Non-Hodgkin’s Lymphoma

I Nyoman Suetri Tapayana0502005049

Lymphoma

• History and Overview• Statistics• What it effects (biology)• Classification and Staging• Symptoms• Causes and Risk Factors• Diagnosis and Treatment

Lymphoma’sWhere They Begin

• Lymphomas are a cancer of the lymphatic system– Lymphatic vessels– Lymph nodes

(underarms, groin, neck, spleen, tonsils and bone marrow)

Lymphoma’sWhere They Begin

• The Lymphatic system is our bodies main fight against infection

• Lymphocytes (B-cell and T-cell)– Carried through our lymphatic system and help

our bodies fight infection– Lymphocytes are carried through the lymph

vessels as well as the blood stream, so cancer can start in nodes and spread anywhere throughout the body.

Lymphatic System

American Medical Association

Non-Hodgkin’s Lymphoma Statisticsfor 2004

• 54,370 new cases • 19,410 deaths– In California Alone there are est. 5,550 new cases and a

Death rate of 1,730 (California has the highest incidence and Death rate for Non-Hodgkin’s Lymphoma

– Non-Hodgkin’s Lymphoma is the 6th and 7th most deadly cancers for men and women

– Recent studies have shown that overweight patients are more likely to die then those patients who are in better shape.

Classification

• Usually classified by how the cells look under a microscope and how quickly they grow and spread– Aggressive lymphomas (high-grade lymphomas)

– Indolent Lymphomas (low-grade lymphomas)

WHO/REAL Classification of Lymphoid NeoplasmsB-Cell Neoplasms

Precursor B-cell neoplasmPrecursor B-lymphoblastic leukemia/lymphoma

(precursor B-acute lymphoblastic leukemia)Mature (peripheral) B-neoplasmsB-cell chronic lymphocytic leukemia / small lymphocytic

lymphomaB-cell prolymphocytic leukemiaLymphoplasmacytic lymphoma‡

Splenic marginal zone B-cell lymphoma (+ villous lymphocytes)*

Hairy cell leukemiaPlasma cell myeloma/plasmacytomaExtranodal marginal zone B-cell lymphoma of MALT typeNodal marginal zone B-cell lymphoma

(+ monocytoid B cells)*Follicular lymphomaMantle cell lymphomaDiffuse large B-cell lymphoma

Mediastinal large B-cell lymphomaPrimary effusion lymphoma†

Burkitt’s lymphoma/Burkitt cell leukemia§

T and NK-Cell NeoplasmsPrecursor T-cell neoplasm

Precursor T-lymphoblastic leukemia/lymphoma(precursor T-acute lymphoblastic leukemia

‡ Formerly known as lymphoplasmacytoid lymphoma or immunocytoma II Entities formally grouped under the heading large granular lymphocyte leukemia of T- and NK-cell types* Provisional entities in the REAL classification

Mature (peripheral) T neoplasmsT-cell chronic lymphocytic leukemia / small

lymphocytic lymphomaT-cell prolymphocytic leukemiaT-cell granular lymphocytic leukemiaII Aggressive NK leukemiaAdult T-cell lymphoma/leukemia (HTLV-1+)Extranodal NK/T-cell lymphoma, nasal type#

Enteropathy-like T-cell lymphoma**Hepatosplenic γδ T-cell lymphoma*Subcutaneous panniculitis-like T-cell lymphoma*Mycosis fungoides/Sézary syndromeAnaplastic large cell lymphoma, T/null cell,

primary cutaneous typePeripheral T-cell lymphoma, not otherwise characterized Angioimmunoblastic T-cell lymphomaAnaplastic large cell lymphoma, T/null cell,

primary systemic typeHodgkin’s Lymphoma (Hodgkin’s Disease)

Nodular lymphocyte predominance Hodgkin’s lymphomaClassic Hodgkin’s lymphoma

Nodular sclerosis Hodgkin’s lymphoma (grades 1 and 2)Lymphocyte-rich classic Hodgkin’s lymphomaMixed cellularity Hodgkin’s lymphomaLymphocyte depletion Hodgkin’s lymphoma

† Not described in REAL classification § Includes the so-called Burkitt-like lymphomas** Formerly known as intestinal T-cell lymphoma # Formerly know as angiocentric lymphoma

Indolent (35%)

Diffuse largeB-cell (31%)Armitage et al. J Clin Oncol. 1998;16:2780–2795.

Mantle cell (6%)

Peripheral T-cell (6%)

Other subtypes with a frequency 2% (9%)

Frequency of NHL Subtypes in Adults

Composite lymphomas (13%)

Ann Arbor Staging SystemStage

I involves a single lymph node region (I) or localized involvement of a single extralymphatic organ or site (IE)

II involves 2 or more lymph node regions on the same side of the diaphragm (II) or localized involvement of a single associated extralymphatic organ in addition to criteria for stage II (IIE)

III involves lymph node regions on both sides of the diaphragm (III) that also may be accompanied by localized involvement of an extralymphatic organ or site (IIIE), spleen (IIIS), or both (IIISE)

IV represents disseminated or multifocal involvement of one or more extralymphatic sites with or without associated lymph node involvement or isolated extralymphatic organ involvement with distant (nonregional) nodal involvement

Subscript letters designate involvement of extralymphatic organs, as follows: L, lung; H, liver; P, pleura; O, bone; M, bone marrow; and D, skin. The designation E is used when extranodal lymphoid malignancies arise in tissues that are separate from but near the major lymphatic aggregates

stages I-IV can be appended by A or B designations. Patients with A disease do not have systemic symptoms. The B designation is applied in patients with any of the following symptoms: unexplained loss of more than 10% of body weight in the preceding 6 months before diagnosis, unexplained fever with temperature above 38°C, and drenching night sweats

Non-Hodgkin’s Lymphoma

• Two main types of Non-Hodgkin’s Lymphoma:

B-Cell and T-Cell Lymphomas–B-Cell lymphomas (80%)–T-Cell lymphomas (15%)

B-Cell Lymphoma (80%) • B-Cells help make antibodies, which are proteins that

attach to and help destroy antigens• Lymphomas are caused when a mutation arises

during the B-cell life cycle• Various different lymphomas can occur during

several different stages of the cycle– Follicular lymphoma, which is a type of B-cell lymphoma is

caused by a gene translocation which results in an over expressed gene called BCL-2, which blocks apoptosis.

B-Cell Cancers

T-Cell Lymphoma (15%)

• The T-cells are born from stem cells, similar to that of B-cells, but mature in the thymus.

• They help the immune system work in a coordinated fashion.– These types of lymphomas are categorized by how

the cell is affected• Anaplastic Large cell Lymphoma, t-cell lymphoma

caused by a gene translocation in chromosome 5

Lymphoma.org

Symptoms

• Painful Swelling of lymph nodes located in the neck, underarm and groin.

• Unexplained Fever• Night Sweats• Constant Fatigue• Unexplained Weight loss• Itchy Skin

Cancer Sourcebook

Causes and Risk Factors

• The Exact causes are still unknown– Higher risk for individuals who:• Exposed to chemicals such as pesticides or solvents• Infected w/ Epstein-Barr Virus• Family history of NHL (although no hereditary pattern

has been established)• Infected w/ Human Immunodeficiency Virus (HIV)

Lymphoma.org

Diagnosis• CBC

– Counts within the reference range in the early stage of disease– Anemia secondary to bone marrow infiltration, autoimmune hemolysis

(particularly associated with small lymphocytic lymphoma [SLL]/chronic lymphocytic leukemia [CLL]), bleeding, anemia of chronic disease

– Thrombocytopenia, leukopenia, or pancytopenia secondary to bone marrow infiltration or autoimmune cytopenias

– Lymphocytosis with circulating malignant cells (common in patients with low-grade lymphomas)

– Thrombocytosis (paraneoplastic syndrome associated with lymphomas or reactive secondary to blood loss)

• Chemistries– Elevated lactate dehydrogenase (LDH) - Poor prognostic factor, correlation with

increased tumor burden– Abnormal liver function test (LFT) results - Secondary to hepatic involvement,

hypermetabolic tumor growth, chronic inflammation– Hypercalcemia - In patients with acute form of adult T-cell lymphoma-leukemia (ATLL)

Diagnosis• X-Rays

– ¼ of patients with NHLs, including identification of hilar or mediastinal adenopathy, pleural or pericardial effusions, and parenchymal involvement

• CT scans – to detect enlarged lymph nodes, hepatosplenomegaly, or filling defects in the liver and

spleen. most widely for initial staging, assessing treatment response, and conducting follow-up

• Magnetic Resonance Imaging (MRI)• Biopsy Excisional lymph node biopsy

– for staging rather than diagnostic– the neoplastic cells may infiltrate in a focal (ie, paratrabecular or nonparatrabecular,

depending on the type of lymphoma), interstitial, or diffuse pattern

• Lymphangiogram– Pictures of the lymphatic system taken w/ x-ray after a special dye is injected to illuminate

lymph nodes and vessels

Treatment

• Non-Hodgkin’s Lymphoma is usually treated by a team of physicians including hematologists, medical oncologists and a radiation oncologist.

• In some cases such as for Indolent lymphomas, the Doctor may wait to start treatment until the patient starts showing symptoms, known as “watchful waiting”

Treatment Options

• Chemotherapy• Radiation• Bone Marrow Transplantation• Surgery• Bortezomib (Velcade)• Immunotherapy

• Using the bodies own immune system combined with material made in a lab.

Survival Rates

• Survival Rates vary widely by cell type and staging.

– 1 Year Survival Rate: 77%

– 5 Year Survival Rate: 56%

– 10 Year Survival Rate: 42%

Cancer.org

International Prognostic Index