Chapter 12 The diseases of Hematopoietic and Lymphoid System Liu weiping Department of Pathology West China School of Medicine Sichuan University

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.

Diseases of hematopoitic and lymphoid system Red cell disorders White cell disorders* Bleeding disorders Disorders that affect the spleen and thymus

White cell disorders Non-Neoplastic Disorders - Reactive lymphoid hyperplasia (lymphadenitis) - Reactive leukocytosis Neoplastic Disorders - lymphomas - myeloid neoplasms - Histiocytic and dendritic-cell neoplasms

Lymph node

Benign lymphoid hyperplasia

Non-specific lymphadenitis - acute non-specific lymphadenitis - chronic non-specific lymphadenitis follicular hyperplasia parafollicular hyperplasia sinus histiocytosis Distinctive infection

Non-specific lymphadenitis

TB Tuberculosis lymph node

Nonspecific inflammation distinctive infection Infection Tumor metastatic tumors lymphoid neoplasms Lymphoproliferative disorders with unknown reason

Lymphomas

Definition Lymphocyte differentiation WHO Classification Clinical manifestation and staging Diagnosis Genitics Epidemiology and etiology

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

Lymphomas - Lymphocyte differentiation Phenotypic and genotypic changes in differentiation of B cells and T cells

Hodgkin lymphoma, HL Non-Hodgkin lymphoma, NHL ▲ B-cell neoplasms ▲ T-cell and NK cell neoplasms Lymphomas - WHO Classification

Lymphomas - staging system

Lymphoma- Diagnosis Clinical manifestations Histopathology Immunophenotypes Genetics

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

Some lymphomas with distinctive genetic abnormalities Types Cytogenetic finding Genetic alteration FL t(14;18)(q32;q21) bcl-2 rearranged* MCL t(11;14)(q13;32) cyclin D1 BL t(8;14)(q24;q32) myc* MALTOMA t( 11;18)(q21;q21) MALT/API2 trisomy 3 ALCL t(2;5)(p23;35) NPM-ALK

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

Hodgkin lymphoma

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.

Hodgkin lymphoma - Subtypes Nodular lymphocyte predominance Hodgkin lymphoma, NLPHL Classical Hodgkin lymphoma, CHL Lymphocyte rich, LR Mixed cellularity, MC Lymphocyte deplete, LD Nodular sclerosis, NS

Lucunar cell CHL Nodular sclerosis

porphyry spleen

Proposed signals mediated “cross talk” between R-S cells and surrounding normal cells in Classical Hodgkin lymphoma

Non Hodgkin Lymphomas

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

Lymphoblastic leukemia/lymphoma TdT

Chronic lymphocytic leukemia / small lymphocytic lymphoma

Follicular lymphoma Bcl-2

Diffuse large B-cell lymphoma

Burkitt lymphoma

Plasma cell myeloma

Extranodal NK/T-cell lymphoma, nasal type

Clinicopathologic differences between HL and NHL HL NHL Patient children/young adults any aged people Stage I / II III / IV Symptoms 40% 15% Site LN, 90% LN, 70% neck/mediastinum extranodal,30% Dissemination predictable random Extranodal uncommon common Leukemia no yes Tumor cell R-S cells lymphocytes

Myeloid neoplasms

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 : 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

Peripheral blood Bone marrow biopsy

Myeloid sarcoma A myeloid sarcoma is a tumour mass consisting of myeloid blasts with or without maturation occurring at an anatomical site other than the bone marrow. Granulocytic sarcoma, so called choloroma, is the most common type of myeloid sarcoma.

Leukemoid reactions Reactive leukocytosis Many immature white cells appear in the blood Response to severe infection, malignant tumor, toxic events or emergencies Reversible

Granulocyte sarcoma MPO

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 : Classification Chronic myelogenous leukemia* BCR-ABL1 positive Chronic neutrophilic leukemia Polycythaemia vera Primary myelofibrosis Essential thrombocythaemia Chronic eosinophilic leukemia Mastcytosis Myeloproliferative neoplasm, unclassifiable

Chronic myelogenous leukemia

CML Blood smear CML BM biopsy

CML- Detection of t(9;21) and ABL/BCR fusion gene

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

Tumors derived from langerhans cells Langerhans cell histiocytosis Langerhans cell sarcoma

Langerhans cell histiocytosis