Mature Lymphoid Neoplasms Notes

Overview of Mature Lymphoid Neoplasms (MLN)

  • Large group of neoplastic conditions of the lymphoid lineage.
  • Characterized by clonal proliferation of mature B and T lymphocytes.
  • Initially classified based on morphology and clinical characteristics.
  • Diagnosis integrates patient’s history, physical exam, morphological, immunologic, cytogenetic, molecular, and clinical features.
  • Defined by site of neoplasm:
    • Leukemias (blood and bone marrow)
    • Lymphomas (lymph nodes and spleen)

Four Broad Groups of Lymphoid Malignancies

  1. Acute Lymphoblastic Leukemia (ALL)

    • Malignant neoplasm mainly involving bone marrow and peripheral blood.
    • Characterized by proliferation of lymphoid lineage blasts.

  2. Chronic Lymphocytic Leukemia (CLL)

    • Proliferation of primarily mature B-lymphocytes in bone marrow and peripheral blood.

  3. Malignant Lymphomas

    • Present as tumor masses mainly in lymphoid organs such as lymph nodes, spleen, tonsils, and thymus.
    • Two types:
      • Non-Hodgkin’s Lymphoma (NHL)
      • Hodgkin’s Lymphoma (HL)

  4. Plasma Cell Neoplasms

    • Composed of immunoglobulin-secreting cells and includes both benign and malignant forms.
    • Predominantly plasma cells.
    • Includes:
      • Monoclonal Gammopathy of Undetermined Significance (MGUS)
      • Multiple Myeloma (MM)
      • Waldenström’s Macroglobulinemia (WM)

Hodgkin Lymphoma (HL)

  • Characterized by the presence of Reed-Sternberg cells:
    • Giant cells with abundant cytoplasm and multinucleated nucleus with macronucleoli.
  • Diagnosis requires evaluating cellular growth patterns and composition; not just the presence of Reed-Sternberg cells.
Classic Hodgkin Lymphoma
  • Mainly identified via biopsy of lymphoid tissues and nodes.
  • Comprises 95% of cases.
  • Occurs across all ages; median age at presentation is 32 with a bimodal distribution.
  • Clinical Symptoms:
    • Enlarged lymph nodes
    • Fever, night sweats, weight loss
  • Spread along lymph node chains is typical.
Staging of HL
  • Requires tissue biopsy and microscopic evaluation for diagnosis.
  • Clinical staging determined by:
    • Patient history
    • Physical examination
    • Laboratory tests, x-rays, and CT-scans.
Cotswold’s Staging Scheme for HL
  1. Stage 1: Single lymph node regions.
  2. Stage II: Two or more lymph node regions on the same side of the diaphragm.
  3. Stage III: Involvement of lymph/structures on both sides of the diaphragm.
  4. Stage IV: Involvement of extra-nodal sites, such as bone marrow.

Treatment and Prognosis

  • Treatment strategy based on staging rather than HL subtype.
  • Main treatment: Chemotherapy, with or without radiation.

Non-Hodgkin's Lymphomas

  • Details not provided in the transcript, but generally includes lymphomas not classified as HL.

Review of CLL

  • Details not provided in the transcript but generally involves chronic malignancy of B lymphocytes.
Prolymphocytic Leukemia (PLL)
  • Rare condition (1-2%) primarily found in older patients (>70 years).
  • More commonly B cell related (75%), but can also be T cell.
  • Characterized by >55% prolymphocytes and distinct cell morphology from CLL.
Hairy Cell Leukemia (HCL)
  • Indolent B-cell lineage disease, median age 50.
  • Characterized by small B lymphocytes with hairy cytoplasmic projections.
  • Found in BM and spleen; can lead to “dry tap” during BM aspiration (fibrotic BM).
Adult T Cell Leukemia/Lymphoma (ATLL)
  • Neoplastic disorder of T cells linked to HTLV-1 retroviral infection.
  • Virus transmission methods: placental transfer, breastfeeding, blood transfusion, sexual contact.
  • Characterized by 'flower cells' with convoluted nuclei.
Burkitt’s Lymphoma/Leukemia
  • Aggressive B-cell cancer with a very high proliferation rate.
  • Characterized by medium to large lymphocytes with basophilic vacuolated cytoplasm.
  • Features a “starry sky” appearance in biopsies due to macrophage presence.
Follicular B-Cell Lymphoma
  • Accounts for 12% of NHL; neoplastic disorder of germinal B cells.
  • Indolent course and generally incurable; presents with lymphadenopathy.
  • Cells have a condensed chromatin pattern and distinct nuclear clefts.
  • Treatment involves a watch-and-wait strategy.
Mantle Cell Lymphoma
  • Characterized by medium-sized lymphoid cells with irregular-shaped nucleus.
  • Associated with lymph node involvement; may mimic PLL.
Diffuse Large B-cell Lymphoma (DLBCL)
  • Most common lymphoma (25%-30% of all Non-Hodgkin cases).
  • Displays a diffuse growth pattern composed of large B-cells.
Mycosis Fungoides (MF)/Sézary Syndrome (SS)
  • Most recognized cutaneous T-cell lymphoma.
  • MF remains confined to the skin, while SS is systemic and involves peripheral blood.
  • Characterized by CD4+ T cells and cerebriform nuclei shape (Sézary cells).

Plasma Cell Neoplasms

Multiple Myeloma (MM)
  • Most prevalent plasma cell disease in bone marrow.
  • Characterized by:
    • Abnormal plasma cell proliferation.
    • Overproduction of monoclonal immunoglobulins affecting various organ systems.
    • Lytic bone disease (osteolytic lesions).
  • Incurable with varying survival rates.
Patophysiology of MM
  • Median age at diagnosis is 67, with higher incidence in males.
  • Possible associations: environmental, occupational, and genetic factors.
  • Plasma cell expansion leads to bone pain and brittle bones due to lytic lesions.
  • Increased calcium levels can lead to kidney stones and possible failure.
Laboratory Evaluation for MM
  • Peripheral Blood (PB):
    • Normocytic normochromic anemia.
    • Rouleaux formation.
    • Thrombocytopenia.
  • Bone Marrow (BM):
    • Essential for evaluation; increased plasma cells (10% to 100%).
    • Elevated calcium levels due to lytic lesions.
Serum Electrophoresis in MM
  • Malignant plasma cells typically produce monoclonal immunoglobulin (detected as M-spike in gamma region).
  • Commonly IgG producing.
Free Light Chains in MM
  • In some cases, plasma cells produce only kappa or lambda light chains.
  • Detected in urine as Bence Jones protein.
  • Major cause of death: infections.
Waldenström’s Macroglobulinemia
  • Characterized by malignant cells (mixed population of lymphocytes, plasma cells, plasmacytoid lymphocytes).
  • No lytic bone lesions.
  • Elevated IgM leads to hyperviscosity syndrome.
  • IgM-spike observed on protein electrophoresis; plasmapheresis may alleviate symptoms.
Monoclonal Gammopathy of Undetermined Significance (MGUS)
  • Benign condition with monoclonal plasma cell proliferation; precursor state for myeloma.
  • Mild M-spike presence without end-organ damage.
  • No immediate treatment required, but close monitoring is essential for life.