Lymphomas and Lymphoproliferative Diseases

Lymphomas and Lymphoproliferative Diseases

Lymphomas are clonal malignancies of lymphoid cells that arise in lymph nodes or extranodal lymphoid tissues.

They are broadly divided into:

• Hodgkin lymphoma (HL)
• Non-Hodgkin lymphomas (NHL)

Lymphoproliferative diseases represent a spectrum from benign/reactive proliferations to malignant lymphoid neoplasms.

General Principles

Pathogenesis

• Derived from B cells (most common), T cells, or NK cells
• Genetic alterations lead to:
  • ↑ proliferation
  • ↓ apoptosis
  • abnormal differentiation

High-yield genetic mechanisms

• t(14;18) → BCL2 ↑ → ↓ apoptosis (follicular lymphoma)
• t(11;14) → cyclin D1 ↑ (mantle cell lymphoma)
• t(8;14) → MYC ↑ (Burkitt lymphoma)

Clinical Features

• Painless lymphadenopathy (most common)
• B symptoms: fever, night sweats, weight loss
• Extranodal involvement (GI, skin, CNS)
• Bone marrow involvement → cytopenias

Hodgkin Lymphoma (HL)

Malignant lymphoma characterized by Reed–Sternberg (RS) cells in a reactive inflammatory background

Pathogenesis

• Originates from germinal center B cells
• Often associated with EBV infection
• RS cells secrete cytokines → attract inflammatory cells

Morphology

• Reed–Sternberg cells:
  • Large, binucleated
  • “Owl’s eye” nuclei
• Mixed inflammatory background

Subtypes

• Nodular sclerosis (most common)
• Mixed cellularity
• Lymphocyte-rich
• Lymphocyte-depleted

Clinical Features

• Contiguous spread between lymph node groups
• Commonly cervical/mediastinal lymph nodes
• B symptoms frequent
• Rare: alcohol-induced lymph node pain

Diagnosis

• Lymph node biopsy
• Immunophenotype: CD15+, CD30+

Prognosis

• Generally good prognosis
• Depends on stage (Ann Arbor staging)

Non-Hodgkin Lymphomas (NHL)

Heterogeneous group of lymphoid malignancies without RS cells

General Features

• Non-contiguous spread
• Frequent extranodal involvement
• Wide range of behavior (indolent → aggressive)

Major B-Cell Lymphomas

Diffuse Large B-Cell Lymphoma (DLBCL)

• Most common NHL
• Aggressive lymphoma of large B cells

Features

• Rapidly enlarging lymph node or extranodal mass
• May arise de novo or from transformation

• Often curable with treatment

Follicular Lymphoma

Indolent lymphoma of germinal center B cells

Pathogenesis

• t(14;18) → BCL2 overexpression → ↓ apoptosis

Features

• Painless generalized lymphadenopathy
• Slow progression

• Long survival but usually not curable

Burkitt Lymphoma

Highly aggressive, rapidly growing lymphoma

Pathogenesis

• t(8;14) → MYC activation
• Often associated with EBV

Morphology

• “Starry-sky” appearance

Clinical Features

• Endemic: jaw involvement
• Sporadic: abdominal masses

• One of the fastest growing human tumors

Small Lymphocytic Lymphoma (SLL)

Tissue counterpart of CLL

Features

• Same neoplastic cells as CLL
• Involves lymph nodes rather than blood

T-Cell and NK-Cell Lymphomas

General Features

• Less common than B-cell lymphomas
• Often more aggressive
• Frequently extranodal

Examples

• Peripheral T-cell lymphoma
• Adult T-cell leukemia/lymphoma (HTLV-1)
• Cutaneous T-cell lymphoma (mycosis fungoides)

Lymphoproliferative Disorders

Disorders characterized by abnormal lymphocyte proliferation, ranging from benign to malignant

Important Types

Monoclonal B-cell Lymphocytosis (MBL)

• Precursor to CLL
• Asymptomatic

Post-Transplant Lymphoproliferative Disorder (PTLD)

• Occurs in immunosuppressed patients
• Often EBV-driven

Diagnosis

• Excisional lymph node biopsy = gold standard
• Immunophenotyping (flow cytometry, IHC)
• Cytogenetics and molecular testing
• Imaging (CT, PET) for staging

Treatment

Depends on type and stage:

• Chemotherapy (e.g., CHOP)
• Immunotherapy (rituximab)
• Radiotherapy
• Stem cell transplantation

References

1. Robbins & Cotran Pathologic Basis of Disease (10th ed.)
2. AMBOSS – Lymphomas
3. WHO Classification of Hematolymphoid Tumors (2022)
4. Harrison’s Principles of Internal Medicine
5. StatPearls (NCBI) – Hodgkin and Non-Hodgkin Lymphomas