Lymphoma Flashcards
What percentage of lymphoma is Hodgkins, and Non-Hodgkins?
Hodgkins = 20% Non-Hodgkins = 80%
Clinical Presentation of Hodgkins Lymphoma
Assymetrical painless lymphadenopathy +/- obstructive/mass effect symptoms +/- constitutional symptoms (weight loss, fever, night sweats, pruritis, fatigue.
Pel-Ebstein Fever seen in minority. Can rarely get pain in affected nodes after alcohol.
Epidemiology of Hodgkins Lymphoma
M>F; bimodal age incidence (20-29 and >60)
EBV associated
Investigations for Hodgkins Lymphoma, how is it diagnosed?
CT/PET
Tissue Diagnosis: LN or BM biopsy - cell stain with CD15 & CD30 –> Reed-Sternberg cell on a background of lymphocytes and reactive cells
Definitive diagnosis = LN biopsy, Staged using PET/CT
What are the characteristics of a Reed Sternberg Cell?
In what percentage of cases are the RS cells found to be infected with EBV?
large size (20–50 micrometres), abundant, amphophilic, finely granular/homogeneous cytoplasm; two mirror-image nuclei (owl eyes) each with an eosinophilic nucleolus and a thick nuclear membrane. 50% of cases cells are infected with EBV
What are the subtypes of HL? What is the most common subtype and what are the prognoses for each?
Nodular sclerosing - most common, 80%, good prog.
Mixed cellularity - 17%, good prog
Lymphocyte Rich - rare, good prog
Lymphocyte depleted - rare, poor prog
Nodular Lymphocyte predominant - not classical HL, 5%, (disorder of the elderly, multiple recurrences)
Stages of Hodgkin’s Lymphoma
Stage 1 - one LN region (can include spleen)
Stage 2 - 2 + LN regions on the same side of the diaphragm
Stage 3 - 2+ LN regions on opposite sides of the diaphragm
Stage 4 - extranodal sites (liver, BM)
A: no constitutional symptoms B: Constitutional symptoms
Treatment for Hodgkins Lymphoma
- Combination Chemotherapy - ABVD: Adriamycin, Bleomycin, Vinblastine and Decarbazine; 2-4 cycles in stage 1/2, 6-8 cycle in stage 3/4
- Radiotherapy - used at end of chemo in bulky areas
- Intensive chemo and autologous SCT - for relapsed patients
Prognosis of Hodgkins Lymphoma
Generally v. good: 50-90% cured
50% for stage 4
Worse prog. in older patients and patients with lymphocyte depleted histology.
Describe the process of Autologous SCT, its advantages and when it is used.
Autologous = patients own SCs are harvested and frozen.
Enables high dose chemo +/- radiotherapy to eradicate malignant cells at the cost of partial or even complete bone marrow ablation. Frozen SCs are then reintroduced into patient.
Used: multiple myeloma and lymphoma, particularly with relapse, less used in leukaemia
Advantages: no graft host disease (GVHD) risk and lower risk of infection
Describe the process of Allogenic SCT, its risks and when it is used.
Allogenic = HLA-matched donor SCs are harvested
Patients own BM is completely eradicated by high-does chemo +/- radiotherapy. Donor Scs are introduced to colonise ‘empty’ BM
Used: Leukaemia
Risks: GVHD, opportunistic infections, infertility and secondary malignancies
How is Non-Hodgkins Lymphoma staged (investigation and classification system)?
Name 2 prognostic markers in NHL.
Ix: CT/PET, BM biopsy, LP
Classification: same as Hodgkins Lymphoma
Prognostic Markers: LDH, Performance status
Name 2 long term side effects of chemotherapy treatment for HL.
Pulmonary Fibrosis
Cardiomyopathy
What is Non Hodgkins Lymphoma?
Neoplastic proliferation of lymphoid cells. Originates in lymphoid tissue (lymph nodes, bone marrow, spleen).
No Reed Sternberg cells on biopsy.
Can have a B or T cell lineage/
Presentation of Non Hodgkin Lymphoma
Painless Lymphadenopathy, compression symptoms, B/constitutional symptoms (weight loss, fever, low grade fever, night sweats, pruritis, fatigue)
What are the 3 ways of classifying NHL?
- Mature or Immature
- Histology: High Grade (Very Aggressive, Aggressive), Low Grade (Indolent)
- Lineage: B or T cell
What are the main T-cell lymphomas? (NHL’s with T cell lineage)
Anaplastic large cell lymphoma Peripheral T cell Lymphoma Adult T cell leukaemia/lymphoma Enteropathy-associated T cell lymphoma (EATL) Cutaneous T cell Lymphoma
What are the main B cell Lymphomas?
Burkitt's Diffuse Large B-Cell (DLBC) Mantle cell Lymphoma Follicular Mucosal Associated Lymphoid Tissue (MALT)
Diffuse Large B cell Lymphoma Low Grade/High Grade B/T cell % of NHL Epidemiology
Aggressive (High Grade) B cell NHL
30-40% of all NHL
Epi: Middle aged and elderly
What mixture of drugs is used in R-CHOP (chemotherapy regimen)?
Rituximab, Cyclophosphamide, Adriamycin, Vincristine, Prednisolone
Follicular NHL
Low Grade/High Grade
B/T cell
% of NHL
Indolent/Low Grade B cell NHL
35% of NHL
What genetic mutation is associated with Follicular NHL? What is the physiological result of this mutation?
t(14:18) translocation, results in over expression of bcl2, an anti-apoptosis protein
MALT Low Grade/High Grade B/T cell % of NHL Epidemiology
Indolent/Low Grade B Cell NHL
(Marginal zone NHL involving extranodal lymphoid tissue)
8% of NHL
Epi: 55-60yo
What causes MALT? What disease is it associated with?
Chronic antigen stimulation
H.pylori –> gastric MALT lymphoma
Sjorgen’s syndrome –> parotid MZL (Marginal Zone Lymphoma)
Hashimotos Thyroiditis –> Thyroid MZL
Mantle Cell Lymphoma
Low/High Grade
B/T cell
Epidemiology
Aggressive (High Grade) B cell NHL (disseminated at presentation)
Epi: Middle Aged, M>F
What are the 3 types of Burkitt’s lymphoma?
Endemic, Sporadic, Immuno-deficiency
What is the genetic mutation associated with Burkitt’s lymphoma? How is this expressed?
t(8;14) translocation
c-myc oncogene overexpression
Stereotypical histology of Burkitt’s Lymphoma.
Starry Sky appearance
What is the treatment for Burkitt’s Lymphoma?
Chemotherapy: Rituximab + Leukaemia protocol
SCT
Stereotypical histology of Diffuse Large B-cell Lymphoma.
Sheets of large lymphoid cells
Stereotypical histology of Mantle Cell Lymphoma.
Angular nuclei
Stereotypical histology of Follicular Lymphoma.
Follicular pattern, nodular appearance
Which type(s) of Burkitt’s lymphoma is/are associated with EBV?
Endemic and Sporadic
Which type(s) of lymphoma has a characteristic jaw involvement and abdominal masses?
Endemic Burkitt’s Lymphoma
Which type of lymphoma is most often seen in HIV /post transplant patients?
Immuno-deficiency Burkitts Lymphoma
What genetic mutation is commonly seen in Mantle Cell Lymphoma? How does this mutation present physiologically?
t(11;14) translocation
Cyclin D1 deregulation
Treatment and Prognosis for Mantle Cell Lymphoma
Rx: R-CHOP, Auto-SCT for relapse
Prog: 3-5 years
Treatment and Management of Gastric MALT Stage I-II disease
Treat the cause!
Eradication therapy: Omep 20mg/Clarith 500mg/amox 1gm BD
Repeat breath test at 2 months
Repeat endoscopy every 6 months for 1st 2 years, then annually
Treatment and Prognosis for Follicular Lymphoma
Rx: Watch and wait, only treat if clinically indicated (compression/painful nodes) with R-CVP chemo
Prog: mostly incurable, med survival = 12-15 years
Treatment for Diffuse Large B Cell Lymphoma
Rx: Rituximab-CHOP, Auto SCT for relapse
What is the most common clinical presentation of MALT Lymphomas?
Dyspepsia or epigastric pain - MALT most commonly arises in the stomach
What genetic mutation in MALT is predictive of poor response eradication therapy?
t(11;18) translocation = API2-MLT fusion gene
Where do most Lymphoma chromosomal translocations occur and why? What oncogenes are commonly involved?
Most often translocations involve the Ig locus, because the Ig promoter is highly active in B cells.
Oncogenes: bc12, bc16, Myc, CyclinD1
What 3 components of the lymphocyte ‘lifestyle’ make it particularly susceptible to genetic mutation?
- Rapid Cell proliferation in immune response
- Dependent on apoptosis (90% of normal cells die) to ensure antibody specificity
- DNA molecules are cut and rejoined & undergo deliberate point mutation to generate Ig and T cell receptor diversity
Which diseases are each of these translocations associated with?
a. t(8;14)
b. t(11;14)
c. t(14;18)
a. Burkitt’s Lymphoma
b. Mantle Cell Lymphoma
c. Follicular Lymphoma
Which diseases are each of these translocations associated with?
d. t(2;5)
e. t(9;22)
f. t(11;18)
a. Anaplastic Large Cell Lymphoma
b. (Philidelphia Chromosome!)CML & AML - realise this shouldn’t really be in Lymphoma!
c. MALT
Which Lymphoma is associated with longstanding Coeliac disease?
Enteropathy-associated T cell Lymphoma (EATL)
How are T cell Lymphomas treated?
Alemtuzumab (anti-CD52)
Which Lymphoma is associated with mycosis fungoides?
Cutaneous T cell Lymphoma
Which T cell Lymphomas are considered High Grade/Aggressive?
Anaplastic large cell lymphoma
Peripheral T-Cell Lymphoma
Adult T cell Leukaemia/Lymphoma
What genetic mutation is seen in Anaplastic large cell lymphoma? What protein expression results?
t(2;5)
ALK-1 protein expression
Who (stereotypically) gets: 1. Anaplastic large cell lymphoma 2. Peripheral T cell Lymphoma 3. Adult T cell Lymphoma (Age/Nationality)
- Children and young adults
- Middle aged and elderly
- Caribbean and Japanese
What is believed to be the cause of Adult T cell Leukaemia/Lymphoma?
Human T cell Leukaemia/Lymphotrophic virus type 1 (HTLV-1)
What protein does Rituximab target?
Rituximab is monoclonal antibody again the protein CD20 (primarily found on the surface of B cells)
Histology of Anaplastic Large cell Lymphoma
Large ‘epithelioid’ lymphocytes that express CD30 and T cell markers.
