Haematology 10 - Lymphoma 1: multidisciplinary Flashcards by Adya Rao

What is multiple myeloma a malignancy of?

Plasma cells

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Why do bacterial infections and autoimmune disorders increase lymphoma risk?

Constant antigenic stimulation

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Why do viral infections increase lymphoma risk?

Direct viral integration of lymphocytes

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Which lymphoma does Sjorgen’s syndrome increase risk of?

Marginal zone lymphoma of the parotid

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Which lymphoma does Hashimoto’s syndrome increase risk of?

Marginal zone lymphoma of the thyroid

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How is HTLV1 transmitted, and which cancer does it increase risk of?

A retrovirus that is transmitted at birth, and increases risk of adult T cell leukaemia lymphoma (an aggressive subtype of T cell NHL)

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Which type of cells are infected by EBV?

B cells

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How are EBV-expressing B cells usually eliminated? What lymphoma does EBV predispose to and how?

Cytotoxic T cell function

B cell NHL

Mechanism:

if you’re previously infected with EBV and then it becomes latent
then when you’re immunosuppressed eg on chemo or during old age, and you get reactivation of the virus, T cells are suppressed so normal cytotoxic T cell killing doesn’t occur –> lymphoma

____

can also precipitate classical Hodkin’s lymphoma….

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What type of lymphoma does h pylori infection predispose to?

Gastric MALT

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Which oncoportein is overexpressed in Burkitt’s lymphoma?

c-myc

Because of t(8.14)

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What are the 2 broad subtypes of Non-Hodgkins lymphoma?

B and T cell type

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What are the subtypes of B cell NHL?

Low grade: follicular, small lymphocytic, marginal zone
High grade: diffuse large cell, Burkitt’s
Aggressive: mantle cell

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What test can prove germinal centre origin of a lymphoma?

For diffuse large b cell lymphoma, which subtype has better prognosis: germinal centre or post germinal centre?

Positive staining for CD10 and bcl6

GERMINAL CENTRE origin has better prognosis

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What is the classification of Burkitt’s lymphoma

High grade peripheral B cell lymphoma

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What gene mutation is associated with follicular lymphoma?

t(14;18) - it causes overexpression of the bcl-2 gene

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Which lymphoma typically has a ‘starry sky appearance’ on histology?

Burkitt’s lymohoma

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Where does TCR gene recombination occur?

Bone marrow

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What are the key enzymes involved in VDJ (TCR gene) recombination?

RAG1 and RAG2

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What are the 2 methods of gene recombination in B cells?

Class switching
Somatic hypermutation

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What is the key enzyme involved in B cell class switching?

Adenosine-induced deaminase

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Which lymphoma are coeliac’s predisposed to?

EATL (enteropathy-associated t cell lymphoma)

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What can PCR be used for in lymphoma diagnosis?

Identifying:

Translocations
TCR rearrangement
IG gene rearrangement

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What is the translocation t(11;14) diagnostic of?

Mantle cell lymphoma

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What is the translocation of t(2;5) associated with?

A better prognosis for aplastic large cell lymphoma (T cell)

**t for T cell; t for two**

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Which lymphoma shows aberrant CD5 and cyclin D1 expression?

Mantle cell lymphoma

Which type of lymphoma can cause either a jaw or abdominal mass?

Burkitt's lymphoma

Recall one good and one bad prognostic indicator in diffuse large b cell lymphoma?

Good: germinal centre phenotype Bad: p53 mutation

What is the grade of peripheral T cell lymphomas?

V aggressive

Which lymphoma is particularly common in Japan and the Caribbean?

Adult T cell leukaemia lymphoma \*\*caused by HTLV-1 which is becoming more common in these areas

What is cutaneous T cell lymphoma known as?

Mycosis fungoides

Which age group tends to be affected by anaplastic large cell lymphoma?

Young adults

What is the t(2;5) translocation associated with?

Anaplastic large cell lymphoma- T cell lymphoma if you have this translocation it is good prognosis

Which type of lymphoma is associated with ALK-1 expression?

Anaplastic large cell lymphoma this is associated with good prognosis

Which type of lymphoma is most likely to involve just one lymph node group?

Hodgkin's

Which type of granulocyte will be present within a classical Hodgkin's lymphoma?

Eosinophil other reactive cells: marophages and plasma cells \*\*in nodular - no reactive cells

Which type of lymphoma is associated with an isolated lymphadenopathy?

Nodular Lymphocyte predominant Hodgkin's lymphoma

Recall the subtypes of classical Hodgkin's lymphoma

Nodular sclerosing - most common, more common in females Mixed cellularity Lymphocyte rich/ depleted - worst prognosis

Which type of Hodgkin's lymphoma would show B cell rich nodules?

Nodular lymphocyte-predominant lymphoma (i.e. not classical hodgkin's lymphoma)

Which type of lymphoma stains positively for CD15 and CD30?

CLASSICAL HODGKIN'S LYMPHOMA

What is the biggest risk of radiotherapy in hodgkin's lymphoma for women?

Breast Ca \*\* chemotherapy is mainstay; radiotherapy is in case of relapse but it carries risk of secondary malignancies

What is the translocation t(8;14) associated with?

Burkitt's lymphoma

What is the best chemotherapy for Burkitt's lymphoma?

Rituximab

What is the histological finding of "angular nuclei" pathognemonic for?

Mantle cell lymphoma

The Durie-Salmon staging system is used for which type of malignancy?

Multiple myeloma

Where are lymphomas found?

Can arise in any lymphoid tissue a) generative b) reactive c) acquired

Are lymphomas usually disseminated or localised in disease?

Usually disseminated as lymphomas circulate in the blood Except Hodkin's lymphoma- tends to affect specific lymph node groups And also early NHL tends to be localised in presentation

CLassification of lymphoid malignancies

What is the difference between lymphoma and lymphoid leukaeimia?

Lymphoma: predominantly affects lymph nodes with possible LATER involvement of blood/bone marrow Lymphoid leukaemia: predominantly affects bone marrow and blood with moderate involvement of lymph nodes

What are the precursor lymphoid neoplasms?

B cell: precursor B cell lymphoblastic leukaemia T cell: precursor T cell lymphoblastic leukaemia

What malignancy do naive B cells give rise to?

Chronic lymphocytic leukaemia

What malignancy do plasma cells give rise to/

Multiple myeloma

What malignancy do mantle cells give rise to?

Mantle cell lymphoma

What malignancy do follicular lymphocytes give rise to?

Follicular lymphoma Follicular lymphocytes- found in germinal centre

Which mutations give rise to lymphoma? Inherited or somatic?

Mostly somatic!! Altho there may be genetic predisposition to mutations, the actual mutation that causes cancer arises from a somatic mutatoin

What lymphoma is prediposed to by HIV?

B cell NHL eg diffuse large b cell and burkitts \*\*Bc HIV also leads to loss of T cell function - less cytotoxic killing

Broad risk factors for lymphoma development

- most cases are sporadic - some specific risk factors- constant antigenic stimulation, viral integration into lymphocytes, loss of T cell function - inherited disorders- genomic instability - iatrogenic- chemo and radio - immunosuppression

In certain NHL subtypes you get chromosomal trnaslocations involving the promoter region: what is it? And what is the proto-oncogene?

IgH: immunoglobulin H proto-oncogenes e.g. c-myc, BCL-2, BCL-6, cyclin-D1

Which type of hodkin's lymphoma is associated with EBV?

Classical- nodular sclerosing \*\*nb: nodular lymphocyte predominant is NOT associated with EBV

How does HL spread?

contiguously, often involves a single lymph node group

What type of fever do you get with HL?

Pel ebstein fever- cyclical fever

Markers of classical vs non classical HL

Hodgkin cells vs reed sternberg cells

hodgkin's cells: mononuclear versions of reed sternberg cells reed strnberg cells: multinucleate giant cells with reactive cells like eosinophils

Treatment of hodkin's lymphoma

Allogenic vs autologous stem cell transplant

basc: allogeniec only preferred in leukaemia because of graft vs tumour effect which can be taken advantage of

3 types of burkitt's lymphoma

Tx of burkitt's

rituximab

mantle cell lymphoma treatment

R-CHOP Auto-sct for relapse

Tx of follicular lymphoa

watch and wait rituximab or obintuxumab+cvp

what tx can be used for t cell NHL?

alemtuzumab- anti CD52 CD52 is the T cell receptor

what is bcl2 inhibitor?

used in cll - it promotes apoptosis of cells