Lymphoma Flashcards
what is the epidemiology of Non-Hodgkin’s
incidence increases with age
male>female
higher in developing countries (EBV)
what is the development cycle of B cells?
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
What is the development cycle of T cells
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
what is the activation process for B cells?
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
what happens to B cells when they forma centroblast?
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)
what is the underlying pathophysiology of Non-Hodgkin’s Lymphoma
• 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
where can these lymphomas occur?
o In lymhnodes = nodal lymphomas
o Elsewhere – extranodal lymphomas
o If get into blood: GI, bone marrow, spine
what are the different types of B cell lymphomas? (7)
Diffuse large B cell lymphoma Follicular lymphoma Burkitt lymphoma Mantle cell lymphoma Marginal zone lymphoma Lymphoplasmacytic lymphoma
what marker do B cell lymphomas express on their surface?
CD20
What are the features of a diffuse B cell lymphoma?
most common
aggressive
what are the features of a follicular lymphoma?
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))
what are the features of a burkitt lymphoma?
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
what are the histological features of a burkitt lymphoma?
Starry sky appearance
Tingable body – macrophages that have eaten neoplastic cells
Scattered among neoplastic lymphocyets that look dark
what are the features of a mantle cell lymphoma?
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
what are the features of a marginal zone lymphoma?
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)
what are the features of a lymphoplasmacytic lymphoma?
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
what are the types of T cells?
adult T cell lymphoma (leukaemia)
Mycosis Fungoides
what are the features of adult T cell lymphomas?
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
what are the features of mycosis fungoides?
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)
What are the symptoms of non-Hodgkin’s lymphomas?
painless superficial lymphadenopathy
systemic symptoms
extranodal
pancytopenia
what are the systemic symtpoms seen in non-hodgkins lymphoma?
fever, drenching night sweats, weight loss
what are the common extranodal symptoms seen in non-hodgkins lymphoma?
GI - bowel obstruction
Bone Marrow - fatigue, easy bruising, recurrent infections
spinal cord - loss of function
also brain, thyroid, skin, hepatosplenomegaly
what are the diagnostic investigations for NH lymphoma?
- 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
staging of NK lymphoma uses what system?
ann arbour system
criteria for stage 1 NH lymphoma
Involvement of a single lymph node(I), or an extralymphatic site (IAE)
criteria for stage 2 NH lymphoma
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)
criteria for stage 3 NH lymphoma
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)
criteria for stage 4 NH lymphoma
Diffuse involvement of one or more extralymphatic tissues (e.g. bone or liver)
A in staging of NH lymphoma means?
no systemic symptoms
B in staging of NH lymphoma means?
weight loss, drenching sweats
X in staging of NH lymphoma means?
bulky disease - widening of mediastinum more than a 1/3 due to presence of a nodal mass
What is the relationship between aggressiveness and curability?
low grade are indolent but incurable
high grade more aggressive but curable
management of low grade NH lymphoma?
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?
treatment of high grade NH lymphoma?
RCHOP
ABVD
what is the RCHOP regime?
Rituximab Cyclophsophamide
Hydroxydanuorubicin
Vincristine
Prednisolone
what is the ABVD regime?
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
what can CD20+ lymphomas be treated with?
Ritiximab
what is G-CSFs?
treatment for neutropenia in lymphoma management
what is the epidemiology of Hodgkins Lymphoma?
- 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!)
what are the causes of Hodgkins Lymphoma?
- Mononucleosis infection – EBV, CMV
- HIV
- Exposure to benzene
- Genetic component – NF-kB
what are Reed Sternberg cells?
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
what is the pathophysiology of Hodgkins Lymphoma?
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
What are the 2 classifications of Hodgkins?
Nodular lymphocyte predominance
Classic Hodgkins
what are the different types of classic hodgkins?
nodular sclerosis
lymphocyte rich
mixed cellularity
lymphocyte-depleted
what are features of nodular sclerosis HL?
Female>male Women & children Most common of classic hodgkins Excellent prognosis Lacunar type RS cells Fibrotic bands Anterior mediastinal
what are the features of lymphocyte rich HL?
Very good prognosis
Infiltrate of lots of small lymphocytes and Reed Sternberg cells
Most common in men
what are the features of mixed cellularity HL?
Eosniophils, plasma cells, histocytes, lymphocytes, neutrophils Reed Sternberg but no fibrotic bands Associated with B symptoms Elderly Abdominal & splenic lymphnodes HIV associated
what are the features of lymphocyte-depleted HL?
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
what are the clinical features of HL?
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
what investigations and features can be used for diagnosis of hodgkins?
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
what features will be present in a core needle biopsy for Hodgkins?
Gross – bulging “fish flesh” appearance, rubbery
Microscopy – reed Sternberg cells Immunohistochemistry CD15+, CD30+
what staging system is used for Hodgkins lymphoma?
same as non hodgkins
Ann-arbour system
what is the treatment of stage 1 or 2 hodgkins lymphoma?
2-4 cycles of ABVD + radiotherapy
what is the treatment of stage 3 or 4 hodgkins lymphoma?
6-8 cycles of AVDC + radiotherapy
what is the treatment for relapsed hodgkins lymphoma?
- Relapsed Refractory = autologous HSCT
* Relapsed after chemo or transplant – brentuximab
