Keywords
Bowel lymphoma - Burkitt's lymphoma - childhood malignancies - non-Hodgkin's lymphoma
Introduction
The pediatric population constitutes 32.4% of the total population of India and malignancy
is an emerging major childhood killer.[1] Primary tumors of the gastrointestinal (GI) tract are rare in children and represent
<5% of all pediatric neoplasms.[2] The scarcity of the disease and variable clinical presentation preclude early diagnosis
when the likelihood of cure exists.
Among GI malignancies, non-Hodgkin's lymphoma (NHL), especially Burkitt's lymphoma
(BL) is the predominant variety.[3] In children, Paediatric gastrointestinal tract lymphoma (PGTLs) tend to occur in
the small and large intestines, as opposed to the stomach in adults.[3]
Although lymphoma is the most common pediatric GI malignancy, there are not many studies
available in the literature. The study documents the experience of pediatric bowel
lymphomas in a tertiary care institute.
Objective
-
To evaluate the clinical presentation of pediatric GI lymphoma
-
To determine the prognosis and prognostic factors of pediatric GI lymphoma.
Materials and Methods
It is a retrospective plus prospective study of GI lymphomas in pediatric age group
presented to Jawaharlal Institute of Postgraduate Medical Education and Research,
Pondicherry, over a period of 7 years (2010–2016). Patient demography, history, examination,
investigations, treatment, and follow-up were recorded.
Dawson et al.'s [4] criteria were used to differentiate primary from secondary bowel lymphoma. The tumor
was considered primary when there is no superficial adenopathy at diagnosis, no mediastinal
adenopathy at chest radiography, normal blood cell counts, no involvement of liver
and spleen, and involvement of only regional lymph nodes at laparotomy.
St Jude's Staging system [5] was used to stage the disease.
Investigations to complete the workup included ultrasonogram, computed tomography
[Figure 1], biopsy of mass, bone scan, and bone marrow biopsy.
Figure
LMB-96 chemotherapy protocol [Figure 2] was used for treating patients. Progressive disease patients received additional
rituximab, ifosfamide, carboplatin, etoposide regimen. Surgery was reserved for residual
tumor and complications of mass.
Figure
Numerical data were expressed in mean ± standard deviation and range. Fisher's exact
t-test was used to find a difference between two groups and Chi-square test was used
to find a difference between three or more groups. P < 0.05 was considered statistically
significant.
Results
A total of 21 patients were found during the study period. Mean age was 6.05 ± 3.34
years with 14 (66.67%) patients aged ≤5 years. The smallest patient was aged 3 years
while the eldest was 14 years. Males were more commonly affected (7:1). Pain abdomen
was the most common presentation (90.5%), followed by distension of abdomen (85.7%)
[Table 1].
Table 1
Clinical presentation of pediatric gastrointestinal lymphoma
|
Presentation
|
n (%)
|
|
Pain abdomen
|
19 (90.5)
|
|
Distension
|
18 (85.7)
|
|
Vomiting
|
11 (52.4)
|
|
Mass per abdomen
|
14 (66.7)
|
|
Intussusception
|
3 (14.3)
|
|
Blood in stools
|
2 (9.5)
|
|
Constipation
|
1 (4.7)
|
|
Intestinal obstruction
|
10 (47.6)
|
In the study, 7 (33.3%) patients presented with radiological intussusception while
2 (9.5%) had actual intussusception [Figure 3] whereas 4 (19%) patients had target sign on imaging suggestive of intussusception.
One (4.7%) patient had a history of surgery for intussusception.{Figure 3}
Figure
Most common site of involvement was terminal ileum (81%) [Table 2]. Thirteen (61.9%) patients had localized disease while 8 (38.1%) patients had diffuse
disease at presentation. Eight (38.1%) cases belonged to Stage II of St. Jude's system
of classification, 7 (33.3%) belonged to Stage III, and 6 (28.6%) belonged to Stage
IV. Eighteen (85.7%) patients had primary GI lymphoma whereas 3 (14.3%) had secondary
GI lymphoma.
Table 2
Site of involvement
|
Site of involvement
|
n (%)
|
|
DJ – Duodenojejunal
|
|
Terminal ileum
|
17 (81)
|
|
DJ junction
|
1 (4.7)
|
|
Jejunoileal
|
2 (9.5)
|
|
Ileocolic
|
5 (23.8)
|
Seven (33.3%) patients were managed with chemotherapy alone while 14 (66.7%) required
some surgical intervention at least. Surgical intervention included resection and
anastomosis (9 patients - 42.9%) [Figure 4], diversion (3 patients - 14.2%), laparotomy and biopsy (1 patient - 4.7%), and laparotomy
and reduction of intussusception (1 patient - 4.7%).
Figure
Histopathology [Figure 5] revealed 15 (71.4%) BL and 6 (28.6%) diffuse large B-cell lymphoma.
Figure
Thirteen (61.9%) patients completed chemotherapy and on follow-up ranging from 1 to
6 years with no evidence of recurrence. One patient is currently undergoing chemotherapy.
There were 8 mortalities (38.1%) in our study. All succumbed during chemotherapy;
6 patients due to progressive disease, one due to uncontrolled sepsis, and the other
due to a complication of central venous access.
Stage of the disease (P - 0.0068) and diffuse disease at presentation (P - 0.0176)
were found to be associated significantly with increased mortality whereas age, sex,
site of involvement, primary/secondary disease, surgical intervention, and histopathology
did not show statistically different outcome [Table 3].
Table 3
Prognostic factors of bowel lymphoma
|
Parameter
|
n
|
Death
|
Percentage
|
Fisher’s exact test (P)
|
|
DLBCL – Diffuse large B‑cell lymphoma; BL – Burkitt’s lymphoma
|
|
Age (years)
|
|
≤5
|
14
|
7
|
50
|
0.173581
|
|
>5
|
7
|
1
|
14.28
|
|
|
Male
|
18
|
8
|
44.44
|
0.257143
|
|
Female
|
3
|
0
|
0
|
|
|
Stage II
|
8
|
0
|
0
|
0.006841
|
|
Stage III and IV
|
13
|
8
|
61.54
|
|
|
Localized
|
13
|
2
|
15.38
|
0.017573
|
|
Diffuse
|
8
|
6
|
75.00
|
|
|
Primary
|
18
|
6
|
33.33
|
1.000000
|
|
Secondary
|
3
|
2
|
66.67
|
|
|
Small bowel
|
15
|
5
|
33.33
|
X2=1.7769
|
|
Large bowel
|
1
|
1
|
100.00
|
P=0.411288
|
|
Both
|
5
|
2
|
50.00
|
|
|
Resection and anastomosis
|
9
|
2
|
22.22
|
X2=3.5979
|
|
Diversion
|
3
|
1
|
33.33
|
P=0.308287
|
|
Biopsy
|
1
|
1
|
100.00
|
|
|
No surgery
|
7
|
4
|
57.14
|
|
|
BL
|
15
|
6
|
40.00
|
1.000000
|
|
DLBCL
|
6
|
2
|
33.33
|
Discussion
Pediatric gastrointestinal tract lymphoma (PGTL) is rare yet the most common bowel
malignancy in childhood.[6] It constituted only 54 (1.2%) of 4547 pediatric malignancy cases registered between
1952 and 1996.[7] The mean age of our study is similar to peak age for NHL of GI tract in children
mentioned in the literature, i.e., 5–15 years.[7] The male to female ratio of childhood GI NHL [2] is reported to be from 7:1 to 1.8:1 which is similar to our study.
Small and large intestines are the most commonly involved sites in pediatric age group
unlike adult patients in whom stomach is the most common site (50%–60%).[6] Most of the pediatric patients present with lymphoma involving distal small bowel
(50%–93%) but can occur anywhere in the GI tract.[8] Our study shows terminal ileum (81%) is the most common site of involvement.
The most common presenting symptom is reported to be abdominal pain, followed by mass
per abdomen [2] and our study follows this order. Nearly, half of children with GI NHL have tumor
infiltrates confined to GI tract with possible regional lymph node involvement.[2] Our study showed localized disease in 61.8% cases.
The ultimate treatment approach in GI lymphoma remains debatable. Recent studies have
proposed the use of chemotherapy alone as an effective treatment option in primary
GI lymphoma in all stages.[9] Surgery is reserved for complications such as obstruction, perforation, and bleeding.
Despite disagreements regarding treatment, the disease stage at presentation and extent
of involvement remain the most important criteria determining survival.[2],[6] Our study showed that advanced Stage (III and IV) at presentation and diffuse disease
at presentation carry increased mortality.
The overall 5- and 10-year survival rates of pediatric GI lymphoma cases treated with
combined surgery, chemotherapy, and radiation remain 52% and 44%, respectively.[8] Our study showed 61.9% patients are free of disease and on follow-up.
Differential diagnosis includes enteritis, inflammatory bowel disease, leiomyoma,
leiomyosarcoma, or gastrointestinal stromal tumor.
Our study has an interesting finding that lymphoma can either mimic or present with
intussusception. About 50% of the study group had radiological intussusception.
Conclusion
Bowel lymphoma in children preferentially involves ileum. Chemotherapy is the mainstay
of treatment in bowel lymphoma. Diffuse disease and advanced Stage (III and IV) at
presentation are poor prognostic factors, associated with high risk of mortality.
In children presenting with recurrent intussusception and beyond the typical age group
of idiopathic intussusception (3 years), lymphoma is to be ruled out.
