Overview

Definition:
-Hodgkin lymphoma (HL) is a malignant lymphoma characterized by the presence of Reed-Sternberg cells in affected lymph nodes
-It is distinct from non-Hodgkin lymphoma and typically originates in lymphocytes within lymph nodes.
Epidemiology:
-HL is one of the most common cancers in adolescents and young adults
-In children and adolescents, it accounts for approximately 3-5% of all childhood cancers and around 10% of lymphomas
-Incidence peaks in two age groups: 15-35 years and over 55 years
-Childhood HL is relatively rare but a significant pediatric malignancy.
Clinical Significance:
-Early and accurate diagnosis and appropriate treatment are crucial for achieving high cure rates in pediatric Hodgkin lymphoma
-Understanding the different treatment regimens and their associated long-term sequelae is vital for pediatric oncologists and residents preparing for DNB and NEET SS examinations, as these impact long-term patient well-being and survivorship.

Clinical Presentation

Symptoms:
-Painless lymphadenopathy, typically in the cervical, supraclavicular, or mediastinal regions
-B symptoms including fever (often >38.5°C), night sweats (drenching), and unintentional weight loss (>10% body weight in 6 months)
-Pruritus
-Cough or dyspnea if mediastinal involvement
-Splenomegaly or hepatomegaly may be present.
Signs:
-Enlarged, palpable, firm, rubbery, non-tender lymph nodes
-Mediastinal widening on chest X-ray
-Hepatosplenomegaly
-Signs of anemia or infection if bone marrow is involved.
Diagnostic Criteria:
-Diagnosis is confirmed by lymph node biopsy showing characteristic Reed-Sternberg cells and a background inflammatory infiltrate
-Staging is based on the Ann Arbor staging system, modified for pediatric use, incorporating clinical and radiological findings and potentially bone marrow biopsy.

Diagnostic Approach

History Taking:
-Detailed history of lymphadenopathy (duration, location, progression, associated pain), systemic symptoms (fever, night sweats, weight loss), pruritus, cough, and exposure history
-Family history of lymphomas or other cancers.
Physical Examination:
-Thorough examination of all lymph node areas (cervical, supraclavicular, axillary, inguinal), palpation of liver and spleen, assessment for respiratory distress, and assessment for skin changes like pruritus
-Complete blood count (CBC) with differential, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) are essential.
Investigations:
-Biopsy of an enlarged lymph node for histopathology and immunohistochemistry (CD15, CD30 positive)
-Imaging: Chest X-ray (CXR) and CT scans of the chest, abdomen, and pelvis to determine disease extent
-PET-CT scan is increasingly used for staging and response assessment
-Bone marrow biopsy is usually performed for initial staging, particularly in higher-risk patients
-Laboratory tests include CBC, ESR, LDH, liver function tests (LFTs), and renal function tests (RFTs).
Differential Diagnosis: Non-Hodgkin lymphoma (NHL), other lymphomas, reactive lymphadenopathy (e.g., viral infections, tuberculosis), metastatic disease, sarcoidosis, and other granulomatous conditions.

Management

Abvd Regimen:
-The standard chemotherapy regimen for many stages of Hodgkin lymphoma in both adults and children is ABVD: Doxorubicin (Adriamycin), Bleomycin, Vinblastine, Dacarbazine
-Pediatric protocols often adjust doses and durations based on stage and risk stratification
-Typical dosing: Doxorubicin 25 mg/m², Bleomycin 5 units/m², Vinblastine 6 mg/m², Dacarbazine 375 mg/m²
-administered every 2 weeks.
Pediatric Regimens:
-Pediatric regimens aim to maximize cure while minimizing long-term toxicity
-Some protocols use dose-reduced or attenuated ABVD for early-stage disease
-For advanced or higher-risk disease, regimens might involve escalation or different drug combinations, but ABVD remains a cornerstone
-Protocols like the Children's Oncology Group (COG) and European intergroup protocols stratify patients into risk groups (e.g., favorable, unfavorable) to tailor treatment intensity
-Some older protocols or specific situations might involve agents like cyclophosphamide or etoposide, but ABVD is generally preferred due to its efficacy and acceptable late effects profile compared to older regimens (e.g., MOPP).
Radiation Therapy:
-Radiation therapy (RT) is used judiciously in pediatric HL, primarily for bulky disease or residual masses post-chemotherapy
-Modern approaches aim to minimize RT volume and dose to reduce late effects, often using involved-site radiotherapy (ISRT).
Supportive Care:
-Management of chemotherapy-related toxicities (nausea, vomiting, mucositis, neutropenia, anemia, thrombocytopenia)
-Prophylaxis against opportunistic infections
-Nutritional support
-Psychological support for patients and families.

Late Effects

Cardiac Toxicity:
-Doxorubicin can cause cumulative cardiotoxicity, leading to cardiomyopathy and heart failure
-Late cardiac events can occur years after treatment.
Pulmonary Toxicity:
-Bleomycin can cause pulmonary fibrosis, leading to interstitial lung disease and reduced lung function
-Regular pulmonary function tests may be indicated.
Infertility:
-Chemotherapy agents, particularly alkylating agents and vinblastine, can impair fertility in both males and females
-Gonadotropin-releasing hormone (GnRH) agonists may be used for fertility preservation
-Radiation to the pelvic area also increases risk.
Secondary Malignancies: Survivors of HL have an increased risk of developing secondary cancers, including acute myeloid leukemia (AML), non-Hodgkin lymphoma, and solid tumors, particularly after radiation therapy and certain chemotherapy agents.
Endocrine Dysfunction:
-Radiation to the neck or mediastinum can affect the thyroid, pituitary, and hypothalamus, leading to hypothyroidism, growth hormone deficiency, and other endocrine issues
-Risk is higher with radiation doses and proximity to these organs.
Osteoporosis: Long-term corticosteroid use (if applicable in treatment protocols) and reduced physical activity can contribute to bone density loss.
Psychosocial Impact: Anxiety, depression, body image issues, and difficulties with social reintegration can persist long after treatment completion.

Prognosis

Factors Affecting Prognosis:
-Stage at diagnosis, presence of bulky disease, performance status, age, specific histological subtype, and response to initial therapy are key prognostic indicators
-Modern treatment has significantly improved outcomes.
Outcomes:
-Overall cure rates for pediatric Hodgkin lymphoma are excellent, often exceeding 90% for early-stage disease and remaining high for advanced stages with appropriate risk-stratified therapy
-Long-term survival is common.
Follow Up:
-Long-term follow-up is essential to monitor for disease recurrence, manage treatment-related late effects, and screen for secondary malignancies
-This typically involves regular clinical examinations, blood tests, and age-appropriate screening investigations (e.g., cardiac screening, pulmonary function tests, mammography, thyroid screening).

Key Points

Exam Focus:
-Remember ABVD (Doxorubicin, Bleomycin, Vinblastine, Dacarbazine) as the cornerstone of HL treatment
-Understand risk stratification in pediatric HL and how it influences treatment intensity
-Late effects are crucial for pediatric oncology questions.
Clinical Pearls:
-Always assess for B symptoms and lymphadenopathy
-Consider PET-CT for accurate staging and response assessment in HL
-Proactive management of potential late effects (e.g., fertility counseling, cardiac monitoring) is a hallmark of survivorship care.
Common Mistakes:
-Confusing Hodgkin lymphoma with Non-Hodgkin lymphoma, especially in diagnostic workup
-Underestimating the importance of late effects in long-term survivors
-Inappropriately using older, more toxic chemotherapy regimens or excessive radiation in modern pediatric HL protocols.