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Week 6 - Non-Hodgkin's Lymphoma Overview
Transcript of Week 6 - Non-Hodgkin's Lymphoma Overview
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NON-HODGKINS LYMPHOMA
General Most common lymphoid maliganacy Heterogenous group resulting from distinct lymphocyte subsets and neoplastic processes >10 subtypes with variable response to treatment Common clonal expansion of lymphoid cells
Epidemiology
Prevalence increases with age Incidence rising 3-5% over past 20 years
Risk factorscongenital disorders (ataxia-telangiectasia, Wiskott-Aldrich syndrome, celiac disease), prior
chemo/radiotherapy, immunosuppressive therapy, Epstein-Barr infection, HIV infection, human T-
cell lymphoma virus [HTLV]-1 infection, Helicobacter pylori gastritis, Hashimoto thyroiditis and
Sjogren syndrome
Aetiology Originates from B cells, T cells or histiocytes (tissue macrophage) Mutations, c-some translocations, altered genes eg. BCL2, c-mYC, FAS, BCL6 88% of NHLs derived from B cells
Presentation
Non-tender enlarged lymph nodes 1/3 casses originate outside lymph nodes (eg. Mucosal surfaces, bone marrow, skin)
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Table 104-1 WHO Classification of Lymphoid Malignancies
B CELL T CELL HODGKIN'S DISEASE
Precursor B cell neoplasm Precursor T cell neoplasm Nodular lymphocyte-predominant
Hodgkin's disease
Precursor B lymphoblastic leukemia/lymphoma
(precursor B cell acute lymphoblastic leukemia)
Precursor T cell lymphoblastic
lymphoma/leukemia (precursor T cell acute
lymphoblastic leukemia)
Mature (peripheral) B cell neoplasms Mature (peripheral) T cell neoplasms Classic Hodgkin's disease
B cell chronic lymphocytic leukemia/small
lymphocytic lymphoma
T cell prolymphocytic leukemia Nodular sclerosis Hodgkin's disease
B cell prolymphocytic leukemia T cell granular lymphocytic leukemia Lymphocyte-rich classic
Hodgkin's disease
Lymphoplasmacytic lymphoma Aggressive NK cell leukemia Mixed-cellularity Hodgkin's disease
Splenic marginal zone B cell lymphoma ( villous
lymphocytes)
Adult T cell lymphoma/leukemia (HTLV-I
+)
Lymphocyte-depletion Hodgkin's
disease
Hairy cell leukemia Extranodal NK/T cell lymphoma, nasal type
Plasma cell myeloma/plasmacytoma Enteropathy-type T cell lymphoma
Extranodal marginal zone Hepatosplenic T cell lymphoma
B cell lymphoma of MALT type
Mantle cell lymphoma Subcutaneous panniculitis-like T cell
lymphoma
Follicular lymphoma Mycosis fungoides/Szary syndrome
Nodal marginal zone B cell lymphoma ( monocytoid
B cells)
Anaplastic large cell lymphoma, primary
cutaneous type
Diffuse large B cell lymphoma Peripheral T cell lymphoma, not
otherwise specified (NOS)
Burkitt's lymphoma/Burkitt cell leukemia Angioimmunoblastic T cell lymphoma
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Prognosis and Treatment
Generally: empiric and usually uses cytotoxic chemo with monoclonal antibody directed at CD20
Aggressive (diffuse large B-cell lymphoma)~40 to 45% in US
Indolent (follicular lymphoma) ~30% in US
F
eatures
Constitutional symptoms and more often at
earlier stagesSpread more diffusely throughout lymph nodesLarger, less differentiated cell types
Rapid growth rateIncreased rate of early mortality
Often more curableExtranodal lymphomas usu in (oropharynx,paranasal sinuses, thyroid, GIT, liver, testicles,skin and bone marrow)
Few Sx but widespread disease
Generally incurable
M
anagement/Treatment
Guided by IPI
Low risk lymphoma: CHOP (cyclophosphamide,doxorubicin, vincristine and prednisone) chemoplus rituximab
Radiotherapy after chemo for bulky tumours
High-risk lymphoma: intensive chemo regimensand rituximab, potentially high dose XRT toowith autologous stem cell transplantation (alsoconsider for relapsing/failure to enter remissionafter induction chemo)
Tositumomab: anti-CD20 mab bound to 131 I(Bexxar) kills via antibody-mediated cellularcytotoxicity, activation of complement-mediated
tumour cell lysis, tumour specific radiation, treats
CD20 antigen expressing relapsed or refractory
Localised disease treated with XRT only
Most have disseminated chronic relapsing andremitting diseaseRarely curative therapy, more palliative
Watch and wait recommended for asymptomatic
patientsFollow up patients until more aggressive disease,major symptoms or organ dysfunctionWithholding chemotherapy does not reduce survivalbut improves quality of life
Symptomscombination of rituximab and alkylatorchemotherapy has high response rates and canalleviate symptoms
Rituximab: binds to B-cell surface Ag CD 20 (found
on vast majority of B cell lymphomas) well
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Type of NHL Epidemiologyand Survival
Features Pathology Images
B-Cell Lymphomas
Small lymphocyticlymphoma Patientsusually >60years old
Nonleukaemic form,generalised lymphadenopathy
B cells express CD5 and CD23,
some CD20 and restricted lightchain
More favourable prognosis if
cells express mutated IGH
genesZAP-70 expressed by leukemia
cells that express unmutated
IGH genes
Diffuse infiltrate of small mature lymphocytes mixed with prolymphocytesand paraimmunoblasts in ill-defined
nodules (proliferation/growth
centres)
Vague nodular appearance,
proliferation centres
Small lymphocytes, mature chromatin pattern
Lymphoplasmacyticlymphoma
Typically dont express CD5,
not usu blood involvementAssoc with Ig M serum protein
causing hyperviscosity or
cryoglobulinemia
(Waldenstrommacrogolbulinema)
Controversial assoc with
t(9;14)(p13;q32)
small lymphocytes and cells withplasmacytoid features (eccentric
nuclei and bluish cytoplasm)
Mantle celllymphoma
Median
survival of ~3
years, can
differ by >5years
Most commonly involves LN,
can involve extranodal sites:
GIT (lymphomatous polyposis)
Diffuse growth pattern usu butcan see nodular or mantle zone
pattern
A) Large bowel with mantle cell lymphoma (multiple lymphomatous
polyposis)
B) Monomorphous small lymphocytes surrounding benign germinal centre
C) Mantle-zone pattern stained with antibody to cyclin D1D) Diffuse pattern with monomorphous infiltrate of small irregular
lymphocytes with many mitotic figures
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Uniform population of small to
medium lymphocytes, irregularnuclei and virtual absence of
large transformed cells
Cells express CD5, CD23 and
Cyclin D1Cyclin D1 expression results
from the chromosomal
translocation t(11;14)(q13;q32)Also have chromosomal
translocations involving
expression of cyclin D2
Burkitts
Lymphoma
30% of
children withNHL
American type: GIT, para-
aortic nodesAfrican type: jaw
Bone marrow involvementLeukemic phase common
EBV relationship with t(8;14)
MYC gene on c-some 8 tranl to
IGH gene on c-some 14t(8;14)(q24;q32)
Can involve light-chain genes
on c-somes 2p12 ( ) and 22q11( )
Dx on morphology, support by
being + CD20, CD10, BCL6; -/focally weakly + BCL2;
growth fraction near 100% as
determined by Ki-67 stain;
MYC transl
A)Starry sky appearance with neoplastic B cells (dark) and tangible body
macrophages (lighter stars)B)Diffuse infiltrate of medium-sized cells with small nucleoli and high mitotic
activity
Diffuse large B-cell 25-30% of all Localised disease with Diffuse large B cells resembling centroblasts or immunoblasts
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lymphoma
=>Mediastinal large
B-cell lymphoma
NHL; 50% of
adults withNHL; elderly
and childhood
populations
Younger
extranodal involvement: GIT,
brain (EBV assoc with AIDS)Derives from germinal centre B
cells (GCBs), activated B cells
(ABCs) and unclassified (not
GCB or ABCs)GCB-type better prognosis
ABC-type: NF- B activation
=> proliferation and survival ofcells
Presents in mediastinum
WHO recog can be
intermediate btw DLBL andclassical HL
CD20 Ab stain
Mediastinal large B-cell lymphoma
large cells w. abundant cytoplasm and diffuse
fibrosis
Follicularlymphoma
40% of adultswith NHL;
elderly patients
Generalized lymphadenopathyBone marrow involvement
~90% derives from germinal
centre t(14;18) causing
overexpression of BCL2antiapoptosis gene
Germinal centre markers
BCL6, CD10; folliculararchitecture with nodular
aggregates of CD21-positive
follicular dendritic cells
Variable mixture of centrocytes
(small cleaved) andcentroblasts (large noncleaved)
Grade 1 (15 centroblasts
A) Grade 2crowded follicles
B) Grade 1small centrocytesC) Grade 3A
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per)
Can have diffuse area (DLBL)transforming to more
aggressive disease
D)Positive BCL2 immunostain
Marginal zone
lymphomas:-Extranodalmarginal zonelymphoma of MALT-Splenic-Nodal
50% of adults
with NHL;elderly and
childhood
populations
Association with Helicobacter
pylori gastritisDerived from MALT
Low-grade malignant
lymphoma of the stomach
Early responds to antibioticsLater include c-somal transl
=>NF- B signalling=>antigen-
independent growthA) benign germinal centres and mantle zones surrounded by expanded pale
marginal zonesB) Salivary gland w. MALT lymphoma, diffuse infiltrate of small
lymphocytes, pale cytoplasm in enlarged salivary gland duct
(lymphoepithelial lesion)
T-cell Lymphomas Note: Mature T cells and NK cell NHLs make up 10-15% of NHLs in West, higher incidence in Asia
Precursor T-celllymphoblasticlymphoma
40% ofchildhood
lymphomasChildren and
young
adolescence
Male pred
Primarily involves the anteriormediastinum and cervical
nodesBone marrow and CNS
involvement common
W/o Rx=>rapid dissemination,
ALL, early death
lymphoblasts
have highnucleus:cytoplas
m, many
mitoses, finely
stippledchromatin,
inconspicuous
nucleoli,round/convolute
d nuclear
contours
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Mycosis fungoidesand Sezarysyndrome
Adults 40-60
yrs
Involve neoplastic peripheral
CD4 TH cellsMycosis fungoides
Begins in skin (rash to plaque
to nodular masses) progressing
to LN, lung, liver and spleenGroups of neoplastic cells in
epidermis are called Pautriers
microabscessesSezary syndrome
Mycosis fungoides with a
leukaemic phase
Circulating cells called Sezarycells (prominent nuclear cleft)
Pautrier microabscess epidermotropism of neoplastic
lymphoid cells (MF)Three Szary cells in blood smear. The nucleus in the larger cell in the upperfield has delicate folds imparting a cerebriform appearance. The two smaller
cells in the lower field have a more condensed chromatin and markedly
lobulated nuclei.marked nuclear
irregularities,
mycosisfungoides
Peripheral T-celllymphoma
One of most
common
mature T-celllymphomas in
adults
Diffuse pattern, effaces normal
nodal architecture, diverse sizes
(large-intermediate,occasionally pred small)
Cell type=no prognostic
relevance
Large cells CD3 Ab stain
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AngioimmunoblasticT-cell lymphoma
Adults
middle agedand elderly
Uncommon
Type of PTCL
Mature T-cell lymphomaSystemic Sx and polyclonal
hypergammaglobulinemia,
rash, anaemia
Monoclonal T-cell R generearrangement
Increased risk for secondary
lymphomas, prognosis poor
small lymphocytes,
plasma cells,immunoblasts,
abundant eosinophils,
burnt out germinal
centres, proliferationof post-capillary
venules
Anaplastic large celllymphoma
Particularly
common in
children
Significant morphologic
variability, large pleomorphic
cells w. horseshoe/kidney-
shaped nuclei and perinucleareosinophilic region
Early: sinuses
Later: obliterate nodalarchitecture
Uniform strong CD30
expression=/>1 T-cell Ag and clonal T-
cell R gene rearrangement
ALK-+ in 1st
30yrs, favourable
prognosisFrom c-somal transl of ALK
gene on c-some 2p23, mostcommon is t(2;5)(p23;q35)nucleophosmin is on c-some 5
Wreath-shaped nuclei CD30 Ab stain
Eosinophilic perinuclear region
ALK Ab stain
Uncommon mature T/NK cell lymphomas
Enteropathy-associated T-cell lymphoma Arises in SI from celiac diseaseExtranodal NK/T-cell lymphoma Nasal type- aggressive EBV-associated neoplasm
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References
http://www.webpathology.com/
http://www.pathconsultddx.com
Sabel Michael S, "Chapter 44. Oncology" (Chapter). Doherty GM: CURRENT Diagnosis & Treatment: Surgery, 13e:
http://www.accessmedicine.com/content.aspx?aID=5316764.
Linker Charles A, Damon Lloyd E, "Chapter 13. Blood Disorders" (Chapter). McPhee SJ, Papadakis MA: CURRENT Medical Diagnosis & Treatment 2011:
http://www.accessmedicine.com/content.aspx?aID=5476.
Gascoyne Randy D, Skinnider Brian F, "Chapter 98. Pathology of Malignant Lymphomas" (Chapter). Lichtman MA, Kipps TJ, Seligsohn U, Kaushansky K,
Prchal, JT: Williams Hematology, 8e: http://www.accessmedicine.com/content.aspx?aID=6237265.
http://www.webpathology.com/http://www.webpathology.com/http://www.pathconsultddx.com/http://www.pathconsultddx.com/http://www.accessmedicine.com/content.aspx?aID=5316764http://www.accessmedicine.com/content.aspx?aID=5316764http://www.accessmedicine.com/content.aspx?aID=5476http://www.accessmedicine.com/content.aspx?aID=5476http://www.accessmedicine.com/content.aspx?aID=5476http://www.accessmedicine.com/content.aspx?aID=5316764http://www.pathconsultddx.com/http://www.webpathology.com/