Hematology Lecture Notes PDF

HEMATOPATHOLOGY : Hawler Medical University College of Medicine Department: Pathology SESSION FOUR: THE LYMPHOID SYSTEM Hawler Medical University College of Medicine Department: Pathology OBJECTIVES:...

HEMATOPATHOLOGY : Hawler Medical University College of Medicine Department: Pathology SESSION FOUR: THE LYMPHOID SYSTEM Hawler Medical University College of Medicine Department: Pathology OBJECTIVES:  Define lymphomas and understand the major differences between Hodgkin’s and Non Hodgkin’s Lymphoma.  Be able to identify the different histological subtypes of Hodgkin's disease.  Be able to identify two important examples of NHL, namely Burkitt’s lymphoma and large cell lymphoma. CONTENTS:  Lymphoid system: - Reactive nodular hyperplasia - Lymphomas: -Hodgkin’s disease -NHL NORMAL LYMPH NODE REACTIVE HYPERPLASIA – L.N FOLLICULAR TYPE At the top is the capsule and just under that a subcapsular sinus where lymphatics enter that drain tissues peripheral to the node. Beneath the capsule is the paracortical zone with lymphoid follicles having a pale germinal center in which the immune responses are often generated. Beneath this are sinusoids extending to the center of the node. REACTIVE HYPERPLASIA – L.N FOLLICULAR TYPE At high magnification is seen a lymph node follicle with a germinal center containing larger lymphocytes undergoing activation. At the lower right is the sub capsular sinus. LYMPHOMAS Lymphomas are a group of diseases caused by malignant lymphocytes that accumulate in lymph nodes and cause the characteristic clinical features of lymphadenopathy. Occasionally, they may spill over into blood ('leukaemic phase') or infiltrate organs outside the lymphoid tissue. Subdivided into:  Hodgkin’s Disease.  Non - Hodgkin’s Lymphomas.  Clinical:  B symptoms: Fever, night sweats, weight loss.  Lymphadenopathy, splenomegaly.  Laboratory:  CBC: Anemia, leukopenia. ch c Chemistry: LDH, uric acid. oa ti  pr nos  Imaging{ A p ag  PET-CT: Lymph node and organ spread. Di  Biopsy Excisional: Preferred for histology.  Histology:  Hodgkin: Reed-Sternberg cells, CD15+, CD30+.  Non-Hodgkin: B-cell (CD20+), T-cell (CD3+).  Molecular:  FISH: t(14;18), MYC.  NGS: Mutations (TP53, BCL2).  Staging:  Ann Arbor Staging, bone marrow biopsy if needed. HODGKIN’S LYMPHOMA: Reed - Sternberg (R.S) cells. Arise in a single node / chain of nodes & spreads characteristically to contiguous L.N Clinically: Most patients present with painless, non-tender, asymmetrical, firm, discrete and rubbery enlarge- ment of superficial lymph nodes Constitutional symptoms are prominent in patients with widespread disease. These may include: fever, profuse sweating, weight loss and pruritits. Hodgkin Lymphoma-Gross appearance Enlargement of cervical nodes(most frequent). Individual nodes discrete. C/S grayish tan or pale tan. HODGKIN’S LYMPHOMA: Reed-Sternberg cell:  True neoplastic element in HL.  Classic RS cells are large ,15 - 45 microns , binucleated / bilobed.  Nucleus contains large inclusion like owl eyed nucleoli surrounded by a clear halo.  Cytoplasm - abundant & weakly esinophilic.  Lymphocyte depleted > Mixed Cellularity > Nodular Sclerosis > Lymphocyte Predominant.  Type Subtypes Key Features Classical Hodgkin Collagen bands, lacunar Nodular Sclerosis (NS) Lymphoma cells. Mixed infiltrate, classical Mixed Cellularity (MC) Reed-Sternberg cells. Lymphocyte-dominated, Lymphocyte-Rich (LR) few Reed-Sternberg cells. Sparse lymphocytes, Lymphocyte-Depleted (LD) abundant Reed-Sternberg cells. Nodular Lymphocyte- Popcorn cells, nodular Predominant Hodgkin NLPHL architecture, CD20+. Lymphoma HODGKIN’S LYMPHOMA – NODULAR SCLEROSIS This is Hodgkin's disease, nodular sclerosis type. Note the bands of pink collagenous tissue dividing the field in this lymph node.. HODGKIN’S LYMPHOMA – Nodular Sclerosis The aggregates of Reed-Sternberg cells and inflammation are separated by broad bands of fibrosis HODGKIN’S LYMPHOMA – NODULAR SCLEROSIS Broad fibrous bands separating the tumor nodules.  HODGKIN’S LYMPHOMA – NODULAR SCLEROSIS These are the lacunar cells which are characteristic for the nodular sclerosis type of H.L, they are scattered large cells with a surrounding prominent clear space, an artifact of formalin fixation.  HODGKIN’S LYMPHOMA- MIXED CELLULARITY (A) At low power, the lymph node appears to be effaced by heterogeneous population, giving a slightly pink color to the node. (B) The Reed- Sternberg variants are few and far between (arrow), with a dominant population of eosinophils (arrowhead). HODGKIN’S LYMPHOMA- MIXED CELLULARITY Hodgkin’s lymphoma, mixed cellularity type. Several mononuclear Hodgkin cells and rare classic Reed-Sternberg cells are present. The polymorphous background cells include mature lymphocytes, histiocytes, and plasma cells.  HODGKIN’S LYMPHOMA- LYMPHOCYTE PREDOMINENCE Numerous mature-looking lymphocytes surround scattered, large, pale-staining lymphohistiocytic variants (“popcorn” cells). NON-HODGKIN LYMPHOMAS EG. BURKITT’S LYMPHOMA. DIFFUSE LARGE B CELL LYMPHOMA. SMALL NONCLEAVED CELL LYMPHOMA, BURKITT'S TYPE Ø It’s a B cell tumor. Ø High mitotic rate is characteristic. Ø Both endemic & non endemic type Ø Affect the children & young adults & usually arise from extranodal sites. Ø Microscopically: Nodal architecture completely effaced by uniform medium-sized cells with rounded nuclei with coarsely clumped chromatin and 2-5 prominent basophilic nucleoli &Scattered between them are tingible body macrophages with prominent nuclear debris surrounded by clear space, giving the characteristic “starry sky” appearance. BURKITT'S LYMPHOMA BURKITT'S LYMPHOMA DIFFUSE LARGE B CELL LYMPHOMA  Nodal architecture completely effaced by large cells.  Open chromatin  Prominent nucleoli.  Nucleus may round, irregular, or cleaved (typically 3 to 4 lymphocyte diameters). DIFFUSE LARGE B CELL LYMPHOMA DIFFUSE LARGE B CELL LYMPHOMA SUMMARY  Lymphoma is divided into Hodgkin’s lymphoma and NHL, and can be seen in all age groups.  RS cells are characteristic for Hodgkin’s disease.  MYELOPROLIFERATIVE NEOPLASMS Hawler Medical University College of Medicine Department: Pathology OBJECTIVES:  Definition of MPN  Types of MPN  Mutations of MPN  Clinical features of MPN  Definition of each PV, ET and MF LIST OF CONTENTS:  Definition  Types  PV  ET  MF  Summary or conclusion  Question MYELOPROLIFERATIVE DISORDERS:  A group of conditions arising from marrow stem cells and characterized by clonal proliferation of one or more haemopoietic components in the bone marrow  Three disorders are included in this classification: 1 Polycythaemia rubra vera (PRV). 2 Essential thrombocythaemia (ET). 3 Myelofibrosis.  Clinical  Symptoms: Fatigue, splenomegaly, thrombosis, pruritus.  Examination: Splenomegaly, hepatomegaly.  Laboratory  CBC:  PV: Elevated Hb/Hct. ch c oa ti pr nos  ET: Thrombocytosis. A p ag  PMF: Anemia, variable counts. Di  Smear: Leukoerythroblastosis (PMF).  EPO: Low in PV.  Molecular  JAK2, CALR, MPL mutations.  Bone Marrow ch c  PV: Hypercellularity, panmyelosis. oa ti pr nos  ET: Megakaryocyte atypia. A p ag  PMF: Fibrosis. Di  Differentials  Polycythemia: Hypoxia, tumors.  Thrombocytosis: Iron deficiency, inflammation.  POLYCYTHEMIA VERA Erythromelalgia  Hepatosplenomegaly  Anemia if ID or marrow fibrosis  Erythromelalgia Liver  Increased skin temp 40%  Burning sensation  Redness Spleen 70%  Pruritis especially after warm bathing.  POLYCYTHEMIA VERA Laboratory features and morphology  Hb, PCV (HCT), and Red cell mass increased Blood film in PV  Increased neutrophils and platelets  NAP score normal or increased  Plasma urate high  Circulating erythroid precursors  Hypercellular bone marrow  Low serum erythropoietin  Iron panel for iron deficiency MYLOFIBROSIS The predominant feature of myelofibrosis is a progressive generalized reactive fibrosis of the bone marrow in association with the development of haemopoiesis in the spleen and liver (known as myeloidmetaplasia). This is the appearance of normal bone marrow at medium magnification. MYELOFIBROSIS  Marrow fibrosis: On hematoxylin and eosin stain, the marrow has a streaming texture (arrow), indicative of strands of collagen separating the hematopoietic cells into nests and channels. MYELOFIBROSIS fibrosis New bone (arrows) MYELOFIBROSIS  Peripheral blood film in myelofibrosis showing leucoerythroblastic change with “tear-drop” cells. Tear drop cell a & b. tear drop cells c. nucleated RBC d. blast e & f. giant plt ESSENTIAL THROMBOCYTOSIS (PRIMARY THROMBOCYTHEMIAIS)  is a nonreactive, chronic myeloproliferative neoplasm in which sustained megakaryocyte proliferation leads to an increase in the number of circulating platelets ET CHARACTERIZED BY THE FOLLOWING  A persistently elevated platelet count greater than 450,000/µL  Megakaryocytic hyperplasia  Splenomegaly  A clinical course complicated by thrombotic or hemorrhagic episodes or both ESSENTIAL THROMBOCYTHEMIA Peripheral blood film in essential thrombocythaemia showing increased numbers of platelets and a nucleated megakaryocyticfragment. SUMMARY  Polycythemia Vera is a clonal stem cell disorder characterized by increased red cell production  Myeloproliferative disorders are characterized by an uncontrolled proliferation of all blood forming elements.  Essential thrombocytosis is a nonreactive, chronic myeloproliferative neoplasm in which sustained megakaryocyte proliferation leads to an increase in the number of circulating platelets QUESTIONS? WHAT IS YOUR DIAGNOSIS?