Pathology Revision 1 PDF

Pathology Revision 1 01 1 PATHOLOGY REVISION 1 ----- Active space ----- Normal Smears 00:00:14...

Pathology Revision 1 01 1 PATHOLOGY REVISION 1 ----- Active space ----- Normal Smears 00:00:14 WBC Granulocytes Agranulocytes Neutrophil Eosinophil Basophil Lymphocyte Monocyte Peripheral smear : 00:00:34 Usually contains only mature cells. 3-5 lobes. Platelet Neutrophil Granules in cytoplasm. RBC Eosinophil Round cell with central 1/3 rd Binucleate pallor. (Spectacle shaped). Monocyte Brick red granules. Largest WBC. Horse shoe shaped Lymphocyte Basophil nucleus. Smallest WBC. Nucleus obscured by Small central blue granules. nucleus. Bone marrow (BM) examination : Bone marrow aspirate : Contains mature and immature cells. Cells Fat globules Pathology Revision v1.0 Marrow 6.5 2023  2 01 Pathology ----- Active space ----- Bone marrow biopsy : Cells RBC Fat Bony trabeculae Bone marrow biopsy Note : % cellularity = (100 - Age of the patient). Bone marrow needles : Bone marrow needles Salah’s needle Klima needle Jamshidis needle Can do aspiration Side screw present and biopsy using the same needle M/C site of bone marrow examination : In adults : ASIS or PSIS or Iliac crest. In children : Anterior surface of the tibia or shin of tibia. ASIS : Anterior Superior Iliac spine PSIS : Posterior Superior iliac spine On aspiration → Dry tap → Then do bone marrow biopsy. Causes of dry tap Aplastic anemia Myelofibrosis Hairy cell leukemia AML-M7 Pathology Revision v1.0 Marrow 6.5 2023  Pathology Revision 1 01 3 WBC Disorders 00:10:20 ----- Active space ----- A. Non Neoplastic Disorders : Normal TLC : 4,000 - 11,000/mm3. Neutrophils : 40-70 % Lymphocytes : 15-40 % Monocytes : 2-8 % Eosinophils : 1-6% Basophils : 30 % blasts in the peripheral blood or bone marrow. Exception : Diagnosis can be made even if blast count < 20 % if Any one of the 3 present t(15:17) t(8:21) Inv 16 Lymphoblast vs myeloblast : Lymphoblast Myeloblast Cell size Small Large Cytoplasm Scanty Moderate Granules in Absent Present cytoplasm Auer rods Absent May be present Faggot cells Absent May be present Coarse or clumped up Opened up or homogenous Chromatin (dark purple) (Pinkish) Nucleoli Inconspicuous 2-5 prominent nucleoli PAS : Positive Myeloperoxidase +ve. Staining (Dot/Block positivity) Non specific esterase +ve. Sudan Black B +ve. Auer rod (Most important Cytoplasm : morphological feature) Scanty. No granules. Opened up chromatin Prominent nucleoli Coarse chromatin Myeloblast Lymphoblast Myeloblast markers : CD 13, CD 33, CD 117, MPO +ve. Pathology Revision v1.0 Marrow 6.5 2023  6 01 Pathology ----- Active space ----- 1. ALL (Acute Lymphoblastic Leukemia) : 00:30:49 Common in younger age group : 2-9 yrs. C/F : Hb / TLC Platelet Organ involvement Anemia. Increased risk of Bleeding Hepatosplenomegaly. Fatigue. infection. tendency. CNS, testis, lymph node can also be involved. Classification of ALL : FAB classification : Based on the morphology (L1, L2, L3).. Note : Practically difficult to differentiate ALL-L2 from AML. WHO Classification : B- ALL T- ALL more common. Less common. Better prognosis. Poor prognosis. Usually seen in children. Usually seen in adults. Mediastinal involvement : Absent. Mediastinal involvement : Present. Loss of function mutation : Gain of function mutation : PAX 5. NOTCH 1 gene. E2A. RUN X1. EBF gene. t(12;21). Peripheral smear : > 20 % lymphoblast Investigations Special Stain : PAS +ve (Dot and block) B-ALL CD 19, CD 20, CD 22, PAX 5, TdT Markers T-ALL CD 1 , CD 2, CD 3, CD 5, CD 7 IOC : Flow Cytometry. Pathology Revision v1.0 Marrow 6.5 2023  Pathology Revision 1 01 7 Peripheral smear- ALL : ----- Active space ----- Hand mirror cells (Cytoplasmic protrusion) seen in ALL Hand mirror cells Note : AML-M6 is also PAS positive but diffuse PAS +ve as compared to ALL which shows block/dot positivity. Prognostic factors : Feature Good prognosis Bad Prognosis Age 2-9 yrs 10 yrs Sex Female male Race Whites Blacks FAB type L1 (Best prognosis) L2, L3 WHO type B-ALL T-ALL Organ involvement : CNS Not involved Involved Testis Lymph node Hyperdiploidy Hypodiploidy Cytogenetics (M/C cytogenetic abnormality in ALL). Trisomy 4, 7, 10 /t(12;21) t(9;22) Leukocyte count TLC 1,00,000/ml 2. AML (Acute Myeloid Leukemia) : 00:41:33 Average age : 15-39 years. Features similar to ALL. Additional features in AML Gum bleeding/hyperplasia Chloroma DIC Pathology Revision v1.0 Marrow 6.5 2023  8 01 Pathology ----- Active space ----- Chloroma : In myeloblastoma/granulocytic sarcoma. MPO : +ve. M/C site : Orbit. Color : Greenish. Arbiskov cells : Monocytes in chloroma. Chloroma : Soft tissue involvement FAB classification : Based on cell type and degree of differentiation (morphology of the blast). FAB classification M0 Undifferentiated. M1 AML with minimal maturation. M2 AML with maturation. M3 Acute promyelocytic leukemia. M4 Acute myelomonocytic leukemia. M4 eos Acute Myelomonocytic leukemia with eosinophilia. M5 Monocytic leukemia. M6 Acute erythroid leukemia. M7 Acute megakaryocytic leukemia. Salient features : AML type Salient features M/C FAB type. AML M2 Translocation : t(8:21). M/C associated with chloroma. Translocation : t(15:17). Associated with DIC. AML M3 Maximum Auer rods. Rx : All trans retinoic acid or arsenic trioxide. Best prognosis. Associated with gum bleeding. Associated with leukemia cutis. AML M4, M5 Non specific esterase +ve. AML M4 : Inv 16. Also called Di Guglielmo disease. AML M6 Diffuse staining with PAS. Least common. CD 41, CD 61 : +ve. AML M7 Associated with Down’s syndrome. Associated with myelofibrosis (D/t platelet derived growth factors) → Dry tap. Pathology Revision v1.0 Marrow 6.5 2023  Pathology Revision 1 01 9 ----- Active space ----- Auer rod Faggot cell MPO positivity in Myeloblast Criss cross pattern of auer rods Myeloproliferative Disorders 00:50:29 1. Chronic Myeloid Leukemia : Middle age to elderly Massive splenomegaly on clinical examination. Pathogenesis : 95 % cases : t(9;22) Philadelphia chromosome BCR-ABL fusion transcript: 22 kDa Constitutive Activation of tyrosine kinase Myeloproliferation inhibit CML Imatinib mesylate ( Gleevac) Formation of BCR- ABL fusion transcript Pathology Revision v1.0 Marrow 6.5 2023  10 01 Pathology ----- Active space ----- Diagnostic criteria of CML in accelerated phase Persistent spleen size Peripheral Cytogenetic Blast 10-19% in Thrombocytopenia and WBc blood basophil evidence of blood and/or (20%. clonal bone marrow. therapy. to therapy. evolution. (OR) Persistent Thrombocytosis (>1000 x 109) unresponsive to therapy. Note : Investigations : Massive splenomegaly Peripheral smear : causes in India : Malaria. Kala Azar. All stages of myeloid CML. maturation Polycythemia vera. Myelofibrosis. Basophilia Gauchers disease. Hairy cell leukemia Peripheral smear looks more like a bone marrow Bone marrow aspirate : Contain Pseudo gaucher cells + Sea blue histiocytes. Pseudo gaucher cells FISH : Investigation of choice. Normal BCR- ABL fusion (Fusion of red and green) Pathology Revision v1.0 Marrow 6.5 2023  Pathology Revision 1 01 11 NAP Score : Neutrophil Alkaline Phosphatase. ----- Active space ----- a. Normal score : 40-100. b. Decreased in CML. Decreased NAP score Paroxysmal nocturnal hemoglobinuria Myelodysplastic syndrome Increased NAP Score Stress Infection Leukemoid reaction Pregnancy Myeloproliferative disorders other than CML Rx of choice in CML : Bone marrow transplantation. 2. Polycythemia vera : 00:59:51 Major criteria Minor criteria 1. Hb 1. Subnormal serum > 16.5 g/dl in men. erythropoetin levels. > 16.0 g/dl in women. 2. Bone marrow trilineage myeloproliferation with pleomorphic megakaryocytes. 3. Presence of JAK2 mutation. Diagnostic criteria : All 3 major criteria or first 2 major + 1 minor criteria Note : All other myeloproliferative disorders except CML, the translocation seen is JAK2 V617F translocation. 3. Essential Thrombocytosis : 01:02:05 Diagnostic criteria : All 4 criteria needed for diagnosis. Platelet count ≥ 4,50,000. JAK2 V617F mutation or no evidence of reactive thrombocytosis. Not meeting WHO criteria for other MPN Megakaryocytic proliferation with large and mature morphology; no or little granulocyte or erythroid proliferation. Pathology Revision v1.0 Marrow 6.5 2023  12 01 Pathology ----- Active space ----- 4. Myelofibrosis : 01:02:52 Diagnostic Criteria : Major criteria Minor criteria 1. Atypical megakaryocytic hyperplasia with 1. Leukoerythroblastosis. reticulin/collagen fibrosis (Due to PDGF 2. Elevated LDH. elaboration). 3. Anemia. 2. Exclusion of WHO criteria for other 4. Palpable splenomegaly. myeloproliferative disorders (CML, MDS, MPDS or PV). 3. JAK2V617F or other clonal markers, if not rule out other clonal markers. Investigations : Peripheral smear Reticulin stain : Silver stain Tear drop cells (Dacrocytes) Bony Fibrosed fibres : trabeculae Black Note : Leukoerythroblastic blood picture : Leukoerythroblastic blood picture also seen in : Myelofibrosis. Hairy cell leukemia. AML-M7. Space occupying lesions of BM. Metastatic cancer. Both immature myeloid and erythroid Myelopthisic anemia. cells in blood picture. Pathology Revision v1.0 Marrow 6.5 2023