Haem - Lymphoma 1 and 2 Flashcards
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
What are the associations with Adult T cell leukaemia lymphoma (ATLL)
HTLV-1 infection
Japanese and Caribbean ethnicity
Histo: flower cells
What is cutaneous T cell NHL associated with
Mycosis fungoides
What is the epidemiology of Hodgkin’s lymphoma
1% of all cancer
Less common than non-Hodgkin’s
M > F
Bimodal age - 20-29yo (most common), >60yo (smaller peak)
What are the symptoms of Hodgkin’s lymphoma
Asymmetric painless lymphadenopathy
Pain in nodules after alcohol ingestion
What are the diagnostic features of hodgkin’s lymphoma on investigation
From germinal centre OR post-germinal centre
Associated with EBV
Histo: sclerosis, Reed-Sternberg cells (binucleate), lymphoma cells, Eosinophils
Markers: CD30+, CD15+, CD20 -ve
Describe the features of nodular sclerosing HL sub-type (epidemiology, symptoms)
Young women (20-29)
Neck nodes and a mediastinal mass → SVC or trachea compression
Spreads contiguously
What are the features of nodular lymphocyte predominant lymphoma (presentation, association, histopathology, diagnostic markers)
Isolated lymphadenopathy
May transform to a high grade B cell NHL
Histo: b cell rich nodules, NO eos/macro
NEGATIVE for CD30 + CD15 (which is seen in classical Hodgkin)
POSITIVE for CD20
Describe the staging of lymphoma
Ann Arbor Staging
A = B symptoms absent
B = B symptoms present
E = involvement of single, contiguous, or proximal extranodal site
I: One node region involved on 1 side of the diaphragm
II: 2+ ipsilateral regions involved on 1 side of the diaphragm
III: Bilateral node involvement on both sides of the diaphragm
IV:
HL: Involvement of extranodal sites beyond those designated by ‘E’ (below)
NHL: Disseminated/multifocal involvement of ≥1 extralymphatic site OR isolated extralymphatic organ involvement with distant node involvement
Describe the treatment of Hodgkin’s lymphoma
Chemotherapy: ABVD (2-6 cycles, 4-weekly intervals) - adriamycin, bleomycin, vinblastine, DTIC (Dacarbazine)
± radiotherapy
Second line: salvage chemotherapy (high dose chemo + HSCT)
Third line: anti-CD30 (Brentuximab Vedotin)+ anti-PD1(nivolumab)
What is the management for NHL
Chemotherapy: R-CHOP (6-8 cycles) - rituximab, cylophosphamide, adriamycin, vincristine, prednisolone
Second line: autologous HSCT
What is the prognosis for NHL
Burkitt’s lymphoma – fastest growing human cancer
Follicular lymphoma (an indolent disease) – possible 25 year survival
HOWEVER, chance of being cured increases with more aggressive neoplasms
What are the prognostic markers for NHL
LDH (marker of cell turnover)
Performance status
HIV serology
Hep B serology (treatment for lymphoma may cause a dormant hep B to reactivated → fulminant liver failure)
What is a common complication of Chemotherapy + radiotherapy for Hodgkin’s lymphoma
Risk of damage to normal tissues (collateral damage)
Associated with increased risk of breast/lung/skin cancer, leukaemia/myelodysplasia
What is the prognosis for Hodgkin’s lymphoma
Elderly patients do worse than the worst-prognosis HL (lymphocyte-depleted type)
It is a highly curable disease, but the prognosis depends on stage
Over 80% in stage I or II disease are cured
50% of stage IV are cured
10% die from relapse within 10 years and 10% die from complications after 10 years
More likely to die of secondary malignancy of CV complications after 5 years
What phenotype is indicative of CLL
Normal T cells are CD5 positive, and CD 19 and 20 negative. While normal B cells are the other way around.
CLL B cells have an unusual phenotype (Monoclonal lymphocytosis with abnormal expression of CD5 = highly suggestive of CLL)
What is the phenotype of T cells
CD3 positive
CD4 or CD8 positive (Th-cell, CTL cell)
CD19 NEGATIVE
CD5 POSITIVE
What is the prognosis for CLL
In a disorder of elderly
- 1/3 never progress
- 1/3 Progress, respond to CLL Rx (death from unrelated disorder)
- 1/3 Progress, require multiple lines of Rx, refractory disease, death from CLL
How is CLL staged
Rai and Binet staging
A: <3 lymphoid areas
B: >3 lymphoid areas
C Hb <100, Platelets <100
What are the complications of CLL
Non-functioning B cell production → hypogammaglobulinaemia → increased infection risk e.g. pneumonia, sinusitis
Metastasis to lymphoid organs e.g. lymph nodes, spleen
Bone marrow failure (anaemia, neutropenia thrombocytopenia)
Richter transformation → high grade lymphoma
Regulation of the surviving normal B cell population → autoimmune disease e.g. autoimmune haemolytic anaemia
What are the prognostic lab factors for CLL
Cytogenetics (FISH panel)
Immunoglobulin gene (IgHV) mutation status
- IgH mutated
- IgH unmutated (Bad)
17p deletion
p53 muted
What are the poor prognostic features of CLL
Deletion of 13q (~133 months survival)
Trisomy 12 (~114)
Deletion of 11q (ATM) (~79)
Deletion of 17p (TP53) - loss of p53 tumour
