Gastrointestinal lymphomatous polyposis

Romanian Journal of Gastroenterology

September 2005 Vol.14 No.3, 273-278

Address for correspondence: Marcel Tanþãu, MD

3rd Medical Clinic

Croitorilor Str. no.19-21

400162, Cluj-Napoca, Romania

Gastrointestinal Lymphomatous Polyposis - Clinical,

Endoscopical and Evolution Features. A Case Report

Marcel Tanþãu1, Alina Tanþãu1, Teodor Zaharia1, Andrei Cucuianu2

1) 3rd Medical Clinic, University of Medicine and Pharmacy. 2) Haematology Clinic, Institute of Oncology, Cluj-Napoca

Abstract

Primary gastrointestinal non-Hodgkin lymphoma ac-

counts for 13-18% of all malignant tumours of small bowel

and only 1 % of large bowel tumours (1). Multiple

lymphomatous polyposis is a rare entity, characterized by

the presence of multiple lymphomatous polyps along the

gut (2). Majority of cases with gastrointestinal primary

lymphoma are classified histologicallly as “mantle cell”

lymphomas.

A 59 year old patient was admitted to our clinic for fatigue

and rectal bleeding. Endoscopic examination of the colon

revealed an infiltrative-exulcerative lesion of the terminal

ileon, a polypoid mass on ileocecal valve and multiple polyps

over the entire colon and rectum. Gastroscopy revealed

polyps into the duodenal bulb. Histopathological and

immunohistochemical studies on biopsy specimens from

colon and duodenum confirmed gastrointestinal non-

Hodgkin lymphoma, probably “mantle cell” lymphoma.

Because she was in an advanced stage she received only

cytostatic treatment. A clinical, endoscopical and histo-

phatological follow up at 3, 6 and 12 months was performed.

Key words

Gastrointestinal tract - lymphomatous polyposis - im-

munohistochemistry - mantle cell lymphoma

Rezumat

Limfomul non-Hodgkin primar gastrointestinal constituie

aproximativ 13-18% din totalul tumorilor maligne ale

intestinului subþire ºi doar 1% din cele ale colonului (1).

Polipoza limfomatoasã multiplã este o entitate rarã ce se

caracterizeazã prin apariþia mai multor tumori polipoide ce

afecteazã diverse segmente ale tractului gastrointestinal (2).

Majoritatea cazurilor de polipozã limfomatoasã gastro-

intestinalã sunt histopatologic clasificate ca limfoame cu

celule “în manta”.

O pacientã de 59 ani a fost internatã în clinica noastrã

pentru astenie ºi rectoragii. Colonoscopia a evidenþiat

multiplii polipi rectali, colonici ºi pe valva ileo-cecalã, iar la

nivelul ileonului terminal o formaþiune infiltrativ-exulceratã.

Bulbul duodenal a fost investigat prin gastroduodeno-

scopie, la acest nivel gãsindu-se câþiva polipi. Examinarea

histologicã ºi imunohistochimicã efectuatã pe biopsiile din

colon ºi duoden au stabilit diagnosticul de limfom non-

Hodgkin gastrointestinal cu celule B, probabil varianta în

manta. Având in vedere stadiul avansat de boalã pacienta a

urmat doar tratament chimioterapic. S- a urmãrit evoluþia la

3, 6 ºi 12 luni de la diagnostic atât clinic cât ºi endoscopic ºi

histopatologic.

Introduction

Primary gastrointestinal lymphoma represents about

4% to 20% of non-Hodgkin lymphomas. The ileocecal

valve is the most frequently involved (35.8%), followed

by the small bowel (31.3%), large bowel (19.4%) and

multiple gastrointestinal involvement (13.4%) (3). In

1961, Cornes described for the first time the multiple

lymphomatous polyposis and in 1984 Isaacson et al

described the mantle cell form of the neoplasic lymphoid

infiltration (2). Mantle cell lymphoma is a clinicopathologic

entity with distinctive morphologic and immunophenotypic

features and a characteristic cytogenetic abnormality, the

t(11;14)(q13;q32) (4). Most mantle cell lymphomas occur in

eldery patients, usually over 40 years (5). An accurate

diagnosis is very important, since this tumor generally carries

a poor prognosis and requires an aggressive treatment (4).

We report the case of a 59-year-old woman presenting

fatigue and rectal bleeding, in whom colonoscopy revealed

multiple polyps on the entire large bowel and rectum and

duodenoscopy showed a few polyps in the duodenal bulb.

Tanþãu et al274

Case report

A 59 year old woman was admitted in November 2003 to

the 3rd Medical Clinic, Cluj Napoca for rectal bleeding and

marked fatigue. She had no important personal pathologic

history (appendectomy). Regarding her family history, her

mother had ischemic heart disease and gallbladder stones.

Her father had diabetus mellitus, and he also had a stroke.

The patient neither did smoke, nor drink alcohol or use

other toxics. She had given birth to two children. The

menopause occurred at the age of 49.

The symptoms of disease started 10 months prior to

admission with marked fatigue. Investigations revealed iron

deficiency anemia, cholesterolosis of the gallbladder and

liver steatosis. She received for two months iron

supplements without symptom improvement.

Two months before admission to our clinic the patient

presented episodes of rectal bleeding. The colonoscopy

revealed colonic polyposis, with lesions of the terminal ileum

and ileocecal valve.

On admission, the general condition of the patient was

good. At physical examination the patient was mildly pale

and had a firm, unpainful submandibular lymphadenopaty

of 1.5 cm diameter, no hepatomegaly, no splenomegaly.

Laboratory studies: ESR=30-50 mm, Hb= 11.4g/dl, red blood

count 4.25 million/mmc, hematocrit = 25.5%, serum iron=

46.2 microg/dl (NV= 50-120 microg/dl). The other blood

tests including white blood count, platelet count, serum

glucose, bilirubin, alkaline phosphatase, gamma-glutamyl-

transpeptidase, aminotransferases, total protein, albumin,

ureea nitrogen, creatinine were normal.

The chest X- ray showed a large left ventricle, the lungs

were normal. On abdominal ultrasonography a hyperecoic

liver and gallbladder cholesterolosis were described. The

pancreas, spleen and kidneys were normal. No retro-

peritoneal nodes were noted.

The colonoscopy revealed an infiltrative-exulcerated

lesion of the terminal ileum of about 2.5 cm diameter; a

polypoid mass of the ileocecal valve and multiple polyps

under 1 cm diameter on ascendent, transverse and

descending colon. More polyps of 1.5 cm were found in the

sigmoid. The entire rectal mucosa was covered by polyps

of more than 2 cm diameter (Figs.1-3). Endoscopic biopsy

samples showed a diffuse and/or nodular infiltration of

lamina propria with atypical lymphocytes of small and

medium size and blastic cells. These lesions suggested a

polypoid lymphoma and the immunohistochemical testing

was required for diagnosis.

Cytokeratin reaction was negative (Fig.5) but the com-

mon leucocyte antigen reaction was positive (Fig.6). T cell

lymphoma and Hodgkin lymphoma (CD3 negative, CD30

negative, respectively) were ruled out (Figs.7,8). B cell non-

Hodgkin lymphoma was confirmed with positive reaction

for common surface antigens (CD 20, CD 79a) (Figs.9,10).

Submandibular lymph node biopsy showed two types

of lymphocytes: small lymphocytes, representing 20-30%

and medium lymphocytes representing the majority. This

suggested non-Hodgkin lymphoma.

Upper digestive endoscopy revealed chronic erosions

in the antrum, a few polyps of 3-4 mm diameter and a sessile

protrusion of about 9 mm diameter in the duodenal bulb,

without lesions in the second part of the duodenum.

Endoscopic biopsy samples showed signs of chronic

gastritis with incomplete intestinal metaplasia and rare

atypic lymphocytes. In the duodenal bulb non-Hodgkin

lymphoma lesions (possible “mantle cell” type) were found.

The duodenum which macroscopically was normal, had

signs of chronic duodenitis and lymphoid hyperplasia

without evidence of malignancy.

The diagnosis was of non-Hodgkin lymphoma in stage

IV, multiple lymphomatous polyposis (probably mantle cell

lymphoma). Six courses of systemic chemotherapy

(vincristin, endoxan, farmarubicin) were administered. The

patient’s status improved on therapy. After the third course

the rectal bleeding disappeared. During the follow-up (at 3

and 6 months) continuous improvement of clinical status

and of the endoscopic appearance was noted (Figs.11-13).

At 12 months of follow-up the patient presented again

bloody diarrhea (3-4 stools per day). The relapse of disease

was endoscopically confirmed. The patient received

monoclonal antibodies with improvement of the clinical

status (Figs.14-16).

Discussion

Mantle cell lymphoma is a distinct clinicophatologic

entity of non-Hodgkin lymphoma, characterized by a

monotonous proliferation of small to medium-sized

lymphocytes with co-expression of CD5 and CD20, an

aggressive and incurable clinical course and frequent

t (11;14)(q13;q32) translocation (4,6). Frequently extranodal

involvement is present, particularly of the bone marrow, the

gastrointestinal tract and the spleen (8).

Primary gastrointestinal lymphoma, mantle cell type, is a

multifocal disease of the digestive tract, which can affect

any part of the digestive tube, ileo-cecal region mostly (7).

The disease occurs in adults, beginning with pain and

bleeding (7). Frequently the disease is diffuse at diagnosis

(7). In our case the diagnosis was delayed by 12 months,

when rectal bleeding occurred. At this time the disease was

generalised.

Macroscopic appearance of mantle cell lymphoma is

variable: from tumoral mass, ulcer, mucosal thickness to

multiple polypoid lesions (7).

A study by Chung et al (5) evaluated 7 subjects with

mantle cell lymphoma involving the gastrointestinal tract

diagnosed during a 6 year period and showed that most

subjects presented multiple polyposis (6/7), bowel wall

thickening or mass formation (5/7), lymph node enlarge-

ment (6/7) and extraabdominal involvement (5/7). In all cases

with polyposis, the small bowel and colon were involved,

and the size of the polyps ranged from 0.1 to 4.0 cm. Poly-

posis was predominant in the rectum. Ascending colon and

the ileum were almost always involved with polyposis. Bowel

wall thickening and mass formation developed exclusively

Gastrointestinal lymphomatous polyposis 275

Fig.1Infiltrative-exulcerative lesion of terminal ileum. Colonoscopic

aspect at admission.

Fig.2 Polypoid lesion of the ileo-cecal valve. Colonoscopic aspect

at admission.

Fig.3 Multiple rectal polyps. Colonoscopic aspect at admis-

sion.

Fig.4 Colon biopsy: lymphoid tissue, nodular or/and diffuse (10X,

hematoxilin-eozin).

Fig.5 Immunofenotyping for cytokeratin: epithelial cells are tinted

in brown.

Fig.6 Immunofenotyping: in brown are cells that present common

leucocyte antigen.

in the ascending colon, rectum or ileum. Some of the patients

presented splenomegaly (3/7), apendiceal enlargement (2/

9), and some had associated adenocarcinomas (3/7).

Endoscopic examinations (upper endoscopy, colono-

scopy) and enteroclysis reveal easily gastrointestinal lesions

but for definite diagnosis immunohistochemical analysis of

Tanþãu et al276

Fig.7 Immunofenotyping: negative for CD3.

Fig.8 Immunofenotyping: negative for CD30.

Fig.9 Immunofenotyping: in brown are cells that present CD20

surface antigen.

Fig.10 Immunofenotyping: in brown are cells that present surface

antigen CD79a.

Fig.11 Terminal ileum. Colonoscopic aspect after chemotherapy.

Fig.12 Ileocecal valve. Colonoscopic aspect after chemotherapy.

biopsy specimens is required. Echoendoscopy helps to

evaluate intestinal wall changes and to detect lymph node

involvement (9).

For establishing prognosis and adequate treatment, this

type of lymphoma must be differentiated from other

histological types that can affect the intestinal tract. Mostly

Gastrointestinal lymphomatous polyposis 277

the differentiation has to be made with MALT lymphoma

(extranodal marginal zone B-cell lymphoma), diffuse large

B-cell lymphoma, follicular lymphoma and peripheral T-cell

lymphoma or T/NK cell (7).

Mantle cell lymphoma has a poor prognosis with the

current therapy; median survival is 2-3 years (10,7). Because

this lymphoma occurs in the elderly population, stem cell

transplantation is not feasible (10).

In the early stages the resection of involved intestinal

segment increases the survival and adjuvant chemotherapy

provides additional benefit (11).

Romaguera et al followed up 25 patients, 65 years or

older, with mantle cell lymphoma treated with cyclo-

phosphamide 1.800 mg/m2, associated with doxorubicin,

vincristin and dexamethasone (hyper-CVAD), alternating

every 3 weeks with high doses of methotrexate and cytarabin

(1g/m2/dose) for up to 8 cycles. The complete remission rate

was 68% and the median survival for the entire group was

15 months (10).

Fig.13 Rectum. Colonoscopic aspect after chemotherapy.

Fig.16 Rectum. Colonoscopic aspect at disease relapse.Fig.14 Terminal ileum. Colonoscopic aspect at disease relapse.

Fig.15 Ileocecal valve. Colonoscopic aspect at disease relapse.

Conclusions

Gastrointestinal lymphomatous polyposis is a rare

disease. It is very important to precisely establish the

histological type of lymphoma as the prognosis and

treatment are related to it.

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