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ORIGINAL ARTICLE
Year : 2016  |  Volume : 53  |  Issue : 2  |  Page : 300-303
 

Primary gastrointestinal lymphomas in children: An experience of 12 years from a tertiary care center of North India


1 Department of Pathology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India
2 Department of Surgery, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India

Date of Web Publication6-Jan-2017

Correspondence Address:
S K Qadri
Department of Pathology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.197718

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 » Abstract 

Background and Aim: Lymphomas are among the dominant solid tumors in children and primary gastrointestinal lymphomas (PGILs), although rare, are the most common extranodal lymphomas and the most common malignancies affecting the gastrointestinal tract in children. This study was undertaken to analyze childhood PGIL with reference to clinical presentation, anatomic distribution, histopathologic, and immunohistochemical (IHC) characteristics. Materials and Methods: In this 12 year combined retrospective and prospective descriptive study, all the cases of PGIL in children were selected according to Dawson's criteria. Results: A total of 11 cases were found which included 9 boys and 2 girls (male:female - 4.5:1) ranging in age from 1 to 14 years (mean 6.6 years). Abdominal pain (81.8%) and intestinal obstruction (63.6%) were the most common presenting features. Grossly, most of the lesions were ulcero-infiltrative (72.7%) and involved the terminal part of the ileum (36.4%) and ileocecal region (27.3%) most commonly. Histopathologically and IHC, all the cases were high-grade lymphomas of diffuse large B-cell type except for one case of mucosa-associated lymphoid tissue lymphoma. No case of Burkitt's lymphoma was found. Conclusion: PGILs are an important cause of morbidity and mortality in children worldwide with considerable variation in their clinicopathological features and treatment modalities. Only some studies are available in literature for comparison. Further studies are required to define the genetic and molecular basis of the different histopathological pattern found in our setting.


Keywords: Children, gastrointestinal, North India, primary gastrointestinal lymphoma


How to cite this article:
Qadri S K, Shah A, Hamdani N H, Baba K M. Primary gastrointestinal lymphomas in children: An experience of 12 years from a tertiary care center of North India. Indian J Cancer 2016;53:300-3

How to cite this URL:
Qadri S K, Shah A, Hamdani N H, Baba K M. Primary gastrointestinal lymphomas in children: An experience of 12 years from a tertiary care center of North India. Indian J Cancer [serial online] 2016 [cited 2020 Apr 5];53:300-3. Available from: http://www.indianjcancer.com/text.asp?2016/53/2/300/197718



 » Introduction Top


Lymphomas are the malignant tumors of lymphoreticular system or their precursors and along with the central nervous system tumors and sarcomas, are the dominant solid tumors in children, constituting 10–12% of all childhood malignancies, about 7–10% of which are non-Hodgkin's lymphoma (NHL), and 4–7% are Hodgkin's lymphoma.[1],[2],[3] Although primary tumors of the gastrointestinal (GI) tract are rare in children, representing <5% of all pediatric neoplasms, primary GI lymphoma (PGIL) of non-Hodgkin's type remains the most common malignancy of GI tract in children.[4],[5],[6] However, PGILs are rare and far less frequent than secondary GI involvement of nodal lymphomas.[7],[8] nonetheless, they are important since their evaluation, diagnosis, management, and prognosis are distinct from that of lymphoma at other sites and other cancers of the GI tract.[9] There is a paucity of data on childhood PGIL from India.[10] Here, we present our experience of PGIL in children diagnosed over a period of 12 years in a tertiary care center of North India. To the best of our knowledge, this is the first study of childhood PGIL from North India.


 » Materials and Methods Top


This descriptive study extended from April 1998 to March 2010, with 8½ years retrospective and 3½ years prospective study periods. All the cases of primary extranodal lymphoma of GI tract in children diagnosed during this 12-year study period in our institution were collected and analyzed with reference to clinical presentation, anatomic distribution, histopathologic, and immunohistochemical (IHC) characteristics.

Inclusion criteria

All the cases were selected according to Dawson's criteria that include (1) absence of peripheral lymphadenopathy at the time of presentation, (2) lack of enlarged mediastinal lymph nodes, (3) normal total and differential white blood cell count, (4) predominance of bowel lesion at the time of laparotomy with only lymph nodes obviously affected in the immediate vicinity, and (5) no lymphomatous involvement of liver and spleen.[11]

Exclusion criteria

All those cases of GI lymphomas that were treated previously for nodal lymphomas or who had peripheral or mediastinal lymphadenopathy or lymphomatous involvement of liver or spleen at the time of presentation were excluded from the study.

The presenting symptoms and extent of disease in the selected patients were determined by analysis of medical records, history, physical examination, baseline investigations, bone marrow aspirations/biopsy, abdominal ultrasound, and/or contrast enhanced computed tomography scan of the abdomen. All pathologic specimens were reviewed and classified according to the World Health Organization (WHO) – Revised European-American Classification of Lymphoid Neoplasms classification. Slides were made from paraffin-embedded tissue blocks and stained with hematoxylin and eosin and reticulin stains. IHC stains for CD45, CD20, CD3, k and λ were performed. The St. Jude staging system for childhood NHL was adopted.[9]


 » Results Top


Eleven cases of childhood PGILs were identified that included nine boys and two girls (male:female ratio - 4.5:1), ranging in age from 1 to 14 years with 6.6 years as the mean age of presentation. The predominant presenting symptoms were abdominal pain (9/11, 81.8%) and vomiting (5/11, 45.4), and the most common clinical and surgical findings were intestinal obstruction (7/11, 63.6%) and pallor (5/11, 45.4%). The duration of illness ranged from 3 days to 5 months [Table 1].
Table 1: Presenting features of primary gastrointestinal lymphoma in children

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The lesions were located in distal part of ileum (4/11, 36.4%), ileocecal region (3/11, 27.3%), cecum (1/11, 9.1%), stomach (1/11, 9.1%), jejunum (1/11, 9.1%), and ascending colon (1/11, 9.1%). On gross examination, the majority of the lesions were ulcero-infiltrative (8/11, 72.7%) and ulcero-proliferative in morphology (3/11, 27.3%) and ranged in largest diameter from 2 to 8 cm. On histopathological examination, except for one case of mucosa-associated lymphoid tissue (MALT) lymphoma (9.1%), all the cases were diagnosed as diffuse large B-cell lymphoma (DLBCL), (90.9%) and comprised large pleomorphic cells with round to oval or irregular nuclei, partially condensed chromatin, and prominent nucleoli. None of the cases of Burkitt's lymphoma was found in our study. IHC, all the cases were positive for B-cell marker, CD20, and none showed positivity for T-cell marker, CD3 [Table 2].
Table 2: Age, sex, site, and histopathology of primary gastrointestinal lymphoma in children

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Surgical exploration was performed in all but one case (gastric lymphoma), in which the diagnosis was confirmed on endoscopic biopsy. According to the St. Jude staging system for childhood NHL, most of the children (7/11, 63.6%) presented in Stage II while others presented in Stage III (3/11, 27.3%) and Stage I (1/11, 9.1%). One patient with Stage I and four patients with Stage II disease were subjected to complete surgical resection followed by chemotherapy. In rest of the two patients with Stage II disease and all the three patients with Stage III disease, incomplete surgical resection could be accomplished which was followed by chemotherapy. One Stage II patient with gastric lymphoma received only chemotherapy. The postoperative period was uneventful in all cases, and there was no immediate postoperative mortality. However, two patients (one 4-year-old female child with cecal disease and another 7-year-old male child with jejunal lymphoma) with Stage III disease died at around 4 and 6 months after surgery, respectively. An 11-year-old child with ascending colon involvement relapsed twice in 2-year follow-up period when other two patients with Stage II disease and another patient with Stage I disease fared well. Remaining patients (five cases) were lost to follow-up.


 » Discussion Top


Although childhood cancers contribute a small fraction (about 2%) of the global cancer burden, yet they are the second most common cause of death after trauma in children aged 5–14 in populations where overall mortality is low and thus, a cause of deep distress for children with cancer and their families.[12],[13],[14] Lymphomas are one of the most common childhood malignancies worldwide with considerable variation.[15] Primary GI-NHL describes lymphoma that originates from the GI tract and represents a heterogeneous disease with regard to various characteristics such as stage, site of involvement, histological subtypes, and treatment offered.[8],[16]

The peak age for GI NHL in children is 5–15 years.[17] and there is male sex preponderance with a male to female ratio ranging from 7:1 to 1.8–2.5:1.[5],[18] In our study, most of the patients (six cases, 54.5%) presented below the age of 5-years, and it is reported that patients younger than 5 years at presentation have only marginally better outcome with a 5-year survival of 82.9% compared to 76.9.[18] The mean age of our patients was 6.6 years with a range 1–14 years and males outnumbering the females (male:female ratio - 4.5:1). A study from Egypt reported similar results with a mean age of 6.6 years, age range of 0.4–17 years, and a male to female ratio of 2.3:1.[18] Consistent results with an age range of 1–8 years were observed in an Indian study where only one case of female PGIL was found among a total of six patients.[10] In another study of 47 children with PGIL registered at the Lymph Node Registry in Kiel, a male to female ratio of 6.8:1 was noticed.[19]

The most common presenting symptom is reported to be an abdominal pain (81.4%), followed by abdominal swelling, vomiting, constipation, diarrhea, intestinal obstruction, malena and bleeding per rectum.[18] Intestinal obstruction was the most common mode of presentation in another study.[10] Our patients predominantly presented with abdominal pain (81.8%) and intestinal obstruction (63.6%).

Although lymphoma can involve any part of the GI tract, the most frequent site among adults is the stomach and small and large intestines in the pediatric age group.[20] The terminal part of the ileum or ileocecal region followed by colon were reported to be the most common sites of involvement in some studies [10],[18] while others found ileocecal region (n = 20) followed by small intestine (n = 17) and the large intestine (n = 7) as the most common sites involved.[19] A consistent pattern of gut involvement was noted in our study where terminal ileum (36.4%) was the most common site followed by ileocecal region (27.3%).

According to the WHO histological classification of NHL in children, B-cell immunophenotypes (Burkitt, Burkitt-like, large B-cell) most commonly predilect the abdomen as a primary site of presentation. Burkitt's NHL is by far, the most common subtype.[21] This fact matches with the results of the studies from Egypt [18],[22] and Kiel.[19] In contrast, all of our patients were diagnosed as DLBCL, except for one case of MALT lymphoma and on IHC, all of them expressed B-cell marker (CD20). DLBCL was also reported to be the most common histological type of primary pediatric GI lymphoma in other studies from Asia.[10],[14]

Childhood NHL is a highly aggressive disease which grows rapidly and disseminates early.[22] Nearly, 50% of children with GI NHL have tumor infiltrates confined to GI tract with possible regional lymph node involvement.[5] The majority of our children presented in Stage II (63.6%) and Stage III (27.2%) disease. This distribution is similar to that of most reported series where Stage II and III represent around 75% of cases with a significant survival advantage in Stage II compared to Stage III and IV.[10],[14],[18],[19],[22]

The optimal management of primary GI NHL remains controversial. Surgery, radiotherapy, and chemotherapy have been used either alone or in combination.[23] Surgical resection is recommended for localized disease; however, several authors have argued for aggressive surgical debulking of all intestinal lymphomas, including those of Stage III and Stage IV.[24] Currently, several series have reported that surgery is not indicated unless complications such as perforation, hemorrhage or obstruction occur, which cannot be managed conservatively; and primary chemotherapy or radiotherapy is recommended in case of localized or advanced disease.[23] Radical tumor resection followed by chemotherapy in early disease and limited or no resection followed by chemotherapy in advanced disease may be the justified approach. However, some studies have proposed the use of chemotherapy alone as an effective treatment option in PGIL in all stages.[10] In our study, except for one case of gastric lymphoma which received chemotherapy alone, rest of all the ten patients (including seven patients of intestinal obstruction) was subjected to surgery which was followed by chemotherapy in five patients (two Stage II and three Stage III patients) in whom complete surgical resection could not be achieved grossly. Despite controversies regarding treatment, the extent or stage of disease at presentation remains the most important criterion determining survival.[19],[22],[24] Similar results were noticed in our study where patients with earlier stages (Stage I and II) fared well compared to Stage III patients. However, one of them had a low-grade lymphoma which may have an effect on survival.


 » Conclusion Top


Lymphomas are among the dominant solid tumors in children and are the most common childhood GI malignancies. PGIL in children is important not only because of being distinct from adult PGIL but also because of being distinct in their evaluation, diagnosis, management, and prognosis from that of lymphoma at other sites and other cancers of the GI tract.

Because of the rarity of PGIL in children, not many studies are available in literature for comparison. Nonetheless, our study presented comparable results with regards to their clinical presentation and anatomical distribution. In our study, terminal part of ileum or ileocecal region was the most common site of involvement, and children most commonly presented with features of acute abdomen in the form of intestinal obstruction. Like few other Asian studies,[10],[14] a higher prevalence of DLBCL was noted in our study; however, none of the cases of Burkitt's lymphoma was found which is contrary to the results of most other studies done worldwide [18],[19],[22] where latter is the most common type of PGIL in children. In this regard, further studies are required to define the genetic and molecular basis for this different histopathological pattern.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 » References Top

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