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Haematology > Lymphoma > Flashcards

Lymphoma Flashcards

1
Q

what is the epidemiology of Non-Hodgkin’s

A

incidence increases with age
male>female
higher in developing countries (EBV)

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2
Q

what is the development cycle of B cells?

A

o Precursor produced in bone marrow
o Naïve b cell develops in bone marrow
o These then leave, enter blood, and settle into follicles in the lymph nodes

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3
Q

What is the development cycle of T cells

A

o T cells develop starts in Thymus from precursors (bone marrow)
 Mature and express wither
• CD4 - helper
• CD8 – cytotoxic
 Circulate in blood and found in paracortex of lymph nodes

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4
Q

what is the activation process for B cells?

A

o B cells differentiate into plasma cells found in medulla (centre)
o B cells have surface markers called CD…
 B cells activate when binds to its surface immunoglobulin
 Some activated will mature directly into plasma cells = Ig antibodies
 Other will go to centre of primary follicle of a lymph node and differentiate into centroblast and start to proliferate/divide

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5
Q

what happens to B cells when they forma centroblast?

A

Form a germinal centre found in the centre of a follicle
Rearrangement of Ig genes
Some undergo class switch (immunoglobulin change)
Within germinal cell, centroblasts mature into centrocyte
Centrocyte that make high affinity for antigen differentiate into
 Plasma cell (medulla)
 Memory B cell – circulate blood, lymph nodes, spleen (mucosa-associated lymphoid tissue)

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6
Q

what is the underlying pathophysiology of Non-Hodgkin’s Lymphoma

A

• Absence of Reed Sternberg cells
• Genetic mutation in lymphocyte (B or T) causes either suppression of apoptosis or promotion of differentiation/growth
o lymphocyte divides uncontrollably = neoplastic cell

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7
Q

where can these lymphomas occur?

A

o In lymhnodes = nodal lymphomas
o Elsewhere – extranodal lymphomas
o If get into blood: GI, bone marrow, spine

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8
Q

what are the different types of B cell lymphomas? (7)

A 
Diffuse large B cell lymphoma
Follicular lymphoma
Burkitt lymphoma
Mantle cell lymphoma
Marginal zone lymphoma
Lymphoplasmacytic lymphoma
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9
Q

what marker do B cell lymphomas express on their surface?

A

CD20

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10
Q

What are the features of a diffuse B cell lymphoma?

A

most common

aggressive

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11
Q

what are the features of a follicular lymphoma?

A

Indolent
From chromosomal translocation of 14 and 18
In the translocation – BCL2 is placed after immunoglobulin heavy chain promotor
(Overexpression of BCL2 (blocks cell death))

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12
Q

what are the features of a burkitt lymphoma?

A

Highly aggressive
From chromosomal translocation
MYC translocated from 8 to 14 – adjacent to IgH promotor = Upregulates MYC gene (cell growth) = increased cell division
In Africa - Extranodal of Jaw, EBV
Not in Africa - Extranodal ileoceal junction

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13
Q

what are the histological features of a burkitt lymphoma?

A

Starry sky appearance
Tingable body – macrophages that have eaten neoplastic cells
Scattered among neoplastic lymphocyets that look dark

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14
Q

what are the features of a mantle cell lymphoma?

A

o Aggressive
o From chromosome translocation
o BCL1 gene from 11 ends up next to Ig promotor on 14
 BCL produces cyclin D1 which promotes cell growth = increased growth

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15
Q

what are the features of a marginal zone lymphoma?

A 
o	Indolent
o	Most common type = mucosa-assoicated lymphoid tissue
	Usually lining of stomach of those with chronic inflammation (h pylori)
o	Nodal (within nodal)
o	Splenic (within spleen)
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16
Q

what are the features of a lymphoplasmacytic lymphoma?

A

o Indolent
o Involves bone marrow, lymph nodes, spleen
o Neoplastic produce immunoglobulins (m proteins)
o High levels in blood causes blood to be thick and viscous = waldenstom macroglobulinemia

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17
Q

what are the types of T cells?

A

adult T cell lymphoma (leukaemia)

Mycosis Fungoides

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18
Q

what are the features of adult T cell lymphomas?

A

o Abnormal white blood cells often enter blood stream
o HTLV – spread through body fluids and infects T cells
o Incorporates viral DNA into T cell DNA = mutation cauing lymphoma

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19
Q

what are the features of mycosis fungoides?

A

o T cell lymphoma of skin
o Causes patches on skin that look fungal
o CD4+ helper t cell – cerebriform nucleus
o If circulate in blood can cause Sezary syndrome (red rash)

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20
Q

What are the symptoms of non-Hodgkin’s lymphomas?

A

painless superficial lymphadenopathy
systemic symptoms
extranodal
pancytopenia

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21
Q

what are the systemic symtpoms seen in non-hodgkins lymphoma?

A

fever, drenching night sweats, weight loss

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22
Q

what are the common extranodal symptoms seen in non-hodgkins lymphoma?

A

GI - bowel obstruction
Bone Marrow - fatigue, easy bruising, recurrent infections
spinal cord - loss of function
also brain, thyroid, skin, hepatosplenomegaly

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23
Q

what are the diagnostic investigations for NH lymphoma?

A
  • Bloods
  • Marrow and node biopsy
  • Staging = Ann arbour system – CT/MRI of chest, abdo, pelvis
  • Send cytology of any effusion; LP for CSF cytology if any CNS signs
24
Q

staging of NK lymphoma uses what system?

A

ann arbour system

25
Q

criteria for stage 1 NH lymphoma

A

Involvement of a single lymph node(I), or an extralymphatic site (IAE)

26
Q

criteria for stage 2 NH lymphoma

A

Involvement of two or more lymph nodes (II), or a lymph node and an extralymphatic site, on the same side of the diaphragm (II E)

27
Q

criteria for stage 3 NH lymphoma

A

Involvement of lymph node regions on both sides of the diaphragm, with (III E) or without (III) extralymphatic involvement, and with involvement of the spleen (IIIS), (III SE)

28
Q

criteria for stage 4 NH lymphoma

A

Diffuse involvement of one or more extralymphatic tissues (e.g. bone or liver)

29
Q

A in staging of NH lymphoma means?

A

no systemic symptoms

30
Q

B in staging of NH lymphoma means?

A

weight loss, drenching sweats

31
Q

X in staging of NH lymphoma means?

A

bulky disease - widening of mediastinum more than a 1/3 due to presence of a nodal mass

32
Q

What is the relationship between aggressiveness and curability?

A

low grade are indolent but incurable

high grade more aggressive but curable

33
Q

management of low grade NH lymphoma?

A

o If asymptomatic none may be needed
o Radiotherapy may be curative in localised disease
o Chlorambucil used in diffuse
o Remission may be mainatiedn with a-interferon or rituximab
 Bendamistine in combo or as sole treatment
o ABVD?

34
Q

treatment of high grade NH lymphoma?

A

RCHOP

ABVD

35
Q

what is the RCHOP regime?

A

Rituximab Cyclophsophamide
Hydroxydanuorubicin
Vincristine
Prednisolone

36
Q

what is the ABVD regime?

A

Adriamycin 25 mg/m2 IV on days 1 and 15
Bleomycin 10 units/m2 IV on days 1 and 15
Vinblastine 6 mg/m2 IV on days 1 and 15
Dacarbazine375 mg/m2 IV on days 1 and 15

37
Q

what can CD20+ lymphomas be treated with?

A

Ritiximab

38
Q

what is G-CSFs?

A

treatment for neutropenia in lymphoma management

39
Q

what is the epidemiology of Hodgkins Lymphoma?

A
  • Less common than NHL
  • Men>women (except nodular sclerosing)
  • Caucasians
  • Bimodal age distribution (15-34, >50)
  • Patient is younger than NHL (disease of the young!)
40
Q

what are the causes of Hodgkins Lymphoma?

A
  • Mononucleosis infection – EBV, CMV
  • HIV
  • Exposure to benzene
  • Genetic component – NF-kB
41
Q

what are Reed Sternberg cells?

A

o Lacunar histiocytes
o Giant malignant cells
o Multi nuclei, owl appearance
o Most commonly derived from germinal centre B cells but can also come from peripheral T cells (rarely)
o CD15 and CD30 antigens are expiressed on these cells
o Normally present in small numbers, but surrounded by large numbers of reactive, normal T cells, plasma cells (activated B cells) and eosinophils – different classifcations depend on which type of cell is surrounding

42
Q

what is the pathophysiology of Hodgkins Lymphoma?

A

start in cervical lymph nodes
Associated with defect in cell mediated immunity = B cells stop expressing surface immunoglobulin due to mutations of Ig genes and/or errors in transcription
NF-kB (transcription factor) activates = development of self regulation (proliferation) = Defects in fas-gene = apoptosis resistance
B cells become massive large cells
Contagious spread

43
Q

What are the 2 classifications of Hodgkins?

A

Nodular lymphocyte predominance

Classic Hodgkins

44
Q

what are the different types of classic hodgkins?

A

nodular sclerosis
lymphocyte rich
mixed cellularity
lymphocyte-depleted

45
Q

what are features of nodular sclerosis HL?

A 
	Female>male
	Women & children
	Most common of classic hodgkins
	Excellent prognosis
	Lacunar type RS cells
	Fibrotic bands 
	Anterior mediastinal
46
Q

what are the features of lymphocyte rich HL?

A

 Very good prognosis
 Infiltrate of lots of small lymphocytes and Reed Sternberg cells
 Most common in men

47
Q

what are the features of mixed cellularity HL?

A 
	Eosniophils, plasma cells, histocytes, lymphocytes, neutrophils 
	Reed Sternberg but no fibrotic bands 
	Associated with B symptoms 
	Elderly
	Abdominal & splenic lymphnodes 
	HIV associated
48
Q

what are the features of lymphocyte-depleted HL?

A

 Least common most aggressive, poorest survival
 Lack of infiltrate but Reed-Sternberg cells are presents
 Slightly different – popcorn cells – express 20, 45, 79a (not CD30)
 Associated with HIV

49
Q

what are the clinical features of HL?

A 
Pel Ebstein fever – fever comes and goes
Lymphadenopathy – localised, PAINLESS
Splenomegaly (not massive)
Nephrotic syndrome - Minimal change disease and Diffuse membranous glomerulopathy
Obstructive jaundice 
Skin – erythema nodosum
Autoimmune haemolytic anemia
Paraneoplastic cerebellar degeneration
Pain in LNS on alcohol consumption
Can also present as acute leukaemia
50
Q

what investigations and features can be used for diagnosis of hodgkins?

A 
CBC – neutrophilia, eosinophilia = MIXED
ESR – may be raised
LFTs – normal (sometimes gamma GT and ALP may be raised)
High LDH
Uric acid – normal or raised 
Chest Xray – mediastinal mass
CT scan for staging
Core needle biopsy
PET scan – initial staging and monitoring
51
Q

what features will be present in a core needle biopsy for Hodgkins?

A

Gross – bulging “fish flesh” appearance, rubbery

Microscopy – reed Sternberg cells Immunohistochemistry CD15+, CD30+

52
Q

what staging system is used for Hodgkins lymphoma?

A

same as non hodgkins

Ann-arbour system

53
Q

what is the treatment of stage 1 or 2 hodgkins lymphoma?

A

2-4 cycles of ABVD + radiotherapy

54
Q

what is the treatment of stage 3 or 4 hodgkins lymphoma?

A

6-8 cycles of AVDC + radiotherapy

55
Q

what is the treatment for relapsed hodgkins lymphoma?

A
  • Relapsed Refractory = autologous HSCT

* Relapsed after chemo or transplant – brentuximab

Haematology (13 decks)

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