LymphomaLymphoma

Dr: Abdelaty Shawky Dr. Gehan Mohamed

Learning objectivesLearning objectives

• Recognizing the definition of lymphoma.• Listing the classification of lymphoma.• Understanding the pathological features of non-

Hodgkin's and Hodgkin's lymphoma.• Understanding the Diagnosis and staging of

lymphoma.

Normal structure of reactive lymph node

Microscopic picture of reactive lymphoid follicles

LymphomaLymphoma• Definition: malignant neoplasm of lymphoid origin,

typically causing solid tissue mass usually in form of

lymphadenopathy but may be presented as extra

nodal mass as in brain or intestine.

Epidemiology of lymphoma

• 5th most frequently diagnosed cancer in both sexes.

• Males > females.

* Causes of lymphoma:

• Genetic alterations causing mutations in chromosomes.

• Infection specially with viruses as Human T- cell leukemia Lymphoma virus, Epstein Bar virus.

• Immunosuppression.

* WHO classification of lymphoid neoplasms:

I. Non-Hodgkin’s lymphoma:I. Non-Hodgkin’s lymphoma:a. B cell lymphoma.b. T cell lymphoma.

II. Hodgkin lymphoma.II. Hodgkin lymphoma.

I. Non-Hodgkin’s I. Non-Hodgkin’s lymphomalymphoma

(NHL)(NHL)

B. Cell lymphomasB. Cell lymphomasA. Precursor B. cell lymphoma: • Lymphoblastic leukemia/ Iymphoma

B. Peripheral B. Cell lymphoma:• Chronic Iymphocytic leukemia/small Iymphocytic Iymphoma.• Lymphoplasmacytic lymphoma• Mantle cell Iymphoma:• Follicular Iymphoma• Marginal Zone Lymphoma.• Burkitt Iymphoma

• B-cell lymphomas constitute the vast majority of lymphomas, accounting for nearly 90% of all lymphomas.

• Immunosuppression, specifically due to HIV infection and immunosuppressive therapy, is associated with a markedly increased incidence of developing mature B-cell lymphomas, particularly diffuse large B-cell lymphoma and Burkitt's lymphoma.

• Diffuse large B-cell lymphoma and follicular lymphoma are the most common types.

• Follicular lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma. marginal zone B-cell lymphoma and lymphoplasmacytic lymphoma, which are generally indolent, but incurable and usually present in a disseminated stage with bone marrow involvement.

• Mantle cell lymphoma and diffuse large B-cell lymphoma represent “intermediate-grade B-cell lymphomas” that generally show a more aggressive clinical behavior, but are potentially curable.

• Burkitt's lymphoma and precursor B-lymphoblastic leukemia/lymphoma are high-grade B-cell lymphomas.

T. CELL and NK cell lymphomasT. CELL and NK cell lymphomasA. Precursor T cell lymphoma: - Lymphoblastic leukemia/lymphoma.

B. Peripheral T-cell and NK cells lymphomas:• Aggressive NK cell leukemia• Nasal and nasal-type NK/T cell Iymphoma.• Mycosis fungoides and sezary syndrome .• Angio-immunoblastic T-cell Iymphoma.• Adult T-cell leukemia/lymphoma (HTLV1+).• anaplastic large cell Iymphoma (ALCL).• Peripheral T. cell lymphoma, unspecified.

• Mature T. cell and natural killer (NK). cell lymphomas are rare, accounting for only 10% to 12% of all Non-Hodgkin lymphoma, and usually are more aggressive than B-cell lymphomas.

• The most common subtypes are peripheral T-cell lymphoma, unspecified and anaplastic large cell lymphoma.

• In general, T-cell and NK-cell malignancies are much more common in Asia and are linked to viral infection with EBV (NK-cell lymphomas) and human T-cell leukemia virus (HTLV-1) (adult T-cell leukemia/lymphoma).

* Sites for non Hodgkin lymphoma:

A. Nodal lymphoma:- Start in the lymph nodes.

B. Extra-nodal lymphoma: - Intestine - Central nervous system - Skin - Brain - testis - spleen - ovary

* Clinical manifestations:• Asymptomatic.• Weight loss, anorexia.• Local manifestations:

• lymphadenopathy, splenomegaly most common• any tissue can be infiltrated .e.g brain, intestine,

testis,……

* Diagnosis of lymphoma:

A. Gross examination:- The affected tissue (lymph node, spleen, others are enlarged, soft fleshy, grayish with foci of hemorrhage and necrosis)

B. Microscopic examination: requires an adequate biopsy before treatment is initiated so we do :

- Haematoxylin and eosin stained sections.

- immunohistochemical stained sections using tumor markers.

NHL, Lymph nodes

NHL, Spleen

NHL, small intestine

* Microscopic picture of Non Hodgkin lymphoma:• Lost normal histologic architecture of the lymph

nodes.• Diffuse infiltration of the lymph node by

monoclonal type of malignant lymphocytes.• Immunohistochemical staining can help in the

diagnosis as: - T cell lymphoma are +ve for CD3.- B cell Lymphoma are +ve for CD20

Microscopic picture of reactive lymphoid follicles

Non Hodgkin Lymphoma (H&E)

Intestinal lymphoma

Immuno-histochemical diagnosis for NHL using CD20 for B cell lymphoma

Hodgkin lymphoma

Thomas Hodgkin(1798-1866)

* Epidemiology of Hodgkin’s lymphoma:

• Less frequent than non-Hodgkin lymphoma.• Peak incidence: two peaks; 15-35 and 50-70

years. • The patients usually presented by enlarged

lymph nodes and may be associated with systemic manifestations in advanced cases.

Classical Hodgkin Lymphoma

* Etiology of Hodgkin’s lymphoma:

• Epstein Bar Virus infection.• May associate Human Immunodeficiency Virus

infection.• possible genetic predisposition.

* A possible model of pathogenesis:

germinalcentreB cell

transformingevent(s)

loss of apoptosis

RS cellinflammatory

response

EBV?

cytokines

* Cell of origin: •B-lymphocyte present in germinal centre can change to Reed-Sternberg cells which is the malignant cell. •The surrounding white blood cells in the affected lymph node are reactive cells ( polyclonal) not neoplastic cells.

Hodgkin lymphoma

Reed-Sternberg cell

* Microscopic picture of Hodgkin lymphoma:

• Lost normal histologic architecture of the lymph node and replacement by:

• Reed sternberg giant cells. • Reactive mixed inflammatory cells. • Immunohistochemically: • R.S cell is +ve for CD15, CD30.

* Classification of Hodgkin's lymphoma:

A. Nodular lymphocyte predominance Hodgkin Iymphoma.B. Classical Hodgkin Iymphoma which include:

– Nodular sclerosis HL.– lymphocyte predominance HL.- Lymphocyte depleted HL.– Mixed cellularity HL.

RS cell and variants

popcorn celllacunar cellclassic RS cell(mixed cellularity

Hodgkin lymphoma)(nodular sclerosisHodgkin lymphoma)

(lymphocytePredominanceHodgkin lymphoma)

Stage I Stage II Stage III Stage IV

* Staging of Hodgkin lymphoma:

A: absence of B symptomsB: fever, night sweats, weight loss

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