Lymphoma Types and Clinical Manifestations
Lymphomas are broadly divided into two major categories: Hodgkin lymphoma (HL) and Non-Hodgkin lymphoma (NHL), with NHL representing approximately 90% of cases and HL accounting for 10%. 1, 2
Major Classification Systems
WHO Classification Framework
The current WHO classification system organizes lymphomas based on cell of origin (B-cell, T-cell, or NK-cell), then subdivides them into precursor versus mature lymphocyte-derived neoplasms, further refined by immunophenotype, genetic features, and clinical characteristics. 1
Non-Hodgkin Lymphoma (NHL)
Most Common NHL Subtypes in the United States
The 13 most common histologic types constitute approximately 90% of NHL cases, with the following distribution: 1
- Diffuse Large B-Cell Lymphoma (DLBCL): 31% - the single most common subtype 1
- Follicular Lymphoma (FL): 22% 1
- Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia (SLL/CLL): 6% 1
- Mantle Cell Lymphoma (MCL): 6% 1
- Peripheral T-Cell Lymphoma (PTCL): 6% 1
- Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma: 5% 1
Notably, more than 50% of all lymphoma cases in the United States are either DLBCL or FL. 1
T-Cell and NK-Cell Lymphoma Subtypes
Among peripheral T-cell and NK/T-cell lymphomas, the distribution is: 1
- PTCL-not otherwise specified (PTCL-NOS): 25.9% 1
- Angioimmunoblastic lymphoma: 18.5% 1
- NK/T-cell lymphoma (NKTCL): 10.4% 1
- Adult T-cell leukemia/lymphoma: 9.6% 1
- Anaplastic large cell lymphoma (ALCL), ALK-positive: 6.6% 1
- ALCL, ALK-negative: 5.5% 1
Hodgkin Lymphoma (HL)
Major Subtypes
According to the WHO classification, HL is divided into two major categories: 1
1. Lymphocyte Predominant Hodgkin Lymphoma (LPHL): 5% of cases
- Malignant cells (L&H cells) have distinct immunophenotype: CD15-/CD30-/CD20+ 1
2. Classical Hodgkin Lymphoma (cHL): 95% of cases Classical HL includes four histologic subtypes: 1
- Lymphocyte rich
- Nodular sclerosing (most common)
- Mixed cellularity
- Lymphocyte depleted
The key distinguishing feature is that classical HL tumor cells (Hodgkin-Sternberg cells) express CD15+/CD30+/CD20-, contrasting with LPHL. 1
Clinical Manifestations
Common Presenting Features
Nodal Presentation:
- Painless lymphadenopathy is the typical presentation 3
- More than 60% of HL patients initially present with enlarged cervical lymph nodes 1
- NHL has 30% extranodal presentation rate, while HL is predominantly nodal (only 5% extranodal) 4
Systemic B-Symptoms (Advanced Disease): The classic triad occurs in more advanced stages: 1, 3
- Fever
- Unexplained weight loss (>10% body weight over 6 months)
- Drenching night sweats
Site-Specific Manifestations by Subtype
MALT Lymphoma has predilection for: 4
- Ocular adnexa
- Salivary glands
- Larynx
- Thyroid gland
Diffuse Large B-Cell Lymphoma commonly involves: 4
- Paranasal sinuses
- Mandible and maxilla
- Waldeyer ring
Burkitt Lymphoma (more frequent in children/young adults): 4
- Maxilla and mandible involvement
- Can cause aggressive bone destruction
Extranodal NHL Manifestations
When NHL presents in extranodal head and neck sites: 4
- Appears as submucosal masses with smooth mucosal surfaces
- Can manifest as polypoid, bulky masses
- Aggressive subtypes (Burkitt, DLBCL, NK/T-cell) cause bone destruction of maxilla, mandible, and paranasal sinus bones that is indistinguishable from squamous cell carcinoma
Imaging Characteristics
On imaging studies, lymphomatous lymph nodes appear: 4
- Homogeneous with variable size (average 2-10 cm diameter)
- Slight to moderate enhancement
- May display necrosis before/after treatment
- Post-treatment calcification possible
- Isodense to muscle on CT with circumscribed, distinct margins
Diagnostic Requirements
An excisional or incisional lymph node biopsy is mandatory for diagnosis - fine needle aspiration is insufficient. 1
Critical diagnostic features include: 1
- Immunophenotyping
- Genetic features via cytogenetics or FISH
- Viral detection (EBV, HHV-8, HTLV-1) when indicated
- Flow cytometry
Unique Histologic Feature of HL
HL is distinctive because tumor cells (Hodgkin-Sternberg or L&H cells) represent only 0.1-1% of the cellular population, with the remainder being a heterogeneous admixture of reactive lymphocytes, histiocytes, eosinophils, plasma cells, and fibroblasts. 1
Risk Factors
Major modifiable risk factors include: 3
- Any tobacco use
- Obesity
Additional contributing factors: 3
- Genetic predisposition
- Infectious etiologies
- Inflammatory conditions