Lymphadenitis

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Lymphadenitis

• Doc. MUDr. L. Boudová, Ph.D.

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Lymphadenitisacute or chronic
Rarely biopsied

• Classification
• predominant histologic pattern
• etiology

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Lymphadenitis - etiology

• MICROBIAL
• viral
• bacterial, mycobacterial
• fungal
• protozoal
• NONMICROBIAL - autoimmune
• storage dis.
• foreign mat.
• miscel.

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Lymph node inflammation

• Lymph node hyperplasia
• 1. follicular
• 2. paracortical
• 3. sinuses
• 4. mixed patterns

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Lymph node inflammation

• Follicular hyperplasia
• bacteria, RA, HIV(early), syphilis,
• Castleman dis.
• Paracortical hyperplasia
• viruses, dermatopathies, vaccination,
• drug hypersensitivity, Kikuchi, SLE,
• draining pus or carcinoma

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Lymphadenitis - histological patterns

• sinusoidal hyperplasia - lymphangiography,
  Whipple dis., sin. histiocytosis with massive
  lymphadenopathy, draining carcinoma
• granulomas - TB, other mycobact., leprosy,
  Whipple, fungi, berylliosis, sarcoidosis,
• Granulomatous-purulentcat scratch, tularemia,
  lymphogr. venereum,Yersinia
• mixed patterns toxoplasmosis

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Red cells

• Men Women
• Hemoglobin (g/l) 140-180 120-160
• Hematocrit () 40-52 36-48
• Red cell count (1012/l) 4.5-6.5 3.9-5.6
• Reticulocyte count () 0.5-1.5
• Mean cell volume (fl) 80-95
• Mean corpuscular hemoglobin (pg) 27-33
• Mean corpuscular hemoglobin concentration (gm/dL)
  33-37

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Red cells

• pathological conditions
• decrease in the circulating red cell mass
• (poss. with structural abnormalities)
• very common - anaemia
• II. increase in the circulating red cell mass
• less common
• polycythemia erythrocytosispolyglobuly
• reactive low levels of oxygen in the PB
• (heart disease, high altitude)
• neoplastic polycythemia vera
• chronic myeloproliferative disease

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Anaemia

• decrease in the total circulating red cell mass
• (hematocrit, hemoglobin concentration)
• Classification A. underlying mechanism
• blood loss
• increased destruction
• decreased production
• B. morphology of erythrocytes
• size (micro-, macro-, normocytic)
• shape (spherocytosis, stomato-,...)
• color (degree of hemoglobinization normo-
  hypo-, hyperchromic)

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• Blood loss
• acute or chronic
• internal or external

• Acute
• Hypovolemia shock
• Anemia normocytic normochromic
• Shift of water hemodilution ? hematocrite
• Compensatory increase of red cell production
• Reticulocytes
• Chronic
• hypochromic sideropenic anemia

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Iron deficiency anemia

• body iron functional storage
• F - 2g, M - 6g
• 1. Lack in diet, low absorption
• 2. Increased requirement
• !!!3. Chronic blood loss!!! - GIT, GYN

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• Increased destruction
• lysis of red cellshemolysis
• intravascular rare (mechanical injury
  artificial valves or microthrombi, exogenous
  toxic agents, complement fixation (transfusion of
  mismatched blood)
• Extravascular - more common, when red cells
  considered foreign or less deformable
• Hemolytic anemia
• Abnormality
• intracorpuscular or extracorpuscular
• hereditary (intra) or acquired (extra)

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Hemolytic anemia

• premature destruction of red cells
• accumulation of the products of the hemoglobin
  catabolism
• BM increased erythropoiesis, extreme
  extramedullary hematopoiesis
• PB reticulocytosis
• high bilirubin gallstones jaundice, blr in
  urine
• chronic duration hemosiderosis
• splenomgaly

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Myelodysplastic syndrome

• clonal disorders of stem cells
• defects of maturation in the BM - ineffective
  hematopoiesis (progressive failure of BM
  function)
• cells in the PB decreased numbers
  pancytopenia defective in function,
  pathological shapes

• BM hypercellular,
• but dysplastic pathological forms, architecture
• blasts may be increased
• (but less than 20, threshold AML versus MDS)

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(Chronic) myeloproliferative neoplasms

• Clonal disorders
• Adults
• 1. Chronic myeloid leukemia
• 2. Polycythemia vera
• 3. Essential thrombocytemia
• 4. Chronic osteomyelofibrosis

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(Chronic) myeloproliferative neoplasms

• Common principles
• 1. Bone marrow stem cell genetic abnormalities,
• neoplastic proliferation of one or more (all) BM
  myeloid series (red, white, megakaryocytes)
• disorder of an individual series more pronounced
  in each of the categories
• 2. Peripheral blood increased numbers of cells
  relatively normal maturation
• 3. Splenomegaly, hepatomegaly
• sequestration of excess blood cells,
  extramedullary hematopoiesis, leukaemic
  infiltration

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Chronic myeloproliferative neoplasms

• Common principles
• 1. Bone marrow stem cell genetic abnormalities,
• neoplastic proliferation of one or more (all) BM
  myeloid series (red, white, megakaryocytes)
• disorder of an individual series more pronounced
  in each of the categories
• 2. Peripheral blood increased numbers of cells
  relatively normal maturation
• 3. Splenomegaly, hepatomegaly
• sequestration of excess blood cells,
  extramedullary hematopoiesis, leukaemic
  infiltration

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Chronic myeloproliferative neoplasms

• phases of the disease in time
• 1. onset insidious
• proliferative phase,
• 2. progression - spent phase -
  osteomyelofibrosis
• - blast phase
• all can (do not have to) progress to AL CML does
  it invariably)

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Chronic myelogenous leukaemia (CML)

• t(9 22) Philadelphia chromosome, bcr-abl gene
  pluripotent stem cell defect
• abnormal fusion protein - increased tyrosine
  kinase activity
• most striking proliferation of G
• increased cellularity
• maturation retained (no hiatus leukaemicus)
• hematopoiesis also extramedullary splenomegaly
  (hepatomegaly)
• PB leukocytosis exceeds even 100 000/ mm3

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LymphomasClonal disorders of lymphoid cells at
various stages of differentiation

• HODGKIN L.
• NON-HODGKIN L.
• immature cells (precursors)
• mature cells
• B
• T

Distinction clinical histological
Note Hodgkin lymphoma is also a (mature)B-cell
lymphoma.
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B-cell lymphoma

• Clonal disorders of B-cells at various stages
• of differentiation
• B-cell lymphomas of immature cells - lymphoblasts
• B-acute lymphoblastic leukaemia - frequent,
  children
• B-lymphoblastic lymphoma - rare
• B-cell lymphomas of mature B-cells
• most commonfollicular, diffuse large B-cell
  lymphoma plasma cell myeloma

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Extranodal marginal zone B-cell lymphoma of MALT

• GIT - stomach
• lung, head, neck (thyroid, salivary, eyes), skin
• antigenic stimulation
• stomach - Helicobacter pylori
• thyroid - Hashimoto
• Sjogren
• IPSID
• localized - good prognosis
• RISK transformation - DLBCL

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Follicular lymphoma

• Over 60
• LN, spleen, later BM
• often asympt.
• Histology
• grades
• transformation - DLBCL

t (1418 bcl2/JHa
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Diffuse large B-cell lymphoma

• aggresive, potentially curable
• COMMON!
• 1/3 of all lymphomas of adults (med. 64 ys)
• nodal OR extranodal (1/3)

GIT, skin, CNS, testis bone, soft tissue,
salivary glands, Waldeyer ring, lung, kidney,
liver, spleen, female genital tract
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Diffuse large B-cell lymphoma

• Primary OR secondary

Chronic lymphocytic leukemia Follicular
lymphoma Marginal zone B-cell lymphoma Nodular
lymphocyte predom. Hodgkin l.
Risk factor immunodeficiency (often EBV)
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Diffuse large B-cell lymphoma

• Morphologic variants
• Centroblastic
• Immunoblastic
• T-cell/histiocyte rich
• Anaplastic
• Plasmablastic
• Clinicopathologic subtypes
• mediastinal (thymic)
• intravascular
• primary effusion, pyothorax associat.

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Diffuse large B-cell lymphomaDifferential
diagnosis

• Tumors
• Haematological lymphomas peripheral - B, T
• precursors - B, T
• myeloid neoplasm
• Non-haematological carcinoma, sarcoma, GIST,
  melanoma, seminoma, glial tumors
• Reactive disorders infectious mononucleosis,
  Kikuchi

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Mediastinal DLBCL

• Thymus
• Female, 30 ys
• Anterior mediastinal mass
• Superior vena cava syndrome
• Clinicopathological differential diagnosis?

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Bleeding disorders
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Bleeding disordersI. Vessels - increased
fragilityII. Platelets - deficiency or
dysfunctionIII.Coagulation disorders

• I. Vessels
• infections, drugs (hypersensitivity, poor
  vascular wall Ehlers-Danlos, scurvy Cushing
  syndrome, old people
• hereditary hemorrhagic teleangiectasia
• amyloid

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Thrombocytopenia

• decreased production
• increased destruction
• sequestration
• dilution
• HIV

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Thrombotic microangiopathiesthrombotic
thrombocytopenic purpura (TTP)hemolytic-uremic
syndrome (HUS)

• Versus
• Disseminated intravascular coagulation
• Common hyaline thrombi
• !!Differences DIC primary importance
• activation of clotting system

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Disseminated intravascular coagulation (DIC)

• secondary complication
• of some serious condition
• consumption coagulopathy
• thrombohemorrhagic diathesis
• acute, subacute, chronic

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Disseminated intravascular coagulation (DIC)

• activation of coagulation sequence
• microthrombi
• - consumption of platelets and clotting factors
• activation of fibrinolysis

secondary
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DICthrombotic and hemorrhagic diathesis
Consequences

• Microthrombi infarctions
• depletion of platelets and clotting factors
• secondary activation of fibrinolysis

hemorrhages
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Mechanisms of DIC trigger1. Release of tissue
factor or thromboplastic substances2.
Widespread endothelial injury
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DIC

• Morphology microthrombi
• Kidneys hemorrhages
• lungs
• brain
• adrenals
• placenta
• CLIN. microangiopathic hemol. anemia, RDS,
  neurologic sympt., oliguria, ac. ren. and circul.
  failure, SHOCK

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HODGKIN LYMPHOMA WHO 2008

• CLASSICAL (95)

• NODULAR LYMPHOCYTE PREDOMINANT

(nodular paragranuloma, 5)

• DIFFER IN TUMOUR CELLS
• BACKGROUND
• CLINICAL FEATURES

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CLASSICAL HL
SUBTYPES NODULAR SCLEROSIS MIXED
CELLULARITY LYMPHOCYTE RICH LYMPHOCYTE DEPLETION

• FEATURES
• COMMON TUMOUR CELLS
• DIFFERENT BACKGROUND ARCHITECTURE
• CLINICAL, EPIDEMIOLOGY
• EBV

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Lymphadenitisacute or chronic
Rarely biopsied

• Classification
• predominant histologic pattern
• etiology

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T-cell lymphoma

• Precursor T-cell lymphomas
• T-acute lymphoblastic leukaemia
• T-lymphoblastic lymphoma
• Mature T-and NK cell neoplasms
• uncommon 10 of all NHL
• Most frequent peripheral T-cell lymphoma,
  unspecified
• large cell anaplastic lymphoma

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Most common T-cell lymphomas

• Leukaemic/disseminated
• adult T-cell leukaemia - HTLV 1
• cutaneous - mycosis fungoides, Sezary syndrome,
  primary cut. anaplast. lymphoma
• other extranodal - extranod. NK/T - nasal,
  enteropathy assoc.
• nodal - peripheral T-cell lymphoma, NOS,
  anaplastic large cell lymphoma

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Enteropathy associated T-cell lymphoma

• coeliac sprue (adults)
• intestinal perforation
• intraepithelial
• T-lymphocytes
• bad prognosis