Hematopoietic and
lymphoid systems
• main entities - disorders
• exam questions and very concise
text - www.lfhk.cuni.cz/patanat
Hematopoietic and lymphoid
systems - exam questions
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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
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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
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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 2nd or 3rd 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 B12
– 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 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
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
• 5 - 10 % 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 - 10 15 %
• hiatus leukemicus
• bone marrow transplantation
Chronic myeloproliferative
disorders
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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, noncharacteristic 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
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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
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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 (HandSchüller-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
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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 -nonneoplastic 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