NON-HODGKINS LYMPHOMAS



NON-HODGKINS LYMPHOMAS

These are a large group of lymphoid tumors ,most commonly of B-cell origin ,whose clinical presentation and natural history are more variable than in Hodgkins lymphoma.

• They are characterized by an irregular pattern of spread and a significant roportion of patients develops extra nodal disease .

• Classification

• A number of classifications have been used over the years and the more recent one is WHO ( world health organization) classification which includes all lymphoid malignancy as well as lymphomas.

• This classification considers the:

• Morphology.

• Cell of origin (determined in practice by immunophenotype as B,T,NK cells ).

• Clinical features and genotype( karyotype and presence of viral genome).

• WHO classification is divided into:

• 1- B-cell disorders which are comprise 85 % of cases and include( the most common types):

• Precursor B-cell neoplasm: B-cell lymphoblastic leukaemia/lymphoma

• Mature B-cell neoplasm:

B-cell small lymphocytic lymphoma

• B-cell prolymphocytic leukaemia

• Hairy cell leukaemia

• Follicular lymphoma

• Mantle cell lymphoma

• Marginal zone lymphoma

• Burkett's lymphoma

• Diffuse large B-cell lymphoma

• 2- T-cell and NK cells which are comprise 15 % of cases and include( the most common types):

• Precursor T-cell neoplasm: T-cell lymphoblastic leukemia/lymphoma.

• Mature T-cell neoplasm:T-cell prolymphocytic leukaemia

• Aggressive NK-cell leukaemia

• Mycosis fungoides/ sezary syndrome

• Adult T-cell lymphoma/leukaemia

• Low-grade and high grade non-Hodgkins lymphoma:

• The non- Hodgkins lymphoma are diverse group of disease and vary from highly proliferative and rapidly fatal diseases to some of the most indolent and well-tolerated malignancies, so it divided into high grade and low grade disease.

•

• The low grade lymphoma are relatively indolent ,respond well to chemotherapy but are very difficult to cure .

• High-grade lymphoma are aggressive and need urgent treatment but are often curable.

• Clinical features

• 1-Superficial lymphadenopathy : the majority of patients present with asymmetrical painless enlargement of lymph nodes in one or more peripheral lymph node regions.

• 2-Constitutional symptoms :fever, weight loss and night sweating occur less frequently than in Hodgkins lymphoma.

• 3-Oropharyngeal involvement in 5-10 % of patient there is disease of oropharyngeal lymphoid structures (waldeyers ring) which may cause sore throat or noisy breathing.

• 4- Presenting features :anaemia, neutropenia with infections or thrombocytopenia with purpura may be presenting features in patients with diffuse bone marrow disease.

• 5- Abdominal disease :the liver and spleen is often enlarged and involvement of retroperitoneal or mesenteric nodes is frequent. The GIT is the most commonly involved after the marrow and patients may present with acute abdominal symptoms.

• 6- Other organs :skin, brain, testis and thyroid may occur .The skin is primarily involved in two, unusual T-cell lymphomas :mycosis fungoides and Sezary syndrome.

• Investigations

• Histology:

• lymph node biopsy is the definitive investigation and morphological examination is assisted by immunophenotype and genetic analysis ,for B-cell lymphoma, expression of either κ or λ light chains confirms clonality and distinguishes the disease from a reactive node, CD antigens expressed on the tumor cell surface is also useful in diagnosis of malignant lymphoma, trephine biopsy of the marrow is also useful.

• Haematological and biochemical finding:

• 1-Normochromic normochromic anaemia is usual but autoimmune haemolytic anaemia is also occur .

• 2- In advanced disease with marrow involvement ,there may be neutropenia, thrombocytopenia ,or leucoerythroblastic blood picture.

• 3- Lymphoma cells (mantle zone cell, cleaved follicular cells and blast cells ) may be found in the peripheral blood in some patients.

• 4- Trephine biopsy of marrow is valuable , bone marrow involvement is found more frequently in low-grade malignant lymphoma.

• 5- The serum lactate dehydrogenase(LDH) level is raised in more rapidly proliferating and extensive disease and used as prognostic marker.

• 6-Immunoglobin electrophoresis may reveal a paraprotein.

• 7-immunophenotypes of the tumor cells .

• 8- Cytogenetics: various subtypes of non-Hodgkins lymphoma are associated with characteristic chromosomal translocations which are a diagnostic and prognostic value such as translocation (8;14) in Burkitts lymphoma and translocation( 14-18) in follicular lymphoma.

•

•

•

• Specific subtypes of non-Hodgkins lymphom

• Low grade non-Hodgkins lymphoma

Follicular lymphoma

• This is the most common form of non-Hodgkins lymphoma.

• Morphology

• The affected lymph nodes have a nodular appearance .

• The tumor cells are slightly larger than the normal lymphocytes and have angular or cleaved nuclei.

• The nuclear chromatin is coarse and condensed.

• The nucleoli are indistinct ,these cells may be seen in peripheral blood.

• Immunophenotype

• The tumor cells expressed B-cell markers CD19,CD10 and CD20 .

• The neoplastic cells characteristically express BCL2 which is a protein that is prevent apoptosis and absent from normal follicular B-cells.

• Karyotype

• The majority of tumor cells have a characteristic translocation (14;18), this translocation leads to in appropriate expression of BCL2 protein.

• Clinical features

• The patients are middle aged or elderly

• Painless lymphadenopathy .

• Involvement of visceral sites is uncommon but the bone marrow almost always contain lymphoma cells at diagnosis.

• Treatment

• Treatment for patients with localized disease by radiotherapy alone which may achieve cure.

• For disseminated disease (stage II-IV), treatment is with chemotherapy , humanized monoclonal antibody and stem cell transplantation which achieve cure especially in young patients .

• Prognosis

• The median survival from diagnosis is approximately 10 years.

• Lymphocytic lymophoma

• This type is closely related to chronic lymphocytic leukaemia(CLL) and appears to be tissue phase of CLL.

• Many patients with this condition are elderly with slowly progressive disease and may not require treatment for a long periods.

• Treatment is the same that for CLL

• Mantle cell lymphoma

• This type is derived from pre-germinal center cells (mantle zone).

• Morphology

• Mantle cell lymphoma involve lymph nodes in a diffuse or nodular pattern.

• The tumor cells are usually slightly larger than normal lymphocytes and have irregular nucleus and inconspicuous nucleoli.

• The bone marrow is involved in the majority of cases and about 20% of patients have peripheral blood involvement .

•

• Immunophenotype

• The tumor cells expresses B-cell markers like CD19,CD20 and CD5.

• Karyotype

• The tumor cells have t(11;14) translocation ,this translocation dysregulates the expression of cyclin D1,which is a cell cycle regulator .

• Clinical feature

• Most patients presented with lymphadenopathy and fatigue and often there is bone marrow infiltration .

• Treatment

• chemotherapy

• Prognosis

• is poor with median survival is approximately 3 years

• Marginal zone lymphoma

• This type is typically extranodal and usually localized ,mucosa-associated lymphoid tissue (MALT) lymphoma comes into this category and usually arise as a consequences of a pre-existing inflammatory or autoimmune disorders at sites such as stomach and thyroid .

• Gastric MALT lymphoma is the most common form and is preceded by Helicobater pylori infection .

• In the early stages it may respond to antibiotic treatment aimed for elimination of H.pylori infection but chemotherapy and/ or radiotherapy with monoclonal antibody may be needed.

• High grade non-Hodgkins lymphoma:

Diffuse large B-cells lymphoma

• This type typically present with rapidly progressive lymphadenopathy associated with high rate of cellular proliferation .

• Progressive infiltration may affect the bone marrow ,gastrointestinal tract ,the spinal cord ,the kidneys or other organs.

• Treatment

• Chemotherapy and monoclonal antibody.

• Prognosis

• Overall long term survival is approximately 65%.

• Burkitts lymphoma

• This type of lymphoma is endemic in some parts of Africa and sporadic in other areas ,hitologically the endemic and sporadic types are identical but the endemic form is associated with EB virus infection.

• Morphology

• The tumor cells are uniform and intermediate in size and have round or oval nuclei containing two to five prominent nucleoli ,there is moderate amount of basophilic cytoplasm which contain small vacuoles .

• A high mitotic rate is very characteristic of this tumor ,as in cell death ,accounting for the presence of tissue macrophages containing nuclear debris ,because these macrophages are often surrounded by a clear zone space which create (starry sky appearance).

• Immunophenotype

• Mature B-cell express B-cell markers CD 19 and CD20 ,also express surface immunoglobulin: κ and λ light chains.

• Karyotype

• Burkitts lymphoma is always associated with translocation involving the MYC gene on chromosome 8 .

• Clinical features

• Both endemic and non-endemic forms affects mainly children and young adult

• In African patient involvement of maxilla or mandible is the common mode of presentation where as abdominal tumors involving the bowel ,retroperitoneal and ovaries are more common in sporadic cases.

• prognosis

• is poor until the introduction of aggressive chemotherapy regimes

• T-cell lymphoma

• T-cell lymphoma that present with lymphadenopathy rather than extranodal disease are a heterogeneous group of rare tumors and are usually of CD4 phenotype.

• The most important forms are:

• * Mycosis fungoides :is a chronic cutaneous T-cell lymphoma that present with sever pruritus ,deeper organs are affected like lymph node, liver .spleen and bone marrow.

• * Sezary syndrome :there is dermatitis ,erythroderma ,generalized lymphadenopathy and circulating lymphoma cells in the blood ,the cells are usually CD4 positive and have folded or cerebriform nuclear chromatin.

• * Adult T-cell lymphoma/leukaemia: this type associated with human T-cell lymphoma/leukaemia virus type 1 infection and patients presented with lymphadenopathy ,hepatic and splenic enlargement, cutaneous infiltration and hypercacaemia.

• Clinical differences between Hodgkins and non-Hodgkins lymphoma

•

|Non-Hodgkin lymphoma |Hodgkins lymphoma |

|More frequent involvement of multiple peripheral |More often localized to a single axial group of lymph|

|nodes |nodes (cervical,mediastinal,pareortic) |

|Non contiguous spread |Contiguous spread |

|Mesenteric nodes and walderers ring commonly |Mesenteric nodes and waldeyers ring rarely involved |

|involved | |

|Extranodal involvement common |Extranodal involvement uncommon |

•

•

•

•

•

•

•

................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download