Non-hodgkin's Lymphoma

Bharat R Agarwal
Pediatric Hematologist-Oncologist, Division of Pediatric Hem-Onco, B.J. Wadia Hospital for Children, Mumbai, India
First Created: 01/04/2001 

Introduction

Non-Hodgkin's Lymphoma (NHL) results from the malignant proliferation of cells of lymphocytic lineage. Although malignant lymphomas are generally restricted to lymphoid tissue such as lymph nodes and spleen, it is not uncommon to find bone marrow involvement in children.

Incidence And Epidemiology

Incidence

  • NHL accounts for 5-7% of malignant diseases in childhood (Europe, United States). It is the third most common childhood malignancy
  • The incidence of NHL is higher in the Middle East, Nigeria, and Uganda (15 of 100,000 children under 5-10 years of age).
  • NHL accounts for 60% of all childhood lymphomas
  • Isolated cases of familial NHL have been known to occur.

Epidemiology

Sex: M:F= 2.5:1

Age: Peak age 5-15 years

Risk factors

Genetic: Immunological defects (Bruton's type of sex-linked agammaglobulinemia, common variable agammaglobulinemia, ataxia telangiectasia, Wiskott-Aldrich syndrome, severe combined immune deficiency)

Post-transplant immunosuppression: Post-bone marrow transplantation (especially with use of T-cell depleted marrow); post-liver or post-heart transplantation.

Drugs: Diphenylhydantoin

Radiation: Children treated with chemo-radiotherapy for Hodgkin's disease

Virus: Epstein-Barr virus (EBV), human immune deficiency virus (HIV)

Pathologic Classification

Table 1 presents the Revised European - American Lymphoma (REAL) classification from the International Lymphoma Study Group. This classification for NHL is based on the currently recognized histologic (morphologic), immunologic, and genetic features; their clinical presentation, and course. Currently, the REAL classification is the preferred classification for NHL.

Table 1: Revised European-American Lymphoma Classification from the International Lymphoma Study Group

B-cell neoplasms

Precursor B-cell neoplasms

Precursor B-lymphoblastic leukemia/lymphoma

Peripheral B-cell neoplasms

  • B-cell CLL/PLL/SLL

  • Lymphoplasmacytoid lymphoma/immunocytoma

  • Mantle cell lymphoma

Follicle center lymphoma, follicular

  • Provisional cytologic grades: I (small), II (mixed), III (large)

  • Provisional subtype: diffuse, predominantly small cell

Marginal zone B-cell lymphoma

  • Extranodal (MALT ± monocytoid B cells)

  • Provisional category: nodal (± monocytoid B cells)

  • Provisional entity: splenic marginal zone lymphoma

Hairy cell leukemia

Plasmacytoma/myeloma

Diffuse large B-cell lymphoma

Burkitt's lymphoma

  • Provisional entity: high-grade B-cell lymphoma, Burkitt-type

T-cell and putative natural killer (NK) cell neoplasms

Precursor T-cell neoplasms

Precursor T-lymphoblastic lymphoma/leukemia

Peripheral T-cell and NK cell neoplasms

  • T-cell CLL/PLL
  • Large granular lymphocyte leukemia
  • Mycosis fungoides/Sezary syndrome
  • Peripheral T-cell lymphomas, unspecified

Provisional categories: medium, mixed, large, lymphoepitheloid

Provisional subtypes:

  • Hepatosplenic T-cell lymphoma

Subcutaneous panniculitic T-cell lymphoma

  • Adult T-cell lymphoma/leukemia
  • Angioimmunoblastic T-cell lymphoma
  • Angiocentric lymphoma
  • Intestinal T-cell lymphoma (± enteropathy)
  • Anaplastic large cell lymphoma (T/null)

  • Provisional ALCL Hodgkin's-like

Note: CLL, chronic lymphocytic leukemia; PLL prolymphocytic leukemia; SLL, small lymphocytic lymphoma, MALT,mucosal-associated lymphoid tissue lymphoma; ALCL, anaplastic large cell lymphoma

From Harris NL, Jaffe ES, Stein H, Banks PM, Chan JKS, Cleary ML, Delsol G et al. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group, Blood 1994, 84: 1361-92.

Fifty percent of NHL in children are small noncleaved, 30% lymphoblastic, and 20% large cell types.

Presentation

The presenting symptoms of NHL depend mainly on the location of the tumor. It may present in a variety of ways, occasionally providing a major diagnostic dilemma because of the protean manifestations of its presentation.

Burkitt's lymphoma may be of the endemic or sporadic variety. Table 2 lists the epidemiologic, immunologic, and molecular features of these two varieties.

Table 2 Epidemiologic, Immunologic, and Molecular Features of Endemic and Sporadic Burkitt's Lymphoma


Features
Endemic
Sporadic
Epidemiologic
Population affected
African
Worldwide
Age affected
Children(peak age, 7 years)
Young adults (peak age, 11 years)
Organ involvement
Jaw, paraspinal, ovary
Marrow, abdomen, nasopharynx, ovary
Epstein-Barr virus
Present in more than 97% of cases
Present in less than 30% of cases
CNS involvement
More frequent than bone marrow involvement
As frequent as bone marrow involvement
Immunologic IgM secretion

Little or none

Prominent
Fc and C3
+
-
CALLA
+
-
IgH gene rearrangement
DH or JH
IgH switch region
Molecular Breakpoints on chromosome 8

Upstream of C-myc

Within C-myc
Site of cell origin
Germinal center of lymph node
Bone marrow

The frequency of involvement, according to primary sites and tumor distribution of NHL at the time of diagnosis, is as follows.

Abdomen:

The primary site in 35% of cases is abdominal - the ileocecal region, appendix, ascending colon, or some combination of these sites. These patients usually present with:

  • Abdominal pain
  • Vomiting and diarrhea
  • Abdominal distension
  • Palpable mass
  • Intussusception
  • Peritonitis
  • Ascites
  • Acute gastrointestinal (GI) bleeding
  • Obstructive jaundice
  • Hepatosplenomegaly

Bleeding and perforation of the intestine occur infrequently in patients with Burkitt's lymphoma. Lymphoma is the most frequent anatomic lesion causing intussusception in children over 6 years of age. When this disease presents insidiously, it may clinically and radiologically resemble Crohn's disease.

Head and Neck:

In 13% of cases, the head and neck are involved, causing enlargement of the cervical node(s) and parotid gland, jaw swelling, and unilateral tonsillar hypertrophy. The disease may present with nasal obstruction, rhinorrhea, hypoacousia, and cranial nerve palsies.

Mediastinum

The frequency of involvement of the mediastinum is 26%. A large anterior mediastinal mass may produce superior vena cava syndrome (distended neck veins, edema of the neck and face, marked dyspnea, orthopnea, dizziness, headache, dysphagia, epistaxis, altered mental status, and syncope associated with bending). In this condition, a large anterior mediastinal mass compresses the superior vena cava (SVC) because of the thinness of its wall and its close apposition to the vertebral column. The rapid growth of the mass does not permit enough time to develop effective collateral circulation to compensate and results in signs and symptoms of SVC compression.

Tumors of the mediastinum have a marked tendency to involve the bone marrow, transform to acute lymphoblastic leukemia, and develop meningeal and gonadal involvement. Many of these tumors is composed of cells of T-lymphocytes lineage. Pleural effusion may be produced by direct pleural involvement and/or may result from the compression of lymphatics by the mediastinal mass. The presence of pericardial effusion may cause cardiac tamponade.

Other Primary Sites

Other sites involved (11%) include skin and subcutaneous tissue, orbit, thyroid, bone (with or without hypercalcemia), kidney, epidural space, breast, and gonads. The peripheral nodes are affected in 14% of cases.


Non-hodgkin's Lymphoma Non-hodgkin's Lymphoma Non-hodgkin's Lymphoma 01/04/2001
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