Hodgkin & Non-hodgkin lymphoma Flashcards
What prognosis of stage 1-2 disease of HL is favourable?
- no large mediastinal lymphadenopathy
- ESR < 50 without B symptoms
- ESR < 30 with B symptoms
- Age ≤ 50 years
- 1-3 lymph nodes involved
What prognosis of stage 1-2 disease of HL is unfavourable?
- large mediastinal lymphadenopathy
- ESR ≥ 50 without B symptoms
- ESR ≤ 30 with B symptoms
- 4 or more lymph node sites involved
What are the classical Hodgkin lymphoma types?
- nodular sclerosing
- lymphocyte rich
- mixed cellularity
- lymphocyte depleted
what’s the other type of Hodgkin lymphoma that’s not classical?
Nodular lymphocyte predominant
what is the most widely used regime for early-stage disease?
2 courses of ABVD chemotherapy followed by 20 Gy radiotherapy to the involved field.
note: if lymph nodes are not bulky omit radiotherapy and do 3 courses of ABVD chemo
if early-stage disease is unfavourable what is the regime?
treat with 4 to 6 courses of ABVD followed by 30 Gy radiotherapy for bulky disease
note: or the first 2 cycles can be replaced by BEACOPP
what is the regime used for advanced stage disease?
6 courses of ABVD are most widely used
or BEACOPP can be used but it’s more toxic
Subsequent radiotherapy is given if residual nodes are more than 1.5 cm diameter, or smaller but remain PET positive. T or F.
True
What drug is used alternatively to bleomycin since bleomycin causes pulmonary toxicity?
anti-CD30 monoclonal antibody conjugate Brentuximab (Adecertis).
new regime called AAVD
note: but it can cause febrile neutropenia and it’s more costly
Hodgkin cells stain with CD30 and CD15, but are usually negative for B-cell antigen expression such as CD10, CD19 or CD20. T or F.
True
PET/CT is widely used after the first two cycles of ABVD and if there is residual active disease, treatment might be switched to more intensive chemotherapy such as BEACOPP. T or F.
True
Inflammatory disease can cause a false positive PET scan. T or F.
True
What is the treatment plan for relapsed cases?
What are the late effects of Hodgkin lymphoma and its treatment?
What is Hodgkin Lymphoma?
What are the clinical features of Hodgkin lymphoma?
What are the haematological and biochemical findings of Hodgkin lymphoma?
How do you diagnose Hodgkin lymphoma?
Nodular sclerosis?
Lymphocyte rich?
Mixed cellularity?
Lymphocyte depleted?
what’s the difference between Hodgkins and non-hodgkins lymphoma?
Hodgkins has nodal involvement and non-hodgkins has nodal and extranodal involvement
what’s the difference between low grade and high grade lymphomas?
low grade disorders are relatively indolent, respond well to treatment but are difficult to cure.
while high grade disorders are aggressive and need urgent treatment but are more often curable
what are the lab investigations/ findings in NHL? hint: 7
- there may be anaemia, neutropenia or thromobocytopenia
- lymphoma cells may be found in peripheral blood in some pts
- trephine biopsy for staging; PET scan shows marrow uptake or if cytopenias are present
- serum LDH is raised (prognostic marker)
- elevation of uric acid may occur
- there may be a paraprotein (Ig electrophoresis)
- HIV status should be tested; can influence prognosis in some subtypes like Burkitts
what are the clinical features of NHL?
- superficial lymphadenopathy (painless)
- constitutional symptoms: fever, night sweats, weight loss
- oropharyngeal involvement: sore throat, obstructed breathing
- symptoms dues to anaemia, infections due to neutropenia or purpura with thrombocytopenia
- abdominal disease: liver & spleen often enlarged
- other organs involved: skin, brain, testis or thyroid
which NHL subtype can HIV positivity influence prognosis in?
Burkitt lymphoma
what is the general principle of treatment for NHL?
usually combination of chemotherapy drugs with a monoclonal antibody directed against the tumour cell
what are the low-grade Hodgkin lymphomas?
- small lymphocytic lymphoma
- lymphoplasmacytoid lymphoma/Waldentrom macroglobulinaemia
- marginal zone lymphomas
- follicular lymphoma
- mantle cell lymphoma
what is small lymphocytic lymphoma?
same morphology and immunophenotype as B-CLL but with <5x10^9/L peripheral blood B cells and no cytopenias
Hyperviscosity syndrome is a common complication of IgM paraproteinemia. T or F.
True
note: IgM paraprotein increases blood viscosity more than equivalent concentrations of IgG or IgA; seen in lymphoplasmacytoid lymphoma/Waldenstrom macroglobulinaemia
where do marginal zone lymphomas arise from?
the marginal zone of B cell germinal follicles of lymph nodes, spleen or mucosa (MALT)
note: its classified based on where it comes from
Gastric MALT lymphoma is the most common form of the MALT lymphomas and is preceded by what kind of infection?
Helicobacter pylori
what is the hallmark of follicular lymphoma?
t(14;18) involving the BCL2 gene which results in the over expression of BCL2 protein
what’s the function of BCL2?
it prevents cells from undergoing apoptosis and increases the lifespan of malignant B cells
The cells of follicular lymphoma are typically positive for which markers?
CD10, CD19, CD20, BCL2 and BCL6
where are mantle cell lymphomas derived from?
pre-germinal centre cells localised in primary follicles or in the mantle region of secondary follicles
MCL has a characteristic phenotype of what?
CD19+ and CD5+ (Like CLL)
CD22+ and CD23-
Presence of which translocation is required for diagnosis of MCL?
t(11;14)
In MCL, a specific translocation juxtaposes the cyclin D1 gene (CCND1) to the immunoglobulin heavy-chain gene, and leads to decreased expression of cyclin D. T or F.
Falses
it leads to increased expression of cyclin D which alters cell cycle behaviour
note: the translocation is t(11;14)
What type of B cells are in MCL and MZL?
naive B cells and memory B cells respectively
what are the high grade NHL?
- diffuse large B cell lymphomas
- primary central nervous system lymphoma
- primary mediastinal B cell lymphoma
- Burkitt lymphoma
- lymphoblastic lymphoma
what’s the definitive investigation done in non-hodgkins?
whole lymph node excision biopsy or more usually core needle biopsy of lymph node or of other involved tissue
translocation found in follicular lymphoma?
t(8;18)
translocation found in mantle cell lymphoma?
t(11;14)
translocation found in Burkitt lymphoma?
t(8;14)
translocation found in anapaestic large cell lymphoma?
t(2;5)
which mutation is found in lymphoplasmacytic lymphoma?
MYD88
oral agents that block activity of the BTK or PI3Kδ proteins are used for?
B cell chronic lymphocytic lymphoma
note: BTK inhibitors=ibrutinib & PI3K inhibitors= idelalisib
which drug inhibits BCL-2 activity?
venetoclax
note: which is useful in DLBCL
(CAR)-T cells developed against specific B-cell-associated targets (like CD19) are used for what?
replaced or refractory patients with some subtypes of lymphoma
In the 85% of cases of NHL that are of B-cell origin, antibodies against CD20 have proven of great benefit. T or F.
True
Which monoclonal antibody drug is used against CD20?
Rituximab
Which monoclonal antibody drug is used against CD30?
Brentuximab
note: used for anaplastic large cell lymphoma & other NHL
Acute hyper viscosity syndrome is treated with what?
repeated plasmapheresis until the underlying disease can be brought under control
note: can be used to relieve symptoms of lymphoplasmacytic lymphoma
Marginal zone lymphomas are thought to occur in response to an antigen or inflammation. T or F.
True
- the cells acquire secondary genetic damage that leads to lymphoma
In MZL, molecular tests show point mutations involving which pathway?
NF-κB pathway
what is the median age of onset for follicular lymphoma?
60 years
Those with disseminated (stage II–IV) disease in follicular lymphoma are generally treated in the absence of symptoms. T or F.
False
- not treated until complications occur (watch and wait)
how is follicular lymphoma treated?
therapy is usually rituximab, either alone or in combination with chemotherapy (B-R or R-CVP or R-CHOP); or it can be combined with Ibrutinib (BTK inhibitor)
what are the 2 major subtypes of mantle cell lymphoma?
one type involving lymph nodes and extra nodal sites and the other a leukaemic non-nodal subtype
what is the characteristic cell pattern seen in mantle cell lymphoma?
deformed pattern of small lymphocytes with angular nuclei (centrocytes)
clinical presentation of the classical type of MCL?
lymphadenopathy
clinical presentation of the leukaemia type of MCL?
systemic symptoms and bone marrow and splenic disease
the nodal type of MCL tends to be more aggressive with high expression of?
Ki67
current treatment regime for MCL?
- chemotherapy, like R-CHOP
- Ibrutinib is effective
- SCT
- maintenance with rituximab
Histologically, the biopsy of DLBCL shows what?
large neoplastic cells with prominent nucleoli
DLBCL is subdivided into which subtypes?
germinal center (GCB) and activated B cell (ABC)
note: they stain with antibodies to BCL6 and CD19 or MUM1
what’s the clinical presentation of DLBCL?
rapidly progressive lymphadenopathy which may also involve the bone marrow, GIT, brain, spinal cord, kidneys, etc
what is the most common cytogenetic changes in DLBCL?
involve the IGH locus on chromosome 14 and the BCL6 gene at chromosome 3q27
Double expressor or double hit DLBCL aberrantly express which gene mutations?
both MYC and either BCL-2 or BCL-6
the mainstay of treatment for DLBCL is?
rituximab in combination with CHOP
Endemic Burkitt lymphoma is seen is which areas?
in areas with chronic malaria exposure
Burkitt lymphoma is associated with what kind of infection?
EBV infection
which gene mutation is over-expressed in Burkitt lymphoma?
the MYC oncogene is overexpressed because it is translocated to an immunoglobulin gene, usually the heavy-chain locus t(8;14)
what is the typical presentation in Burkitt lymphoma?
usually a child, presenting with massive lymphadenopathy, often of the jaw
what does the histological picture of Burkitt lymphoma look like?
- very high proliferative index of over 95%
- shows sheets of lymphoblasts and starry sky tingible body macrophages
what are the types of T cell non-hodgkin lymphoma?
- peripheral T cell non-hodgkin lymphoma unspecified
- angioimmunoblastic lymphadenopathy
- mycosis fungoides
- sezary syndrome
- adult T cell leukaemia/lymphoma
- enteropathy-associated T-cell lymphoma
- anaplastic large cell lymphoma
- extranodal NK/T cell lymphoma
what is mycoses fungicides?
a chronic cutaneous T-cell lymphoma that presents with severe pruritus and psoriasis-like eczematoid skin lesions (can later become plaques and ulcerated tumours)
what is seen in Sezary syndrome?
there is dermatitis and generalised erythroderma, but also lymphadenopathy and circulating T-lymphoma cells
Anaplastic large cell lymphoma is usually associated with the t(2;5)(p23;q35) translocation which leads to the overexpression of which gene?
overexpression of ALK
how is anaplastic large cell lymphoma treated?
- Crizotinib (ALK inhibitor)
- Brentuximab (cuz its also CD30+)
Cattleman disease may in some subtypes progress to a B-cell lymphoma. T or F.
True
The multicentric form of castleman disease is most common in subjects with what kind of infection?
HIV infection (when the cells contain HHV8)
