Overview
Definition:
B-cell lymphomas in adolescents constitute a group of malignant neoplasms originating from B lymphocytes, characterized by uncontrolled proliferation and accumulation in lymphoid tissues and extranodal sites
This category includes subtypes like diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma, and lymphoblastic lymphoma (which can have B-cell lineage).
Epidemiology:
Lymphoma is among the most common pediatric cancers
B-cell lymphomas represent a significant proportion of these
Incidence varies with subtype, with Burkitt lymphoma being more common in equatorial regions and in association with Epstein-Barr virus (EBV)
DLBCL is less common than Hodgkin lymphoma but is the most frequent non-Hodgkin lymphoma in adolescents.
Clinical Significance:
Early recognition and accurate diagnosis are crucial for effective management and improved outcomes in adolescent B-cell lymphomas
The diverse clinical presentations and rapid progression of some subtypes necessitate a high index of suspicion and prompt investigation by healthcare professionals
Understanding imaging findings aids in staging and treatment planning.
Clinical Presentation
Symptoms:
Constitutional symptoms (B symptoms) are common: Fever (>38°C) without an identifiable source
Drenching night sweats
Unexplained weight loss (>10% of body weight in 6 months)
Localized lymphadenopathy, often painless and rapidly enlarging
Visible or palpable masses in the neck, axilla, or groin
Abdominal pain or distension, especially with intra-abdominal disease
Symptoms related to organ compression or infiltration: dyspnea, cough, dysphagia, bone pain, neurological deficits.
Signs:
Enlarged, firm, discrete, or matted lymph nodes
Hepatosplenomegaly
Palpable abdominal masses
Signs of bone marrow infiltration: pallor, petechiae, purpura, increased susceptibility to infections
Signs of CNS involvement: cranial nerve palsies, altered mental status, seizures
Skin lesions (rare).
Diagnostic Criteria:
Diagnosis is primarily based on lymph node or tissue biopsy
Definitive classification relies on histopathology and immunohistochemistry according to the WHO classification of lymphoid neoplasms
Clinical staging (e.g., Ann Arbor staging system, modified for non-Hodgkin lymphoma) is essential.
Diagnostic Approach
History Taking:
Detailed history of presenting symptoms, focusing on duration, progression, and associated constitutional symptoms (B symptoms)
Inquiry about recent infections, travel history, and family history of malignancies
Previous medical history, including immunocompromise or EBV exposure, is important
Red flags include rapidly growing lymphadenopathy, presence of B symptoms, and significant organomegaly.
Physical Examination:
Thorough head-to-neck, axillary, and inguinal lymph node examination
Assessment for hepatosplenomegaly and abdominal masses
Neurological examination to detect CNS involvement
Examination of skin and extremities
Evaluation of vital signs for fever.
Investigations:
Complete Blood Count (CBC) with differential: may show anemia, thrombocytopenia, leukocytosis, or leukopenia
Peripheral smear: can reveal atypical lymphocytes or lymphoblasts
Lactate dehydrogenase (LDH): elevated in aggressive lymphomas, indicating tumor burden and proliferation
Uric Acid: often elevated due to rapid cell turnover
Liver Function Tests (LFTs) and Renal Function Tests (RFTs): to assess organ involvement and baseline function
Bone Marrow Biopsy: essential for staging and detecting bone marrow infiltration
Chest X-ray: to assess mediastinal or hilar lymphadenopathy and pulmonary involvement
CT scans (Chest, Abdomen, Pelvis): crucial for staging, defining tumor extent, and identifying extranodal sites
MRI: useful for CNS involvement, bone marrow assessment, and evaluation of soft tissue masses
Positron Emission Tomography (PET) scan: highly sensitive for staging, assessing treatment response, and detecting residual disease, often used in combination with CT (PET-CT)
Ultrasound: useful for initial evaluation of superficial lymphadenopathy and abdominal masses.
Differential Diagnosis:
Infectious causes: Tuberculosis, Toxoplasmosis, EBV infection (infectious mononucleosis), HIV-related lymphadenopathy
Other malignancies: Hodgkin lymphoma, other non-Hodgkin lymphomas, metastatic solid tumors
Inflammatory conditions: Sarcoidosis, Rheumatoid Arthritis, Kawasaki disease.
Imaging And Staging
Role Of Imaging:
Imaging plays a critical role in initial diagnosis, defining the extent of disease (staging), guiding biopsy, monitoring treatment response, and detecting recurrence
Different modalities are used based on suspected site and clinical suspicion.
Ct Scan:
CT is the workhorse for staging extranodal disease, evaluating lymphadenopathy size and location, and assessing organ involvement (liver, spleen, kidneys)
It helps identify masses, assess their relationship to adjacent structures, and guide interventional procedures.
Mri Scan:
MRI offers superior soft tissue contrast, making it invaluable for evaluating CNS involvement, spinal cord compression, and assessing bone marrow infiltration
It can also be used for characterizing specific soft tissue masses and differentiating solid tumors from other lesions.
Pet Ct Scan:
PET-CT is highly sensitive for detecting metabolically active lymphoma, improving staging accuracy, and assessing response to therapy
It helps identify occult disease sites not readily apparent on CT alone and is crucial for interim and end-of-treatment response assessment.
Ultrasound:
Ultrasound is useful for characterizing superficial lymph nodes, assessing testicular masses, and guiding fine-needle aspiration or core biopsy of superficial lesions
It can also provide real-time assessment of abdominal organs.
Staging Systems:
The Ann Arbor staging system (modified for non-Hodgkin lymphoma) is commonly used, classifying disease into four stages based on lymph node involvement and extranodal sites
Staging is essential for prognostication and guiding treatment intensity.
Management
Initial Management:
Prompt biopsy for histopathological diagnosis is paramount
Initiation of supportive care, including hydration, pain management, and management of hyperuricemia or hypercalcemia if present
Consultation with pediatric oncology team is essential.
Chemotherapy:
Multi-agent chemotherapy is the cornerstone of treatment
Regimens are subtype-specific and intensity-guided by stage and prognostic factors
Common regimens include: for Burkitt lymphoma: COPADEM, hyperCVAD
for DLBCL: R-CHOP, DA-EPOCH-R
Treatment duration varies from months to over a year.
Radiation Therapy:
May be used as part of initial treatment for localized disease, consolidation for residual disease, or for palliation of symptomatic sites
Its role is more limited in diffuse lymphomas compared to Hodgkin lymphoma.
Stem Cell Transplantation:
Autologous or allogeneic stem cell transplantation may be considered for relapsed or refractory disease, particularly for aggressive subtypes or when standard chemotherapy fails.
Supportive Care:
Management of chemotherapy side effects: antiemetics, growth factors, antibiotics for febrile neutropenia
Nutritional support, psychosocial support, and rehabilitation are vital components of care.
Prognosis
Factors Affecting Prognosis:
Key prognostic factors include the specific subtype of lymphoma, stage of disease at diagnosis, presence of B symptoms, performance status, involvement of bone marrow or CNS, LDH levels, and response to initial therapy
Age and genetic factors can also play a role.
Outcomes:
With modern multimodal therapy, cure rates for adolescent B-cell lymphomas are generally high, especially for subtypes like Burkitt lymphoma and DLBCL
Outcomes vary significantly by subtype and stage
Long-term survival rates can exceed 80-90% for favorable risk groups.
Follow Up:
Survivors require regular long-term follow-up to monitor for disease recurrence, manage late effects of treatment (e.g., cardiac dysfunction, secondary malignancies, infertility), and provide psychosocial support
Follow-up schedules are typically intensive in the first few years post-treatment.
Key Points
Exam Focus:
Adolescent B-cell lymphomas (Burkitt, DLBCL, B-ALL) are distinct from adult lymphomas and often have a more aggressive course but a better prognosis with intensive therapy
Always consider B symptoms (fever, night sweats, weight loss) in the differential diagnosis of lymphadenopathy
Imaging (CT, PET-CT) is crucial for staging and response assessment.
Clinical Pearls:
Rapidly growing lymphadenopathy in an adolescent warrants prompt investigation
Don't underestimate the significance of constitutional symptoms
Early involvement of pediatric oncology is critical for optimal management
Remember to assess for CNS involvement, especially in high-risk subtypes.
Common Mistakes:
Delaying biopsy due to presumed benign causes
Inadequate staging leading to under-treatment
Failing to consider B-cell lineage when presented with aggressive non-Hodgkin lymphoma in children and adolescents
Underestimating the importance of supportive care during intensive chemotherapy.