ORIGINAL ARTICLE

Intussusception as a presenting feature of Burkitt lymphoma:implications for management and outcome

R. J. England • K. Pillay • A. Davidson •

A. Numanoglu • A. J. W. Millar

Accepted: 19 September 2011 / Published online: 4 October 2011

� Springer-Verlag 2011

Abstract

Purpose Intussusception is a recognised but unusual

presenting feature of Burkitt lymphoma. We sought to

identify the clinical features associated with intussuscep-

tion in this setting, and assess the outcome following pro-

tocol directed chemotherapy.

Methods A retrospective case note review was performed on

patients treated for Burkitt lymphoma at our institution

between 1976 and 2010. Cases presenting with intussusception

were identified from hospital records and oncology database.

Results Fourteen of the 210 children seen with a diag-

nosis of Burkitt lymphoma during the study period (6.7%)

developed intussusception. Median age was 6.1 years

(range 2.5–10.9). Twelve patients presented with recurrent

abdominal pain, and two patients with a jaw mass associ-

ated with endemic Burkitt lymphoma. Nine patients

underwent a right hemicolectomy with ileo-colic anasto-

mosis, and five had segmental small-bowel resections.

Three patients had bone marrow involvement at diagnosis,

two of whom died. All patients received chemotherapy.

Median follow-up was 6.07 years (range 0.1–28.8).

Conclusions Small bowel lymphoma should be consid-

ered in children presenting with intussusception above the

normal infantile peak age range. The presentation is often

insidious, and complete obstruction may not be apparent.

However, when surgically resected, the majority can

achieve a good outcome with additional chemotherapy.

Keywords Intussusception � Lymphoma � Small bowel �Diagnosis

Introduction

The management of paediatric B-cell non-Hodgkin lym-

phoma (B-cell NHL) has evolved from an original emphasis

on early debulking surgery followed by chemotherapy, to a

greater reliance on more intensive regimens aimed at

improving survival in advanced disease, either by avoiding

surgery altogether or reducing operative complications [1–

3]. In Southern Africa, Burkitt lymphoma (BL) is a common

form of B-cell NHL. It is divided into three subtypes, all of

which are seen in this population. The most common is

sporadic BL, which is associated mainly with abdominal

disease followed by endemic BL, similar to the form seen in

migrants from the malaria belt countries of equatorial Africa

[4]. The third form is associated with HIV, and appears to

portend a poorer prognosis than the other forms [4].

In patients with abdominal disease, the bowel is more

commonly affected than other organs [5]. As with other

conditions that cause swelling of lymphoid tissue in the

small bowel, the occurrence of intussusception becomes

possible and may lead to obstruction. The presentation of

lymphoma in this way is well recognised [6–8].

R. J. England (&) � A. Numanoglu � A. J. W. Millar

Department of Paediatric Surgery, Red Cross War Memorial

Children’s Hospital, University of Cape Town,

Klipfontein Road, Rondebosch, Cape Town 7700,

South Africa

e-mail: r.england@doctors.org.uk

K. Pillay

Division of Anatomical Pathology, Red Cross War Memorial

Children’s Hospital, University of Cape Town, Cape Town,

South Africa

A. Davidson

Department of Paediatrics and Child Health,

Haematology/Oncology Service, Red Cross War Memorial

Children’s Hospital, University of Cape Town, Cape Town,

South Africa

123

Pediatr Surg Int (2012) 28:267–270

DOI 10.1007/s00383-011-2982-5

In South Africa the diagnosis of intussusception is fre-

quently delayed and requires operative correction or

resection in 81% of the cases [9]. With the emphasis now

on limited surgery in Burkitt lymphoma, we sought to

determine the presentation of BL causing intussusception,

and the impact that resection had on outcome.

Materials and methods

We performed a retrospective case note review of all

patients with Burkitt lymphoma presenting with intussus-

ception. The cases were identified primarily from the

Oncology Registry held by the Paediatric Oncology Unit at

the Red Cross Children’s Hospital (RCCH). This holds

data from 1976 up to the present time. Since 2004, we were

also able to cross-check cases with the database of opera-

tive notes held by the Department of Paediatric Surgery

also at RCCH. The data for earlier cases of intussusception

were not retrievable. Files were scrutinised for demo-

graphic data in addition to presenting symptoms, investi-

gations, attempts at non-operative hydrostatic or pneumatic

reduction, surgical management and complications. Histo-

logical findings, chemotherapy regimens and outcome were

also recorded. Detailed information regarding the change in

chemotherapy protocols used during the period of this

study has previously been reported [5]. Statistical analysis

in this small group was not appropriate.

Results

Demographics and presentation

There were 210 cases of BL seen between 1976 and 2010.

Fourteen cases (6.7%) of intussusception were identified.

There were ten males and four females. The median age

was 6.1 years (range 2.3–10.9). No patient was HIV posi-

tive. Twelve patients presented with episodic or recurrent

colicky abdominal pain for a median of 4 weeks (range

3 days to 4 months). Two patients presented with a jaw

mass associated with endemic BL. One of these patients

was thought to have mumps, but represented with

abdominal pain 3 months later. She was found to have an

ileo-colic intussusception with tumour spread to the right

ovary. Another 5-year-old patient with Fetal Alcohol

Syndrome, had jaw swelling for 6 weeks, he also had a

palpable abdominal mass and bilateral testicular enlarge-

ment. Five of the 14 patients had palpable abdominal

masses on presentation. In two patients the significance of

the mass was overlooked due to its mobile nature, one was

treated for worm bolus and another was thought to be

constipated, but had treatment for Giardia following

endoscopic biopsy of the duodenum. Iron deficiency

anaemia was discovered after 4 months leading to an

ultrasound of the abdomen, although episodes of dark

blood in the stool had been noted earlier. At surgery an

irreducible but patent ileo-colic intussusception was

resected (Figs. 1, 2). Bloody stool with the appearance of

red currant jelly was also noted in one other patient who

suffered from colicky pain for 4 weeks.

Operative and histopathological findings

Eleven patients had an ileo-colic intussusception, one had

an ileo-ileal intussusception, which formed a matted mass

and two patients had compound invagination producing an

ileo-ileo-colic intussusception. Hydrostatic reduction using

barium was attempted in two cases (ages 2.6 and

5.6 years). One was reducible but a filling defect was

Fig. 1 Pathological specimen of irreducible ileo-colic intussuscep-

tion with a Burkitt lymphoma as a lead-point

Fig. 2 Pathological specimen with probe demonstrating incomplete

obstruction of ileo-caecal lumen (same patient as Fig. 1)

268 Pediatr Surg Int (2012) 28:267–270

123

noted, which led to operative resection. The other was only

partially reducible and so surgery was mandatory. Nine

patients had a right hemicolectomy and ileo-colic anasto-

mosis, including one patient who had an intussusception

reduced operatively, which then recurred 2 months later at

which point he underwent a right hemicolectomy. Five

patients underwent segmental ileal resections for lead

points. A compound ileo-ileo-colic intussusception was

partially reduced but the ileo-ileo component had to be

resected. Histology demonstrated tumour at the resection

margins in this case. No positive margins were seen in the

right hemicolectomy group. Two patients underwent sec-

ond look laparotomies as per protocol (1986–1987) where

no evidence of recurrence was noted. Microscopically, all

the cases had characteristic appearances on haematoxylin

and eosin sections, showing a proliferation of atypical

lymphoid cells with a ‘‘starry sky’’ appearance on low

power as a result of interspersed macrophages engulfing

apoptotic debris. Immunohistochemistry was available for

most cases, which for the specimen depicted in Fig. 1

demonstrated lymphoid cells positive for CD20, CD10 and

bcl6; negative for bcl2 and Tdt, and showed a proliferation

index of almost 100% on the Ki67 stain.

Further management

There were seven stage 2 patients; four stage 3 patients and

three stage 4 patients. All three stage 4 patients had marrow

involvement and two had CNS involvement; in all there

was delay in diagnosis or treatment. One was referred from

a neighbouring country, another was treated for mesenteric

adenitis for a month and the third case (described above)

had an operative reduction followed by recurrent intus-

susception and delayed resection.

All patients received chemotherapy. Prior to 1997,

patients received the COMP regimen (COMP arm of the

United Stated Children’s Cancer Group protocol CCG-

551), and three patients (all stage 2) since then were treated

with a more intensive regimen (French Paediatric Oncol-

ogy Society protocol LMB-89) [5]. All stage 4 patients

relapsed. One survived after extensive radiotherapy and

two succumbed, one opting for palliative care. Median

follow-up time is 6.07 years (range 0.1–28.8).

Discussion

The patients presenting with Burkitt lymphoma in the

Western Cape of South Africa generally have the sporadic

rather than the endemic form and, therefore, have a higher

incidence of abdominal disease at presentation [4, 5]. Of

those with abdominal disease, most have involvement of

the large or small bowel, although other organs including

liver, kidneys, uterus and gonads can occur. Even in those

with HIV infection this pattern of involvement is similar

although the response to treatment has been poor [4].

High-grade B-cell non-Hodgkins lymphoma has a fast

cell turnover leading to rapid growth of tumours and a

propensity to tumour necrosis [2, 5, 10]. These character-

istics increase the risk of an acute abdomen not only as an

initial presentation but also during the course of treatment.

However, they also mean that the tumour is highly

responsive to intensive chemotherapy, and this has led to a

change in the management of abdominal disease. Early

treatment tended to focus on surgical resection, and good

outcomes for localised completely resected disease could

be achieved. Second look surgery was routine to ensure

complete clearance. However, for advanced disease, sur-

gical resection was often incomplete and surgical compli-

cations were significant. Outcome was poor with survival

rates less than 40% [11]. Primary surgery is now limited to

diagnostic biopsy where this cannot be achieved by other

means, and management of the acute abdomen in the post

chemotherapy induction phase when bowel perforation

may occur with dissolution of the tumour [2, 3, 12]. In

some cases laparoscopic biopsy helps to reduce surgical

complications further [2, 5, 13].

Surgery is, however, still required when the diagnosis of

lymphoma is not suspected, but the patient presents with an

acute abdomen. Burkitt lymphoma has been diagnosed

following laparotomies for appendicitis, bowel perforation,

obstruction and haemorrhage [10–12]. In one series of 57

B-cell NHL patients with abdominal disease, 67% required

initial surgery, nearly half of these due to a surgical

emergency [2], the others required surgery for diagnostic

purposes or planned resection of small localised tumours.

Eleven of these emergent cases were for intussusception.

This association between lymphoma and intussusception

was highlighted by Wayne et al. [6] who noted six cases

aged between 6 and 9 years in a series of 378 intussus-

ceptions. All presented with colicky abdominal pain, a

feature noted in 12 of our patients. The nature of this pain

favours an obstructive lesion as opposed to an alternative

diagnosis such as appendicitis. A mass was noted in half of

the patients in their series and bloody stool in four patients.

These cardinal symptoms of intussusception were present

in a significant number of our patients, and yet the diag-

nosis was overlooked or presentation delayed. The lym-

phoma was second only to Meckel’s diverticulum as a

pathological lead point. There was debate in the discussion

section as to whether an intussusception with a tumour lead

point could ever be hydrostatically reduced and, therefore,

escape detection by laparotomy. We describe one case

where a hydrostatic barium enema was able to reduce the

intussusception, but the filling defect was clearly seen

leading to operative resection. Now that pneumatic

Pediatr Surg Int (2012) 28:267–270 269

123

reduction is favoured, due to the dangers of barium if

perforation occurs, it would be interesting to assess whe-

ther these tumours can still occasionally be reduced, and

subsequently noted on follow-up ultrasound or contrast

enema imaging.

The presentation of intussusception in South Africa has

been characterised, and is different to that seen in Europe

[9]. The patients were \2 years of age in 91% of cases.

Hence most patients present with idiopathic intussuscep-

tion. Lead points were found in 2.1% patients. No cases of

BL were diagnosed in participating centres during the

study period, although we record one case transferred for

chemotherapy from another centre, following a laparot-

omy. In addition, patients present late with a median delay

of 2.3 days due to social and transport difficulties. This

correlates with reduced success from non-operative

reduction, and an operative rate of 81% with many

requiring resection for necrotic bowel.

Delay in presentation or diagnosis was significant in this

series, and in three cases was associated with advanced

disease at final presentation. The older age distribution of

patients in our series compared with idiopathic intussus-

ception in South Africa probably explains, why the diag-

nosis of intussusception was not considered earlier. Also,

despite the rapid growth of Burkitt lymphoma, the median

duration of symptoms was 4 weeks. Figure 1 demonstrates

a pathological specimen of a girl who was misdiagnosed

for 4 months but never became completely obstructed

(Fig. 2). At surgery her intussusception was partially

reduced up to the ileo-caecal valve. The mass remained

mobile over this period, and as in one other case led to

diagnostic confusion. While ultrasound may not accurately

diagnose a lead point, the importance of this investigation

is the early diagnosis of intussusception in patients with

suggestive symptoms.

Surgical resection and anastomosis was performed in all

our cases successfully without complication. One case had

a positive margin following partial reduction of a com-

pound ileo-ileo-colic intussusception and segmental small

bowel resection only. In retrospect, it may have been

appropriate to perform a complete right hemicolectomy at

the initial laparotomy. However, she received 2 years of

COMP chemotherapy, and has been followed up for over

28 years with no recurrence. Stage three patients with

residual abdominal disease following resection of the

intussusception all responded well to chemotherapy. No

relapses have occurred in patients without bone marrow

involvement at diagnosis.

It appears that the prognosis of most cases of localised

Burkitt lymphoma presenting with intussusception is good,

despite delay in diagnosis, attributable to both the generally

poor social circumstances of the population and the growth

pattern of a distal ileal tumour. Adequate surgical resec-

tion, combined with modern regimens of intensive che-

motherapy, has reduced the complication rate and overall

morbidity of this disease. However, the diagnosis should be

made promptly, and intussusception should be considered

at all ages in children presenting with recurrent colicky

abdominal pain, especially if a mass is palpable or blood is

present in the stool. The presence of a pathological lead

point of an intussusception should be sought in patients

over 2 years of age even if pneumatic reduction has been

successful.

Acknowledgments The authors are grateful for the diligence of

their colleagues in the Department of Paediatric Oncology in main-

taining a long term registry that has made this study possible.

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