Transcript Myeloid neoplasms

Zhu keqing 竺可青
Pathology Department
Zhejiang University
School of Medicine
2013-3-25
Diseases of hematopoitic and
lymphoid system 淋巴造血系统疾病
• Red cell disorders
• White cell disorders*
• Bleeding disorders
• Disorders that affect the spleen and thymus
Characteristics
• The organs and tissues are not confined to a single
anatomic site.
• The cells are constantly in “traffic”.
• The diseases often appear as systemic involvements.
White cell disorders
• Non-Neoplastic Disorders
- Reactive lymphoid hyperplasia (lymphadenitis)
- Reactive leukocytosis 类白血病反应
• Neoplastic Disorders
- lymphomas 淋巴瘤
- myeloid neoplasms 髓性肿瘤
- Histiocytic and dendritic-cell neoplasms 组织
细胞与树突状细胞瘤
Lymph node reactive hyperplasia/non-specific lymphadenitis
•
概念：各种损伤或刺激引起淋巴结的淋巴细胞和组织细胞增生，淋巴结肿大。
•
病因：感染因子（细菌病毒）、化学药品、毒素、代谢毒性产物、异物。
•
结局：刺激抗原消失，淋巴结结构部分消失。
淋巴结的特殊感染
• 淋巴结结核
• 淋巴结真菌感染（曲菌/新型隐球菌）
• 组织细胞坏死性淋巴结炎 （HHV-6)
Benign lymphoid hyperplasia （小结）
• Non-specific lymphadenitis
- acute non-specific lymphadenitis
- chronic non-specific lymphadenitis
follicular hyperplasia
parafollicular hyperplasia
sinus histiocytosis
• Distinctive infection
The WHO Classification of the Lymphoid Neoplasms
I. Precursor B-Cell Neoplasms
• Precursor-B lymphoblastic leukemia/lymphoma
II. Peripheral B-Cell Neoplasms
• Chronic lymphocytic leukemia/small lymphocytic lymphoma
• B-cell prolymphocytic leukemia
• Lymphoplasmacytic lymphoma
• Splenic and nodal marginal zone lymphomas
• Extranodal marginal zone lymphoma
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma
• Hairy cell leukemia
• Plasmacytoma/plasma cell myeloma
• Diffuse large B-cell lymphoma
• Burkitt lymphoma
The WHO Classification of the Lymphoid Neoplasms
III. Precursor T-Cell Neoplasms
• Precursor-T lymphoblastic leukemia/lymphoma
IV. Peripheral T-Cell and NK-Cell Neoplasms
• T-cell prolymphocytic leukemia
• Large granular lymphocytic leukemia
• Mycosis fungoides/Sézary syndrome
• Peripheral T-cell lymphoma, unspecified
• Anaplastic large cell lymphoma
• Angioimmunoblastic T-cell lymphoma
• Enteropathy-associated T-cell lymphoma
• Panniculitis-like T-cell lymphoma
• Hepatosplenic γδT-cell lymphoma
• Adult T-cell leukemia/lymphoma
• NK/T-cell lymphoma, nasal type
• NK-cell leukemia
The WHO Classification of the Lymphoid Neoplasms
V. Hodgkin Lymphoma
• Classical subtypes
• Nodular sclerosis
• Mixed cellularity
• Lymphocyte-rich
• Lymphocyte depletion
• Lymphocyte predominance
1. 概念 Lymphomas-
Definition
• Clonal tumors of mature and immature
lymphocyte including B-cells, T-cells and
Natural Killer (NK) cells and so on.
• Malignant tumors of immune system.
• Involved organs and tissues:
- Lymphoid organsand tissues
- Extranodal tissues
- Bone marrow
- Peripheral blood
2. Lymphomas-
Lymphocyte
differentiation
Phenotypic and genotypic changes in differentiation of B cells and T cells
3 Lymphomas-
WHO Classification
Hodgkin lymphoma, HL
Non-Hodgkin lymphoma, NHL
▲ B-cell neoplasms
▲ T-cell and NK cell neoplasms
STAGING, HD & NHD
• I
ONE NODE or NODE GROUP
• II
MORE than ONE, but on ONE side of diaph.
• III BOTH sides of diaph., but still in nodes only
• IV OUTSIDE of NODES, e.g., liver, marrow, etc.
• A
• B
No systemic symptoms
fever and/or night sweats and/or 10% weight loss
5. Lymphoma-Diagnosis
• Clinical manifestations
• Histopathology
• Immunophenotypes
• Genetics
5. Lymphoma- Diagnosis
• Biopsy
• Histologic classification
• Immunophenotype analysis
• Genetic analysis:
- Ig and/or TCR Gene rearrangement analysis
- Karyotype analysis
- Detection of chromosome translocation or
fusion genes by FISH or PCR etc
6. Lymphoma-Epidemiology and
etiology
• Chromosome translocation and oncogenes
• Inherited genetic factors
• Viruses
- Human T-cell leukemia virus-1, HTLV-1
- Epstein-Barr virus, EBV
- Kaposi sarcoma herpesvirus / human
herpesvirus-8, KSHV/HHV-8
- Hepatitis C virus
• Bacteria
- Helicobacter Pylori, HP
- Chlamydia psittaci; C. pneumoniae; C.
trachomatis
• Environment factors
• Although Reed-Sternberg cells are
requisite for the diagnosis,
• they must be present in an appropriate
background of non-neoplastic
inflammatory cells (lymphocytes, plasma
cells, eosinophils). 背景
Hodgkin lymphoma - Subtypes
• Nodular lymphocyte predominance Hodgkin
lymphoma, NLPHL
• Classical Hodgkin lymphoma, CHL
Lymphocyte rich,
Mixed cellularity,
Lymphocyte deplete,
Nodular sclerosis,
LR
MC
LD
NS
Hodgkin lymphoma- characteristics
• A special entity of lymphoma and occupies up to 20% of
all lymphomas.
• Children and young adults are more commonly involved.
• The tumor arises in a single node or chain of nodes
spreads to the anatomically contiguous nodes.
•
the neoplastic cells: Reed-Sternberg (R-S) cell and its
variants.
Non-Hodgkin lymphoma- characteristics
• 80% to 90% of all lymphomas are NHLs
• Extranodal lymphoma occupies about 1/3 of all
NHLs.
• Histopathologic classification is more complex.
• Clinical manifestations are closely related to the
sites involved.
• A spectrum from lymphomas to leukemias.
WHO classification for tumors of
lymphoid tissues - NHL
B cell neoplasms
• precursor B cell neoplasms
• mature( peripheral ) B cell neoplasms
T and NK cell neoplasms
• precursor T cell neoplasms
• mature( peripheral ) T and NK cell neoplasms
NHL – Examples
• Lymphoblastic leukemia/lymphoma
• Chronic lymphocytic leukemia / small lymphocytic
lymphoma，CLL/SLL
• Follicular lymphoma, FL
• Diffuse large B-cell lymphoma，DLBCL
• Burkitt lymphoma, BL
• Plasma cell myeloma
• Extranodal NK/T-cell lymphoma, nasal type
Clinicopathologic differences
between HL and NHL
HL
Patient children/young adults
Stage
I / II
Symptoms
40%
Site
LN, 90%
neck/mediastinum
Dissemination predictable
Extranodal
uncommon
Leukemia
no
Tumor cell
R-S cells
NHL
any aged people
III / IV
15%
LN, 70%
extranodal,30%
random
common
yes
lymphocytes
Myeloid neoplasms
髓性肿瘤
Myeloid neoplasms - Definition
Myeloid neoplasms arise within hematopoietic
stem cells and typically give rise to monoclonal
proliferations that diffusely replace normal
bone marrow cells.
Myeloid neoplasms : 6类
Classification
• Myeloproliferative neoplasms, MPN
• Myeloid and lymphoid neoplasms with eosinophilia and
abnormalities of PDGFRA, PDGFRB or FGFR1
• Myelodysplastic / myeloproliferative neoplasms,
MDS/MPN
• Myelodysplastic syndromes, MDS
• Acute myeloid leukemia ( AML) and related precursor
neoplasms
• Acute leukemia of ambiguous lineage
Acute myeloid leukemia ( AML)
• AML are tumors marked by a blockage in the
differentiation of early myeloid cells.
• Immature myeloid cells accumulate in the
marrow, replacing normal elements, and
frequently circulate in the peripheral blood.
AML- clinical manifestations
•
• Anemia
• Hemorrhage
• Bone pain
• Fatigue
• Fever
• Hepatosplenomegaly
• Lymphadenopathy
AML - Diagnosis
Laboratory findings:
• Peripheral blood
increased number of white cells
immature white cells
• BM aspiration
immature white cells
Leukemoid reactions 类白血病反应
• Reactive leukocytosis
• Many immature white cells appear in the blood
• Response to severe infection, malignant tumor,
toxic events or emergencies
• Reversible
Myeloproliferative neoplasms, MPN
Definition:
• MPN are clonal haematopoitic stem cell neoplasms
characterized by proliferation in the bone marrow of one
or more of the myeloid lineages.
• MPN is characterized by hypercellularity of the BM with
effective haematopoietic maturation and increased
number of granulocytes, red blood cells and/or platelets
in the PB.
Myeloproliferative neoplasms : 8 类Classification
•
• Chronic myelogenous leukemia* BCR-ABL1 positive
•
Chronic neutrophilic leukemia
•
Polycythaemia vera
• Primary myelofibrosis
• Essential thrombocythaemia
• Chronic eosinophilic leukemia
• Mastcytosis
• Myeloproliferative neoplasm, unclassifiable
Myeloid neoplasms- Etiology
• Genetic abnormalities
- chromosome translocation
- gene mutation
- gene deletion and gain
• Radiation exposure
• Environment factors
Treatment
• Chemotherapy
• Radiotherapy
• Antibiotic therapy
• Bone marrow transplantation
• Biological therapy
Summary
• Both AML and MPN are all clonal haematopoitic
stem cell disorders.
• Lab findings are important for establishing
diagnosis of the tumors.
• Characteristic genetic abnormalities were found in
most of cases.
• No alternation presented between AML and MPN.
Histiocytic and dendritic
cell neoplasms
Histiocytic and dendritic cell neoplasms
- Classification
• Histiocytic sarcoma
• Dendritic cell sarcoma
• Tumors derived from Langerhans cells
• Interdigitating dendritic cell sarcoma
• Follicular dendritic cell sarcoma
• Other rare dendritic cell tumors
• disseminated juvenile xanthogranuloma 播散性幼
年性黄色肉芽肿
Tumors derived from langerhans cells
• Langerhans cell histiocytosis
• Langerhans cell sarcoma
小结
•
•
•
•
1. 淋巴结良性增生
2. 淋巴瘤 (HL)
3. 类白血病反应
4. 了解NHL、髓性肿瘤、组织细胞与树突
状细胞肿瘤