l ymphoma 101 armaan khalid. w hat is l ymphoma ? cancer of the lymph nodes lymphoma > leukaemia...
TRANSCRIPT
LYMPHOMA 101Armaan Khalid
WHAT IS LYMPHOMA?
Cancer of the lymph nodes Lymphoma > Leukaemia Commonly manifest by the development of
lymphadenopathy at single/multiple sites Classified on basis of histological appearance
Hodgkin’s lymphoma (HL) Non-Hodgkin’s lymphoma (NHL)
HODGKIN’S LYMPHOMA (HL)
Involves primarily the lymph nodes ♂:♀ is 1.3:1 Peak incidence is in 3rd decade Tumour of B Cell origin Presence of Reed-Sternberg Cells on
pathology Often presents @ a single site & spreads in a
predictable fashion
AETIOLOGY OF HL
?Link with EBV Evidence linking previous infectious
mononucleosis with HL 40% of patients ↑ EBV titres @ time of
diagnosis
IT’S ALL ABOUT THE REED-STERNBERG’S
Hallmark of HL is Reed-Sternberg cells Large cell w enlarged multilobulated nucleus,
prominent nucleoli & abundant eosinophilic cytoplasm
RS cell variants exist in HL subtypes Staging based on the Ann Arbor Classification
Used to stage both HL & NHL
CLASSIFICATION OF HL
Nodular Sclerosing HL (70%) Typically seen in young adults/adolescents &
involving Mediastinal & neck LN Characteristic cell is the lacunar type RS cells Overall prognosis is good
Mixed Cellularity HL (25%) Most common HL in pt > 50y/o, ♂ predominance Classical RS cells abundant Assoc with B symptoms Commonly affects abdominal LN & spleen Most common HL subtype in HIV +ve population
‘CLASSIC’ REED-STERNBERG CELLS
*Common in mixed-cellular subtype HL
‘LACUNAR-TYPE’ RS CELLS
*Common in nodular sclerosis subtype HL
CLASSIFICATION OF HL
Lymphocyte-rich HL (5%) Characterised by an inflitrate of many small
lymphocytes & RS cells; often an indolent disease
Lymphocyte-depleted HL (1%) Rare & lacks cellular infiltrate with numerous RS
cells Seen in HL assoc with HIV Patients usually w advanced stage disease
Nodular Lymphocyte-predominant HL (5%) Characterised by large number of small resting
lymphocytes admixed with benign histiocytes Classical RS cells difficult to find
Lympho-histiocytic (L&H) variant RS cell (popcorn cell)
PATHOGENESIS OF HL
??? Central issue: Lymphocytes of the B-cell
lineage not expressing immunoglobulins escape apoptosis
?Role of EBV Interferes w normal immune regulatory
mechanisms Often localised to single site & spreads in
pedictable fashion
CLINICAL FEATURES
LN enlargement, esp. Cervical LN Painless & of rubbery consistency Supra-diaphragmatic LNs affected in 80%
Hepatosplenomegaly B symptoms (40%)
Fever, drenching night sweats, weight loss > 10% in 6/12
Pruritis, fatigue, anorexia, lethargy, malaise Sg/Sx due to organ involvement
Due to mass effect (Bone, Lung, Cardiac, Gut) SVC Syndrome
Due to biochemical derangement
BEFORE & AFTER
WHAT IS CAUSING THE BLOCKAGE?
SUPERIOR VENA CAVA SYNDROME
Obstruction of the SVC by an upper mediastinal mass
Sg/Sx Difficulty breathing/swallowing Stridor, swollen, oedematous facies Venous congestion
Ix Imaging (CXR, CT chest, Invasive contrast
venogram) Rx
Based on what is causing the obstruction Steroids, diuretics, stenting, chemo/radioRx
DIFFERENTIALS
Infectious Mononucleosis Lung Ca (Small Cell) HL NHL Rheumatoid Arthritis Sarcoidosis SLE
INVESTIGATIONS
FBE ESR LFT Serum LDH (Correlates with ‘bulk’ of disease) CXR HIV screening CT scan PET scan Bone marrow aspirate & trephine (BMAT) LN biopsy
ANN ARBOR STAGING CLASSIFICATION
Ann Arbor Staging System
Stage I Involvement of 1 LN region or single extra-lymphatic site
Stage II Involvement of >1 LN region on the same side of the diaphragm
Stage III Involvement of LN regions on both sides of the diaphragm
Stage IV Diffuse/disseminated involvement of >1 extranodal organs/tissue
FURTHER DESIGNATIONS TO ANN ARBOR
Further Applicable Designation to the Ann Arbor
A No symptoms
B B symptoms (Fever, night sweats, weight loss)
X Bulky disease (Widening of mediastinum > 1/3)
E Involvement of single extranodal site that is contiguous/proximal to known nodal site
MANAGEMENT
Rx taken with curative intent Rx based on:
Anatomical distribution of disease ‘Bulk’ Presence/Absence of ‘B’ symptoms
EARLY STAGE (IA, IIA, NO BULK)
Brief chemotherapy + radiotherapy Example: ABVD or BEACOPP
A = Adriamycin (Doxorubicin) B = Bleomycin V = Vinblastine D = Dacarbazine
ADVANCED DISEASE
Cyclical combination chemoRx w or w/o radioRx
Gold standard: ABVD Pt w bulk disease receive radioRx Curative 50-60% Risk of myelosuppression, infertility, 2°
malignancy & organ damage
NON-HODGKIN’S LYMPHOMA (NHL)
Classified separately from HL 70% - 80% are of B Cell origin Incidence 15/100 000 per year in devt
countries Slight ♂ predominance Median age of presentation 55-75y/o Can be classified on the basis of origin
Tumours of B cells Tumours of T cells Tumours of NK cells
AETIOLOGY NHL
Unknown cause; wide geographical variation ?Envt factors
EBV (Burkitt’s lymphoma) ↑% of lymphoma in pts with AIDS H. Pylori in gastric MALT lymphoma
BURKITT LYMPHOMA (AFRICAN SUBTYPE)
PATHOGENESIS NHL
Malignant clonal expansion of lymphocytes Due to errors in gene rearrangements or
recombinations Translocation errors with specific genes
Burkitt’s (c-myc)
CLINICAL FEATURES
Same as HL*
Same as HL
INVESTIGATIONS
CLINICAL DIFFERENCES B/W HL & NHL
Hodgkin’s Lymphoma Non-Hodgkin’s Lymphoma
Often localised to a single axial group of nodes (cervical, mediastinal, para-aortic)
More frequent involvement of multiple peripheral nodes
Orderly spread by contiguity Non-contiguous spread
Mesenteric nodes & Waldeyer ring rarely involved
Mesenteric nodes & Waldeyer ring commonly involved
Extranodal involvement uncommon
Extranodal involvement common
FOLLICULAR B CELL LYMPHOMA
HOPC Asymptomatic w painless generalised lymphadenopathy
Occurs ↓% in Asian population & predominantly in older people (>20-30y/o)
Ix indicates multiple site involvement (Bone marrow infiltration is common)
Runs a remitting & recurring clinical course Death due to:
Rx resistant disease Transformation to Diffuse Large B Cell Lymphoma
Bad prognostic factor, less curable Effects of Rx
MANAGEMENT
Treat the symptoms, not the numbers Leave the asymptomatic pt alone Watchful waiting & repeat biopsies
ChemoRx + RadioRx rCHOP
r = Rituximab C = Cyclophosphamide H = Hydroxydaunorubicin (Doxorubicin) O = Oncovin (Vincristine) P = Prednisolone
WHAT IS RITUXIMAB?
Trade name: Rituxan or Mabthera Chimeric monoclonal antibody against CD20,
found primarily on the surface of B cells CD20 widely expressed on B cells, but is
absent on terminally differentiated plasma cells
Basically, it induces apoptosis of CD20+ cells
DIFFUSE LARGE B CELL LYMPHOMA
Commonest NHL (50% adults) & invariably fatal w/o Rx
Treat to cure, expectant management inappropriate >50% of young pts are cured Contra: Co-morbidities & pt’s will
HOPC Rapidly progressive lymphadenopathy,
symptomatic Infiltration of extranodal organs
Morphology Nuclei of neoplastic B cells are huge (x3-4 of
resting lymphocytes)
DIFFUSE LARGE B CELL LYMPHOMA
MANAGEMENT
Rx decision based on staging Cyclical chemoRx + radioRx
rCHOP Bad prognostic factors
Disease progression during Rx Failure to achieve complete remission during
initial Rx
BURKITT’S LYMPHOMA
Uncommon in the Western world Endemic to Africa
Close assoc w EBV Rapidly fatal w/o Rx HOPC lymphadenopathy, abdo mass, BM &
CNS infiltration (leukaemia & meningitis) Morphology
Starry sky pattern Assoc w translocations involving MYC gene
BURKITT’S LYMPHOMA
MANAGEMENT
Supportive Rx Hydration Prevent Tumour Lysis Syndrome!
Cyclical chemoRx + radioRx rEPOCH
r = Rituximab E = Etoposide P = Prednisolone O = Oncovin (Vincristine) C = Cyclophosphamide H = Hydroxydaunorubicin (Doxorubicin)
?African setting
PERIPHERAL T CELL LYMPHOMA (UNSPECIFIED)
Most common type of adult T-cell lymphoma Most common subtype of peripheral T Cell
lymphoma Often disseminated & aggressive
MANAGEMENT
Treated similarly to B Cell lymphomas Cyclical chemoRx + RadioRx Refer to haematologist
In general, overall Rx strategies are similar but success of complete remission is ↓ than B Cell lymphomas
TUMOUR LYSIS SYNDROME
Iatrogenic cause, Rx causes massive breakdown of tumour cells
Intracellular contents released into circulation Metabolic derangement
Uric acid, potassium & phosphate
Complications Can precipitate Acute Renal Failure
Mgmt Identify high-risk pts Allopurinol given prophylactically Close monitor of electrolytes Baseline ECGs & follow-ups
CASE STUDY #1
62 y/o woman referred for Ix of neck mass HOPC
Enlarging L neck lump over last 6/52, no pain Fatigue, unwell & LOW 3kg
O/E Afebrile, no pallor/jaundice & peripheral oedema BP 170/105 & prominent but undisplaced apex beat L supraclavicular LN (firm, non-tender) Abdo NAD, soft, tender X2 enlarged LN in L groin Urinalysis +1 protein
Other Info Hx of HTN (felodipine 5mg bd) Non-smoker & social drinker
QUESTION TIME
What further info should be elicited from Hx/Ex?
DDx? Ix? Staging the pt? Mgmt & considerations?
INTERESTING FACT OF THE DAY: BREAST IMPLANTATION & LYMPHOMA
Epidemiological studies indicate link b/w silicone breast implants & anaplastic large cell lymphoma (ALCL) ALCL devt in at least 60 women
2/3 occurred in silicone implants 1/3 occurred in saline implants
Considered to be related because ALCL occurred uniformly in breast tissue
FDA labelled silicone as inert, Grade 2 Later relabelled to Grade 3 (somewhat
dangerous)