1. Lymphomas & Leukemias General Pathology Histogenetic Classification
of Neoplasms
Lymphomas & Leukemias
(Hemoblastomas & Hemoblastoses)
Jaroslava Dušková
Inst. Pathol. ,1st Med. Faculty, Charles Univ. Prague

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

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

4. NEOPLASIA – classification
HISTOGENETIC (cell of origin)
mesenchymal
epithelial
neuroectodermal
mixed, teratoma
choriocarcinoma
mesotelioma

5. 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

6. Lymphomas and Leukemias - clinical symptomathology
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)

7. Tumours of Haemopoietic and Lymphoid Tissues
Pathology & Genetics
Tumours of Haemopoietic and Lymphoid Tissues
WHO 2001

8. Principles of Classification
primarily according to lineage
myeloid
lymphoid
histiocytic/dendritic cell
mast cell
within each category
morphology
immunophenotype
genetic features
clinical syndromes

9. 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
in lymph
nodes

10. 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
defunct – zaniklý, zašlý
OTHER ORGANS
diffuse or tumorous infiltration

11. 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
defunct – zaniklý, zašlý
HISTOHOMOLOGOUS ORGANS colonised – liver, spleen, nodes

12. 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
in lymph
nodes

13. Myeloid Diseases Chronic myeloproliferative diseases – CMPD
Myelodysplastic/myeloproliferative diseases – MDS/MPD
Myelodysplastic syndromes - MDS
Acute myeloid leukaemias - AML

14. 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

15. 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

16. Myeloid Diseases Myelodysplastic/myeloproliferative diseases – MDS/MPD
Chronic myelomonocytic leukaemia
Atypical chronic myeloid leukaemia
Juvenile myelomonocytic leukaemia
MDS/MPD - unclassifiable

17. 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

18. 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

19. Myeloid Diseases
Acute myeloid leukaemias - AML clonal expansion of myeloid blasts in bone marrow blood or other tissue

20. Leukemia
Acute
morphology: aplastic anemia agranulocytosis, thrombocytopenia
AML adults
ALL children

21. 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

22. 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
in lymph
nodes

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

24. Lymphoid Neoplasms B cell (lymphomas & leukaemias) T and NK cell -“-
Hodgkin lymphomas

25. Lymphoid Neoplasms Precursor B-cell neoplasm
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

26. 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 –

27. 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

28. Lymphoplasmocytic lymphoma LPL /Waldenström macroglobulinemia
small B lymhocytes lymphoma
bone marrow, LN, spleen
older adults
monoclonal IgM serum paraprotein
hyperviscosity symptoms
Wm může být i u jiných ML, není synonymum pro LPL

29. 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)

30. Lymphoid Neoplasms B cell (lymphomas & leukaemias) T and NK cell -“-
Hodgkin lymphomas

31. Lymphoid Neoplasms (16 nosology units in 2001 WHO classif.)
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
EB virus HTLV-1, většina nezn. etiol

32. 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

33. Mycosis fungoides and Sezary Syndrome
adults M:F 2:1
years lasting course
trunk erruptions
rarely generalization

34. Lymphoid Neoplasms B cell (lymphomas & leukaemias) T and NK cell -“-
Hodgkin lymphomas

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

36. 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

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

38. 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

39. 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
in lymph
nodes

40. 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