Definition/General
Introduction:
Classical Hodgkin Lymphoma (cHL) is a unique lymphoid malignancy characterized by Reed-Sternberg (RS) cells and Hodgkin cells in an inflammatory background
It represents 95% of Hodgkin lymphoma cases and has an excellent cure rate.
Origin:
Arises from germinal center or post-germinal center B-cells
Reed-Sternberg cells are the neoplastic component but represent <5% of tumor cells
Inflammatory background is reactive.
Classification:
WHO Classification includes 4 subtypes: Nodular Sclerosis (most common), Mixed Cellularity, Lymphocyte Rich, and Lymphocyte Depleted
Ann Arbor staging system used.
Epidemiology:
Bimodal age distribution: peaks at 20-30 and >55 years
Male predominance in mixed cellularity and lymphocyte depleted
EBV association in 40% of cases.
Clinical Features
Presentation:
Painless lymphadenopathy (90%)
Mediastinal mass common (60% in nodular sclerosis)
B-symptoms in 30%
Alcohol-induced pain in affected nodes (rare but characteristic).
Symptoms:
Painless lymph node enlargement
Fever, night sweats, weight loss (B-symptoms)
Chest symptoms (cough, dyspnea)
Pruritus
Fatigue.
Risk Factors:
EBV infection (especially in developing countries)
Immunosuppression (HIV, transplant)
Family history
Higher socioeconomic status (young adults).
Screening:
No specific screening
Diagnosed by lymph node biopsy
Staging by CT/PET scans
Bone marrow biopsy if indicated
Pulmonary function tests if mediastinal disease.
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Gross Description
Appearance:
Enlarged lymph nodes with intact capsule
Cut surface shows gray-white to tan appearance
Nodular sclerosis shows thick fibrous bands
Necrosis may be present.
Characteristics:
Node size variable (2-10 cm)
Firm consistency
May show areas of sclerosis
Capsular thickening possible
Adjacent nodes may be matted.
Size Location:
Cervical, mediastinal, axillary nodes most common
Contiguous spread typical (unlike NHL)
Extranodal involvement uncommon at presentation.
Multifocality:
Tends to spread contiguously from node to node
Mediastinal involvement common
Extranodal spread late in disease course.
Microscopic Description
Histological Features:
Reed-Sternberg cells and Hodgkin cells in inflammatory background
RS cells are large multinucleated cells with prominent nucleoli
Inflammatory cells include lymphocytes, eosinophils, neutrophils, histiocytes.
Cellular Characteristics:
Reed-Sternberg cells: Large (>20 μm), multinucleated, prominent nucleoli
Hodgkin cells: Large mononuclear variants
Background: Mixed inflammatory cells.
Architectural Patterns:
Nodular sclerosis: Thick collagen bands, lacunar cells
Mixed cellularity: Scattered RS cells, mixed inflammation
Lymphocyte rich: Abundant lymphocytes
Lymphocyte depleted: Few lymphocytes, fibrosis.
Immunohistochemistry
Positive Markers:
CD15 positive (85%)
CD30 positive (99%)
PAX5 weak positive
EBV-LMP1 positive (40%)
OCT2/BOB1 weak/negative.
Negative Markers:
CD20 negative (usually)
CD45 negative
CD3 negative
ALK negative
EMA negative (except LP subtype).
Diagnostic Utility:
CD15+/CD30+ profile diagnostic in appropriate context
PAX5 weak positivity confirms B-cell origin
Helps distinguish from other large cell lymphomas.
Molecular Subtypes:
EBV-positive cases more common in mixed cellularity and developing countries
PD-L1 expression frequent (therapeutic target).
Molecular/Genetic
Genetic Mutations:
Complex cytogenetics with gains of 2p, 9p, 12q
REL amplification
JAK2 mutations
B2M mutations
EBV integration in EBV-positive cases.
Molecular Markers:
Clonal immunoglobulin gene rearrangements
NF-κB pathway activation
JAK-STAT pathway alterations
PD-L1/PD-L2 alterations.
Prognostic Significance:
EBV status has prognostic implications in some populations
International Prognostic Score (IPS) uses clinical factors
Stage most important factor.
Therapeutic Targets:
CD30-targeted therapy (brentuximab vedotin)
PD-1 inhibitors (nivolumab, pembrolizumab)
JAK inhibitors under investigation.
Differential Diagnosis
Similar Entities:
Anaplastic large cell lymphoma
Primary mediastinal B-cell lymphoma
Nodular lymphocyte predominant Hodgkin lymphoma
Metastatic carcinoma
Reactive hyperplasia.
Distinguishing Features:
cHL: CD15+/CD30+/CD20-
ALCL: ALK+/CD30+/EMA+
PMBCL: CD20+/CD30+/CD15-
NLPHL: CD20+/CD15-/CD30-
Carcinoma: Cytokeratin+.
Diagnostic Challenges:
Distinction from ALCL (especially ALK-negative)
Recognition of RS cells in fibrotic background
Syncytial variant vs large cell lymphoma.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
[specimen type], measuring [size] cm
Diagnosis
Classical Hodgkin Lymphoma, [subtype]
Subtype Classification
Subtype: [Nodular Sclerosis/Mixed Cellularity/Lymphocyte Rich/Lymphocyte Depleted]
Histological Features
Shows Reed-Sternberg cells and Hodgkin cells in [inflammatory background description]
Reed-Sternberg Cells
Reed-Sternberg cells: [morphological description], [lacunar cells if NS subtype]
Immunohistochemistry
Reed-Sternberg cells: CD15+, CD30+, PAX5 (weak), CD20-, CD45-
EBV Status
EBV-LMP1: [positive/negative], EBER ISH: [positive/negative]
Staging Factors
Staging: [Ann Arbor stage if known], B-symptoms: [present/absent]
Prognostic Factors
Prognostic factors: [stage, bulk disease, B-symptoms, age, histology]
Final Diagnosis
Final diagnosis: Classical Hodgkin Lymphoma, [subtype], [stage if known]