Leukemia and lymphoma PATHOLOGY REVISION NOTES
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PATHOLOGY REVISION NOTES BASED ON HIGH YIELD TOPICS AND LECTURE NOTES LEUKEMIA AND LYMPHOMA HIGH YIELD TOPICS MEDICINE HEMATOLOGY BASICS IMAGE BASED QUESTIONS PERIPHERAL SMEAR
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Leukemia and lymphoma PATHOLOGY REVISION NOTES
- 1. 22-04-2018 Leukemia and lymphoma TONY SCARIA 2010 KMC Leukemoid reaction • Persistent leucocytosis above 50000 cells /mm3 • Major causes • a/c severe infections • Severe haemorrhages • a/c hemolysis • Malignancies • Downs syndrome • Asplenia • DKA TONY SCARIA 2010 KMC
- 2. 22-04-2018 TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 3. 22-04-2018 • Immature forms present • Early mature neutrophils are seen in leukemoid reaction • Immature forms typically seen in CML • LAP score is elevated in leukemoid reaction • Depressed in CML • No orgnaomegaly • Organomegaly + in CML • Basophilia eosinophilia thrombocytosis • In CML • Absent in leukemoid reactionsTONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 4. 22-04-2018 • Leucocytosis is not seen in typhoid TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 5. 22-04-2018 TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 6. 22-04-2018 TONY SCARIA 2010 KMC • Auer rods • Most definitive sign of myeloid differentiation • Cluster of auer rods faggot TONY SCARIA 2010 KMC
- 7. 22-04-2018 TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 8. 22-04-2018 In ALL • Cytochemical stain PAS +ve • Dot like • Block like TONY SCARIA 2010 KMC PAS positivity is due to glycogen deposits in lymphoblast TONY SCARIA 2010 KMC
- 9. 22-04-2018 In M6 of AML • Diffuse positivity by PAS TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 10. 22-04-2018 Myeloblast with auer rods TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 11. 22-04-2018 MPO positivity for granules in myelocytes TONY SCARIA 2010 KMC Non specific esterase staining for M3 M4 M5 The blasts show a strong positive reaction for non-specific esterase, as observed by the dense orange cytoplasmic staining. This reaction is positive in monocytic cells, and negative in granulocytes. TONY SCARIA 2010 KMC
- 12. 22-04-2018 TONY SCARIA 2010 KMC ALL TONY SCARIA 2010 KMC
- 13. 22-04-2018 Etiology TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 14. 22-04-2018 TONY SCARIA 2010 KMC • Tdt(terminal deoxytransferase ) a DNA polymerase present in Pre B ALL & Pre T ALL TONY SCARIA 2010 KMC
- 15. 22-04-2018 Cytogenetics in Pre B ALL • B cell ALL is associated with • loss of function mutation in PAX5, E2A and EBF or • balanced t (12;21) affecting ETV6 and RUNX1 genes (normally required for B cell development). • Hyperdiploidy MC cytogenetic change • Trisomy 4 7 & 10 • Hypoploidy • Both hypoploidy & hyperploidy are pesent in pre B ALL TONY SCARIA 2010 KMC Loss of function mutation of E2A EBF PAX5 TONY SCARIA 2010 KMC
- 16. 22-04-2018 TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 17. 22-04-2018 CD10 common ALL antigen Pre B ALL express TdT CD 10 CD 19 CD20 PAX5 TONY SCARIA 2010 KMC Pre T ALL • 15 % cases • Teenage (13 – 17 yrs of age ) in boys • Presents as a mediastinal mass in thymus • Early testicular involvement & early CNS manifestation d/t meningeal spread TONY SCARIA 2010 KMC
- 18. 22-04-2018 Molecular patho genesis in Pre T ALL • Gain of function mutation in NOTCH 1 TONY SCARIA 2010 KMC Pre T ALL • Teenagers • Thymic involvement • Testicular involvement poor prognosis TONY SCARIA 2010 KMC
- 19. 22-04-2018 Immunophenotype in pre T ALL • TdT • CD1 • CD2 • CD5 • CD7 TONY SCARIA 2010 KMC Good prognosis • Age 2-10 years • Female sex • white race • Peripheral blast count <10,000 • Pre B-cell phenotype(CALLA +ve) • L1 morphology • Absence of mediastinal mass • Absence of CNS involvement • Absence of testicular involvement • Hyperdiploidy (>50 chromosomes) • t(12;21) or t (9:12) • Trisomy 4,7 and 10 Bad prognosis • Age <1 year or > 10 years • Male sex • Black • Peripheral blast count >50,000 • Pre T-cell phenotype • L2 L3 morphology • Mediastinal mass • CNS involvement • Testicular involvement • Pseudodiploidy or • t (9;22) (Philadelphia chromosome) or t (8;14) or t (4;11) TONY SCARIA 2010 KMC
- 20. 22-04-2018 TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 21. 22-04-2018 TONY SCARIA 2010 KMC AML TONY SCARIA 2010 KMC
- 22. 22-04-2018 AML • Adults 15 to 40 years • Acquired oncogenic mutation • Accumalation of immature blast cells in marrow • marrow failure pancytopenia TONY SCARIA 2010 KMC Etiology • Environmental • Chemicals like benzene & alkylating agents • Ionizing radiation • Smoking • Hereditary factors • Downs syndrome • Fanconis anemia • AT • Blooms syndrome • Turner syndrome TONY SCARIA 2010 KMC
- 23. 22-04-2018 TONY SCARIA 2010 KMC Haematological conditions predisposing to AML • CML with blast crisis • Myeloproliferative disorder • Myelodysplasia • PNH • Aplastic anemia TONY SCARIA 2010 KMC
- 24. 22-04-2018 • Diagnosis • Blast cell count > 20 % or more in peripheral blood or bone marrow TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 25. 22-04-2018 TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 26. 22-04-2018 AML with recurrent genetic abnormalities • AML t(8:21) RUNx1 fusion gene (M2) • AML inv (16) M4E0 • Acute promyelocytic leukemia t (15:17) M3 • AML t 11q 23 MLL fusion gene bad prognosis • AML with normal cytogenetics & mutated NPM (nucleophosmin) TONY SCARIA 2010 KMC AML therapy related • Alkylating therapy MDS like cytogenetics changes (5q-7q-)latency of 2-8 years • Following of topoisomerase II inhibitors 1-3 yrs of latency TONY SCARIA 2010 KMC
- 27. 22-04-2018 AML with MDS like features • Dysplastic changes & cytogenetics of 5q 7q 20 q TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 28. 22-04-2018 TONY SCARIA 2010 KMC AML M0 • Difficult to diagnose • No maturation • MPO /PAS –ve TONY SCARIA 2010 KMC
- 29. 22-04-2018 AML M3 t(15:17) • Multiple auer rods (Faggot cells) • Heavily granulated strong MPO+positivity • Granules contain procoagulant DIC • Common in young female DIC manifest as menorrhagia TONY SCARIA 2010 KMC AML M3 TONY SCARIA 2010 KMC
- 30. 22-04-2018 AML M5 gingival hyperplasia TONY SCARIA 2010 KMC pancytopenia TONY SCARIA 2010 KMC
- 31. 22-04-2018 Criteria for remission in AML • Platelet count > 1lakh • Neutrophil >1500 • Bone marrow blast <5 % and absent auer rods • Absence of extra medullary lesion TONY SCARIA 2010 KMC Chloroma TONY SCARIA 2010 KMC
- 32. 22-04-2018 Chloroma / myeloid sarcoma /granulocytic sarcoma • Solid tumour with myeloblast • Extramedullary manifestation of AML • May be hidden manifestation of AML (common in M2 / monocytic (M3orM4) • Follow up for development of AML with bone marrow transplantation • Mc seen in skin of orbit & periorbital tissue TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 33. 22-04-2018 Arbinskov cells are monocytes in chloroma TONY SCARIA 2010 KMC Markers for granulocytic sarcoma • CD 33 • CD 43 • CD 117 • Myeloperoxidase • Lysozyme TONY SCARIA 2010 KMC
- 34. 22-04-2018 CLL TONY SCARIA 2010 KMC CLL • Absolute lymphocyte count > 5000 cell/mm3 • Males are more commonly affected • > 60 yrs • Most common lymphoma in western world TONY SCARIA 2010 KMC
- 35. 22-04-2018 CF Symptoms • Fatigue (commonest presentation) • Infections d/t hypogammaglobulinemia Signs • Lymphadenopathy • Initially cervical generalised • Hepatosplenomegaly • TONY SCARIA 2010 KMC • Both cell types are affected • B cell types & T cell types (B cell >> t cell) • Hypogammaglobulinemia + • Auto Ab against RBC AIHA TONY SCARIA 2010 KMC
- 36. 22-04-2018 • diagnostic criteria for CLL are: • • Peripheral blood lymphocyte count >5000 cells/mm3with <55% cells being atypical. • • Bone marrow aspirate showing >30 % lymphocytes TONY SCARIA 2010 KMC • deletion of 13q • commonest and has good prognosis • Tumour suppressor genes miR15 a & miR16- 1+ on chr 13 • Deletion 11q • trisomy 12q and • deletion of 17p have poor prognosis TONY SCARIA 2010 KMC
- 37. 22-04-2018 • IOC • Flowcytometry • Used to detect lymphocytosis & immunophenotyping • Immunophenotyping} CD 5 CD23 CD19 cD20 TONY SCARIA 2010 KMC Peripheral smear • Smudge cells /parachute cells/basket cells • Slide artefact • Tumour cells appear as fragile disrupted tumour cells formation • Due to lack of vimentin (cytoskeletal protein required for rigidity & integrity of cells Smudge cells are also seen in infections CLL a/c leukemia TONY SCARIA 2010 KMC
- 38. 22-04-2018 Lymph node biopsy • Large mitotic cells known as prolymphocytes • Divide & form diagnostic proliferation centres • Distortion of architecture • Diffue effacement of LN architecture • Commonest • d/t proliferation cenrtres • Pseudofollicular pattern • Rare TONY SCARIA 2010 KMC Diffuse effacement of LN TONY SCARIA 2010 KMC
- 39. 22-04-2018 Basket cells in CLL TONY SCARIA 2010 KMC Bad prognosis • Expression of ZAP 70 • Presence of NOTCH 1 mutation • Deletions of 11q 17 p or trisomy 12 TONY SCARIA 2010 KMC
- 40. 22-04-2018 ZAP 70 a/w poor prognosis TONY SCARIA 2010 KMC ZAP 70 is a/w drug resistance TONY SCARIA 2010 KMC
- 41. 22-04-2018 TONY SCARIA 2010 KMC Transformations in CLL • Prolymphocytic transformation • Cb worsening of cytopenia increasing splenomegaly & large number of prolymphocytes in circulation • Richter syndrome TONY SCARIA 2010 KMC
- 42. 22-04-2018 Richter syndrome • Transformation of CLL in to DLBL • Presents as rapidly enlarging mass in spleen or LN TONY SCARIA 2010 KMC Myelodysplastic syndrome TONY SCARIA 2010 KMC
- 43. 22-04-2018 Myelodysplastic syndrome • Clonal stem cell disorder • Ineffective haematopoesis • Transformation to AML • DD of megaloblastic anemia TONY SCARIA 2010 KMC • 1. Primary MDS – Develops slowly usually after 50 years of age. • 2. Secondary or Therapy related MDS (t-MDS) – • Usually 2 to 8 years after toxic drug or radiation exposure. The secondary MDS gets transformed to AML most frequently and so has a poorer prognosis. TONY SCARIA 2010 KMC
- 44. 22-04-2018 TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 45. 22-04-2018 Erythroid lineage shows ringed sideroblast • Iron laden mitochondria in perinuclear area • Visible as blue granules in Prussian blue staining • Also ssen in • MDS • Pb poisoning • Sideroblastic anemia TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 46. 22-04-2018 MDS is cb DOHLE bodies in granulocytic lineage • Damaged RER • Also seen in MDS • Sepsis • Chediak higashi syndrome TONY SCARIA 2010 KMC Granulocytic lineage also has pseudo pelger huet anomaly • Neutrophil with bilobed nuclei • MDS • AML with dysplastic maturation • CML during accelerated phase TONY SCARIA 2010 KMC
- 47. 22-04-2018 Megakaryocyte lineage pawn ball appearance • Either a single nuclear lobe or multiple separate nuclei TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 48. 22-04-2018 TONY SCARIA 2010 KMC Rx • erythropoetin • G CSF • Lenalidomide • Azacytidine • antimetabolite that inhibits DNA methylation • BM transplantation TONY SCARIA 2010 KMC
- 49. 22-04-2018 Myeloproliferative disorders • CML • Polycythemia vera • Essential thrombocythemia • c/c idiopathic myelofibrosis • c./c neutrophilic leukemia • c/c eosinophilous leukemia TONY SCARIA 2010 KMC Common feature of MPD • Increased proliferative drive in the marrow • Extra medullary haematopoesis • Spent phase transformation • Cb marrow fibrosis & peripheral blood cytopenia • a./c leukemia transformation TONY SCARIA 2010 KMC
- 50. 22-04-2018 • MPD may undergo transformation in to a/c leukemia • Diagnosed by BM examination • Blood count • To determine proliferating cell line • Marrow infiltration decrease in normal cells TONY SCARIA 2010 KMC CML TONY SCARIA 2010 KMC
- 51. 22-04-2018 Philadelphia chromosome / reciprocal translocation / Chr t (9:22) TONY SCARIA 2010 KMC • LAP score will be elevated in accelerate & blast crisis • But decreased in chronic phase TONY SCARIA 2010 KMC
- 52. 22-04-2018 P/S in CML • Leucocytosis (>1,00,000) • Blast count <10 % • Consist of neutrophils (band forms metamyelocytes & myocytes) eosinophils & basophils TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 53. 22-04-2018 TONY SCARIA 2010 KMC • Pseudo gaucher cells with wrinkled cytoplasm TONY SCARIA 2010 KMC
- 54. 22-04-2018 TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 55. 22-04-2018 TONY SCARIA 2010 KMC Prognostic markers • Soklal index • Age • Blast (circulating) • Cytogenetic changes • Platelet count • Spleen size • Hasford index • Age • Blast (circulating ) • Basophils & eosinophils • Platelet count • Spleen size TONY SCARIA 2010 KMC
- 56. 22-04-2018 TONY SCARIA 2010 KMC Rx • Allogenic or syngenic bone marrow transplant • Patients in early chronic phase • Imatinib (also used in treatment of GIST) • DOC • Dasatinib or IFN alpha • Rx of accelerated or blast phase • Hydroxyurea • Arsenic can also be used • Leukapheresis & splenectomyTONY SCARIA 2010 KMC
- 57. 22-04-2018 TONY SCARIA 2010 KMC Polycythemia rubra • the most common of the chronic myeloproliferative disorders • characterized by the increased number of erythroid, granulocytic and megakaryocytic cells (panmyelosis) • Mutation in JAK 2 tyrosine kinase pathway • Can be • Polycythemia rubra vera (primary polycythemia) • Secondary polycythemia TONY SCARIA 2010 KMC
- 58. 22-04-2018 TONY SCARIA 2010 KMC • Increased red cell mass • Microcytosis with erythrocytosis • Hb >18.5 in in males 16.5 in females • Hyperviscosity stagnation of blood flow • Thrombosis • Deoxygenation cyanosis TONY SCARIA 2010 KMC
- 59. 22-04-2018 • Extra medullary hematopoesis organomegaly • Bone marrow trilineage hyperplasia • High cell turn over hyperuricemia • Platelet dysfunction bleeding & thrombotic events • Basophilia histamine release aquagenic pruritus & peptic ulcer TONY SCARIA 2010 KMC • Erythropoietin is elevated in secondary polycythemia • Decreased or normal in PCV TONY SCARIA 2010 KMC
- 60. 22-04-2018 • Causes of secondary polycythemia • Hypoxia • High altitude • Lung Ca • Smoking • COPD • Congenital cyanotic heart ds • Secondary tumours producing erythropoietin • Renal cyst • Hypernephroma • Hydronephrosis • Renal A stenosis • Cerbellar haemangioblastoma • Hepatoma • Pheochromocytoma TONY SCARIA 2010 KMC Features of polycythemia • Increased levels of vitamin B12 • Microcytosis with erythrocytosis • Increased LAP score • Decreased ESR • Decreased ESR • Polycythemia • Afibroginemia • CHF • Microcytosis with erythrocytosis • c/c hypoxia • PCV • Beta thalassemia TONY SCARIA 2010 KMC
- 61. 22-04-2018 • Rx • venesection • Anagrelide • Decreases platelet production • CTx • Hydroxyurea • Radioactive phosphorous TONY SCARIA 2010 KMC • Spurious / low plasma volume polycythemia • Gaisbock syndrome • Decrease in plasma volume relative increase in red cell count Hb haematocrit TONY SCARIA 2010 KMC
- 62. 22-04-2018 TONY SCARIA 2010 KMC Essential thrombocythemia TONY SCARIA 2010 KMC
- 63. 22-04-2018 Diagnostic criteria • Sustained platelet count >4.5 lakhs/mm3 • BM biopsy • Megakaryocyte proliferation with large & mature morphology • Not meeting WHO critera for CML PV PMF MDS • Demonstration of JAK2 mutation or other clonal marker • No evidence of reactive thrombocytosis TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 64. 22-04-2018 Rx • Aspirin low dose 60mg/day • Busulfan /hydroxyurea • Interferon alpha • Radioactive phosphorous • Anagrelide TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 65. 22-04-2018 Primary myelofibrosis TONY SCARIA 2010 KMC Tear drop cells + leucoerythroblastic picture TONY SCARIA 2010 KMC
- 66. 22-04-2018 • BM biopsy for marrow fibrosis • Initially hypercellular • Then becomes hypocellular • Abnormal megakaryocytes with unusual nuclear shapes • Dilated marrow sinusoids TONY SCARIA 2010 KMC Silver staining for reticulin TONY SCARIA 2010 KMC
- 67. 22-04-2018 Staining with masons trichrome S TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 68. 22-04-2018 Myeloproliferative / myelodysplastic neoplasm TONY SCARIA 2010 KMC • Clonal myeloid disorders • Both dysplastic & proliferative features not classified in MDS /MPN • Chronic myelomonocytic leukemia (CMML) • Juvenile myelomonocytic leukemia • Atypical CML TONY SCARIA 2010 KMC
- 69. 22-04-2018 CMML • Most common MDS MPN • Absence of Philadelphia chromosome TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 70. 22-04-2018 JMML • children <2yrs • 2% child hood leukemia • Children with NF1 are at increased risk for development of JMML TONY SCARIA 2010 KMC Major criteria (all the three) • Absence of Ph chromosome • Peripheral monocytes greater than 1*10^9 /L • Less than 20 % blast Minor criteria • HbF raised • Immature granulocytes in peripheral blood • WBC count > 1*10^9 /L • Clonal chromosomal abnormality (monosomy 7) • GM CSF hypersensitivity of myeloid progenitors in vitroTONY SCARIA 2010 KMC
- 71. 22-04-2018 Atypical CML TONY SCARIA 2010 KMC • Rx • Very aggressive • But chemosensitive TONY SCARIA 2010 KMC
- 72. 22-04-2018 Peripheral B cell neoplasm TONY SCARIA 2010 KMC Basics TONY SCARIA 2010 KMC
- 73. 22-04-2018 TONY SCARIA 2010 KMC Mantle cell lymphoma • B cell lymphoma • Arises from naive B cells • Males of 50 – 60 yrs • Presents as painless lymphadenopathy TONY SCARIA 2010 KMC
- 74. 22-04-2018 T(11:14) is seen in mantle zone lymphoma Bcl 1 = cyclin D! TONY SCARIA 2010 KMC • Express cyclin D1 (= Bcl1) & surface Ig • CD 5+ CD23-ve (CD5 +ve CD 23 +ve in CLL) • Charcteristic pattern of spread is also known as LYMPHOMATOID POLYPOSIS LYMPHOMATOID POLYPOSIS TONY SCARIA 2010 KMC
- 75. 22-04-2018 Diffuse large b cell lymphoma • Most common NHL • Most malignant WORST prognosis • Affects older individual Medial age of 60 years • mature B cell tumour TONY SCARIA 2010 KMC Immunophenotyping of DLBL • CD 19 CD20 • Variable expression of germinal center markers such as Bcl-6 or CD10 • Surface Ig+ TONY SCARIA 2010 KMC
- 76. 22-04-2018 Cytogenetics of DLBL • Translocations involving Bcl-6 • Translocation t(14:18) overexpression of Bcl-2 decreased apoptosis • MYC tranlocatins TONY SCARIA 2010 KMC Special types of DLBL • Immunodeficiency associated large B cell lymphoma • In severe T cell immunodeficiency like HIV & bone marrow transplantation • Neoplastic cells are latently infected with EBV • Restoration of T cell immunity regression of tumour • Primary effusion lymphoma • Seen in elderly • As malignant pleural or ascetic effusion • Tumour cells anaplastic lack T or B cell markers • Tumour cells are infected with human Kaposi sarcoma herpes virus TONY SCARIA 2010 KMC
- 77. 22-04-2018 Follicular lymphoma • B cell lymphoma arising from germinal centre • LN biopsy • Centrocytes • Small cells with cleaved nuclear contours & scanty cytoplasm (buttock cells ) • Centroblast • Large cells with open nuclear chromatin several nucleoli modest amount of cytoplasm TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 78. 22-04-2018 • BM biopsy paratrabecular lymphoid aggregates in follicular lymphoma TONY SCARIA 2010 KMC Translocation of 14 : 18 follicular lymphoma Over expression of Bcl2 30-50 % transform in to DLBCL TONY SCARIA 2010 KMC
- 79. 22-04-2018 Cytogenetics of follicular lymphoma • CD19 CD20 • Arising from germinal centre Bcl -6 & CD10 TONY SCARIA 2010 KMC Marginal zone lymphoma MALToma • Mucosa associated lymphoid issue MALToma • Resembles normal marginal zone B cell • Most common site is stomach • 3 characteristic features • a/w c/c inflammatory conditions • like psojgrens syndrome • Hashimotos thyroiditis • Stomach H pylori infection • Remain localized for long periods • Regress on removal of inciting stimulus • Upregulation of Bcl10 or MALT1 TONY SCARIA 2010 KMC
- 80. 22-04-2018 TONY SCARIA 2010 KMC Cytogenetics a/w MALToma • t(11:18)resistant to Ctx • T(14:18) • T(1:14) TONY SCARIA 2010 KMC
- 81. 22-04-2018 Burkitts lymphoma • Peripheral B cell neoplasm • ALL L3 • most common cause of tumour lysis syndrome TONY SCARIA 2010 KMC T(8:14)in burkitts lymphoma TONY SCARIA 2010 KMC
- 82. 22-04-2018 TONY SCARIA 2010 KMC C-myc gene on chromosome 8 TONY SCARIA 2010 KMC
- 83. 22-04-2018 3 categories of burkitts lymphoma • African endemic • Sporadic (non endemic) • HIV associated aggressive TONY SCARIA 2010 KMC African endemic • Most commonly affects face /mandible • Children / young adults • All cases will be latently infected with EBV TONY SCARIA 2010 KMC
- 84. 22-04-2018 Sporadic (nonendemic ) BL • Seen in children /young adults • Presents as Illeocaecal / peritoneal mass • 15 – 20 % latently infected with EBV TONY SCARIA 2010 KMC HIV associated aggressive lymphomas • 25 % of the patients are latently infected by EBV TONY SCARIA 2010 KMC
- 85. 22-04-2018 Starry sky pattern due to apoptotic tumour cell laden foamy macrophages TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 86. 22-04-2018 • Immunophenotyping reveals the cells expressing • bcl-6 protein, • surface Ig, CD19, CD20 and • CD10 (CALLA) TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 87. 22-04-2018 Immunostaining of burkitts lymphoma • Ki 67 • MIB1 • PCNA • AgNOR TONY SCARIA 2010 KMC Hairy cell leukemia TONY SCARIA 2010 KMC
- 88. 22-04-2018 Hairy cell leukemia • Middle aged • Male (M:F=6:1) • Indolent course • Peripheral B cell neoplasm TONY SCARIA 2010 KMC • Hairy cells are best seen by phase contrast microscopy TONY SCARIA 2010 KMC
- 89. 22-04-2018 Triad of HCL • Pancytopenia • Massive splenomegaly (no lymph node enlargement) • Most common presentation • Vasculitis like syndrome (erythema nodosum) TONY SCARIA 2010 KMC TRAP positivity TONY SCARIA 2010 KMC
- 90. 22-04-2018 TONY SCARIA 2010 KMC Fried egg appearance of hairy cell in bone marrow /honey comb appearance TONY SCARIA 2010 KMC
- 91. 22-04-2018 Immunophenotyping • Pan B markers • CD 19 CD 20 surface Ig • Monocyte specific • CD11c • CD25 • Characteristically expression of hairy cell leukemia • CD103 • T cell specific • Annexin A1 • Best & specific TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 92. 22-04-2018 • Rx • Chemosensitive • Cladiribine & deoxycoformycin • Splenectomy for severe pancytopenia • Good prognosis TONY SCARIA 2010 KMC Peripheral T cell neoplasm TONY SCARIA 2010 KMC
- 93. 22-04-2018 Mycosis fungoides • Tumour of CD4 + helper T cells • Epidermotropism • d/t cutaneous localizaition of tumour cells • Chemokine receptors CCR4 & CCR10 TONY SCARIA 2010 KMC Pautriers microabscess TONY SCARIA 2010 KMC
- 94. 22-04-2018 TONY SCARIA 2010 KMC Cerebriform nuclei TONY SCARIA 2010 KMC
- 95. 22-04-2018 TONY SCARIA 2010 KMC Mycosis fungoides (cutaneous T cell lymphoma) • NHL presenting with skin infiltration • MC primary cutaneous lymphoma of T cell origin • In middle aged males and blacks • C/F • Pruritic localised erythematous plaques on trunk > 5 cm TONY SCARIA 2010 KMC
- 96. 22-04-2018 Pautrier microabscess is characteristic of MF. pleomorhic lymphocytes as clusters in epidermis TONY SCARIA 2010 KMC Sezary syndrome • Advanced MF with lypmpadenpathy and visceral spread • Generalised exfoliative erythroderma • Circulating atypical lymphocytes(sezrry cells) • Detected by T – cell rearrangement test TONY SCARIA 2010 KMC
- 97. 22-04-2018 • Mycosis fungoides is an indolent cutaneous T-cell lymphoma (indolent course) but is inevitably fatal (not easily amenable to treatment), except for patients in stage I. • Localised d/s • Topical N2 mustard, corticosteroids,bexarotene PUVA • Advanced • PUVA+ oral retinoids • Electron beam therapy • denileukin • Romidepsin • Vorinostat • Alemtuzumab(anti – CD 52 Ab) • histone deacetylase inhibitors TONY SCARIA 2010 KMC • It has 3 phases • Inflammatory premycotic phase • Plaque phase • Tumor phase TONY SCARIA 2010 KMC
- 98. 22-04-2018 TONY SCARIA 2010 KMC sezary syndrome • Leukemic phase of disease • Sezry cells in peripheral smear • Cerebriform nuclei • Generalized exfoliative erythroderma TONY SCARIA 2010 KMC
- 99. 22-04-2018 Large granular lymphocytic leukemia • Occuring mainly in adults • Neutropenia anemia • Pure red cell aplasia anemia • a/w • Rheumatological disorder • feltys syndrome • RA • Splenomegaly • Neutropenia TONY SCARIA 2010 KMC Adult T cell leukemia • Neoplasm of CD4 + T cells • Endemicity • CF • Lymhadenopathy • HSM • Skin lesions TONY SCARIA 2010 KMC
- 100. 22-04-2018 HTLV 1 tax gene TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 101. 22-04-2018 • Clover leaf cells / flower cells TONY SCARIA 2010 KMC Anaplastic large cell lymphoma TONY SCARIA 2010 KMC
- 102. 22-04-2018 TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 103. 22-04-2018 NK cells TONY SCARIA 2010 KMC NK cell granuloma • Extranodal Midline • Destructive nasopharyngeal mass • Invade vessels ischemic necrosis • EBV associated • CD 16 & 56 • CD 3 –ve TONY SCARIA 2010 KMC
- 104. 22-04-2018 Miscellaneous TONY SCARIA 2010 KMC Post transplantation lympho proliferative ds • Diverse group of abnormal lymphoid growth • Consisting of both hyperplasia & neoplasia • Majority are Bcell origin • Rarely t cell or NK cell TONY SCARIA 2010 KMC
- 105. 22-04-2018 Hodgkins lymphoma TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 106. 22-04-2018 TONY SCARIA 2010 KMC • Arises single node and spreads by contiguous spread • Reed sternberg cells • derived from the germinal center B cell • induces the accumulation of reactive lymphocytes, macrophages and granulocytes • Neoplastic giant cell • Owl eye appearance • Also seen in IMN • NHL (immunoblastic NHL) • Carcinoma & sarcoma TONY SCARIA 2010 KMC
- 107. 22-04-2018 TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 108. 22-04-2018 • “owl-eye” appearance • due to the presence of symmetric (mirror image) bilobed nucleus with prominent nucleoli surrounded by clear space • PAX 5 is best marker for reed Sternberg cell TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 109. 22-04-2018 • Classical reed Sternberg cells • Express PAX5 CD15 & CD30 • Lymphohistiocytic variant • Will express germinal center B cells (CD20 & Bcl 6) TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 110. 22-04-2018 TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 111. 22-04-2018 NODULAR SCLEROSIS TYPE • MOST COMMON IN WORLD • abundant collagen + • Mediatinal involvement common TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 112. 22-04-2018 Mixed cellularity • Most common in developing countries • Biphasic incidence Young age >55 years TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 113. 22-04-2018 Lymphocyte rich histiocytes TONY SCARIA 2010 KMC Lymphocyte depleted • Lymphocyte depleted • Mummified RS cells TONY SCARIA 2010 KMC
- 114. 22-04-2018 Lymphocyte predominant • Popcorn cell • L&H variant • fluffy, lobulated nucleus having fine chromatin and small nucleoli. TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 115. 22-04-2018 TONY SCARIA 2010 KMC CF of hodgkins lymphoma • Alcohol increases symptoms • Pel ebstein fever • Fever which cyclically increase in one or two weeks • Painless rubbery enlargement of LN • Paraneoplastic syndrome in HL • Secondary amyloidosis (AA) • Alchol induced pain in LN TONY SCARIA 2010 KMC
- 116. 22-04-2018 Adverse prognostic factors • Age > 45 yrs • Male • Hb <10.5gm/dL • Leucocyte count >15000 • Lymphocytopenia • Absolute lymphocyte count <600/ul • Lymphocyte <8 % • Serum albumin <4gm/dL • Stage IV TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 117. 22-04-2018 Best prognosis • Lymphocyte predominant >> nodular sclerosis TONY SCARIA 2010 KMC Bad prognosis • Mediastinal involvement • Lymphocyte depletion type • Systemic symptoms TONY SCARIA 2010 KMC
- 118. 22-04-2018 Ann arbor staging TONY SCARIA 2010 KMC Rx • ABVD is more effective than MOPP TONY SCARIA 2010 KMC
- 119. 22-04-2018 IMN • Atypical lymphocytes in peripheral smear • DOWNEY CELLS • Atypical lymphocytes activated CD8 –T (cytotoxic) cells • Ballerina skirt appearance TONY SCARIA 2010 KMC PLASMA CELL NEOPLASMS TONY SCARIA 2010 KMC
- 120. 22-04-2018 Plasma cell neoplasm • Neoplasm of terminally differentiated B cells TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 121. 22-04-2018 Multiple myeloma • Clonal plasma cells >10 % on BM biopsy • Or in any quantity in biopsy from other tissues plamcocytoma • Monoclonal protein in either serum or urine • Except in cases of true non secretory myeloma • Evidence of end organ damage • CRAB • Calcium elevation >11.5 Hypercalcemia • Renal insufficiency (s creatinine >2mg/dl • Anemia (haemoglobin <10gm/dl) • Bone lesions (lytic lesion/osteoporosis with compression#) TONY SCARIA 2010 KMC Plasma cell leukemia TONY SCARIA 2010 KMC
- 122. 22-04-2018 • Multiple myeloma • Age group 65 and 70 yrs TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 123. 22-04-2018 Radiographically • Punched out lesions will be seen • Vertebrae is most commonly involved • Vertebra>>ribs>>skull>.pelvis >>femur >> clavicle TONY SCARIA 2010 KMC Hypercalcemia • Hypercalcemia metasatic calcification TONY SCARIA 2010 KMC
- 124. 22-04-2018 TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 125. 22-04-2018 Immunity • Hypogammaglobulinemia decreased humoral immunity • Cellular immunity is normal TONY SCARIA 2010 KMC Hyperviscosity syndrome TONY SCARIA 2010 KMC
- 126. 22-04-2018 TONY SCARIA 2010 KMC Old diagnostic criteria TONY SCARIA 2010 KMC
- 127. 22-04-2018 • Definitive diagnosis is with bone marrow examination TONY SCARIA 2010 KMC Marked rouleaux formation d/t M proteins TONY SCARIA 2010 KMC
- 128. 22-04-2018 Plasma cells TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 129. 22-04-2018 FlAme cells (IgA myeloma) TONY SCARIA 2010 KMC Russel bodies are inclusions in Endoplasmic reticulum TONY SCARIA 2010 KMC
- 130. 22-04-2018 Mott cells multiple russel bodies TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 131. 22-04-2018 Complications of multiple myeloma • Systemic amyloidosis • Hyperviscosity syndrome • Renal failure • Hypercalcemia • Spinal cord compression TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 132. 22-04-2018 TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 133. 22-04-2018 Poor prognostic factors for multiple myeloma • Serum β2 macroglobulin >6mg/dl • Best prognostic marker • CRP > 6mg/dl • Presence of plasmablastic morphology • Bone marrow biopsy diffuse pattern & prominent angiogenesis • Serum LDH raised • Serum creatinine > 2mg/dl • Plasma cell labelling index > 3 % • Cytogenetics • Deletion of 13q 11p • Monosomy 13 • Hypodiploidy TONY SCARIA 2010 KMC In multiple myeloma • Anion gap is less than normal • Bcz M protein is cationic leads to retention of chloride TONY SCARIA 2010 KMC
- 134. 22-04-2018 Rx • Thalidomide • Leflunomide • Bortezomib proteasome inhibitor TONY SCARIA 2010 KMC • Plasma cell leukemia • Plasma cells more than 20 % of cells • Absolute plasma cell count of more than 2000cells /mm3 TONY SCARIA 2010 KMC
- 135. 22-04-2018 • Nonsecretory myeloma • No M band in serum or urine • All other symptoms of MM+ • Rare TONY SCARIA 2010 KMC Waldenstroms macroglobulinemia • B cell neoplasm • Affecting 60 -70 yrs • No bone destructin TONY SCARIA 2010 KMC
- 136. 22-04-2018 TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 137. 22-04-2018 MGUS • presence of M spike without associated disease of the B cells. MGUS is the • commonest cause of monoclonal gammopathy. Around 1% of the patients with MGUS progress to develop multiple myeloma per year. It is usually a diagnosis of exclusion. • Patients of MGUS have less than 3 g/dL of monoclonal protein in the serum and no Bence Jones proteinuria • Normal calcium • Rx • Symptomatic • Follow up TONY SCARIA 2010 KMC Heavy chain disease TONY SCARIA 2010 KMC
- 138. 22-04-2018 Langerhancell histiocytosis TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 139. 22-04-2018 • Cleaved nucleus • Several granules in cytoplasm BIRBECK granules TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 140. 22-04-2018 Clinicopathological entities of LCH • Letterer – siwe disease • Multifocal multisystem • Aggressive systemic disorder occurring before 2 yrs of age • Presents like seborrheic dermatitis • Bone destruction involving all bones of body • Eosinophilic granuloma • Unifocal & multifocal unisystem • Mc presentation is calvarial skull defect • Hand schuller Christian syndrome • Calvarial bone defects • Diabetes insipidus • Exophthalmos • Pulmonary lan TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 141. 22-04-2018 TONY SCARIA 2010 KMC Exophthalmos TONY SCARIA 2010 KMC
- 142. 22-04-2018 Flow cytometry TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 143. 22-04-2018 TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 144. 22-04-2018 Forward scatter • To determine cell size TONY SCARIA 2010 KMC Side scatter • For density of cell (granularity vacuoles membrane size ) • Granulocytes & monocytes have more granularity hence more scattering TONY SCARIA 2010 KMC
- 145. 22-04-2018 • Pan-B cell markers are CD19, 20 and 21. CD21 is also acts as the receptor of EBV. TONY SCARIA 2010 KMC Clinical uses of flow cytometry • Diagnosis of PNH • Reticulocyte enumeration • Leukemia & lymphoma phenotyping • transplant rejection • Lymphocytosis TONY SCARIA 2010 KMC
- 146. 22-04-2018 TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 147. 22-04-2018 Massive splenomegaly • CML • Idioathic myelofibrosis • Gauchers ds • Hairy cell leukemia • Tropical splenomegaly • Malaria • Hypersplenism TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 148. 22-04-2018 Digeorge syndrome T cell deficiency TONY SCARIA 2010 KMC Microdeletion @ 22q11.2 digeorge syndrome TONY SCARIA 2010 KMC
- 149. 22-04-2018 TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 150. 22-04-2018 TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 151. 22-04-2018 Alder reily anomaly • In mucopolysacharidose • AR inherited MPS • Mucopysaccharidoses TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 152. 22-04-2018 May hegglin anomaly • AD • Associated with macrothrombocytes • Giant platelets with thrombocytopenia TONY SCARIA 2010 KMC TONY SCARIA 2010 KMC
- 153. 22-04-2018 TONY SCARIA 2010 KMC Kikuchis disease • Necrotising histiocytic lymphadenitis TONY SCARIA 2010 KMC
- 154. 22-04-2018 Kimuras disease • Eosinophilic lymphadenitis TONY SCARIA 2010 KMC • The LAP score is usually decreased in chronic myelogenous leukemia and paroxysmal nocturnal hemoglobinuria, while it is increased in leukemoid reaction and polycythemia vera. TONY SCARIA 2010 KMC