Hematopoietic and lymphoid systems

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Hematopoietic and lymphoid systems

• main entities - disorders
• exam questions and very concise text -
  www.lfhk.cuni.cz/patanat

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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-Hodgkins lymphomas
• Hodgkins disease
• Acute leukemias
• Chronic leukemias
• Myeloproliferative disorders
• Plasma cell dyscrasias
• Histiocytoses
• Storage diseases

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Anemia - causes

• posthemorrhagic
• hemolytic
• impaired red cell production

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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)

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Hemolytic anemias - general features

• increased rate of RBCs destruction
• increased amount of iron
• hypercellular bone marrow
• reticulocytes in peripheral blood

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Hemolytic anemias - RBCs destruction

• intracorpuscular (intrinsic) - hereditary,
  acquired are rare
• extracorpuscular (extrinsic) - acquired,
  immunity, mechanical trauma, infections

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Intracorpuscular anemias

• hereditary
• acquired

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Hereditary

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

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Acquired

• paroxysmal nocturnal hemoglobinuria

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Extracorpuscular anemias

• immunity related
• mechanical trauma
• infections

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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 2nd or 3rd
  gravidity (faster IgG response).

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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

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Infections

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

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Anemias of diminished erythropoiesis

• lack of
• iron
• folic acid
• vitamin B12
• less frequently - pyridoxin, thiamin

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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

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Folic acid and vitamin B12 (Cobalamin) deficiency
anemia (megaloblastic)

• folic acid deficiency - gravidity, severe
  alcoholics, drug abusers. Sometimes celiakia,
  malabsorbtion.
• B12 - like folic acid deficiency, in addition -
  peripheral nerves and spinal chord demyelinization

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Aplastic anemia

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

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Myelophtisis

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

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Bleeding disorders - hemorrhagic diatheses

• vascular fragility - vitamin C deficiency -
  scurvy
• DIC, thrombocytopenia, coagulopathies

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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

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DIC - morphology

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

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Thrombocytopenia

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

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Coagulation disorders

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

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Leukemias

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

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Leukemias - classification

• maturation
• acute leukemias
• chronic myeloproliferative disorders
• cell types
• lymphatic
• myeloid

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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

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ALL (acute lymphoblastic leukemia)

• 80 of childhood leukemias
• 5 - 10 Philadelphia chromosome (22 ? 9)
• prognosis - relatively good, 90 - remission, if
  translocation ? worse prognosis

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AML (acute myeloid leukemia)

• adult middle age
• prognosis bad, 5-year survival - 10 - 15
• hiatus leukemicus
• bone marrow transplantation

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Chronic myeloproliferative disorders

• CML
• CLL
• polycytemia vera
• HCL
• myeloid metaplasia with myelofibrosis
• essential thrombocytemia

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CML (chronic myeloid leukemia)

• adults middle or younger age
• pyoid bone marrow
• Philadelphia chromosome - 90 patients
• bad prognosis

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CLL (chronic lymphatic leukemia)

• older age
• long asymptomatic period, non-characteristic
  symptoms
• course and prognosis variable
• related to malignant lymphomas

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Polycytemia vera

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

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Hairy cell leukemia

• chronic B-cell line leukemia
• fine cytoplasmic projections - immunohistochemistr
  y, phase contrast, EM
• hepatomegaly, splenomegaly
• therapy - purine analogues

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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

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Leukemias - general morphology

• bone marrow soft - pyoid (CML)
• splenomegaly - CML
• lymph nodes enlargement - CLL
• hepatomegaly - CML, CLL
• sometimes other organs infiltrated

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Non-neoplastic white cells disordes

• leukopenia - neutropenia (agranulocytosis)
• impaired granulopoiesis - bone marrow failure
• destruction of granulocytes - immunity, drugs
• reactive leukocytosis - infections
• infectious mononucleosis - EBV

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Plasma cell dyscrasias

• multiple myeloma
• localized plasmacytoma
• Waldenströms macroglobulinemia
• heavy-chain disease
• primary amyloidosis
• monoclonal gammopathy of undetermined
  significance

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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

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Histiocytoses X

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

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Malignant lymphomas

• non-Hodgkins lymphomas
• Hodgkins lymphoma

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Non-Hodgkins lymphomas

• nodular
• diffuse
• Working Formulation, Kiel Classification, REAL,
  WHO

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Malignant lymphomas - some entities

• ML of CLL type
• follicular centre ML
• diffuse large cell ML
• Burkitts lymphoma

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Extranodal ML

• mycosis fungoides
• Sézarys syndrome
• MALToma

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Hodgkins ML

• nodular lymphocyte predominance Hodgkins
  lymphoma
• classical Hodgkins lymphoma
• lymphocyte rich
• nodular sclerosis
• mixed cellularity
• lymphocytic depletion

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Hodgkins 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.

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Lymph nodes -non-neoplastic diseases

• reactive lymphadenitis
• acute non-specific
• chronic non-specific
• speciphic lymphadenitis
• TBC (BCG)
• Cat Scratch Disease

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Spleen - overview

• enlargement
• massive
• moderate
• mild
• rupture
• necrosis

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Thymus - overview

• thymic hyperplasia
• tumors
• thymoma
• benign thymoma - 90
• thymic carcinoma

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Thymomas

• epithelial predominance
• lymphocyte predominance
• mixed
• appendant disease - myasthenia gravis