Lymphomas
Definition
- malignant disorders of the immune system involving the uncontrolled proliferation of lymphocytes
- most patients present with lymphadenopathy, but sometimes they present with symptoms related to the growth of an extranodal lymphoma.
Etiology
- Unknown
- Proposed – clonal expansion of lymphoid cells that have undergone a maturation arrest at some point in their ontologic development.
- The following have been attributed to the maturation arrest.
1) Viruses
Ø EBV – African Burkitt’s Lymphoma
Ø HTLV-1 – T cell lymphoma or leukemia
- seen in several geographical areas, (Japan and Central America)
2) Genetic Alterations
Ø t(8:14) translocation – Burkitt’s lymphoma
Ø t(14:18) in follicular, small cleaved cell lymphomas
Ø patients with congenital immunologic disorders have an increased incidence of developing lymphomas
- X-linked immunodeficiency, Bruton type X-linked agammaglobulinemia, and hereditary ataxia-telangiectasia
Ø Also, those receiving immunosuppressive drugs are prone to develop lymphomas
3) Infection
4) Radiation
Ø Remember it plays a major etiologic role in the development of AML, but contributes only weakly to the development of lymphoma.
5) Chemicals and drugs
General Clinical Features of Lymphomas
- ENLARGED LYMPH NODES
Ø If infection:
q Soft and tender
q Less than 2 cm in diameter
q Located in areas that drain common infections
Ø Potentially malignant nodes are generally:
q Firm, hard, or rubbery
q Fixed to underlying tissue
q Multiple
q Non-tender
q > 2 cm in diameter
q located in unusual sites
- Presenting Signs and Symptoms
Extremely variable and relate to site and extent of the disease
- Most lymphomas are B-cell malignancies and may be accompanied by immunohemolytic anemia or immunothrombocytopenia
- Non-Hodgkin’s lymphomas
Ø multicentric
Ø tend to spread widely early in the disease
Ø peripheral blood leukemic phase is not uncommon
- Lymphomas have a peak incidence in the late 50s. Although it is rare in children and young adults, it is usually an aggressive and potentially rapidly fatal disease in this age group.
Classification of Lymphomas
- classification takes into account
1) nodal architecture
2) degree of cellular differentiation
3) Immunologic classification (80% are B cell in origin)
NCI Working Formulation of Non-Hodgkin’s Lymphomas
Diffuse, small lymphocytic
Low Grade Follicular, predominantly small cleaved cell
Follicular, mixed, small cleaved and large cell
Follicular, predominantly large cell
Intermediate grade Diffuse, small cleaved cell
Diffuse, mixed, small and large cell
Diffuse, large cell
Large Cell immunoblastic
High Grade Lymphoblastic
Small noncleaved cell
Staging of Lymphomas
- prognosis can be predicted by the stage of the disease
- Lymphangiography, laparotomy, and splenectomy are commonly used in determining the stage
Modified Definitions of Clinical Stages of Lymphomas
I Involvement of a single lymph node region or single organ
II Involvement of 2 or more lymph node regions on same side of the diaphragm or with limited extranodal tissue
III Involvement of lymph node regions on both sides of the diaphragm
IV Multiple or disseminated loci or involvement of one or more extra-lymphatic organs or tissues
- The suffix A or B can be added depending on whether the patient has systemic signs and symptoms (B= fever, night sweats, or unexplained weight loss)
Therapy of Lymphomas
- combination chemotherapy usually
- Vincristine, prednisone, cyclophosphamide, Adriamycin, methotrexate
Prognosis of Lymphomas
- Low grade Lymphomas
Ø typically slow growing
Ø quick to respond to relatively little chemo or radiation
Ø frequently require little or no therapy for months to years
Ø HIGH recurrence RATE
Ø 55-65% 10 year survivors
Ø 5-15% 10 year disease free survivors
- High Grade Lymphomas
Ø aggressive
Ø high growth rate
Ø short natural history
Ø resist mild forms of therapy
Ø high % of those that achieve remission (40-60%) continue in remission long term after chemo
Specific Lymphomas:
Diffuse Small Lymphocytic Lymphoma
- low grade lymphoma
- 1o occurs in older patients
- B cell in origin
- Involvement of the bone marrow is present in almost all cases
- Frequently spills out into the peripheral blood – corresponds to Chronic Lymphocytic Leukemia
Follicular Small Cleaved Cell Lymphoma
- most common form of follicular NHL
- B cell in origin
- Have irregular “cleaved” nuclear contour, characterized by prominent clefts and nuclear foldings
- Characteristic cytogenetic abnormality: t(14:18)
Diffuse Large Cell Lymphoma
- one of types of NHL seen in AIDS patients
- currently classified as intermediate type – but will likely be reclassified as high-grade
Lymphoblastic Lymphoma
- Closely related to T-cell acute lymphoblastic leukemia (ALL)
- Affects predominantly males (2:1)
- MOST patients under 20 years of age
- Prominent mediastinal mass
- Rapidly progressive with early dissemination to bone marrow and meninges common
Small Noncleaved Cell Lymphoma (Burkitt’s Lymphoma)
- African Burkitt’s has strong association with EBV
- t(8:14) involving the c-myc oncogene
- In Africa, usually presents as a jaw mass
- In U.S., occurs more commonly in the GI tract or gonads
Ø occurs mostly in children and young adults
Ø common type of lymphoma in AIDS patients
- MICRO
Ø tumors cells are large lymphoid cells
Ø dark blue cytoplasm
Ø small vacuoles
Ø blast-like nucleus
- In tissue sections…
Ø starry-sky appearance due to benign macrophages distributed among the tumor cells
Adult T-Cell Leukemia/Lymphoma
- Uncommon type of NHL
- Associated with the HTLV-1 virus
Ø virus has tropism for CD4+ cells
Ø very long latent period (can be decades)
- Skin lesions, generalized lymphadenopathy, hepatosplenomegaly, hypercalcemia, and an elevated WBC with multilobulated lymphocytes
- Extremely aggressive – median survival is 8 mths
Mycosis Fungoides and Sezary Syndrome
Mycosis fungiodes
Ø T cell (CD4+) lymphoma involving skin
Ø Frequent disease progression with nodal and visceral dissemination
- Sezary syndrome
Ø related condition in which the skin has generalized exfoliative erythroderma
Ø associated leukemia of Sezary cells that have the same cerebriform appearance noted in tissue infiltrates of mycosis fungoides
MALT lymphoma
- lymphomas of mucosa associated lymphoid tissue
- low grade
- occur in: stomach, conjunctivae, lung, salivary glands, and skin.
- Often occur when there is a background of chronic immune stimulation
- Usually localized
Tags: Adult T-Cell, agammaglobulinemia, ataxia-telangiectasia, Burkitt's Lymphoma, congenital immunologic disorders, extranodal lymphoma, hepatosplenomegaly, Hypercalcemia, Large Cell Lymphoma, lymphadenopathy, Lymphoblastic Lymphoma, Lymphocytes, lymphomas, Mycosis Fungoides, Non-Hodgkin's Lymphomas, Sezary Syndrome
