A 4-year-old boy was admitted to hospital after presenting with a 1-week history of an enlarging left-sided jaw mass as well as progressive swelling of the left eye for 3 days prior to presentation. He also had a reduced appetite.

Findings on examination :

The most obvious finding was a painless left-sided jaw mass, which displaced the left-sided molars as well as left-sided periorbital swelling and proptosis. There was also associated left cervical and submandibular lymphadenopathy. On further examination, the only other significant finding was hepatosplenomegaly (Fig. 15.3).

Herein listed are available results for this case scenario:

Abdominal ultrasound: multiple enlarged lymph nodes were seen throughout the abdomen; hepatosplenomegaly was noted; no other abnormal findings.

The NHLs constitute a mixed group of malignancies with a lymphoid clonality of either B- or T-cells in common. Childhood NHLs differ substantially from those seen in adults according to histology, aggressiveness, their primary extra-nodal localization as well as the fact that they often have medullary and central nervous system (CNS) involvement. Nowadays, more than 90 % of children with early stage disease can be cured by modern treatment protocols and good supportive care.

In the classification of lymphoma , those of B-cell origin are distinguished from those with a T-cell origin. Thus, the NHLs of B-cell origin are: BL and Burkitt-like lymphoma, diffuse large B-cell lymphoma and precursor B-cell lymphoblastic lymphoma, while the T-cell lymphomas are anaplastic large cell lymphomas (systemic and cutaneous) and precursor T-cell lymphoblastic lymphomas (Table 15.1). Other rare types include lymphoproliferative disease associated with immunodeficiency, pediatric follicular lymphoma, primary CNS lymphoma, and peripheral T-cell lymphoma.

Non-Hodgkin lymphoma is one of the most frequent childhood cancers (about 7 % of all childhood cancers). Factors influencing the incidence are age, gender, ethnicity, and histology. In most Western country registries, NHL is the third most common cancer, after acute leukemia and brain tumors. Children affected are mostly 3 years and older. NHL rarely occurs in infants and a male predominance is seen in most studies.

The geographical distribution of NHL is heterogeneous and reflects the impact of environmental factors. BL is particularly frequent in sub-Saharan Africa, where it is the common childhood cancer, is endemic to the region, and therefore termed “endemic Burkitt lymphoma .” In the rest of the world, the term “sporadic Burkitt lymphoma ” is used. HIV-associated BL occurs in patients with the HIV disease. Almost 85 % of endemic cases are associated with Ebstein Barr virus (EBV) infection, compared to 15 % of sporadic cases. The role of EBV in carcinogenesis, however, is not elucidated. Children with acquired or inherited immunodeficiency have an increased risk of developing NHL, usually of B-cell origin (Table 15.2).

The most common clinical presentation is that of lymphadenopathy and/or a painless abdominal mass (40 %) or mediastinal mass (30 %). This can cause symptoms caused by compression, particularly mediastinal compression. Symptoms and signs of bone marrow failure as a result of infiltration may be present. CNS complaints and signs may also occur, indicating advanced disease. The history of complaints is usually short, because of the highly aggressive nature of NHLs, especially BL, which has a doubling time of 18–24 h.

Because of the rapid rate of proliferation, if a NHL is suspected, the diagnosis should be made urgently in the fastest way possible. In areas where the Burkitt tumor is endemic, a clinical diagnosis may be made if there is no time for special investigations or where radiological/pathological investigations are not available.

Ideally, the diagnosis should be confirmed histologically. The exception is where BL is strongly suspected, and there is insufficient time to make a diagnosis or special investigations are not available. WHAT is extremely important is to confirm the diagnosis of NHL in the quickest, least invasive way, since the tumor is so aggressive and the patients may be gravely ill with TLS, renal failure, bowel perforation, superior vena cava syndrome, etc.

If a pathologist skilled in the interpretation of cytology is available, a fine needle aspiration may be performed for cytological interpretation as well as flow cytometry. Otherwise, an urgent biopsy may be performed, if the patient is stable enough to tolerate anesthesia. Alternatively , ascites fluid or a pleural effusion sample may be sent for cytology and flow cytometry.

The three most frequent histopathological types are BL (30 % of NHL) and Burkitt-like lymphoma (10–20 %), precursor T- or B-cell lymphoblastic lymphoma (20 %), and large cell anaplastic lymphoma (10 %). In Table 15.4 the immunohistochemistry of these types are compared.