Non- Hodgkin Lymphoma Flashcards
What are Non- Hodgkin Lymphomas?
The non-Hodgkin lymphomas (NHL) are a large group of clonal lymphoid tumours, about 85% of B cell and 15% of T or NK (natural killer) cell origin
What are the classifications of Non- Hodgkins Lymphoma?
- Mature B-cell
- T-cell neoplasms
True our False? Low Grade Non- Hodgkin Lymphomas are relatively indolent, respond well to chemotherapy or immunotherapy, and have a lengthy median survival but are very difficult to cure.
TRUE!!
True or False? High-grade lymphomas are aggressive and need urgent treatment, but are more often curable.
TRUE!!
What are the Clinical Features of Non- Hodgkin Lymphoma?
- Superficial lymphadenopathy
- Constitutional symptoms - Fever, night sweats and weight loss can occur, but are less frequent than in Hodgkin lymphoma.
- Oropharyngeal involvement - ‘sore throat’ or noisy or obstructed breathing.
- Symptoms due to anaemia, infections due to neutropenia or purpura with thrombocytopenia
- Abdominal disease - Hepatomegaly & Splenomegaly
- Other organs - Involvement of the skin, brain, testis or thy- roid is not infrequent. The skin is also primarily involved in two closely related T-cell lymphomas: mycosis fungoides and Sézary syndrome.
Epstein- Barr Virus is associated with which malignancies?
- Burkitt Lymphoma
- Hodgkin lymphomas
- Post-transplant lymphoproliferative disorder ( PTLD) * Extranodal NK/T-cell lymphoma - nasal type
Fill in the blanks . “ ___________ virus is associated Adult T-cell leukaemia/lymphoma.”
HTLV-1
Which virus is assoicated with Primary effusion lymphoma and also multicentric Castleman disease?
HHV- 8 ( Human Herpesvirus-8, also called Kaposi sarcoma Herpesvirus (KSHV)
HIV is associated with which neoplasms?
- High-grade B-cell lymphoma
- Primary CNS lymphoma
- Hodgkin lymphoma
True or False? “ Hepatitis B is associated with Splenic marginal zone lymphoma.”
Hepatitis C is associated with Splenic marginal zone lymphoma!
Which bacteria is associated with Burkitt lymphoma?
Protozoan: Malaria
How is the histology of Non- Hodgkins lymphoma tested?
Whole lymph node excisional biopsy, or more usually core needle (e.g. Trucut) biopsy of lymph node or of other involved tissue (e.g. bone marrow or extranodal tissue), is the definitive investigation
True or False? For B-cell lymphomas, expression of either only κ or only λ light chains by lymphoid cells confirms clonality and distinguishes neoplastic disease from a reactive node in which both κ and λ light chains are expressed.
TRUE!!
What are the Laboratory findings in NHL?
- Anaemia, neutropenia or thrombocytopenia
- Mantle cells
- Cleaved follicular cells
- Blast cells
- Trephine biopsy of marrow may be valuable in staging if risk of involvement is high, e.g. high-grade lymphomas, if positron-emission tomography (PET) scan shows marrow uptake or if cytopenias are present.
- Increased LDH ( used as a prognostic marker)
- Increased serum uric acid
- Immunoglobulin electrophoresis may reveal a paraprotein.
- HIV status should be tested as indicated
What is the Genetic mutation associated with Hairy Cell Leukaemia?
BRAF
What is the Genetic mutation associated with Lymphoplasmacytic lymphoma ?
MYD88
What are the cytogenetics associated with MALT lymphoma?
- t(11;18) [BIRC3-MALT1]
- t(1;14) [BCL9-IGH]
What is the Genetic mutation associated with MALT lymphoma?
Activation of NFκB pathway
What is the cytogenetics associated with Follicular lymphoma?
t(14;18) [IGH-BCL2]
What are the genetic mutations associated with Follicular lymphoma?
Mutations in genes such as CREBBP, EZH2 and KMT2D (MLL2), which influence chromatin remodelling.
What is the cytogenetics associated with Mantle Cell Lymphoma?
t(11;14) [IGH-CCND1]
What are the Genetic mutations associated with Mantle cell lymphoma?
ATM, CCND1, TP53 and genes influencing chromatin modification
What is the cytogenetics associated with Diffuse large B-cell lymphoma ?
t (14;18) [IGH-BCL2]
What is the cytogenetics associated with Gene mutations?
MYD88, CD79B, NOTCH1/2, EZH2, BCL2, BCL6, MYC
What are the cytogenetics associated with Burkitt lymphoma?
- t (8;14) [MYC-IGH]
- t (2;8) [IGK-MYC]
- t (8;22) [MYC-IGL]
A cytogenetic mutation of t (2;5) [NPM1-ALK] is associated with which neoplasm?
Anaplastic large cell lymphoma
What is the Genetic mutation associated with Anapaestic large cell lymphoma?
ALK
True or False? In B cell lymphomas the IMMUNOGLOBULIN GENES are clonal rearranged while in T- Cell Lymphoma there Is a Clonal rearrangement of T- CELL RECEPTOR GENES.
TRUE!!
What is the General Treatment for NHL?
When treatment is started, it is usually in the form of a combination of chemotherapy drugs together with a monoclonal antibody directed against the tumour cell.
Give an example of a BCL-2 inhibitor?
Venetoclax
What are new drugs that can aid in the treatment of NHL?
- Oral agents that block activity of the BTK or PI3Kδ proteins.
- Anaplastic lymphoma kinase (ALK) drugs
- Drugs that inhibit BCL-2 activity e.g. venetoclax.
- Chimeric antigen receptor (CAR)-T cells ( targets CD-19)
- Monoclonal therapy - Rituximab , Ofatumumab and obinutuzumab ( Anti-CD20)
Which drug is an Anti CD-30 Drug?
Brentuximab
What are the clinical features of Small lymphocytic lymphoma?
- Less than 5×109/L peripheral blood B cells
- NO cytopenias due to bone marrow involvement.
- Lymphadenopathy is typical
True or False? Lymphoplasmacytoid lymphoma (Waldenström macroglobulinaemia) is mostly seen in women over 50 years.
FALSE!! It is mostly seen in MEN over 50 years of age.
What is the monoclonal immunoglobulin associated with Lymphoplasmacytoid lymphoma (Waldenström macroglobulinaemia) ?
(Ig) M paraprotein
What is the cell of origin for Lymphoplasmacytoid lymphoma (Waldenström macroglobulinaemia) ?
Post - Germinal Centre B cell.
What are the clinical features of Lymphoplasmacytoid lymphoma (Waldenström macroglobulinaemia) ?
- Insidious onset often with fatigue and weight loss.
- Hyperviscosity syndrome - Ig M paraprotein increases blood viscosity more than equivalent concentration of IgG or IgA.
- Visual upset
- Engorged veins in Retina
- Haemorrhages, exudates and a blurred disc .
- Features of cryoprecipitation, such as Raynaud phenomenon, may be present.
- Anaemia
- Bleeding tendency may result from macroglobulin interference with coagulation factors and platelet function.
- Neurological symptoms
- Dyspnoea
- Heart failure
- Moderate lymphadenopathy
- Enlarged spleen or liver
- Increased ESR
How is Lymphoplasmacytoid lymphoma (Waldenström macroglobulinaemia) diagnosed?
Diagnosis is made by the findings of a monoclonal serum IgM together with bone marrow or lymph node infiltration with lymphoplasmacytoid cells.
What is the mutation associated with Lymphoplasmacytoid Lymphoma (Waldenström macroglobulinaemia) ?
MYD88
CXCR4
What is the treatment for Lymphoplasmacytoid Lymphoma (Waldenström macroglobulinaemia) ?
Combination treatment with an anti-CD20 antibody such as rituximab and chemotherapy is generally given.
- Chemotherapy options include cyclophosphamide, fludarabine, bendamustine or bortezomib
- Autologous or allogeneic stem cell transplantation (SCT) is considered for advanced disease.
What is the MOA of Rituximab?
Rituximab binds to CD20 on the surface of B cells and elicit a number of mechanisms:
(a) antibody-dependent cell-mediated cytotoxicity
(b) complement-mediated lysis of tumour cells
(c) direct apoptosis of the target cell.
What is treatment for Hyperviscosity Syndrome?
Repeated plasmapheresis until the underlying disease can be brought under control.
Where do Marginal zone lymphomas arise from?
B cell germinal follicle
True or False? Marginal Zone lymphomas are high grade lymphomas.
FALSE!! They are low- grade lymphomas.
Fill in the blanks. “ Marginal Zone Lymphomas are classified according the anatomical site at which they arise, such as the ______________ or ____________.”
Spleen, mucosa (MALT) or lymph node (nodal).
What is the Most common form of MALT lymphoma?
Gastric MALT lymphoma is the most common form and is preceded by Helicobacter pylori infection.
Fill in the blanks. “ ________________ , a type of Marginal zone lymphoma may result from Chlamydia infection.”
Ocular Adnexal Lymphoma
Where does MALT lymphoma normally arise?
They usually arise in the stomach , respiratory tract, skin and salivary glands.
What is the median age for Follicular Lymphoma?
Median age of onset of 60 years.
What are the clinical features of Splenic Marginal Zone lymphoma?
- Splenomegaly
- Circulating ‘villous’ lymphocytes that may be mistaken for hairy cell.
- Follicle has a “ STARRY - SKY “ appearance
What is the cytogenetic abnormalities in Follicular Lymphoma?
t (14;18)
What are the biomarkers for cells in Follicular Lymphoma?
CD10 +
CD19 +
CD20 +
BCL2 +
BCL6 +
Which grading of Follicular Lymphoma has the worst prognosis?
Grade IIIb - and are generally treated according to diffuse large B-cell lymphoma (DLBCL) guidelines
Fill in the blanks. “ In Follicular Lymphoma , the histological appearances are graded as I–III according to the relative proportion of ___________ & _______.”
Large cell Centroblasts and Small cleaved Centrocytes
Patients with Stage I follicular lymphoma can be treated with?
Radiotherapy Alone
What is the course of treatment for patients with Stage II- IV , Follicular Lymphoma?
No symptoms - “ Watch and Wait” but treatment is introduced when complications occur.
What is the treatment for Follicular Lymphoma?
*Bendamustine (B-R)
* Cyclophosphamide, vincristine and prednisolone (R-CVP), with an anthracycline added for more aggressive cases (R-CHOP)
Which combination therapy can be used that results in deep, durable remissions.
Ibrutinib is also active and when combined with rituximab
What are examples of PI3K inhibitors?
- Idelalisib, duvelisib and copanlisib
What are examples of BTK inhibitors?
Ibrutinib and acalabrutinib
True or False? Mantle Cell Lymphoma is derived from post- germinal centre cells localized in the follicles.
FALSE!! Mantle Cell Lymphoma is derived from PRE- GERMINAL centre cells localized in the primary follicles or in the mantle region of secondary follicles
What are the two major sub-types of Mantle Cell Lymphoma
- One classical involving lymph nodes and extranodal sites.
- One a leukaemic, non-nodal subtype.
What are the phenotypes of Mantle Cell Lymphoma?
Similar to CLL
CD19 +
CD5+
CD22 +
CD 23 NEGATIVE
What is the genetic mutation associated with Mantle Cell Lymphoma?
t (11;14)
- translocation juxtaposes the cyclin D1 gene CCND1 to the immunoglobulin heavy-chain gene, and leads to increased expression of cyclin D1 which alters the cell cycle behaviour.
What are the Clinical Features of Mantle Cell Lymphoma?
- Lymphadenopathy
- Leukaemic type with systemic symptoms and blood bone marrow and splenic disease.
*
True or False? In Mantle Cell Lymphoma , the nodal disease tends to be more aggressive, with high expression of Ki67.
TRUE!!
What are the current treatments for Mantle Cell Lymphoma?
- Chemotherapy, such as R-CHOP (as for DLBCL) or bendamustine-rituximab combinations for older (>65 years) patients. For younger, fitter patients more intensive reg- imens may be used, such as R-CHOP/high-dose methotrexate or cytosine arabinoside/cisplatin.
- Ibrutinib and acalabrutinib are effective and are being in- creasingly used in various combinations for both initial therapy and relapsed disease.
- Autologous or allogeneic haemopoietic SCT.
- Maintenance with rituximab is given for patients in remission following chemotherapy, with or without autologous SCT, and delays relapse.
Cells with an ‘ Angular nuclei’ is seen in which pathology?
Mantle Cell Lymphoma
What are the sub-types of Diffuse are B- Cells Lymphoma?
- Germinal centre (GCB)
- Activated B cell (ABC) subtypes
Which antibodies are stained by Diffuse Large B- Cell Lymphoma?
- BCL6
- CD19
- MUM1
According to the International Prognostic Index (IPI) , which factors are useful in the outcome of therapy for Diffuse Large B- Cell Lymphoma?
Age
Performance Status
Stage
Number of extranodal site
Serum LDH
True or False? The Mantle Cell International Prognostic Index (MIPI), based on age, performance status, serum LDH and leucocyte count, is useful in the outcome of Mantle Cell Lymphoma
TRUE!!
What are the cytogenetic changes involved in Diffuse Large B Cell Lymphoma?
- The most common cytogenetic changes involve the IGH locus on chromosome 14
- BCL6 gene at chromosome 3q27
- Translocation of the BCL2 gene
True or False? Double expressor or ‘double hit’ DLBCL aberrantly express both MYC and either BCL-2 or BCL-6 proteins due to mutations/rearrangements in the corresponding genes .
TRUE!!
What is the Main treatment Diffuse Large B- Cell Lymphoma?
CHOP – cyclophosphamide, hyroxodaunorubicin (dox- orubicin), vincristine (Oncovin) and prednisolone – given in 3-weekly cycles, typically for six to eight courses, although four courses are adequate for younger lower-risk patients.
Fill in the blanks. “ ___________________ is an antibody–drug conjugate targeting CD79b.”
Ventoclax and polatuzumab vedotin
Fill in the blanks. “ _________________ is a rare diffuse large B-cell lymphoma, more common in older patients and those with HIV infection. “
Primary central nervous system lymphoma
What are the Genetic mutations underlying Primary central nervous system lymphoma?
MYD88
CD79b
CDKN2A
How is the diagnosis for Primary Central Nervous System Lymphoma done?
Stereotactic biopsy and tumour cells may also be found in the cerebrospinal fluid.
What is the treatment for Primary Central Nervous System Lymphoma?
- High Dose Methotrexate with partner cytotoxic agents, e.g. high-dose cytosine arabinoside and rituximab.
- Anti-HIV therapy is added if the patient is HIV positive
In which organ does Primary mediastinal B-cell lymphoma arises?
In the thymus ( young and adolescent ages)
What are the genes expressed in Primary Mediastinal B- Cell Lymphoma?
PAX5
BCL-6
( CD19, CD20, CD22, CD79b).
” Half of cases have amplification of the REL gene on chromosome 2q16, and tumour suppressor SOCS1 is mutated or deleted in a similar proportion of cases. “ is associated with which pathology?
Primary Mediastinal B- Cell Lymphoma
Fill in the blanks. “ Endemic Burkitt Lymphoma is located in __________.”
Africa
- seen in areas with chronic malaria exposure and is associated with Epstein–Barr virus (EBV) infection.
What is the oncogene that is overexpressed because it is translocated to an immunoglobulin gene, usually the heavy-chain locus t(8;14) and less commonly to one of the light chains ?
MYC oncogene
True or False? Burkitt Lymphoma is common seen in kids.
TRUE!!
’ Burkitt- BurKID’ lol
What are the clinical features of Burkitt Lymphoma?
- Massive lymphadenopathy ( usually massive in jaw)
- ‘STARRY SKY’ tingible body macrophages.
True or False? Sporadic Burkitt lymphoma may occur anywhere in the world and EBV infection is seen in 20% of cases.
TRUE!!
Which Non- Hodgkin Lymphoma is Terminal deoxynucleotide transferase (Tdt) POSITIVE and occurs mainly in children and young adults?
Lymphoblastic lymphomas
What are the clinical features of Angioimmunoblastic lymphadenopathy ( T- Cell NHL)
Elderly patients
* Lymphadenopathy
* Hepatosplenomegaly
* Skin rashes
* A polyclonal increase in serum IgG
What is the treatment for Angioimmunoblastic lymphadenopathy ?
Patients are treated with chemotherapy or histone deacetylase inhibitors.
True or False? In Mycosis fungoides , tumour cells circulate in the blood.
FALSE!! In contrast to Sézary syndrome, tumour cells DO NOT circulate in the blood.
What is Mycosis fungoides?
Mycosis fungoides is a chronic cutaneous T-cell lymphoma that presents with severe pruritus and psoriasis-like eczematoid skin lesions that later become plaques and ulcerated tumours.
What are examples of Histone deacetylase inhibitors ?
Vorinistat and romidepsin
What is the treatment for Mycosis fungoides?
- Phototherapy & Chemotherapy
- Histone deacetylase inhibitors vorinistat and romidepsin are approved for treatment of relapsed and progressive cutaneous T-cell lymphomas.
- Brentuximab is also useful in CD30+ patients.
What are the clinical features of Sézary syndrome?
- Dermatitis
- Generalised Erythroderma
- Lymphadenopathy
- Circulating T- lymphoma cells
- CD4 + with folded cerebriform nuclear chromatin cells.
What is the treatment for Sézary syndrome?
Initial treatment is by local irradiation, topical chemotherapy or photochemotherapy with psoralen and ultraviolet light (PUVA)
Which Non- Hodgkin Lymphoma is associated with gluten-induced enteropathy have a poor response to treatment?
Enteropathy-associated T-cell lymphomas
Which Non- Hodgkin lymphoma is associated with large cells with a ‘Horse-show shaped nucleus’?
Anaplastic Large Cell Lymphoma
True or False? Anaplastic large cell lymphoma is particularly common in adults and is usually of T-cell phenotype.
FALSE!!! Anaplastic large cell lymphoma is particularly common in CHILDREN and is usually of T- CELL phenotype!!
What are the genetic mutations associated with Anaplastic Large Cell Lymphoma?
- t(2;5) (p23;q35) translocation
- CD 30 +
- Overexpression of ALK
Which drug is a specific inhibitor of ALK activity and is a valuable treatment in Anaplastic Large Cell Lymphoma?
Crizotinib
Fill in the blanks. “ Extranodal NK/T cell lymphoma occurs mainly in ___________ and is associated with ___________.”
This disease occurs mainly in Asia and Central and South America. It is associated with EBV infection
True or False? The multicentric form of Cattleman disease which is usually associated with systemic symptoms, is most common in subjects with HIV infection.
TRUE!!
What is the treatment for Localized Castleman disease?
Surgery
What is the treatment for Multicentric Castleman disease?
Corticosteroids, chemotherapy or immunotherapy.
Fill in the blanks. “ In Castleman Disease , Microscopi- cally the LOCALIZED form usually shows a ___________, and the MULTICENTRIC form usually shows _________.”
LOCALIZED = Hyaline vascular appearance
MULTICENTRIC= proliferation of plasma cells
