Non-Hodgkin's Lymphoma

Non-Hodgkin lymphoma (NHL).

NHL is a heterogeneous group of lymphoproliferative malignancies with differing patterns of behavior and responses to treatment.

NHL usually originates in the lymphoid tissues and can spread to other organs. However, unlike Hodgkin lymphoma, NHL is much less predictable and has a far greater predilection to disseminate to extranodal sites.

Non-Hodgkin Lymphoma

Two main types of Non-Hodgkin’s Lymphoma:

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

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 type

Predisposing factors of NHL.

1- Chromosomal translocations and molecular rearrangements.2- Environmental factors .3- Chemicals that have been linked to development of NHL include a variety of pesticides and herbicides4- chemotherapy and/or radiation therapy are at increased risk of developing NHL.5- Viruses have been implicated in the pathogenesis of NHL, including the Epstein-Barr virus in Burkett lymphoma 6- Immunodeficiency states that seem to predispose to NHL include congenital immunodeficiency states (e.g., ataxia telangiectasia, Wiskott-Aldrich syndrome, 7- Increased incidence of GI lymphomas is observed in patients with celiac sprue and inflammatory bowel disease

Staging of NHL:The stage of NHL describes how many groups of lymph nodes are affected, where they are in the body, and whether other organs such as the bone marrow or liver are involved. Stage 1 The lymphoma is only in one group of lymph nodes, in one particular area of the body.

Stage 2 More than one group of lymph nodes is affected, but all the affected nodes are contained within either the upper half or lower half of the body. The upper half of the body is above the sheet of muscle underneath the lungs (the diaphragm), and the lower half is below the diaphragm.

Stage 3 Lymphoma is present in lymph nodes in both the upper and the lower parts of the body (i.e. in lymph nodes both above and below the diaphragm).

Stage 4 The lymphoma has spread beyond lymph nodes to other lymphatic organs – for example, to sites such as the bone marrow, liver or lungs. The stage usually includes the letter A or B, which describes whether the B symptoms are present or not (e.g. stage 2B).

Clinical Features

• Lymphadenopathy• Cytopenias• Systemic symptoms• Hepatosplenomegaly• Fever• Night sweats

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

Small lymphocytic lymphoma

(B-SLL) represents only about 4% of adult NHL. It usually occurs in adults with generalized lymph node disease (lymphadenopathy).

This disease manifests more often as B-cell chronic lymphocytic leukemia (B-CLL) than as B-SLL

Small cells lymphomaSmall cells lymphoma

Follicular lymphoma It represents 70% of all the low-grade B-cell lymphomas.

It is the second most common lymphoma in the United States and comprises 20% of all NHL. Men and women are affected in nearly equal numbers, and the average age of onset is 55 years.

Most patients tend to have widespread, advanced-stage disease at diagnosis. Despite this fact, the disease is slow to progress

Follicular non-Hodgkin lymphoma (NHL) showing characteristic Follicular non-Hodgkin lymphoma (NHL) showing characteristic nodular pattern in a lymph nodenodular pattern in a lymph node

Diffuse large cell lymphoma

It is the most common type of lymphoma, accounting for approximately one-third of all NHLs, regardless of grade.

Patients typically report a history of a rapidly enlarging, symptomatic mass.

Approximately two-thirds of all patients have widespread disease at diagnosis.

Diffuse large B-cell non-Hodgkin lymphoma (NHL). Large cells with abundant cytoplasm and large round-ovoid nuclei with thick nuclear membrane and multiple prominent nucleoli.

Burkitt’s Lymphoma

African variety: jaw tumor, strongly linked to Epstein-Barr Virus infection.

In U.S., about 50% EBV infection. May present as abdominal mass. Most rapidly growing human tumor.

Typical chromosome abnormality: c-myc oncogene linked to one of the immunoglobulin genes.

Burkitt's lymphoma tends to occur most often in children and in adults with compromised immune systems.

There are three distinct forms of this disease: endemic, sporadic, and immunodeficient.

Endemic Burkitt's lymphoma is seen among the young of equatorial Africa.

Sporadic Burkitt's lymphoma often involves the abdomen, and it spreads to the bone marrow in about 20% of patients.

Burkett lymphoma. Normal architecture is entirely replaced by lymphoma cells and evenly dispersed macrophages, starry sky