Molecular Pathology of Lymphomas

Details

Title

Molecular Pathology of Lymphomas

Type

Stage Two

Module code

HLS325

Requirement

Compulsory

Module objective

By the end of the training period trainees will, in respect to the molecular pathology of lymphomas be able to

• analyse, synthesise, evaluate and apply knowledge
• perform, adapt and master a range of technical and clinical skills and procedures and
• demonstrate the attitudes and behaviours necessary for professional practise as a Consultant Clinical Scientist dealing with the complexities, uncertainties and tensions of professional practise at this level.

Knowledge and understanding

By the end of the training period the trainee will be able to demonstrate the ability to analyse, evaluate and synthesise relevant knowledge and its application to their professional practice in relation to:

• Entity and not “grade” based principle of classification of lymphoid malignancies including recognition of clinical, morphological, immunophenotypic and genetic features required for accurate characterisation of individual entities.
• Entities recognised in the current WHO classification of lymphoid neoplasms (2008 revision) including:
  • Mature B-cell neoplasms: Chronic lymphocytic leukaemia / small lymphocytic lymphoma : B-cell prolymphocytic leukaemia : Splenic marginal zone lymphoma: Hairy cell leukaemia: Splenic lymphoma/leukaemia (unclassifiable) including splenic diffuse red pulp small B-cell lymphoma and hairy cell leukaemia variant: Lymphoplasmacytic lymphoma: Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma): Nodal marginal zone lymphoma: Follicular lymphoma: Primary cutaneous follicle centre lymphoma: Mantle cell lymphoma : Diffuse large B-cell lymphoma not otherwise specified and specific variants of large B-cell lymphomas: Burkitt lymphoma: B-cell lymphoma, unclassifiable, with features intermediate between large B-cell lymphoma and Burkitt lymphoma: B-cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma and classical Hodgkin lymphoma.
  • Mature T- and NK- cell neoplasms: T-cell prolymphocytic leukaemia: T-cell large granular lymphocytic leukaemia: Chronic lymphoproliferative disorder of NK cells: Aggressive NK cell leukaemia: EBV-positive T-cell lymphoproliferative disorder of childhood: Adult T-cell leukaemia/lymphoma: Extranodal NK/T cell lymphoma nasal type: Enteropathy associated T-cell lymphoma: Hepatosplenic T-cell lymphoma: Subcutaneous Panniculitis-like T-cell lymphoma: Mycosis fungoides: Sezary syndrome: Primary cutaneous CD30 positive T-cell lymphoproliferative disorder: Primary cutaneous gamma-delta T-cell lymphoma: Primary T-cell lymphoma not otherwise specified: Angioimmunoblastic T-cell lymphoma: Anaplastic large T-cell lymphomas ALK positive and ALK negative.
  • Hodgkin lymphoma: Nodular lymphocyte predominant: Classical Hodgkin lymphoma.
  • Immunosuppression (IS) associated lymphoproliferative disorders (LPD): LPD associated with primary immunodeficiencies: Lymphomas associated with HIV infection: Post transplant lymphoproliferative disorders: Other iatrogenic immunodeficiency associated LPD.
• Epidemiology and pathophysiology of lymphoid neoplasms.
• Clinical, morphological, immunophenotypic, cytogenetic & molecular genetic characteristics of individual lymphoid malignancies.
• Principles of disease staging and prognostication.
• Pathogenetic role and practical diagnostic utility of chromosomal/gene mutations, rearrangements and numerical abnormalities in lymphoid malignancies including:
  • Immunoglobulin and other gene somatic hypermutation: p53: CCND1: BCL2: BCL6: MUM1: PAX5: BCL10: MALT1/2: MYC: ALK
• Activity of specific molecular pathways as basis for specific and targeted therapies (different mechanisms of activation of NF-kB pathway: MYC and BCL2 gene expression analysis by immunohistochemistry and clinical/therapeutic implications).
• Role of B and T cell clonality in diagnosis.
• Design and technical aspects of clonality assessment utilising the BIOMED-2 primer sets.
• Most common reactive conditions in the differential diagnosis of lymphomas with emphasis on pitfalls in clonality assessment:
  • Non-specifc follicular and paracortical hyperplasia: Viral lymphadenitidies including infectious mononucleosis, Infectious granulomatous lymphadenitidies and sarcoidosis, Autoimmune disease associated lymphoid hyperplasia, Kikuchi lymphadenitis, Light chain restricted reactive B-cell lymphoid proliferations.
• Minimal residual disease.

Technical and clinical skills

By the end of the training period the trainee will be able to demonstrate a critical understanding of current relevant research, theory and knowledge and its application to the performance, adaptation and mastery of the following skills to:

• Have a knowledge of practical laboratory aspects of lymphoma diagnosis including conventional histology, immunohistochemistry, in situ hybridisation, flow cytometry, conventional and interphase genetic investigations and molecular studies.
• Have a multidisciplinary laboratory approach to lymphoma diagnosis incorporating histology, immunhistochemistry, flow cytometry, genetic and molecular data.
• Produce a fully interpretative clinical diagnostic laboratory report and incorporate diagnostic data into integrated pathology reports.

By the end of the training period the trainee will be able to apply knowledge of the molecular pathology of lymphomas to perform, adapt and master the clinical skills necessary to manage and understand the:

• clinical presentation, staging, prognosis and basic principles of lymphoma management including “targeted” therapies.
• impact of genetic/molecular features and other biomarkers on clinical management and targeted/individualised therapies of lymphoma.
• mechanisms of drug resistance including resistance-mutations.
• role of MRD monitoring in the clinical management of lymphoid neoplasms.