Hematopoietic and lymphoid systems main entities - disorders exam questions and very concise text -

Hematopoietic and lymphoid systems - exam questions Posthemorrhagic and hemolytic anemias Anemias of diminished erythropoiesis; pernicious anemia Polycythemia Bleeding disorders DIC Lymph node pathology - review Spleen pathology - review Thymus pathology - review Non-Hodgkin’s lymphomas Hodgkin’s disease Acute leukemias Chronic leukemias Myeloproliferative disorders Plasma cell dyscrasias Histiocytoses Storage diseases

Anemia - causes posthemorrhagic hemolytic impaired red cell production

Blood loss - posthemorrhagic anemias acute - hypovolemia, shock, rapid hemodilution, slowly increasing hematopoesis (sufficient amount of iron) chronic - GIT, female genital tract - iron loss (increased hematopoesis)

Hemolytic anemias - general features increased rate of RBCs destruction increased amount of iron hypercellular bone marrow reticulocytes in peripheral blood

Hemolytic anemias - RBCs destruction intracorpuscular (intrinsic) - hereditary, acquired are rare extracorpuscular (extrinsic) - acquired, immunity, mechanical trauma, infections

Intracorpuscular anemias hereditary acquired

Hereditary spherocytosis sickle cell anemia thalassemia - T. maior, T. minor glucose-6-phosphate dehydrogenase deficiency

Acquired paroxysmal nocturnal hemoglobinuria

Extracorpuscular anemias immunity related mechanical trauma infections

Immunity related autoimmune anemias Erythroblastosis fetalis (hemolytic disease of the newborn) - related mainly to Rh system (D- antigen), less to AB0 systém. Passage of fetal RBCs through the placenta during last trimester (no cytotrophoblast) or during childbirth. Mother antibodies cross the placenta. Concurent AB0 incompatibility protects the mother against Rh immunization - RBCs removed from maternal circulation. The blood dose - 1 ml. IgG response - cross the placenta, IgM - does not cross, the response faster in 2 nd or 3 rd gravidity (faster IgG response).

Mechanical trauma prostethic valves - more in metallic or plastic prostheses than in bioprostheses microangiopathic hemolytic anemia - squeezed RBCs in narrowed vessels - DIC, SLE, malignant hypertension

Infections malaria - 4 subtypes of plasmodia, Asia, Africa - Anopheles (mosquito) Plasmodium falciparum - malignant tertian malaria

Anemias of diminished erythropoiesis lack of –iron –folic acid –vitamin B 12 –less frequently - pyridoxin, thiamin

Iron deficiency anemia (sideropenic) lack of iron in the food - veggies; malabsorption - sprue increased demand - gravidity chronic loss - GIT, menstrual bleeding morphology - microcytosis, low RBCs volume, pallor, spoon-shaped nails

Folic acid and vitamin B 12 (Cobalamin) deficiency anemia (megaloblastic) folic acid deficiency - gravidity, severe alcoholics, drug abusers. Sometimes celiakia, malabsorbtion. B 12 - like folic acid deficiency, in addition - peripheral nerves and spinal chord demyelinization

Aplastic anemia pancytopenia, erythrocytopenia, agranulocytosis, thrombocytopenia in half number of cases - idiopatic sometimes after irradiation, myelotoxic drugs

Myelophtisis bone marrow metastases - breast, lungs, prostate multiple myeloma, TBC

Bleeding disorders - hemorrhagic diatheses vascular fragility - vitamin C deficiency - scurvy DIC, thrombocytopenia, coagulopathies

DIC Blood clotting - starts from soft tissue (tissue thromboplastin) or endothelial damage (factor XII.) Causes: 1/ release of clotting factors - amniotic fluid embolization, cytoplasmic granules - promyelocytic leukemia, mucus - Ca, Gram-negative sepsis 2/ extensive endothelial damage, burns, SLE

DIC - morphology fibrin microthrombi within capillaries - kindeys, brain, heart, lungs, adrenal gland (Waterhouse - Friderichsen sy), hypophysis (Sheehan sy) acute DIC - bleeding, chronic - thrombotic

Thrombocytopenia Idiopathic thrombocytopenic purpura (ITP) Thrombotic thrombocytopenic purpura (TTP) (m. Moschowitz) - microthrombi composed of platelets

Coagulation disorders acquired - prothrombin, f. VII., IX., and X. - hepatic damage hereditary - hemophilia A hemophilia B

Leukemias leukemic form aleukemic form leukemic infiltration of the liver, spleen, lymph nodes primary site - bone marrow

Leukemias - classification maturation: acute leukemias chronic myeloproliferative disorders cell types: lymphatic myeloid

Acute leukemias clinical course –sudden onset –anemia, fever, infections, hemorrhagic diathesis –bone pain (bone marrow expansion) –generalized lymphadenopathy (ALL), splenomegaly, hepatomegaly –CNS symptoms - headache, vomitus, paralysis

ALL (acute lymphoblastic leukemia) 80 % of childhood leukemias % Philadelphia chromosome (22  9) prognosis - relatively good, 90 % - remission, if translocation  worse prognosis

AML (acute myeloid leukemia) adult middle age prognosis bad, 5-year survival % hiatus leukemicus bone marrow transplantation

Chronic myeloproliferative disorders CML CLL polycytemia vera HCL myeloid metaplasia with myelofibrosis essential thrombocytemia

CML (chronic myeloid leukemia) adults middle or younger age “pyoid” bone marrow Philadelphia chromosome - 90 % patients bad prognosis

CLL (chronic lymphatic leukemia) older age long asymptomatic period, non- characteristic symptoms course and prognosis variable related to malignant lymphomas

Polycytemia vera proliferation of erythroid, myeloid and megakaryocytic line increased blood viscosity, blood volume borne marrow highly cellular hypertension, thromboses, bleeding

Hairy cell leukemia chronic B-cell line leukemia fine cytoplasmic projections - immunohistochemistry, phase contrast, EM hepatomegaly, splenomegaly therapy - purine analogues

Myeloid metaplasia with myelofibrosis bone marrow fibrotic, hypocellular neoplastic stem cells within the spleen unknown ethiology of bone marrow fibrosis splenomegaly, trilinear hematopoiesis in the spleen, prominent megakaryocytes

Leukemias - general morphology bone marrow soft - “pyoid” (CML) splenomegaly - CML lymph nodes enlargement - CLL hepatomegaly - CML, CLL sometimes other organs infiltrated

Non-neoplastic white cells disordes leukopenia - neutropenia (agranulocytosis) –impaired granulopoiesis - bone marrow failure –destruction of granulocytes - immunity, drugs reactive leukocytosis - infections infectious mononucleosis - EBV

Plasma cell dyscrasias multiple myeloma localized plasmacytoma Waldenström’s macroglobulinemia heavy-chain disease primary amyloidosis monoclonal gammopathy of undetermined significance

Multiple myeloma morphology osteolytic lesions - prominent mainly in the scull histologically - diffuse infiltration by neoplastic plasma cells kidney - myeloma nephrosis - neoplastic plasma cells, casts within distal tubules

Histiocytoses X acute disseminated Langerhans’ cell histiocytosis (Letterer - Siwe) unifocal and multifocal - eosinophilic granuloma multifocal histiocytosis (Hand- Schüller-Christian disease)

Malignant lymphomas non-Hodgkin’s lymphomas Hodgkin’s lymphoma

Non-Hodgkin’s lymphomas nodular diffuse Working Formulation, Kiel Classification, REAL, WHO

Malignant lymphomas - some entities ML of CLL type follicular centre ML diffuse large cell ML Burkitt’s lymphoma

Extranodal ML mycosis fungoides Sézary’s syndrome MALToma

Hodgkin’s ML nodular lymphocyte predominance Hodgkin’s lymphoma classical Hodgkin’s lymphoma –lymphocyte rich –nodular sclerosis –mixed cellularity –lymphocytic depletion

Hodgkin’s ML - staging I. Single lymph node region or single extralympatic organ. II. Two or more lymph node regions or limited contiguous extralymphatic organ on the same side of diaphragm. III. Two or more lymph node regions or limited contiguous extralymphatic organ on both sides of diaphragm. IV. Multiple, disseminated foci of involvement, both sides of diaphragm + bone marrow.

Lymph nodes -non- neoplastic diseases reactive lymphadenitis –acute non-specific –chronic non-specific speciphic lymphadenitis –TBC (BCG) –Cat Scratch Disease

Spleen - overview enlargement –massive –moderate –mild rupture necrosis

Thymus - overview thymic hyperplasia tumors thymoma »benign thymoma - 90 % »thymic carcinoma

Thymomas epithelial predominance lymphocyte predominance mixed appendant disease - myasthenia gravis