Transcript Pigmenty - Univerzita Karlova v Praze

General Pathology
Histogenetic Classification
of Neoplasms
Lymphomas & Leukemias
(Hemoblastomas & Hemoblastoses)
Jaroslava Dušková
Inst. Pathol. ,1st Med. Faculty, Charles Univ. Prague
Leukemia
def.
- diffuse neoplastic proliferation
of the hemopoietic marrow cell
granulocytic
lymphocytic
Lymphoma
def.
malignant neoplasms of cells native to
lymphoid tissue (lymphocytes,
histiocytes) and their precursors and
derivatives.
non Hodgkin (B,T)
Hodgkin
NEOPLASIA – classification
HISTOGENETIC (cell of origin)






mesenchymal
epithelial
neuroectodermal
mixed, teratoma
choriocarcinoma
mesotelioma
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
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)
Pathology & Genetics
Tumours of Haemopoietic
and Lymphoid Tissues
WHO 2001
Principles of Classification

primarily according to lineage
myeloid
lymphoid
histiocytic/dendritic
mast cell

within each category
morphology
immunophenotype
genetic features
clinical syndromes
cell
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
Most of
Mature B cell neoplasms
them
Mature T and NK cell neoplasms
originate
/ may
Hodgkin lymphoma
originate
Histiocytic and dendritic cell neoplasms
in lymph
Histiocytic sarcoma
nodes
Dendritic cell neoplasms
Mastocytosis
Lymphomas and Leukemias general macroscopy features
LYMPH NODES
 enlargement (painless)
HEMOPOETRY
HISTOHOMOLOGOUS
ORGANS
enlargement
BONE MARROW
 pyoid (yellowish) or
gray infiltration
 activation of reserve
zones
OTHER ORGANS
diffuse
or tumorous
infiltration
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
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
Most of
Mature B cell neoplasms
them
Mature T and NK cell neoplasms
originate
/ may
Hodgkin lymphoma
originate
Histiocytic and dendritic cell neoplasms
in lymph
Histiocytic sarcoma
nodes
Dendritic cell neoplasms
Mastocytosis
Myeloid Diseases




Chronic myeloproliferative diseases – CMPD
Myelodysplastic/myeloproliferative diseases –
MDS/MPD
Myelodysplastic syndromes MDS
Acute myeloid leukaemias AML
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
Myeloid Diseases
 Chronic
myeloproliferative diseases – CMPD
– CML (Philadelphia chromosome –t(9,22)(q34;q11)
– Chronic neutrophilic leukaemia
– Chronic eosinophilic leukaemia
– Polycythemia vera
– Chronic idiopathic myelofibrosis
– Essential thrombocythemia
Myeloid Diseases

Myelodysplastic/myeloproliferative diseases –
MDS/MPD
– Chronic myelomonocytic leukaemia
– Atypical chronic myeloid leukaemia
– Juvenile myelomonocytic leukaemia
– MDS/MPD - unclassifiable
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 < 20%
(xAML)

development to acute leukaemia or death of bone marrow
failure
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
Myeloid Diseases
Acute myeloid leukaemias -
AML
clonal expansion of myeloid blasts in bone
marrow blood or other tissue
Leukemia
Acute
morphology:
AML ALL -
aplastic anemia
agranulocytosis,
thrombocytopenia
adults
children
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
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
Most of
Mature B cell neoplasms
them
Mature T and NK cell neoplasms
originate
/ may
Hodgkin lymphoma
originate
Histiocytic and dendritic cell neoplasms
in lymph
Histiocytic sarcoma
nodes
Dendritic cell neoplasms
Mastocytosis
Lymphoma
def.
malignant neoplasms of cells native to
lymphoid tissue (lymphocytes,
histiocytes) and their precursors and
derivatives.
non Hodgkin (B,T)
Hodgkin
Lymphoid Neoplasms

B cell

T and NK cell

Hodgkin lymphomas
(lymphomas & leukaemias)
-“-
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
Small Lymphocytic Lymhpoma (SLL) /
Chronic Lymhocytic Leukemia (CLL)
Small B-lymphocytes, proliferating cells (prolymphocyte, paraimmunoblast)
peripheral blood lymphocytes >10x109/ 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 –
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 (95%B)
Hairy cell leukemia tricholeukemia
– small B lymphoid cells
Lymphoplasmocytic lymphoma LPL
/Waldenström macroglobulinemia
 small
B lymhocytes lymphoma
 bone marrow, LN, spleen
 older adults
 monoclonal IgM serum paraprotein
 hyperviscosity symptoms
Burkitt´s 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)
Lymphoid Neoplasms

B cell

T and NK cell

Hodgkin lymphomas
(lymphomas & leukaemias)
-“-
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
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
Mycosis fungoides and Sezary Syndrome
 adults
M:F 2:1
 years lasting course
 trunk erruptions
 rarely generalization
Lymphoid Neoplasms

B cell

T and NK cell

Hodgkin lymphomas
(lymphomas & leukaemias)
-“-
Lymphogranuloma Malignum
Hodgkin
def.
malignant lymphoma containing
diagnostic RS or Hodgkin tumorous
cells in a rich cellular background
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
Classical HL
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
(CHL)
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
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
Most of
Mature B cell neoplasms
them
Mature T and NK cell neoplasms
originate
/ may
Hodgkin lymphoma
originate
Histiocytic and dendritic cell neoplasms
in lymph
Histiocytic sarcoma
nodes
Dendritic cell neoplasms
Mastocytosis
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
 m. Letterer Sive
(bone)
(skin , hepatosplenomegaly, lymph nodes)

Dendritic cell neoplasms

Mastocytosis