular
lymphocyte expansion of the lamina propria constituted by small-
cleaved lymphoid cells together with some large cells of centrob-
lastic type (Fig. 1). The immunohistochemical study demonstrated
that the lymphoid nodules were CD20, CD79a, and CD10 positive
and cyclin D1 negative (Fig. 2). The nodules were surrounded by
T lymphocytes and numerous B cells CD10+ spread out from the
nodules to the interfollicular areas of the lamina propria. BCL-2
protein expression was intensively positive in the nodule centers.
Molecular study of the rearrangements of the Ig heavy chain (IgH)
and BCL-2 gene was performed by a polymerase chain reaction
(PCR) technique. The former disclosed a polyclonal pattern
whereas the later was negative. A diagnosis of follicular lympho-
ma was established, mainly based on the presence of CD10-posi-
tive lymphocytic infiltration in the lamina propria. The lymphoma

Fig. 1 Neoplastic infiltration of the lamina propria of the ampulla
by follicular growth pattern. H&E, ×10
Fig. 2 CD10-positive cells are observed in the follicular areas as
well as the interfollicular space. ×20
was classified as a follicle center lymphoma, follicular, grade1 ac-
cording to the WHO classification [8].
At the moment of diagnosis, the patient was asymptomatic, ex-
cept for the intermittent dyspepsia. Physical examination was nor-
mal. Peripheral blood counts and serum biochemistry including
liver function tests, uricemia, immunoglobulins, LDH, and β2-
microglobulin levels showed no alterations. A computed tomogra-
phy (CT) scan of the thorax, abdomen, and pelvis was normal. The
bone marrow trephine biopsy showed no abnormalities.
The diagnosis of FL of the ampulla of Vater in stage IAE was
then established. The patient was treated with six courses of
CHOP chemotherapy (cyclophosphamide 750 mg/m2, Adriamycin
50 mg/m2, vincristine 2 mg, and prednisone 60 mg/m2) every
3 weeks. No major complications were observed during therapy.
After the third course of CHOP, a new upper endoscopy displayed
no abnormalities and the biopsies performed were basically nor-
mal. At the end of chemotherapy, all the diagnostic maneuvers
were normal and the patient was considered in complete response
(CR). Two years later the patient remained asymptomatic and the
upper gastrointestinal endoscopies with biopsies performed yearly
are completely normal.
229
Discussion
Gastrointestinal (GI) primary lymphomas are the most
frequent extranodal lymphomas, accounting for 30–40%
(Table 1). The stomach is the most common site for
lymphomas followed by the colorectal region and the
terminal ileum [1]. The duodenum is less frequently af-
fected [7, 9]. Concerning histological subtypes, MALT
and high-grade B-cell lymphomas represent the vast ma-
jority, whereas follicular lymphomas have an incidence
reported of only 1–3.8% [7, 10]. Primary GI follicular
lymphomas usually arise in the small intestine, particu-
larly in the terminal ileum. Although duodenal lympho-
mas are rare, a handful of cases of lymphomas localized
in the papilla of Vater have been reported. Most of them
were MALT lymphomas [2, 3, 4, 5, 6]. The first case of
FL arising in the ampulla of Vater was described by
Misdraji et al. [6] in a 56-year-old female patient pre-
senting with obstructive jaundice mimicking a pancreatic
carcinoma. More recently, Yoshino et al. [7] summarized
five other cases of FL of the ampulla of Vater; all of
them were women with an average age of 52 years.
These authors reported an unexpectedly high incidence
of FL around the papilla of Vater, suggesting that the dis-
tinctive histological structure of this region may be of
pathogenic significance. Notwithstanding, this elevated
incidence may be due to the higher frequency of upper
gastroendoscopic studies in the Japanese population due
to gastric pathology. No relationship with H. pylori in-
fection has been reported in these cases.
All the above-mentioned reports focus on the difficul-
ties in diagnosing FL of the duodenum, since in most
cases bioptic material is not conclusive. In fact, in the
first case, the endoscopic biopsies were reported as nega-
tive for malignancy and the diagnosis was made by the
duodenopancreatectomy specimen. The surgical treat-
ment was complemented by preoperative and postopera-
tive radiotherapy. The regional lymph nodes were affect-
ed, whereas no evidence of distant dissemination was
found. Moreover, in the Japanese series, the endoscopic
biopsy was diagnostic in only two cases, and in four of
them a surgical resection was carried out. Immunohisto-
chemical techniques are of paramount importance to es-
tablish a diagnosis. The differential diagnosis of FL
(CD10+, bcl-2+) should include reactive follicular hy-
perplasia (CD10+, bcl-2 –) (11), mantle cell lymphoma
(CD10–, CD5+, CD23–, cyclin D1+), and MALT lym-
phoma (CD10–). The fact that the IG rearrangement was
polyclonal does not preclude the diagnosis, since this is
not infrequent in paraffin-embedded endoscopic biop-
sies. Most likely this is due to technical reasons [12, 13].
Another entity that should be kept in mind is multiple
lymphomatous polyposis, which is frequently associated
with a mantle cell lymphoma although also reported as-
sociated with FL [11]. Primary carcinoma or pancreatic
tumor should always be ruled out, since they are the
most common neoplastic processes in this area. Finally,
in this case, it was also important to rule out the possibil-
ity of a nodal lymphoma involving extranodal tissues.
230
Table 1 Clinicopathologic features of primary lymphoma of the ampulla of Vater (AV). CR clinical remission, RT radiotherapy, CT che-
motherapy, NR not reported

No Age Sex Clinical Extension Endoscopic Pathology Treatment Response Follow-up

(ref.) features findings (endoscopic (months)
biopsy/surgical
resection)

1 [7] 66 F Control Regional Small polyps FL (biopsy) Whipple CR? 50+

lymph at AV
nodes
2 [7] 37 F NR NR Multiple FL (biopsy) None 2+
small polyps
3 [7] 42 F Pyrosis No Irregular FL (surgery) Surgical CR? 17+
mucosa resection
4 [7] 52 F Irritable Regional Small polyps FL (surgery) Surgical CR? 33+
bowel lymph at AV resection
signs nodes
5 [7] 65 F NR No Multiple FL (surgery) Surgical CR? 32+
protrusions resection
at AV
6 [6] 56 F Jaundice Pancreas Ampullary FL (surgery) RT CR 5+
+ regional mass Whipple
lymph + duodenal
nodes ulcer
7a 55 M Dyspepsia No Enlargement FL CT CR 24+
AV
8 [3] 53 F Pyrosis No Deformation Low-grade None Spontaneous 72+
and B-NHL regression
inflammation (biopsy)
of AV
9 [5] 55 F NR No H. pylori MALT Surgical CR NR
infection resection
10 [4] 65 F Pyrosis No Polypoid MALT CT CR 7+
mass at AV (biopsy)
11 [2] 57 F Jaundice Pancreas Polypoid MALT Whipple CR 26+
+ regional tumor at AV (surgery)
lymph
nodes
a Present case

The CT scan as well as the ultrasound endoscopy were
determinant for the diagnosis of a primary lymphoma of
the ampulla of Vater.
The treatment of ampullary lymphomas, including
MALT and FL, is very heterogeneous in the literature. This
includes the wait and see policy, tumor resection, and sys-
temic treatment. Aggressive surgery accounts for most of
the cases reported. A case of a low-grade B-cell ampullary
lymphoma with spontaneous regression after 6 years of
follow-up has been reported [6]. Moreover, one case of du-
odenal MALT lymphoma, localized at the bulbar zone, re-
sponded after eradicative treatment for H. pylori, although
no evidence of infection had been found [14]. Ventrucci et
al. [4] reported the unique case of MALT papillary lym-
phoma treated with chemotherapy (eight courses of COP)
with the patient reaching a complete response. In the pres-
ent case, CT was chosen as treatment for the following rea-
sons: (1) a watch and wait attitude was not considered ap-
propriate for a localized lymphoma that may disseminate,
(2) surgical resection is related to significant morbidity,
higher than that for CT, and (3) endoscopic resection has a
troublesome follow-up. Therefore, the standard CT for an
early stage FL was administered with an excellent response
(CR after only three courses of CT).
Acknowledgements The authors thank Dr. Peter G. Isaacson for
the review of this case.
References
1. Cirillo M, Federico M, Curci M, et al. (1992) Primary gastro-
intestinal lymphoma: a clinicopathological study of 58 cases.
Haematologica 77:156–161
2. Pawade J, Lee CS, Ellis DW, et al. (1994) Primary lymphoma
of the ampulla of Vater. Cancer 73:2083–2086
3. Zhu L, Slee GR, Domenico DR, et al. (1995) B-cell lymphoma
of ampulla of Vater: observation for six years (letter). Pancreas
10:208–210
4. Ventrucci M, Gherlinzoni F, Sabattini E, et al. (1998) Primary
MALT lymphoma of the papilla of Vater. Dig Dis Sci 43:
214–216
5. Toshima M, Aikawa K, Soga K (1999) Primary duodenal
MALT lymphoma. Intern Med 38:957–961
6. Misdraji J, Fernandez del Castillo C, Ferry JA (1997) Follicle
center lymphoma of the ampulla of Vater presenting with jaun-
dice: report of a case. Am J Surg Pathol 21:484–488
7. Yoshino T, Miyake K, Ichimura K, et al. (2000) Increased inci-
dence of follicular lymphoma in the duodenum. Am J Surg
Pathol 24:688–693
8. World Health Organisation Classification of neoplastic dise-
ases of the hematopoietic and lymphoid tissues: report of the
clinical advisory committee meeting. Airlie House, Virginia,
November 1997

9. Najen AZ, Porcar JL, Rush BF (1984) Primary non-Hodgkin’s
lymphoma of the duodenum: case report and literature review.
Cancer 54:895–898
10. LeBrun DP, Kamel OW, Cleary ML, et al. (1992) Follicular
lymphomas of the gastrointestinal tract. Am J Pathol 140:
1327–1335
11. Moynihan MJ, Bast MA, Chan WC, Delabie Jan, Wickert RS,
Wu G, Weisenburger DD (1996) Lymphomatous polyposis.
A neoplasm of either follicular mantle or germinal center cell
origin. Am J Surg Pathol 20:442–452
12. Hoeve MA, Krol AD, Philippo K, Derksen PW, Veenendaal
RA, Schuuring E, Kluin PM, van Krieken JH (2000) Limita-
231
tions of clonality analysis of B cell proliferations using CDR3
polymerase chain reaction. Mol Pathol 53:194–200
13. Theriault C, Galoin S, Valmary S, Selves J, et al. (2000) PCR
analysis of immunoglobulin heavy chain (IgH) and TcR-
gamma chain gene rearrangements in the diagnosis of lympho-
proliferative disorders: results of a study of 525 cases. Mod
Pathol 13:1269–1279
14. Nagashima R, Takeda H, Maeda K, Ohno S, Takahashi T
(1996) Regression of duodenal mucosa-associated lymphoid
tissue lymphoma after eradication of Helicobacter pylori.
Gastroenterology 111:1674–1678