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9.1 Describe the features considered important by WHO for the classification of lymphoid neoplasms.
The WHO classification was developed from the Revised European American classification of Lymphoid neoplasms (REAL). It incorporates a combination of morphology, immunophenotypic, genetic, molecular and clinical features that help to provide an accurate diagnosis.
9.2 Describe the information that can be obtained with Immunophenotyping techniques.
Immunophenotyping by either immunocytochemistry or flow cytometry provides information on the cellular phenotype of lymphomas. This is achieved through the use of panels of antibodies. Immunocytochemistry provides cellular localisation together with morphology on sequential sections of fixed tissue. By contrast flow cytometry usually provides a simultaneous ‘read out’ for several antibodies using cell suspensions prepared from fresh samples of blood, bone marrow or tissue.
9.3 What are the phases of B-cell development and where do they take place?
Naïve B-cells exit the bone marrow and circulate between blood, lymph node and other secondary lymphoid tissues in search of an antigen that will match the randomly determined B-cell receptors carried on their cell membranes.
9.4 What is meant by the term somatic hypermutation?
Somatic hypermutation is a naturally occurring event where random mutations are introduced into the immunoglobulin genes. This takes place within the germinal centres and the primary function is to convert low affinity into high affinity immunoglobulins.
9.5 When are clonality studies by PCR indicated?
Clonality studies are indicated in three main scenarios.
1. At diagnosis when the differentiation is between a reactive and malignant situation.
2. Minimal residual disease testing for the presence of malignant cells.
3. Prognostic information in the assessment of somatic hypermutation status in CLL.
9.6 What are the two types of chromosomal translocations seen in lymphoid neoplasms?
The main types of translocations are formation of a fusion gene and overexpression of a normal gene. The formation of a fusion gene, coding for chimeric proteins commonly leads to a proliferation advantage or loss of cell cycle control. The overexpression of a normal gene is commonly under the transcriptional control of the immunoglobulin heavy chain gene promoter.
9.7 What are the advantages of FISH over conventional cytogenetics?
Conventional cytogenetics requires dividing cells whereas FISH can use fresh and formalin fixed paraffin embedded tissue. Cytogenetics is more time consuming and labour intensive in comparison to FISH. FISH is also capable of detecting certain deletions and insertions that may be missed by cytogenetics. A disadvantage of FISH is that it can only determine specific gene changes, whereas cytogenetics will assess the entire karyotype in an unbiased manner.