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