Non Hodgkin Lymphoma
Non Hodgkin Lymphoma: Excerpt from The 5-Minute Pediatric Consult
Anne F. Reilly, MD, MPH
Non Hodgkin Lymphoma - BASICS
Non Hodgkin Lymphoma - description
- Non-Hodgkin lymphoma (NHL) is a malignant proliferation of cells of lymphocytic or histiocytic lineage that spread in a pattern similar to the migration of normal lymphoid cells.
- No uniform staging system exists for childhood NHL. The St. Jude Children’s Research Hospital staging system is as follows:
- Stage I: Single tumor (extranodal) or single nodal area, excluding mediastinum or abdomen
- Stage II: Single tumor with regional nodal involvement, 2 or more tumors or nodal areas on one side of the diaphragm, or a primary GI tract tumor (resected) with or without regional node involvement
- Stage III: Tumors or lymph node areas on both sides of the diaphragm, any primary intrathoracic or extensive intra-abdominal disease (unresectable), or any primary paraspinal or epidural tumors
- Stage IV: Bone marrow or CNS disease regardless of other sites; marrow involvement defined as 0.5–25% of malignant cells
Non Hodgkin Lymphoma - epidemiology
- 3rd most common childhood malignancy (~12% cancers in individuals <20 years of age in developed countries)
- Male/Female ratio: 3:1
Non Hodgkin Lymphoma - incidence
1–1.5 per 100,000:
- Higher frequency of endemic Burkitt-type in equatorial African countries (10–15 per 100,000 children younger than age 5–10)
- Incidence increases steadily with age; in children, usually seen in 1st 2 decades of life (unusual in those <3 years of age)
Non Hodgkin Lymphoma - risk-factors
Environmental factors:
- Drugs: Immunosuppressive therapy and diphenylhydantoin
- Radiation: Atomic-bomb survivors and ionizing radiation
- Viruses: Epstein-Barr virus (EBV), human immunodeficiency virus (HIV); EBV present in >95% of cases of endemic Burkitt versus <20% cases of sporadic
Non Hodgkin Lymphoma - genetics
Genetic predisposition: Increased risk in patients with immunologic defects (e.g., Bruton agammaglobulinemia, ataxia–telangiectasia, Wiskott-Aldrich, severe combined immunodeficiency)
Non Hodgkin Lymphoma - pathophysiology
In contrast to adult lymphomas, childhood NHL is almost never nodular alone and rarely occurs in peripheral nodal areas.
Pediatric NHL can be divided into 3 major categories according to the National Cancer Institute (NCI) formulation:
- Small noncleaved-cell lymphomas (B cell):
- 40% of childhood NHL
- Subdivided into Burkitt and non-Burkitt based on the degree of pleomorphism
- A variety of B-cell markers is usually present (e.g., CALLA, CD20).
- Expresses surface immunoglobulins (Ig), most bearing IgM of either κ or λ light-chain subtype
- Terminal deoxyribonucleotidyl transferase (TdT) is negative.
- Characteristic chromosomal translocation, usually t(8;14), rarely t(8;22) or t(2;8); all translocations involve the c-myc proto-oncogene.
- Lymphoblastic lymphomas:
- Comprise 30% of childhood NHL
- In children, 90% T-cell and 10% B-cell origin
- Predominantly of thymocyte (T-cell) origin: Morphologically identical to acute leukemia T lymphoblasts. Bone marrow involvement of >25% blasts is considered leukemia.
- T-cell lymphomas are positive for TdT and have a T-cell immunophenotype (e.g., CD7).
- Most lack chromosomal translocations and seldom involve T-cell receptor genes on chromosomes 7 and 14q.
- Large-cell lymphomas:
- 30% of childhood NHL
- 2/3 are a large noncleaved or cleaved type of B-cell origin; these can be diffuse large B-cell lymphoma (DLBCL) or mediastinal large cell lymphoma (LCLM).
- 1/3 are anaplastic large cell lymphoma (ALCL) and are positive for CD30 (Ki-1).
- ALK (anaplastic lymphoma kinase) positivity seen in systemic ALCL disease; ALK negative more often localized/cutaneous ALCL. ALK negative is rare in children.
Non Hodgkin Lymphoma - etiology
Unknown
Non Hodgkin Lymphoma - DIAGNOSIS
A diagnosis needs to be made expeditiously, as pediatric lymphomas generally have a rapid growth rate.
Non Hodgkin Lymphoma - signs & symptoms
- B-cell lymphomas:
- Systemic manifestation (e.g., fever, weight loss, anorexia, fatigue) if disseminated; less likely if tumor localized
- Lump in neck unresponsive to antibiotics
- Abdominal mass with pain, swelling, change in bowel habits, nausea, or vomiting
- T-cell lymphomas:
- Mediastinal tumor symptoms include cough, hoarseness, dyspnea, orthopnea and chest pain, anxiety, confusion, lethargy, headache, distorted vision, syncope, and a sense of fullness in the ears.
- Marrow involvement: Bleeding and/or bruising, bone pain, pallor, fatigue
Non Hodgkin Lymphoma - physical exam
- Small noncleaved-cell lymphomas:
- Intra-abdominal mass (up to 90%):
- Involving ileocecal region, appendix, ascending colon, or a combination
- Lymphadenopathy may be present in inguinal or iliac region.
- Hepatosplenomegaly may be present.
- Acute abdomen with intussusception, peritonitis, ascites, and acute GI bleeding
- Lymphoma is the most frequent cause of intussusception in children >6 years.
- In endemic Burkitt lymphoma, jaw tumors are the most frequent; orbital involvement in infants; abdominal masses in 50%
- Other sites: Testis, unilateral tonsil hypertrophy, peripheral lymph nodes, parotid gland, skin, bone, CNS, and marrow
- Lymphoblastic lymphoma:
- Mediastinal mass (50–70%), possibly pleural effusion present with decreased breath sounds, rales, and cough with or without superior vena cava (SVC) syndrome or superior mediastinum syndrome (SMS):
- Signs include swelling, plethora, and cyanosis of the face, neck, and upper extremities; diaphoresis; stridor; and wheezing.
- Lymphadenopathy (50–80%); primarily above diaphragm
- Abdominal involvement uncommon: Likely to involve only liver and spleen
- Cranial nerve involvement: Rarely
- Large-cell lymphomas:
- Sites: Mediastinum, bone, inguinal nodes, skin
- Bone marrow and CNS involvement: Rare at diagnosis
Non Hodgkin Lymphoma - tests
- Establish diagnosis with least invasive method.
- Bone marrow aspirate and biopsy may establish the diagnosis without further testing.
- Fluid from ascites in patients with abdominal disease or pleural fluid should be obtained for cytology, immunophenotyping, and cytogenetics.
- Take a biopsy of an enlarged lymph node.
Non Hodgkin Lymphoma - lab
- CBC
- Liver and renal function studies
- Serum lactate dehydrogenase (LDH) and uric acid levels
- Ascitic, CSF, or pleural fluid:
- Cytology
- Immunophenotyping
- Cytogenetics
Non Hodgkin Lymphoma - imaging
- Abdominal ultrasound
- Chest radiographs: Posteroanterior and lateral
- CT scan of chest, abdomen, and pelvis
- Gallium scan or PET scan
- Bone scan (optional or if gallium/PET scan suggests bone involvement)
- MRI (especially for bone involvement)
Non Hodgkin Lymphoma - diag-proced-surgery
- Adequate surgical biopsy
- Bone marrow aspiration and biopsy
- Lumbar puncture with CSF cytology
Non Hodgkin Lymphoma - differencial diagnosis
- Abdominal mass:
- Newborn: Hydronephrosis, renal cysts, Wilms tumor, or neuroblastoma
- Older children: Constipation, full bladder, hamartoma, hemangioma, cysts, leukemic or lymphomatous involvement of the liver and/or spleen, Wilms tumor, or neuroblastoma
- Mediastinal mass:
- Anterior: Masses of thymic origin, teratomas, angiomas, lipomas, or thyroid tumors
- Middle: Metastatic or infectious lesions involving the lymph nodes, pericardial or bronchogenic cysts, esophageal lesions, or hernias
- Posterior: Neurogenic tumors (e.g., neuroblastoma, ganglioneuroma, neurofibroma), enterogenous cysts, thoracic meningocele, or hernias
Non Hodgkin Lymphoma - TREATMENT
Non Hodgkin Lymphoma - general measures
A multidisciplinary approach is imperative to ensure the best therapy.
- Prechemotherapy management:
- Allopurinol, hydration, and urinary alkalinization to promote uric acid excretion; rasburicase can be used for uric acid levels >8 mg/dL.
- Vigorous hydration with maintenance of brisk urine flow to prevent tumor lysis syndrome
- Monitor uric acid, BUN, calcium, creatinine, potassium, and phosphate levels closely.
- Management of relapse:
- Relapse indicates extremely poor prognosis.
- No uniform approach to rescue therapy; different chemotherapy combinations may induce a new response.
- For patients with chemosensitive relapse, salvage therapy followed by high-dose therapy with stem cell support is recommended, because this may result in prolonged survival.
Non Hodgkin Lymphoma - special-therapy
Non Hodgkin Lymphoma - radiotherapy
- Adds no therapeutic benefit in children with limited disease
- Used occasionally as emergent treatment for SVC obstruction or CNS or testicular involvement
- Cranial radiotherapy given for CNS-positive children with lymphoblastic lymphoma
- Increases short- and long-term toxicity
Non Hodgkin Lymphoma - medication
- Chemotherapy:
- Histology and stage determine choice of a particular protocol.
- Because of a high conversion rate of lymphomas to leukemias, prophylactic CNS treatment is given (except in patients with totally excised intra-abdominal tumor).
- Duration: 1–8 months; lymphoblastic lymphomas longer, up to 24 months
- Drugs: Cyclophosphamide, vincristine, methotrexate (IV and intrathecal [IT]), prednisone, daunorubicin, asparaginase, cytarabine, thioguanine, carmustine, hydroxyurea, hydrocortisone, doxorubicin, mercaptopurine, etoposide
- Common side effects: Hair loss, myelosuppression with transfusions required, nausea/vomiting
- Immunotherapy: Rituximab:
- A chimeric monoclonal antibody directed against the CD20 antigen, which is almost universally expressed on tumor cells in pediatric B-cell NHL
- A new active agent for patients with lymphoma
- Has been used successfully in patients with relapsed/refractory B-cell NHL
- Few overlapping side effects with the combination of rituximab and conventional chemotherapeutic agents
Non Hodgkin Lymphoma - surgery
- Performed if total resection can be achieved
- Additional indications: Intussusception, intestinal perforation, suspected appendicitis, or serious GI bleeding
- Avoid extensive surgery in patients with NHL.
Non Hodgkin Lymphoma - FOLLOW UP
- Patient monitoring weekly to monthly with CBC and physical examination
- Radiologic imaging at intervals during and off therapy
- Monitor for toxicity-related complications:
- Cardiac
- Gonadal function
- Second malignancies
Non Hodgkin Lymphoma - prognosis
- Important prognostic factors for outcome include tumor burden at presentation.
- Favorable:
- Stages II and I with primary site head and neck (nonparameningeal), peripheral nodes, or abdomen (≥80% 2-year survival)
- Unfavorable:
- Stage III or IV
- Parameningeal stage II
- Stage IV with CNS involvement (worst)
- Incomplete initial remission within 2 months (50–80% 2-year survival)
Non Hodgkin Lymphoma - complications
- Tumor lysis syndrome:
- Combination of hyperuricemia, hyperkalemia, and hyperphosphatemia with hypocalcemia, resulting in uric acid nephropathy that leads to renal failure
- Correct before starting chemotherapy.
- GI obstruction, perforation, bleeding, intussusception
- Inferior vena cava obstruction and venous thromboembolism
- Neurologic (e.g., paraplegia, increased intracranial pressure)
- SVC syndrome and SMS: Associated with lymphoblastic lymphomas that invade the thymus and nodes surrounding the vena cava and airways
- Massive pleural effusion
- Cardiac tamponade or arrhythmia
Non Hodgkin Lymphoma - patient-monitoring
Late effects from therapy:
- Cardiomyopathy from anthracyclines
- Impaired reproductive function or infertility from alkylating agents or radiation
- Second malignant neoplasms from etoposide and alkylators
- Psychologic consequences of severe illness
Non Hodgkin Lymphoma - bibliography
- Coiffier B, Haioun C, Ketterer N, et al. Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: A multicenter phase II study. Blood. 1998;92:1927–1932.
- Kjeldsberg CR, Meadows A, Siegel S, et al. Children’s Cancer Group Study CCG-E08. Chromosome abnormalities may correlate with prognosis in Burkitt/Burkitt-like lymphomas of children and adolescents: A report from Children’s Cancer Group Study CCG-E08. J Pediatr Hematol Oncol. 2004;26:169–178.
- Magrath I. Lymphocyte differentiation pathways: An essential basis for the comprehension of lymphoid neoplasia. J Natl Cancer Inst. 1981;67:501.
- Murphy SB, Fairclough DL, Hutchison RE, et al. Non-Hodgkin’s lymphomas of childhood: An analysis of the histology, staging and response to treatment of 338 cases at a single institution. J Clin Oncol. 1989;7:186–193.
- Pinkerton CR. Continuing challenges in childhood non-Hodgkin’s lymphoma. Br J Haematol. 2005;130:480–488.
Rheingold SR, Lange BJ. Oncologic emergencies. In: Pizzo PA, Poplack DG, eds. Principles and Practice of Pediatric Oncology. 4th ed. Philadelphia: JB Lippincott; 2002:1177–1203.Shad A, Magrath I. Diagnosis and treatment of non-Hodgkin’s lymphoma in childhood. In: Wernik P, Canellos G, Putcher J, eds. Neoplastic Diseases of the Blood. 3rd ed. New York: Churchill Livingstone; 1996:925.
Non Hodgkin Lymphoma - CODES
Non Hodgkin Lymphoma - icd9
200 Non-Hodgkin lymphoma
Non Hodgkin Lymphoma - FAQ
- Q: Did I do something to cause this?
- A: No. Most cases are sporadic and not associated with diet, underlying immune dysfunction, or viral illness.
- Q: When will my child be “cured”?
- A: For patients with small- or large-cell lymphomas, relapse most commonly occurs in the 1st 10 months. Therefore, a child may be considered cured if he or she remains in remission after the 1st year off therapy. A patient with lymphoblastic lymphoma is considered cured if he or she remains in remission after ~3 years from onset of therapy.
- Q: Is this contagious?
- A: No. Siblings may have slightly higher inherent risk than the general population, but they are not at risk from the affected child.
>>>
Book Source Details
- Book Title: The 5-Minute Pediatric Consult
- Author(s): M. William Schwartz MD; et al.
- Year of Publication: 2008
- Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.
More About Hodgkin's Disease
More Medical Textbooks Online about Hodgkin's Disease
Review other book chapters online related to Hodgkin's Disease:
Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.
|
|
More About This Book:
Title: The 5-Minute Pediatric Consult
Authors: M. William Schwartz MD; et al.
Publisher: Lippincott Williams & Wilkins
Copyright: 2008
ISBN: 0-7817-7577-9
|
|
» Next page: Surveys relating to Hodgkin's Disease
Rate This Website
What do you think about the features of this website?
Take our user survey and have your say:
Website User Survey
Medical Tools & Articles:
Next articles:
Tools & Services:
Medical Articles:
Forums & Message Boards
- Ask or answer a question at the Boards:
