Non-Hodgkin Lymphomas Overview

Study Notes

Non-Hodgkin Lymphomas (NHLs)

NHLs are a heterogeneous group of hematologic malignancies derived from clonal expansion of B cells, T cells, or their precursors.
They are characterized by the infiltration of lymph nodes and other tissues by neoplastic lymphoid cells.
NHLs are more common than Hodgkin's lymphoma.
Incidence increases with age, with a median age of 50 years.
Multiple peripheral nodes are frequently involved, often with non-contiguous spread.
Mesenteric nodes and the Waldeyer ring are frequently involved.
Extranodal involvement is common, affecting various organs.
NHLs can exhibit indolent or aggressive behavior.

Characteristics of Non-Hodgkin Lymphomas (NHLs)

Microscopically, NHLs demonstrate loss of nodal architecture, with all cells being malignant and an absence of Reed-Sternberg cells.
Immunohistochemically, B cells express CD20 and T cells express CD3.

Some Examples of B Cell NHLs

Diffuse Large B-Cell Lymphoma (DLBCL):
- The most common form of NHL.
- Occurs across all ages, but more frequent in individuals over 60.
- Often arises at extranodal sites.
- Aggressive course.
- Highly associated with rearrangements or mutations of the BCL6 gene.
- Characterized by a diffuse pattern of growth of large transformed lymphoid cells with prominent nucleoli and multiple mitotic figures.
- B cells exhibit variable expression of CD10 and surface Ig.
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL):
- Accounts for 3% of adult lymphomas and 30% of all leukemias.
- Occurs in older adults.
- Usually involves nodes, marrow, and spleen.
- Most patients have peripheral blood involvement.
- Indolent course.
- Diffuse effacement by small lymphocytes with round nuclei, condensed chromatin, and scant cytoplasm.
- CD5+ B-cell expressing surface Ig.
Burkitt Lymphoma:
- Endemic in Africa, sporadic elsewhere.
- Often associated with Epstein-Barr virus infection.
- Predominantly affects children and young adults.
- Often presents at extranodal sites with visceral involvement.
- Highly aggressive tumor of B cells.
- Associated with translocations t(8;14) involving the c-MYC proto-oncogene.
- Characterized by diffuse involvement by intermediate-sized B cells, excess mitoses & apoptosis.
- Exhibits a "starry sky" appearance.
- Immunophenotyping reveals CD10+ B cells & surface Ig expression.
Follicular Lymphoma:
- The second most common NHL.
- Affects middle-aged individuals, with equal prevalence in males and females.
- Usually involves lymph nodes, marrow, and spleen.
- The most common form of indolent NHLs.
- Associated with t(14;18) with BCL-2 overexpression.
- Exhibits a nodular growth pattern formed of small, mixed small & large, or large cells.
- Prognosis depends on the proportion of large cells.
Marginal Zone Lymphoma (MALT Lymphoma):
- Accounts for 7% of adult lymphomas.
- Extranodal MALT lymphoma, affecting any mucosa (GIT, conjunctiva, respiratory).
- Arises at sites of chronic immune stimulation.
- Often remains localized for long periods.
- Indolent tumors.

Some Examples of T Cell NHLs

Peripheral T-Cell Lymphoma:
- The most common adult T-cell lymphoma.
- Often disseminated.
- Exhibits a spectrum of small to large lymphoid cells with irregular nuclear contours.
- CD3+ mature T-cell phenotype.
- Generally aggressive.
Mycosis Fungoides:
- The most common cutaneous lymphoid malignancy.
- Presents with localized or more generalized skin involvement.
- Small lymphoid cells often infiltrate the epidermis (Pautrier microabscesses).
- CD4+ mature T cells.
- Generally indolent.
- Sézary syndrome: a more aggressive variant characterized by diffuse skin erythema and peripheral blood involvement.

Plasma Cell Neoplasms

B-cell proliferations containing neoplastic plasma cells that secrete monoclonal Ig or Ig fragments.

Multiple Myeloma (Plasma Cell Myeloma)

Incidence higher in men and older adults, with a peak between 65-70 years of age.
Commonly associated with:
- Bone pain due to lytic bone lesions.
- Hypercalcemia.
- Renal failure.
- Anemia.
- Acquired immune abnormalities.
- Increased levels of monoclonal Ig (M protein) in blood and/or light chains (Bence Jones proteins) in urine.
Presents as destructive bone lesions mostly involving the axial skeleton (vertebral column, ribs, skull, pelvis, femur, clavicle and scapula), often leading to pathologic fractures.
Bony disease dominates, but can spread late in its course to lymph nodes and extra-nodal sites.
Radiographically, bone lesions appear as punched-out defects (1-4 cm in diameter).
Grossly, consist of soft, gelatinous, red tumor masses.
Microscopically, formed of sheets of plasma cells at different stages of maturation.