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1. Lymphadenopathy; non-Hodgkin lymphoma; Hodgkin lymphoma; Langerhans cell histiocytosis; mast cell disorders; plasma cell dyscrasias (monoclonal gammopathies); spleen disorders. Prepared by Dr Irakli Glonti [email protected] 2024

2. Lymphoid tissue Two types of lymphoid tissue exist: Central (bone marrow and thymus) and Peripheral (blood, spleen,liver, lymph node, and mucosa-associated). Within central lymphoid tissue, cells arise and differentiate into mature lymphocytes; they then migrate into peripheral lymphoid tissues and circulate throughout the body

3. Lymphoma Lymphoma is the third most common cancer in children, with an annual incidence of 13-14 per million children. The two broad categories of lymphoma, Hodgkin disease and non-Hodgkin lymphoma (NHL), have such different clinical manifestations and treatments that they are considered separately.

4. Hodgkin Disease Epidemiology The role of Epstein-Barr virus (EBV) is supported by serologic studies and the frequent presence of EBV genome in biopsy material. Males predominate in patients younger than 10 yr of age at diagnosis, with roughly equal gender incidence in adolescence. Pre-existing immunodeficiency, either congenital or acquired, increases the risk of developing Hodgkin disease. A genetic predisposition or a common exposure to the same etiologic agent could account for an apparent increased risk in twins and first-degree relatives ranging from 3- to 7-fold.

5. Pathogenesis The Reed-Sternberg cell, a large cell (15-45 μm in diameter) with multiple or multilobulated nuclei, is considered the hallmark of Hodgkin disease There is now general agreement that the Reed-Sternberg cell arises from germinal center B-cells in most cases.

6. Pathognomonic

7. Reed Sternberg & CD20 (+)

8. Histologic subtypes lymphocyte predominant, nodular sclerosing mixed cellularity lymphocyte depleted. Most cases previously classified as lymphocyte depleted are now considered to represent high-grade non-Hodgkin lymphoma.

9. Clinical Manifestations Painless, firm, cervical, or supraclavicular lymphadenopathy is the most common presenting sign. Inguinal or axillary lymphadenopathy sites are uncommon areas of presentation. An anterior mediastinal mass is often present and can rapidly disappear with therapy Clinically detectable hepatosplenomegaly is rarely encountered. Depending on the extent and location of nodal and extranodal disease, patients might present with symptoms and signs of airway obstruction, pleural or pericardial effusion, hepatocellular dysfunction, or bone marrow infiltration (anemia, neutropenia, or thrombocytopenia). Nephrotic syndrome is a rare but recognized presenting manifestation of Hodgkin disease           

10. SYMPTOMS Systemic symptoms considered important in staging Unexplained fever Weight loss Drenching night sweats. Less common non-prognostic significance are pruritus, lethargy, anorexia, pain that worsens after ingestion of alcohol. Because of the impaired cellular immunity, concomitant tuberculous or fungal infections may complicate Hodgkin disease and predispose to complications during immunosuppressive therapy. In the pre-vaccine era varicella-zoster infections occurred at some time during the course of the disease in about 30% of cases.

11. Diagnosis Any patient with persistent, unexplained lymphadenopathy unassociated with an obvious underlying inflammatory or infectious process should have a chest radiograph to identify the presence of a mediastinal mass before undergoing node biopsy. Formal excisional biopsy is preferred over needle biopsy to ensure that adequate tissue is obtained, Hodgkin disease is rarely diagnosed with certainty on frozen section. Ideally, a portion of the biopsy specimen should be frozen and stored to allow for additional studies.

12. Classification Most cases of NHL in children are high-grade, diffuse neoplasms. Three histologic subtypes are recognized: lymphoblastic, usually of T-cell origin; small non-cleaved cell lymphoma (SNCCL), with Burkitt and non-Burkitt subtypes and of B-cell origin large cell lymphoma (LCL), with diffuse and anaplastic subtypes and of T-, B-, or indeterminate cell origin. The diagnosis and classification of childhood NHL requires considerable hematopathology expertise and adequate diagnostic tissue, both fresh and frozen.

13. Chromosomal Translocations Different chromosomal translocations are specific for some histologic subtypes and involve various proto-oncogenes, resulting in malignant transformation through a variety of mechanisms. In SNCCL (Burkitt type), one of three chromosomal translocations [t(8;14), t(8;22), t(2;8)] results in approximation of the MYC proto-oncogene on chromosome 8 to a regulatory region of one of the immunoglobulin chain genes, resulting in dysregulation of MYC ; In anaplastic LCL, fusion of the NPM gene on chromosome 5 with the ALK gene on chromosome 2 leads to formation of a chimeric protein that can influence cell growth and proliferation.

14. LABORATORY FINDINGS Pretreatment Studies for Staging Pediatric Non-Hodgkin Lymphoma Complete blood cell count Serum electrolytes, Uric acid, lactate dehydrogenase, creatinine, calcium, phosphorus Liver function tests Chest radiograph and chest CT if abnormal Abdominal and pelvic ultrasonography and/or CT Gallium scan and/or bone scan Bilateral bone marrow aspirate and biopsy Cerebrospinal fluid cytology

15. Laboratory findings Laboratory findings vary, depending on sites or organs involved. Elevated serum uric acid levels and other features of tumor lysis syndrome often complicate the presentation of SNCCL. Elevated serum level of lactate dehydrogenase is a measure of tumor burden and may occur with any NHL subtype. A normal CBC does not preclude marrow involvement. CT or MRI of the chest or abdomen or both provides key information on disease extent. Surgical staging is not necessary.

16. Symptoms of non-Hodgkin lymphoma needing urgent referral Lymphadenopathy (>1 cm persisting for 6 weeks) Hepatosplenomegaly Three or more of the following symptoms: Fatigue Night sweats Weight loss Itching Breathlessness Bruising Recurrent infection Bone pain