Haem - Lymphoma 1 and 2 Flashcards
(45 cards)
Define lymphoma
Neoplastic (malignant) proliferation/tumour of lymphoid cells to form discrete tissue masses
In which sites may lymphoma be found
Lymph nodes, bone marrow and/or blood (the lymphatic system)
Lymphoid organs; spleen or the gut-associated lymphoid tissue
Skin (often T cell disease; e.g. Mycoses Fungoides)
Rarely “anywhere” (Sanctuary sites: CNS, ocular, testes, breast, etc.)
What are the types of lymphoid malignancies
Hodgkin’s
- Classical
- Nodular lymphocyte predominant
Non-Hodgkin’s
- B cell (most common - 80%)
- T cell
What are the types of classical Hodgkins lymphoma
Nodular sclerosing
Mixed cellular
Lymphocyte depletion
Lymphocyte rich
What are the types of B cell non-Hodgkin lymphoma
Low grade
MALToma
Small lymphocytic lymphoma (CLL)
Follicular
High grade
Diffuse large B cell lymphoma (DLBCL)
Mantle cell
Aggressive
Burkitt’s
What are the types of T cell non-Hodgkin lymphoma
Anaplastic large cell lymphoma
Adult T cell leukaemia lymphoma (ATLL)
Enteropathy-associated T-cell lymphoma (EATL)
Cutaneous (mycoises fungoides)
What are the positives and negatives of DNA instability in the immune system
Positive
Allows for recombination → diversity
Rapid proliferation for rapid response to infection
Apoptosis dependency for specificity, elimination of self-reactive clones
Negative
Recombination → unwanted point mutations
Rapid proliferation → replication errors
Apoptosis dependency: apoptosis may be switched off
What are the stages of immunoglobulin and TCR gene recombination
- VDJ recombination in the bone marrow involving RAG1 and RAG2
- Class switch recombination: somatic hypermutation in the germinal centre - heavy chain of Ig changed and the oncogenes are brought closer to the promoter
What are the divisions of the lymphoreticular system
- Generative lymphoreticular (LR) tissue - generation/maturation of lymphoid cells in bone marrow and thymus
- Reactive LR - immune reaction in lymph nodes and spleen
- Acquired LR tissue - local immune reaction in extra-nodal tissue (skin, stomach, lungs)
Describe the histology of a lymph node
Germinal centre of B cells and antigen presenting cells
Surrounded by the mantle zone - naive, unstimulated B cells
Surrounded by a paracortical T cell zone
Lymph node sinuses between follicles
What investigations should be done for lymphoma
Bloods:
- LDH: raised
- Albumin
- U&Es
- HIV, hep B serology ± HTLV-1 (ensure hep B will not reactivate)
Anatomical stage
- bone marrow biopsy
- CT/PET
- Lumbar puncture if risk of CNS involvement
Cytology (cells aspirated from lump)
Histology (tissue sections)
Cytogenetics
FISH - chromosomal translocations
PCR - chromosomal translocations, gene rearrangement
What are the lymphoma CD markers for NHL
CD19, CD20 = B-cells
CD3, CD5 = T-cells
Which Ig are associated with B cell lymphomas
Follicular NHL: IgH-BCL2
Mantle Cell lymphoma: IgH-Cyclin D1
Burkitt Lymphoma: IgH-MYC
What are the symptoms of lymphoma
Painless progressive lymphadenopathy (neck, axilla groin)
Compression symptoms
- Renal failure
- Obstructive jaundice
- Large blood vessels
- Bowel obstruction
- Trachea
- Oesophageal
Infiltration
- Brain: stroke, lOC, memory problems
- Skin rash: plaques, ulceration, nodules
- Ocular: blindess
- Liver: liver failure
Recurrent infections
B symptoms: fever, night sweats, weight loss
What should be looked at for histology of a lymphoma
- Architecture: nodular, diffuse
- Histology: small round, small cleaved, large cells
Immunophenotyping: - Cell types (CD markers)
- Cell distribution
- loss of surface proteins
- Abnormal expression of proteins
- Clonality of B cells
What are the features of follicular lymphoma (epidemiology, time course, molecular, histopathology)
Middle-aged or elderly
Indolent, relatively incurable
t(14;18) involving bcl-2 gene
Histo: neoplastic follicles, positive CD10 and bcl-2 staining, centroblasts (lymph node biopsy)
What are the features of small lymphocytic lymphoma (association, epidemiology, histopathology)
CLL
Associated with Richter transformation (presents with NEW B symptoms)
Middle aged or elderly
Histo: small lymphocytes, arises from naive B cells, CD5 and CD23 positive
What are the features of marginal zone lymphoma/MALToma (cause, timeline, management)
Response to chronic antigenic stimulation
Post germinal centre memory B cell
Indolent but could transform
Management: remove the antigenic stimulation
Give examples of MALT and their causes
H. pylori → gastric
Sjogren’s → parotid gland
Hashimotos → thyroid MZL
Psittaci infection → lacrimal gland
What are the features of diffuse large B cell lymphoma (epidemiology, histopathology, prognosis)
Middle aged and elderly
Histo: from germinal centre/post-germinal centre, sheets of large lymphoid cells
p53+: Poor prognosis
What are the features of mantle cell lymphoma (epidemiology, histopathology, molecular associations, prognosis)
Middle aged males
Histo: seen in the mantle zone, arising from pre-germinal centre cells, expression of CD5 and cyclin D1, clefted nuclei
Molecular: t(11;14), cyclin D1 overexpression
Prognosis: 2-5 years
What are the features of Burkitt’s lymphoma (presentation, association, histopathology, molecular associations)
Jaw/abdo mass when young
Associated with EBV
Histo: starry-sky appearance, arises from germinal centre cells
Molecular: C-myC translocation (8;14) OR (2;8) OR (8;22)
What are the features of anaplastic large cell lymphoma (epidemiology, histopathology, molecular associations, prognostic factors)
Younger patients
Histo: large epithelioid lymphocyte, anaplastic
Molecular: t(2;5)
Alk-1 protein expression = better prognosis
Describe enteropathy associated T-cell lymphoma (cause and association, histology, presentation, response to treatment, prevention)
Caused by chronic antigen stimulation to gluten/gliadin → associated with coeliac disease
Histology: Mature T cells TdT, CD19
Presentation:
- Abdo pain, obstruction, perforation, GI bleeding
- Malabsorption
- Systemic symptoms
Responds poorly to chemotherapy, generally fatal
Can be prevented by strict adherence to a gluten-free diet
