Lymphoid Neoplasia

Overview of Lymphoid Neoplasms

Definition: A diverse group of hematologic malignancies originating from lymphocytes (B cells, T cells, and NK cells) or their precursors. These cancers involve the uncontrolled proliferation of abnormal lymphocytes, leading to various clinical and pathological manifestations
Hallmarks:
- Clonal Proliferation: These disorders arise from a single, genetically abnormal lymphocyte that proliferates excessively
- Variable Differentiation: The cells may be immature (blasts) or more mature lymphocytes, depending on the specific type of neoplasm
- Disruption of Normal Hematopoiesis: The malignant cells often crowd out normal blood cells in the bone marrow and lymphoid organs, leading to cytopenias (anemia, thrombocytopenia, and/or neutropenia)
Classification:
- The World Health Organization (WHO) classification is the most widely used system
- Lymphoid neoplasms are broadly classified into:
  - Precursor Lymphoid Neoplasms: Involve immature lymphoid cells (lymphoblasts)
  - Mature Lymphoid Neoplasms: Involve more mature B cells, T cells, or NK cells
- Within each of these categories, disorders are further classified based on:
  - Cell Morphology
  - Immunophenotype (expression of cell surface markers)
  - Genetic Abnormalities (cytogenetics and molecular genetics)
  - Clinical Features
Key Differentiations:
- Leukemia vs. Lymphoma: This distinction is often blurred, but generally:
  - Leukemias primarily involve the bone marrow and peripheral blood.
  - Lymphomas primarily involve lymph nodes and other lymphoid tissues (spleen, thymus, etc.). However, many lymphoid neoplasms can involve both the bone marrow and lymphoid tissues.
- Acute vs. Chronic:
  - Acute: Aggressive neoplasms with rapid proliferation of immature cells (blasts).
  - Chronic: More indolent (slow-growing) neoplasms with proliferation of more mature cells.

Precursor Lymphoid Neoplasms

These involve immature lymphoid cells (lymphoblasts) and are aggressive malignancies.

B-Lymphoblastic Leukemia/Lymphoma (B-ALL/LBL):
- Definition: A neoplasm of precursor B cells (B lymphoblasts). If it primarily involves the bone marrow, it is called acute lymphoblastic leukemia (ALL). If it primarily involves lymph nodes or other extramedullary sites, it is called lymphoblastic lymphoma (LBL)
T-Lymphoblastic Leukemia/Lymphoma (T-ALL/LBL):
- Definition: A neoplasm of precursor T cells (T lymphoblasts). Similar to B-ALL/LBL, it is classified as leukemia or lymphoma based on the primary site of involvement

Mature Lymphoid Neoplasms {-}

These neoplasms involve more mature B cells, T cells, or NK cells and are generally less aggressive than precursor neoplasms.

B-Cell Neoplasms
- Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL):
  - Definition: A common indolent (slow-growing) neoplasm of mature, usually naive B cells. When the disease primarily involves the blood and bone marrow, it is called chronic lymphocytic leukemia (CLL). When it primarily involves the lymph nodes, it is called small lymphocytic lymphoma (SLL)
- Diffuse Large B-Cell Lymphoma (DLBCL):
  - Definition: An aggressive lymphoma composed of large, transformed B cells
- Follicular Lymphoma:
  - Definition: An indolent lymphoma characterized by a follicular (nodular) growth pattern in lymph nodes
- Burkitt Lymphoma:
  - Definition: A highly aggressive B-cell lymphoma characterized by rapid proliferation and a high rate of cell turnover
T-Cell and NK-Cell Neoplasms
- Peripheral T-Cell Lymphomas (PTCL):
  - A diverse group of lymphomas derived from mature T cells or NK cells
- Adult T-Cell Leukemia/Lymphoma (ATLL):
  - A T-cell leukemia/lymphoma caused by the human T-cell lymphotropic virus type 1 (HTLV-1)

General Diagnostic Approach to Lymphoid Neoplasms

Clinical Evaluation: History, physical exam, symptoms (e.g., lymphadenopathy, B symptoms)
Complete Blood Count (CBC) and Peripheral Blood Smear: Assess cell counts and morphology
Lymph Node Biopsy: If lymphadenopathy is present
Bone Marrow Aspiration and Biopsy: Assess bone marrow involvement
Flow Cytometry: Immunophenotyping to identify cell surface markers
Cytogenetic Analysis: To detect chromosomal abnormalities
Molecular Testing: To detect gene mutations and fusion genes
Imaging Studies (CT Scan, PET/CT): To stage the disease and assess for organ involvement

Key Terms

Lymphoid Neoplasm: Malignancy originating from lymphocytes
Acute Lymphoblastic Leukemia (ALL): Aggressive leukemia of lymphoblasts
Lymphoblastic Lymphoma (LBL): Lymphoma of lymphoblasts
Chronic Lymphocytic Leukemia (CLL): Indolent leukemia of mature B cells
Small Lymphocytic Lymphoma (SLL): Lymphoma of mature B cells, similar to CLL
Diffuse Large B-Cell Lymphoma (DLBCL): Aggressive lymphoma of large B cells
Follicular Lymphoma: Indolent lymphoma with a follicular growth pattern
Burkitt Lymphoma: Highly aggressive lymphoma with a MYC translocation
Peripheral T-Cell Lymphomas (PTCL): Diverse group of lymphomas from mature T cells or NK cells
Adult T-Cell Leukemia/Lymphoma (ATLL): T-cell leukemia/lymphoma caused by HTLV-1
Lymphadenopathy: Swollen lymph nodes
Splenomegaly: Enlarged spleen
Immunophenotyping: Identification of cell surface markers using flow cytometry
Cytogenetic Analysis: The study of chromosomes and their abnormalities
Molecular Testing: Techniques to detect gene mutations and fusion genes

Myeloproliferative

Acute Lymphoid