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March 2000, Volume 50, Issue 3

Original Article

Childhood Non-Hodgkin’s Lymphoma: An Immunophenotypic Analysis

Sajid Hussain Shah  ( Department of Pathology, The Aga Khan University Hospital, Karachi. )
Suhail Muzaffar  ( Department of Pathology, The Aga Khan University Hospital, Karachi. )
Shahid Pervez  ( Department of Pathology, The Aga Khan University Hospital, Karachi. )
Sheema H.Hassan  ( Department of Pathology, The Aga Khan University Hospital, Karachi. )

Abstract

Objective: To observe the frequency of histological subtypes of childhood non-Hodgkin`s lymphoma and its immunohistochemical profile.
Setting: All cases of non-Hodgkin’s lymphoma diagnosed in children (<15 years) in the section of histopithology at the Aga Khan University Hospital Karachi during the period of three years.
Methods: These consecutive cases were evaluated on H&E stained sections and then immunohistochemistry analysis of these tumors was performed by employing Peroxidase Anti-Peroxidase (PAP) technique.
Results: The present series included 61 cases of non-Hodgkin’s lymphoma. NHL was more common in males as compared to females with male to female ratio of 5.8:1. High grade NHL comprised 87% of childhood lymphoma. The mode of presentation in majority of NHL (57%) was extranodal. Burkitt’s lymphonia (33%) was the most prevalent histological subtypes, followed by lymphoblastic (28%), diffuse large cell (15%), diffuse mix small and large cell (13%), small non cleaved Non-Burkitts (7%) and immunoblastic (4%). Immunophenotypic analysis of the childhood Non-Hodgkin’s lymphoma revealed that 67% of the Non-Hodgkin’s Iy mphoma are cell type while 33% are those of T-cell lineage.
Conclusion: NHL was more common in males. Majority of NHL in children were high grade tumors. Burkitt’s lymphoma was the most frequent histological subtype. T-cell NUL comprised a significant portion of childhood lymphomas (JPMA 50:89,2000).

Introduction

Non-Hodgkin’s lymphoma (NHL) is one of the most common group of malignant solid tumors encountered in children1-7. NHL is an extremely heterogeneous group of malignant tumors, which exhibit variability in histological features, growth pattern, antigenic phenotype and biological behavior.
Marked geographic and ethnic variation has been observed in the frequency and distribution of histologic subtypes of Non-Hodgkin’s lymphoma all over the world8. Non-Hodgkin’s lymphoma is more prevalent in African countries like Nigeria and Uganda as compared to USA, UK and Japan7,8.
The childhood non-Hodgkin’s lymphomas are more common in boys than in girls8. In children, high grade lymphomas are more frequently encountered and this category includes small non cleaved cell (Burkitt’s and Non-Burkitt’s) lymphorna, lymphoblastic lymphoma, large cell and immunoblastic lymphoma9. NHL is more frequently extranodal in the younger age group while in adults it is more commonly nodal in origin8,10.
Immunohistochemical analysis is not only helpful in the diagnosis of lymphoma but phenotyping has got prognostic significance as well. In Revised European American classification of Lymphoid neoplasm (REAL). the immunophenotyping of the neoplastic lymphoid cells is considered necessary for the characterization and grading of the lymphoma”.
Sometime, childhood NHL poses a formidable diagnostic challenge due to the close morphological resemblance to the other sm all round cell tumors. It becomes very important to difThrentiate between these tumors because most childhood, NHL tumors respond to the specific chemotherapeutic regimens. which have improved the survival rates in these cases12.
The objective of this study was to observe the frequency of histological subtypes of Non-Hodgkin’s lymphoma in childhood and its immunoh istochem ical profile.

Materials and Methods

This study included sixty one consecutive cases of non-Hodgkin’s Iymphoma which were diagnosed in children (<15 years) in the section of histopathology at the Aga Khan University Hospital Karachi during the period of three years (1995-97). International working formulation was used for the classification of these tumors. Initially these tumors were evaluated on H&E stained sections and then lmmunohistochemical analysis was perform ed by employing Peroxidase Anti-Peroxidase (PAP) technique. The antibodies used in immunoh istochem ical staining included Leukocyte Common Antigen (LCA), PAN B (CD20. L26). PAN T (UCHL 1). granulocyte associated antigen ((iAA Leu Ml). Ki-l (CD 30), Desmin. Vimentin. Neuron specific enolase (NSE) and Cytokeratins depending upon the nature of lesion. Special stains such as reticulin, periodic acid schiff(PAS) and periodic acid schiff with diastase (PASD) were performed whenever required. Relevant, clinical details like age. sex and site of lesion were also recorded.

Results

A total of 366 cases of malignant tumors were diagnosed in children which included 61(16.7%) cases of Non-Hodgkin’s lymphoma (NHL) and 40 (10.9%) cases of Hodgkin’s disease. The age ranged from 7 months to 14 years with mean and median of 8.7 years and 9 years respectively. NI-IL was more common in males as compared to females with male to female ratio of 5.8: I. High grade NHL comprised 87% of childhood lymphoma followed by intermediate grade (13%). In most of the cases of NHL (57%), the mode of presentation was extranodal. Amongst the extranodal sites, gut was the most frequent site for these malignant tumors. Burkitt’s lymphonia (33%) was the most common histological subtype, followed by lymphoblastic (28%). diffuse large cell (15%) and diffuse mix small and large cell (13%). Less frequent histological types included small non-cleaved Non-Burkitt’s (7%) and immunoblastic (4%). The results are summarized in Table.

Burkitt’s lymphomas were mostly extranodal (abdominal) while lymphoblastic was nodal in origin.
I mmunophenotypic analysis of the childhood Non-Hodgkin’s lymphoma revealed that 67% of the Non-Hodgkin\\\'s lvmphomas were B-cell type while 33% were those ofT-cell lineage.

Discussion

Considerable variation in the prevalence ofNHL has been observed alongwith distribution of its histological types and immunophenotyic pattern in the different regions of the world8,13,14. In equatorial Africa, Burkitt’s lymphoma comprised about half of all tumors in children8.
Lymphornas was the most common solid tumour in children in the present study. Higher prevalence of lymphoma in children has been reported in different series from various centres of Pakistan15-17.
According to the Western literature, Non-Hodgkin’s lymphoma is more prevalent than Hodgkin’s disease and it Non-Hodgkin’s lymphonias (90%) in children are those of high grade18. Similar findings were observed comprises 60% of all childhood !ymphomas7. Majority of in the present study. In our series, Non-Hodgkin’s lymphoma constituted 56.1% of childhood lyrnphoma. Majority of the cases of NHL (87%) were those of high grade. Non-Hodgkin’s lymphoma and Hodgkin’s disease were more frequent in males as compared to females. Similar observation was reported in other series8,16,17,19.
In the present series, Burkitt’s lymphoma was the most frequent histological subtype (33%) of Non-Hodgkin’s lymphoma, which correlates well with the figure of 34% reported in the Western series18. A relatively high frequency of Burkitt’s lymphoma (43%) has been reported in a series from Armed Forces Institute of Pathology (AFIP) Rawalpindi20. In the present series, Burkitt’s lymphomas were predominantly presented in extranodal location and in 46% cases the mode of presentation was abdominal mass. A similar observation was made in a series from AFIP, Rawalpindi21.
Sporadic cases of Burkitt’s lymphorna usually involve the abdominal legion while endemic cases predominantly arise in the jaw8. Lyinphoblastic lymphoma comprised 28% of all NHL. In the other series, lymphoblastic lymphoma constituted 29-33% of all cases of NHL18-20, Diffuse large cell lymphoma constituted 1 5% of all NHL, which compares well with the figure of 16.6% from AFIP, Rawalpindi20. But it was significantly low from the figure of 27% reported in the Western literature18.
In the present series, the extra-nodal NHL comprised 57% of all cases which is quite high as compared to the figure of 36% from AFIP, Rawalpindi20. It might be because of the geographical variation as our department receives biopsy material mainly from the Southern part of the country while AFIP, Rawalpindi covers most of the Northern part of the Pakistan.
Immunohistochemical analysis of NHL revealed that 67% of NHL were of B-cell phenotype while 33% were of T-Cell lineage.
T-Cell lymphoma exhibit significant clinical and prognostic differences from B-cell lym phoma’ T-cel l immunophenotype in diffuse large cell sub-group is associated with poor prognosis22. The application of immunohistochemical technique has gained paramount importance for the diagnosis and evaluation of the prognosis of non-Hodgkin’s lymphoma.

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