General Pathology

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General Pathology

• Histogenetic Classification
• of Neoplasms
• Lymphomas Leukemias
• (Hemoblastomas Hemoblastoses)

Jaroslava Dušková Inst. Pathol. ,1st Med.
Faculty, Charles Univ. Prague
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Leukemia

• def.
• - diffuse neoplastic proliferation
• of the hemopoietic marrow cell
  granulocytic
• lymphocytic

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Lymphoma

• def.
• malignant neoplasms of cells native to lymphoid
  tissue (lymphocytes, histiocytes) and their
  precursors and derivatives.
• non Hodgkin (B,T) Hodgkin
  

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NEOPLASIA classification

• HISTOGENETIC (cell of origin)
• mesenchymal
• epithelial
• neuroectodermal
• mixed, teratoma
• choriocarcinoma
• mesotelioma

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Main functions of the bone marrow and lymph nodes

• hematopoetry
• immune response
• Hematopoetry
• gr. haima- blood, poiétria - art of composition
  characterized by great beauty of expression

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Lymphomas and Leukemias - clinical
symptomathology

• LYMPHOMA
• painless lymphadenomegaly
• infiltrated organs
• hepatosplenomegaly
• bone marrow involvement ( leukemia)

• LEUKEMIA
• anaemia / fatigue
• immunodepression infections, fever
• haemorrhagic diathesis epistaxis, ecchymoses
• bone pain
• hepatosplenomegaly
• CNS meningeal (ALL)

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Pathology Genetics

• Tumours of Haemopoietic and Lymphoid Tissues
• WHO 2001

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Principles of Classification

• primarily according to lineage
• myeloid
• lymphoid
• histiocytic/dendritic cell
• mast cell
• within each category
• morphology
• immunophenotype
• genetic features
• clinical syndromes

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NEOPLASMS OF HEMATOPOIETIC AND LYMPHOID TISSUE
(WHO 2001, abbreviated)

• Myeloid neoplasms
• Chronic myeloproliferative disorders
• Myeloproliferative / myelodysplastic diseases
• Myelodysplastic syndromes
• Acute myeloid leukemias
• Lymphoid neoplasms
• Precursor B and T cell neoplasms
• Mature B cell neoplasms
• Mature T and NK cell neoplasms
• Hodgkin lymphoma
• Histiocytic and dendritic cell neoplasms
• Histiocytic sarcoma
• Dendritic cell neoplasms
• Mastocytosis

Most of them originate / may originate in
lymph nodes
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Lymphomas and Leukemias - general macroscopy
features

• LYMPH NODES
• enlargement (painless)

• BONE MARROW
• pyoid (yellowish) or gray infiltration
• activation of reserve zones

• HEMOPOETRY HISTOHOMOLOGOUS ORGANS
• enlargement

• OTHER ORGANS
• diffuse or tumorous infiltration

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Lymphomas and Leukemias - general histology
features

• LYMPH NODES
• architecture partly / fully obscurred with the
  neoplastic population
• subcapsullar sinus defunct
• nodular / diffuse
• transcapsullar spread

• BONE MARROW
• hypercellular
• architecture partly / fully obscurred with the
  neoplastic population
• haemopoetry activation in the formerly fatty
  (reserve) marrow

HISTOHOMOLOGOUS ORGANS colonised liver, spleen,
nodes
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NEOPLASMS OF HEMATOPOIETIC AND LYMPHOID TISSUE
(WHO 2001, abbreviated)

• Myeloid neoplasms
• Chronic myeloproliferative disorders
• Myeloproliferative / myelodysplastic diseases
• Myelodysplastic syndromes
• Acute myeloid leukemias
• Lymphoid neoplasms
• Precursor B and T cell neoplasms
• Mature B cell neoplasms
• Mature T and NK cell neoplasms
• Hodgkin lymphoma
• Histiocytic and dendritic cell neoplasms
• Histiocytic sarcoma
• Dendritic cell neoplasms
• Mastocytosis

Most of them originate / may originate in
lymph nodes
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Myeloid Diseases

• Chronic myeloproliferative diseases CMPD
• Myelodysplastic/myeloproliferative diseases
  MDS/MPD
• Myelodysplastic syndromes - MDS
• Acute myeloid leukaemias - AML

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Chronic Myeloproliferative Diseases CMPD

• def.
• clonal proliferation of one or more of the
  myeloid lineages (granulocytic, erythroid,
  megakaryocytic)
• hemopoietic stem cells in the bone marrow
• hepatomegaly, splenomegaly
• development into myelofibrosis or acute blast
  phase

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Myeloid Diseases

• Chronic myeloproliferative diseases CMPD
• CML (Philadelphia chromosome t(9,22)(q34q11)
• Chronic neutrophilic leukaemia
• Chronic eosinophilic leukaemia
• Polycythemia vera
• Chronic idiopathic myelofibrosis
• Essential thrombocythemia

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Myeloid Diseases

• Myelodysplastic/myeloproliferative diseases
  MDS/MPD
• Chronic myelomonocytic leukaemia
• Atypical chronic myeloid leukaemia
• Juvenile myelomonocytic leukaemia
• MDS/MPD - unclassifiable

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Myelodysplastic syndromes - MDS

• def.
• bone marrow failure and dysplasia in one or more
  myeloid cell lineages
• the number of blasts is in the blood or marrow lt
  20 (xAML)
• development to acute leukaemia or death of bone
  marrow failure

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Myeloid Diseases

• Myelodysplastic syndromes - MDS
• Refractory anaemia
• Refractory anaemia with ringed sideroblasts
• Refractory anaemia with multilineage dysplasia
• Refractory anaemia with excess blasts
• MDS associated with isolated del(5q) chromosome
  abnormality
• MDS - unclassifiable

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Myeloid Diseases

• Acute myeloid leukaemias - AML clonal
  expansion of myeloid blasts in bone marrow blood
  or other tissue

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Leukemia

• Acute
• morphology aplastic anemia
  agranulocytosis, thrombocytopenia
• AML - adults
• ALL - children

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Myeloid Diseases

• Acute myeloid leukaemias - AML
• AML with recurrent cytogenetic abnormalities
• AML with multilineage dysplasia
• AML and MDS therapy- related
• AML not otherwise categorised
• 19 nosology units

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NEOPLASMS OF HEMATOPOIETIC AND LYMPHOID TISSUE
(WHO 2001, abbreviated)

• Myeloid neoplasms
• Chronic myeloproliferative disorders
• Myeloproliferative / myelodysplastic diseases
• Myelodysplastic syndromes
• Acute myeloid leukemias
• Lymphoid neoplasms
• Precursor B and T cell neoplasms
• Mature B cell neoplasms
• Mature T and NK cell neoplasms
• Hodgkin lymphoma
• Histiocytic and dendritic cell neoplasms
• Histiocytic sarcoma
• Dendritic cell neoplasms
• Mastocytosis

Most of them originate / may originate in
lymph nodes
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Lymphoma

• def.
• malignant neoplasms of cells native to lymphoid
  tissue (lymphocytes, histiocytes) and their
  precursors and derivatives.
• non Hodgkin (B,T) Hodgkin
  

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Lymphoid Neoplasms

• B cell (lymphomas leukaemias)
• T and NK cell --
• Hodgkin lymphomas

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Lymphoid Neoplasms

• B cell lymphomas leukaemias
• (17 nosology units in 2001 WHO classif.)
• Precursor B-cell neoplasm
• Mature B-cell neoplasms (85 nH ML)
• B-cell proliferations of uncertain malignant
  potential

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Small Lymphocytic Lymhpoma (SLL) /
Chronic Lymhocytic Leukemia (CLL)

• Small B-lymphocytes, proliferating cells
  (prolymphocyte, paraimmunoblast)
• peripheral blood lymphocytes gt10x109/ l,
• bone marrow lymphocytic infiltration
• splenomegaly, hepatomegaly,
  lymphadenopathy
• immunodeficiency, bleeding, disordered healing
• Clinical behaviour
• INDOLENT
• leukemisation common
• occasional transformation to aggressive
  lymphoma / leukemia
• Dg Morphology confusing - immunophenotyping
  necessary
• CD23, CD5, cyclin D1

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Leukemia

• Chronic
• morphology bone marrow infiltration
  splenomegaly
• hepatomegaly
• enlarged lymph nodes
• clinic may remain silent for a long time
• CML related to myeloproliferative disorders
• CLL close to nH ML (95B)
• Hairy cell leukemia tricholeukemia
• small B lymphoid cells

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Lymphoplasmocytic lymphoma LPL /Waldenström
macroglobulinemia

• small B lymhocytes lymphoma
• bone marrow, LN, spleen
• older adults
• monoclonal IgM serum paraprotein
• hyperviscosity symptoms

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Burkitts Lymphoma

• highly malignant small B cell lymphoma EBV
  (DNA) related
• endemic in Africa, sporadic elsewhere
• high mitotic rate
• starry sky appearance (due to non neoplastic
  macrophages admixture)

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Lymphoid Neoplasms

• B cell (lymphomas leukaemias)
• T and NK cell --
• Hodgkin lymphomas

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Lymphoid Neoplasms

• T and NK cell lymphomas leukaemias
• (16 nosology units in 2001 WHO classif.)
• Precursor T-cell neoplasm
• Mature T-cell neoplasms (EB virus HTLV-1)
• T-cell proliferations of uncertain malignant
  potential

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Mycosis Fungoides and Sezary Syndrome

• Def.
• MF mature T- cell lymphoma presenting in the
  skin with patches/plaques and characterized by
  epidermal and dermal infiltration of small to
  medium size T-cells with cerebriform nuclei
• SS generalized mature T- cell lymphoma
  characterized by the presence of erythroderma ,
  lymphadenopathy and T-cells with cerebriform
  nuclei aggresive form of MF

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Mycosis fungoides and Sezary Syndrome

• adults MF 21
• years lasting course
• trunk erruptions
• rarely generalization

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Lymphoid Neoplasms

• B cell (lymphomas leukaemias)
• T and NK cell --
• Hodgkin lymphomas

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Lymphogranuloma Malignum Hodgkin

• def.
• malignant lymphoma containing diagnostic RS or
  Hodgkin tumorous cells in a rich cellular
  background

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Lymphoid Neoplasms WHO 2001

• Hodgkin lymphomas HL
• Nodular lymphocyte predominant HL
• Classical HL
• Nodular sclerosis classical HL
• Lymphocyte-rich classical HL
• Mixed cellularity classical HL
• Lymphocyte-depleted classical HL

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Classical HL (CHL)

• 85 of HL
• Nodular sclerosis CHL (NSHL)
• Most frequent, young adults
• Very good prognosis with treatment
• Lymphocyte-rich CHL (LRCHL)
• Rare
• Very good prognosis with treatment
• Mixed cellularity CHL (MCHL)
• Frequent, adults
• Medium prognosis
• Lymphocyte depleted CHL (LDHL)
• Very rare, immunocompromised patients
• Poor prognosis

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Nodular Lymphocyte Predominant HL
15 of HL B-lymphoma Differential diagnosis
may be very difficult Highly atypical
CD30-/CD15-/CD20/CD45 L/H cells popcorn
cells Reactive cells Lymphocytes,
histiocytes, plasma cells, no eosinophils Nodular
growth No fibrosis Very good prognosis with
treatment even in relapsing disease
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NEOPLASMS OF HEMATOPOIETIC AND LYMPHOID TISSUE
(WHO 2001, abbreviated)

• Myeloid neoplasms
• Chronic myeloproliferative disorders
• Myeloproliferative / myelodysplastic diseases
• Myelodysplastic syndromes
• Acute myeloid leukemias
• Lymphoid neoplasms
• Precursor B and T cell neoplasms
• Mature B cell neoplasms
• Mature T and NK cell neoplasms
• Hodgkin lymphoma
• Histiocytic and dendritic cell neoplasms
• Histiocytic sarcoma
• Dendritic cell neoplasms
• Mastocytosis

Most of them originate / may originate in
lymph nodes
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Histiocytic and Dendritic Cell Neoplasms

• Macrophage/histiocytic neoplasm (CD68, CD 1)
• Langerhans cells
• m. Hand Schüller- Christian HSCH triad calva
  defects, diab.insip., exophtalmos
• eosinophilic granuloma (bone)
• m. Letterer Sive (skin , hepatosplenomegaly,
  lymph nodes)
• Dendritic cell neoplasms
• Mastocytosis