Leukemia and Lymphoma Leukemia and Lymphoma Dental ViewsDental Views
By Fatin Al – Sayes By Fatin Al – Sayes MD, Msc ,FRcpath MD, Msc ,FRcpath Associate Professor Associate Professor
Consultant HematologyConsultant Hematology
HematologicalHematological MalignanciesMalignancies
Malignant transformation is now known to be Malignant transformation is now known to be associated with changes in the function of various associated with changes in the function of various cellular gene called oncogenes. These genes code cellular gene called oncogenes. These genes code for proteins which are normally involved in cell for proteins which are normally involved in cell proliferation and differentiation. proliferation and differentiation. Malignant cells replace the normal cells e.g. in the Malignant cells replace the normal cells e.g. in the bone marrow by a clonal population of malignant bone marrow by a clonal population of malignant cell arising from a single cells with an acquired cell arising from a single cells with an acquired genetic alteration (somatic mutation).genetic alteration (somatic mutation). Possible mechanisms of oncogenesis chemicals, Possible mechanisms of oncogenesis chemicals, radiation, drugs…radiation, drugs…
Leukemia'sLeukemia's
A group of disorders characterized by accumulation of A group of disorders characterized by accumulation of abnormal white cells in the bone marrow. These abnormal abnormal white cells in the bone marrow. These abnormal cells cause bone marrow failure and raised circulating WBC & cells cause bone marrow failure and raised circulating WBC & infiltrate organinfiltrate organ..
25,00025,000 – – 30,00030,000 cases per year in USAcases per year in USA
50%50% are acuteare acute
High mortality without RXHigh mortality without RX
Classification of LeukemiaClassification of Leukemia Acute leukemiaAcute leukemia Chronic leukemia Chronic leukemia
EtiologyHereditary
Ionizing irradiation
Chemicals
Drugs
Viruses
Immune systems
Chronic bone marrow dysfunction
Acute Leukemia'sAcute Leukemia's Acute Lymphoid Leukemia (ALL)Acute Lymphoid Leukemia (ALL) Acute Myeloid Leukemia (AML)Acute Myeloid Leukemia (AML)
Immature Cell (Blast) InfiltrationImmature Cell (Blast) Infiltration
Acute Lymphoid Leukemia (ALL)Acute Lymphoid Leukemia (ALL) Common in children ( 3 – 10 ) yearsCommon in children ( 3 – 10 ) years
Cure rate in children is 85%Cure rate in children is 85%
Cure rate in adults are 30% Cure rate in adults are 30%
ClassificationsClassifications Pre-B-ALLPre-B-ALL B-ALL (Burkitt)B-ALL (Burkitt) T-ALL T-ALL
ALLALL
Acute Myeloid Leukemia (AML)Acute Myeloid Leukemia (AML) 8o% in adults8o% in adults
20%20% in childrenin children
M0 totally undifferentiatedM0 totally undifferentiated
M1 with no differentiationM1 with no differentiation
M2 with some differentiationM2 with some differentiation
M3 acute promyelocytic( DIC )M3 acute promyelocytic( DIC )
M4 myelomonocytic leukemiaM4 myelomonocytic leukemia
M5 monocytic leukemiaM5 monocytic leukemia
M6 erythroleukemiaM6 erythroleukemia
M7 megakaryoblastic leukemiaM7 megakaryoblastic leukemia
AMLAML
AML – moAML – mo
AML - M1AML - M1
AML _ M2AML _ M2
AML _ M3AML _ M3
AML _ M4AML _ M4
AML _ M5AML _ M5
AML – M6AML – M6
AML – M7AML – M7
SymptomsSymptoms
Weakness and fatigue
Lymphadenopathy
Fever
Weight loss
Recurrent infection
Bleeding
Pallor
Echymosis
Lymphadenopathy
Oral bleeding
Oral lesions
Loose teeth
Signs
DiagnosisDiagnosis* * Laboratory Findings:Laboratory Findings:
CBC: WBC, Diff., Hb, Plt.CBC: WBC, Diff., Hb, Plt. Blood Film: BlastBlood Film: Blast Bone marrow study Bone marrow study
Bone marrow aspirationBone marrow aspiration
Immunological markerImmunological marker
CytogeneticCytogenetic Electrolytes & kidneys, liver function testsElectrolytes & kidneys, liver function tests Radiological studiesRadiological studies CNS examination ± CNS examination ±
Chronic LeukemiaChronic Leukemia
Chronic Myeloid Leukemia (CML)Chronic Myeloid Leukemia (CML) Chronic Lymphocytic Leukemia (CLL)Chronic Lymphocytic Leukemia (CLL)
- B-CLL majority- B-CLL majority
- T-CLL uncommon - T-CLL uncommon
Chronic LeukemiaChronic Leukemia Chronic Myeloid Leukemia (CML)Chronic Myeloid Leukemia (CML) Chronic Lymphocytic (CLL)Chronic Lymphocytic (CLL)
B-CellB-Cell T-CellT-Cell
B-CLLB-CLL T-CLLT-CLL
B-PLLB-PLL T-PLLT-PLL
Hairy Cell LeukemiaHairy Cell Leukemia Sezary LeukemiaSezary Leukemia
(HCL)(HCL)
Plasma Cell LeukemiaPlasma Cell Leukemia Adult T-Cell Adult T-Cell
LeukemiaLeukemia
(rare)(rare) Lymphoma Lymphoma
Chronic leukemia VS acute leukemia
Affects older age group
slower , insidious onset of symptoms
More functional mature WBC,s
Mild anemia and mild thrombocytopenia
Chronic Lymphocytic LeukemiaChronic Lymphocytic Leukemia
CLL accounts for 25% of the leukemia's CLL accounts for 25% of the leukemia's in Elderlyin Elderly
Male predominanceMale predominance..
The accumulation of the large numbers The accumulation of the large numbers of apparently mature lymphocytes to of apparently mature lymphocytes to 50-100 times the normal lymphoid 50-100 times the normal lymphoid mass in blood, bone marrow, spleen & mass in blood, bone marrow, spleen & liverliver..
Clinical FindingsClinical Findings::..Is often discovered accidentallyIs often discovered accidentally
Lymphadenopathy during an examination of unrelated Lymphadenopathy during an examination of unrelated FindingsFindings
HepatosplenomegalyHepatosplenomegaly
Rarely fever , night sweat , weight lossRarely fever , night sweat , weight loss
CBC ,leukocytosisCBC ,leukocytosis
95%95% mature appearing lymphocytesmature appearing lymphocytes
..22 . .BM Diffuse infiltration with small lymphocytes. Erythroid, BM Diffuse infiltration with small lymphocytes. Erythroid, myeloid are reduced. If an autoimmune hemolytic anemia myeloid are reduced. If an autoimmune hemolytic anemia develops, erythroid elements prominentdevelops, erythroid elements prominent..
PrognosisPrognosis
Usually very goodUsually very good
Range from 5 – 10 yearsRange from 5 – 10 years
Malignant LymphomasMalignant Lymphomas-- Hodgkin’s diseaseHodgkin’s disease
- -Non-Hodgkin’s LymphomasNon-Hodgkin’s Lymphomas
There is replacement of normal lymphoid There is replacement of normal lymphoid structure by collections of abnormal cellsstructure by collections of abnormal cells..
Hodgkin’s Disease HDHodgkin’s Disease HD
HD is a malignant tumorHD is a malignant tumor
If the disease is localized to a single peripheral lymph node If the disease is localized to a single peripheral lymph node region, it is subsequently progress by contiguity within region, it is subsequently progress by contiguity within lymphatic systemlymphatic system..
HD being characterized by the presence of Reed Sternberg HD being characterized by the presence of Reed Sternberg (RS) cells (neoplastic) and associated with inflammatory (RS) cells (neoplastic) and associated with inflammatory cellscells..
EBV genome has been detected approximately 20-50%EBV genome has been detected approximately 20-50%..
- -The origin of the malignant cell (RS) was not firmly The origin of the malignant cell (RS) was not firmly established except recentlyestablished except recently
- -RS cells express features of cellular activationRS cells express features of cellular activation
Clinical FeaturesClinical Features - -It has bimodal age incidenceIt has bimodal age incidence
- - in young adult (age 20-30 years)in young adult (age 20-30 years) - - after the age of 50after the age of 50
- -Male: Female – 2:1Male: Female – 2:1 - -Most patients present with painless non-tender, Most patients present with painless non-tender,
asymmetrical rubbery enlargement of a superficial LNsasymmetrical rubbery enlargement of a superficial LNs - inguinal node- inguinal node 6-12%6-12% - mediastinal mass- mediastinal mass 6-11% (NS)6-11% (NS) - cervical node- cervical node 60-70%60-70% - axilliary node- axilliary node 10-15%10-15%
Splenomegaly in 50% of patientsSplenomegaly in 50% of patients - fever- fever - sweating- sweating - weight of loss pruritus - weight of loss pruritus
Haematological FindingsHaematological FindingsNo anemia or normocytic anemiaNo anemia or normocytic anemia
22 . .One-third have a leucocytosisOne-third have a leucocytosis
33 . .Eosinophilia is frequentEosinophilia is frequent
44 . .Advanced disease-lymphopeniaAdvanced disease-lymphopenia
55 . .Platelet count is N or highPlatelet count is N or high
66 . .ESR usually raised its useful monitoring markerESR usually raised its useful monitoring marker
77 . .BMA , trephine BiopsyBMA , trephine Biopsy
Immunological FindingsImmunological Findings
- -Reduced cell-mediated immune reactionReduced cell-mediated immune reaction
* * InfectionInfection
- -Humoral immunity is maintained until later Humoral immunity is maintained until later stagesstages
Mostly of B- lymphocyte originMostly of B- lymphocyte origin
The incidence of this disorder is increasing at The incidence of this disorder is increasing at an annual rate of 4% for men and 3% for an annual rate of 4% for men and 3% for womenwomen
VirusesVirusesHTLV-1HTLV-1EBEBHIVHIV
? ?Hep-C VirusHep-C Virus
Non-Hodgkin’s Lymphomas Non-Hodgkin’s Lymphomas (NHL)(NHL)
Cytogenetics and OncogenesCytogenetics and OncogenesBurkett's Lymphoma Burkett's Lymphoma ~~ MYCMYCt (8:14), t (8:22), t( 2:8)t (8:14), t (8:22), t( 2:8)Immuno Suppression e.gImmuno Suppression e.g . .
Coeliac DiseaseCoeliac DiseaseDermatitis herpetiformDermatitis herpetiform
Autoimmune diseases Autoimmune diseases ~ ~ NHL NHL frequency frequency
Continuation of Non-Hodgkin’s Lymphomas (NHL)
Peripheral LymhadenopathyPeripheral Lymhadenopathy
Abdominal or mediastinal massesAbdominal or mediastinal masses
C.N.S.or bone marrow involvementC.N.S.or bone marrow involvement
Waldeyer’s rings 15-30Waldeyer’s rings 15-30% %
Constitutional symptoms e.g. fever,night sweat, and Constitutional symptoms e.g. fever,night sweat, and weight lossweight loss
Anemia, neutropenia, & thrombocytopeniaAnemia, neutropenia, & thrombocytopeniaInvolvement of other organs e.g. skin, brain, testes, Involvement of other organs e.g. skin, brain, testes, etcetc..
Clinical FeaturesClinical Features
TreatmentTreatment
-- Supportive if requiredSupportive if required
- -RadiotherapyRadiotherapy
Chemotherapy (cyclical)Chemotherapy (cyclical)
Oral findingsOral findings
UlcerationsUlcerations
Masked or unusual infectionsMasked or unusual infections
Sub mucosal hemorrhageSub mucosal hemorrhage
Spontaneous gingival bleedingSpontaneous gingival bleeding
ParesthesiasParesthesias
Potential problems related to Potential problems related to dental Treatmentdental Treatment
Excessive bleedingExcessive bleeding
InfectionsInfections
Poor wound healingPoor wound healing
Oral lesionsOral lesions
MucositisMucositis