j0305257 General pathology General pathology V. Neoplasms II (hematooncology). Pathology of lymph nodes. j0305257 Summary •Hematopoiesis û •Myeloid neoplasms û •Lymphoid neoplasms ðNon-Hodgkin lymphomas ðHodgkin lymphomas ð •Reactive lympadenopathy j0305257 Hematopoiesis •from hematopoietic stem cell • •HSCs (Hematopoietic Stem Cells): pluripotent, ability of self-renewal (replication) • Þdue to asymetric cell division variable progenitor cells arise : •fenotypically identical cells – HSCs •fenotypically different cells – multipotent cells (progenitors of myeloid cell line or progenitors of lymhoid cell line) • •Regulation of hematopiesis through specific growth factors •GF receptors expressed during the development/differentiation on blood cells • û û j0305257 Hematopoetic stem cells • in BM (<0,1% of cells) Multipotent progenitors Multipotent progenitors Committed precursors Late precursors and mature forms •morphologically differentiated diferenciace krvinek.jpg Kumar et al.: Robbins&Cotran Pathologic Basis of Disease, 8th Edition. j0305257 Hematooncology •Leukemia (hemoblastosis) •Diffuse replacement of normal BM by leukemic cells with their subsequent variable accumulation in peripheral blood (=leukemization) •Infiltration of peripheral organs (liver, spleen, lymph nodes, meninges, gonads,….) • •Lymphoma (hemoblastoma) •Neoplastic/lymphoma cells form tumor/neoplastic mass (nodal and/or extranodal) ð !Lymphomas may also present by leukemic infiltrates and leukemias also form solid neoplastic massess j0305257 Hematooncology ð •Mutations that inhibit normal differentiation and maturation of progenitor cells, or mutations disrupting the regulation of progenitor and precursor cells by growth factors ð Þunregulated clonal expansion of immature hematopoietic cells → inhibition of normal hemopoiesis → release of immature blast into circulation, infiltration of peripheral organs ð ð ð j0305257 Hematooncological diseases û Myeloid neoplasms -from stem cells that normally give rise to the formed blood elements (granulocytes, red cells, platelets) -3 categories û → acute myelogenous leukemias û → myeloproliferative disorders û → myelodysplastic syndromes û û Lymphoid neoplasms û→ non-Hodgkin lymphomas û(incl. lymphocytic leukemias and plasma cell dyskrasias) û→ Hodgkin lymphomas û û Histiocytic neoplasms j0305257 Etiopathogenesis of hematooncological diseases •??? • •hereditary syndromes •Inherited genetic instability (Bloom´s sy, ataxia teleangiectasia…), Down´s sy, NF type I… • •oncogenic viruses •HTLV-1, EBV, HSV-8 • •chronic stimulation of immune system •Helicobacter pylori, gluten-sensitive enteropathy (celiac sprue) • •iatrogenicity •radiotherapy, chemotherapy • •smoking û j0305257 TUMORS of HAEMATOPOETIC and LYMPHATIC TISSUES ûMyelodysplastic syndromes: clonal stem cell disorders, ineffective haematopoesis→ cytopenias; dysplastic maturation. De novo or after radio/chemotherapy. Progressive marrow failure. May → AML. ûMyelodysplastic/myeloproliferative diseases overlapping features, variably effective haematopoesis, dysplasia j0305257 TUMORS of HAEMATOPOETIC and LYMPHATIC TISSUES ûacute myeloid leukaemia + related precursor neoplasms - clonal expansion of myeloid blasts in bone marrow, blood or other tissues (myeloid sarcoma). ûClass. acc. genetic abnormalities (in young, good response to therapy and behaviour), multilineage dysplasia (i. e. following MDS, older, drug resistance), therapy-related; other – acc. morphology (modified FAB) j0305257 TUMORS of HAEMATOPOETIC and LYMPHATIC TISSUES ûacute myeloid leukaemia possible tumor manifestation (myeloid sarcoma) ûGeneral clinical signs in acute leukaemia û rapid onset; marrow failure → anaemia, neutropenia (bacterial, fungal infection), thrombocytopenia (bleeding, epistaxis, haematomas) ûinfiltrates in liver, spleen, LN, any other tissue ûTH: chemoth., bone marrow transplantation j0305257 TUMORS of HAEMATOPOETIC and LYMPHATIC TISSUES ûHistiocytic and dendritic cell neoplasms ûfrom mononuclear phagocytes (macrophages, dendritic antigen-presenting cells) – common bone marrow precursor ûfollicular dendritic cells non-myeloid, from mesenchymal stem cell ûtrue histiocytic neoplasm uncommon (Langerhans cell histiocytosis, benign disseminated juvenile xanthogranuloma) û j0305257 LYMPHOID NEOPLASMS ûBoth lymphoid leukaemias and lymphomas included ûHodgkin lymphoma ûNon-Hodgkin lymphomas (B cell neoplasms, T and NK cell n.); ûIn B, T+NK – 2 main subcategories: precursor n. (earliest stages of differentiation; acute lymphoblastic leukaemia/lymphoma) û mature (peripheral) n . (B~normal stages of differentiation,85%; T~post-thymic; rare NK) j0305257 MYELOID NEOPLASMS ûHematopoiesis •Myeloid neoplasms • •Lymphoid neoplasms ðNHL ðHL •Reactive lymphadenopathy Origin from hematopoietic stem cells that typically give rise to monoclonal proliferation replacing normal bone marrow cells. j0305257 Myeloid neoplasms 1.Myelodysplastic syndrome (MDS) 2. 2.Acute myeloid leukemia (AML) 3. 3.Chronic myeloproliferative disorders û ûHematopoiesis •Myeloid neoplasms • •Lymphoid neoplasms ðNHL ðHL •Reactive lymphadenopathy j0305257 •Disordered and ineffective maturation of myeloid progenitors • •Bone marrow: hypercellular or normo-cellular •Peripheral blood: cytopenia of one or more cell lines •Risk of transformation into AML û(abnormal stem cell clone genetically unstable→additional mutations→AML) Þ ð •Mostly in older individuals •Infections, anemia, hemorrhages •incidence 1-2/100 000 (in older individuals 40/100 000!) û MDS ûHematopoiesis •Myeloid neoplasms • •Lymphoid neoplasms ðNHL ðHL •Reactive lymphadenopathy j0305257 AML •Inhibition of normal myeloid differentiation of HSC or myeloid progenitor û •Replacement of normal BM elements by leukemic blasts •Hiatus leukemicus •Immature blasts released into peripheral blood •Leukemic infiltrates in bone marrow, liver, spleen, lymph nodes…. •Rarely AML presents as a solid mass (granulocytic sarcoma) •Generally very poor prognosis Þ ÞClinical signs of marrow failure ð → anemia (fatigue, palor) → trombocytopenia (abnormal bleeding) û → leukopenia (infections - fever) û • •primarily in older adults (median age 50) û û û ûHematopoiesis •Myeloid neoplasms • •Lymphoid neoplasms ðNHL ðHL •Reactive lymphadenopathy j0305257 AML AML nátěr j0305257 AML •WHO classification (only informative) •I. AML WITH GENETIC ABERRATIONS ðAML with t(8;21)(q22;q22); prognosis☺- M2 subtype; morphology: Full range of myelocytic maturation; Auer rods easily found; abnormal cytoplasmic granules ðAML with inv(16)(p13;q22); ☺ - M4eo; Myelocytic and monocytic differentiation; abnormal eosinophilic precursors with abnormal basophilic granules ðAML with t(15;17)(q22;11-12); +/-; M3; Numerous Auer rods, often in bundles within individual progranulocytes; primary granules usually very prominent; high incidence of DIC ðAML with t(11q23;v); L; M4, M5; Usually some degree of monocytic differentiation ðAML with normal cytogenetics ; J; FAB subtype variable Detected by immunohistochemical staining for NPM •II. AML WITH MDS-LIKE FEATURES ðWith prior MDS; L; Variable Diagnosis based on clinical history ðAML with multilineage dysplasia; L; Variable Maturing cells with dysplastic features typical of MDS ðAML with MDS-like cytogenetic aberrations; L; Variable Associated with 5q-, 7q-, 20q-aberrations ûHematopoiesis •Myeloid neoplasms • •Lymphoid neoplasms ðNHL ðHL •Reactive lymphadenopathy j0305257 AML •III. AML, THERAPY-RELATED; prognosis LL; FAB subtype Variable If following alkylator therapy or radiation therapy, 2- to 8-year latency period, MDS-like cytogenetic aberrations (e.g., 5q-, 7q-); if following topoisomerase II inhibitor (e.g., etoposide) therapy, 1- to 3-year latency, translocations involving MLL (11q23) û •IV. AML, NOT OTHERWISE SPECIFIED ðAML, minimally differentiated;+/-; M0 subtyp; Negative for myeloperoxidase; myeloid antigens detected on blasts by flow cytometry ðAML without maturation;+/-; M1; >3% of blasts positive for myeloperoxidase ðAML with myelocytic maturation; +/-; M2; Full range of myelocytic maturation ðAML with myelomonocytic maturation; +/-; M4; Myelocytic and monocytic differentiation ðAML with monocytic maturation;+/-; M5; nonspecific esterase-positive monoblasts and pro-monocytes predominate in marrow and blood; in M5b subtype, mature monocytes predominate in the blood ðAML with erythroid maturation;+/-, M6; defined by >50% dysplastic maturing erythroid precursors and >20% myeloblasts; pure erythroid subtype (M6b) defined by >80% erythroid precursors without myeloblasts ðAML with megakaryocytic maturation;+/-; M7;Blasts of megakaryocytic lineage predominate; detected with antibodies against megakaryocyte-specific markers (GPIIb/IIIa or vWF); often associated with marrow fibrosis; most common AML in Down syndrome û ûHematopoiesis •Myeloid neoplasms • •Lymphoid neoplasms ðNHL ðHL •Reactive lymphadenopathy j0305257 Chronic myeloproliferative disorders •Neoplastic myeloid progenitors retain the capacity to undergo terminal differentiation but exhibit increased or dysregulated growth û •Peripheral blood: increase in one or more lines of the formed elements (red cell, platelets, and/or granulocytes) û •Neoplastic progenitors homing to secondary hematopoietic organs (spleen, liver, lymph nodes,…) û →hepatosplenomegaly, lymphadenopathy, extramedullar hematopoiesis û •chronic diseases of adults û •due to genetic alterations ass. with increased tyrosine kinases activity(=acquired genetic disorder)→therapy by tyrosine kinase inhibitors û û ûHematopoiesis •Myeloid neoplasms • •Lymphoid neoplasms ðNHL ðHL •Reactive lymphadenopathy j0305257 Chronic myeloproliferative disorders ð 1.Chronic myeloid leukemia (CML) 2. 2.Essential thrombocythemia 3. 3.Polycythemia vera 4. 4.Primary myelofibrosis ûHematopoiesis •Myeloid neoplasms •Lymphoid neoplasms ðNHL ðHL •Reactive lymphadenopathy j0305257 CML •Acquired genetic abnormality: BCR-ABL fusion gene (t(9;22)), derivative chromosome 22 on 9 – Philadelphia chromosome, chimeric protein: BCR-ABL tyrosine kinase û •CML originates from a pluripotent stem cell • •Clinical course: slow progression (fatigability, weakness, weight loss) – accelerated phase – blast crisis (~ AML like) • •Therapy: ðimatinib mesylate (inhibitor of the BCR-ABL tyrosine kinase) ðbone marrow transplantation ûHematopoiesis •Myeloid neoplasms • •Lympohid neoplasms ðNHL ðHL •Reactive lymphadenopathy j0305257 CML •Adults (25-60 years, peak in 4th-5th decade) • •Elevated leukocyte count (>100,000 cells μ/l) û •Hypercellular bone marrow û (hyperplasia of granulocytic and megakaryocytic precursors) û •Circulating cells: predominantly neutrofils, metamyelocytes and myelocytes, myeloblasts <5 % • •Extreme hepatosplenomegaly, spleen up to 20 kg • •Extramedullary hematopoiesis • û ûHematopoiesis •Myeloid neoplasms • •Lymphoid neoplasms ðNHL ðHL •Reactive lymphadenopathy j0305257 CML CML nátěr j0305257 CML – leukemic cells in liver sinusoids CML v játrech, 100x.jpg j0305257 LYMPHOID NEOPLASMS /LYMPHOMAS ûHematopoiesis û ûMyeloid neoplasm •Lymphoid neoplasms ðNHL ðHL •Reactive lymphadenopathy Classification: → non-Hodgkin lymphomas (incl. lymphocytic leukemias and plasma cell dyskrasias) → Hodgkin lymphomas j0305257 Non-Hodgkin lymphomas/ WHO classification Peripheral T-/NK-Cell Neoplasms Peripheral B-Cell Neoplasms Precursor T-Cell Neoplasms - precursor T-cell leukemia/lymphoma (T-cell acute lymphoblastic leukemia) Precursor B-Cell Neoplasms - precursor B-cell leukemia/lymphoma (B-cell acute lymphoblastic leukemia) T-Cell Neoplasms B-Cell Neoplasms j0305257 Non-Hodgkin lymphomas/ WHO classification ûHematopoiesis û ûMyeloid neoplasms •Lymphoid neoplasms ðNHL ðHL •Reactive lymphadenopathy I.Precursor B-Cell Neoplasms •B-cell acute lymphoblastic leukemia/lymphoma (B-ALL) II.Peripheral B-Cell Neoplasms •B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) •B- prolymphocytic leukemia •Lymphoplasmacytic lymphhoma •Follicular lymphoma (FL) •Extranodal marginal zone lymphoma (MALT lymphoma) •Mantle cell lymphoma (MCL) •Splenic and nodal marginal zone lymphoma •Hairy cell leukemia •Plasmacytoma/plasma cell myeloma •Diffuse large B-cell lymphoma (DLBCL) •Burkitt lymphoma j0305257 Non-Hodgkin lymphomas/ WHO classification ûHematopoiesis û ûMyeloid neoplasms •Lymphoid neoplasms ðNHL ðHL •Reactive lymphadenopathy III.Precursor T-Cell neoplasms. •T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) IV.Peripheral T-/NK-Cell Neoplasms •T- cell prolymphocytic leukemia •Mycosis fungoides/Sézary syndrome •Peripheral T-cell lymphoma, NOS •Angioimmunoblastic T-cell lymphoma •Anaplastic large-cell lymphoma •Enteropathy-type T-cell lymphoma •Panniculitis-like T-cell lymphoma •Hepatosplenic γδ T-cell lymphoma •NK/T-cell lymphoma, nasal type •NK-cell leukemia •Adult T-cell leukamia/lymphoma (HTLV1) j0305257 31 LYMPHOID NEOPLASMS (B-cell) – cells of origin f8-02_b.jpg kopie j0305257 LYMPHOID NEOPLASMS (B-cell) – immunophenotype of cells of origin f8-02_b.jpg TdT TdT CD79a TdT CD79a CD20 CD79a CD20 CD79aCD138 CD79aCD138 CD79a CD20 CD79a CD20 CD79a CD20 CD10/Bcl6 kopie j0305257 Nodal lymphomas ûHematopoiesis û ûMyeloid neoplasms •Lymphoid neoplasms ðNHL ðHL •Reactive lymphadenopathy Norm_Anatom_Uzlina_Schem_Ioachim1994_1-3_Upr Marginal zone FL→DLBCL Burkitt MCL CLL DLBCL Peripheral T-cell ALCL. T- B- Angioimmunoblastic j0305257 B-cell acute lymphoblastic leukemia/lymphoma (B-ALL) •most frequent malignancy in children û (peak at age 4) • •Infiltration of bone marrow, lymph nodes, liver, spleen… • •Neoplastic blasts antiTdT positive (terminal deoxynucleotidyl transferase) • •Highly aggressive, but chemosensitive û (Þ children 2 to 10 years – best prognosis) û ûHematopoiesis û ûMyeloid neoplasms •Lymphoid neoplasms ðNHL ðHL •Reactive lymphadenopathy j0305257 B-ALL, immunohistochemistry: antiTdT prek lym TdT Bone trabecula - osteoporosis osteoblast Normoblasts lymphoblasts kopie j0305257 CLL/SLL ûHematopoiesus û ûMyeloid neoplasms •Lymphoid neoplasms ðNHL ðHL •Reactive lymphadenopathy •most frequent leukemia in adults •generalized lymphadenopathy, hepatosplenomegaly, BM infiltration… •neoplastic small lymphocytes-like cells, prolymphocytes in proliferative centres •transformation into high grade lymphoma (into DLBCL = Richter´s syndrome) •usually slowly progressive (10 years and more) lymphocyte prolymfocyt paraimunoblast j0305257 CLL v játrech, 100x.jpg B-CLL/SLL: liver - portal infiltration j0305257 CLL1, tuk, 100x.jpg B-CLL/SLL: infiltration in lymph node 1 2 1 Diffuse infiltration in lymph node 2 Infiltration of perinodal adipose tissue j0305257 CLL-detail B-CLL/SLL: lymph node infiltration prolymphocytes small neoplastic lymphocytes j0305257 Obrázek1 B-CLL/SLL: bone marrow infiltration (anti CD 20 IHC) Nodular infiltration by small lymphocytes Intersticial infiltration Region of dominant hemopoiesis B-cells stained brown j0305257 Mantle cell lymphoma •intermediate grade/aggressive NHL, middle aged pacients/older adults • •progressive despite treatment • •in LN mantle type of growth •small cell lymphoma/small lymphocytic cells + epiteloid histiocytes + hyalinized vessels • •also BM, spleen, GIT… involved • •t(11;14) ûHematopoiesis û ûMyeloid neoplasms •Lymphoid neoplasms ðNHL ðHL •Reactive lymphadenopathy j0305257 MCL Structure of lymph node replaced by monomorphous lymphoid infiltration. Neoplastic cells bigger than lymphocytes. Hyalinized vessels. j0305257 MCL400xMITO_CÉVY MCL j0305257 MCL – cyclinD1 MCL200xCYCLIN j0305257 Follicular lymphoma •app. 40 % NHL, older adults • •slowly to moderately progressive (5-10 years) • •Transformation into high grade NHL (DLBCL) • •generalized lymphadenopathy: ðin LN nodular/(diffuse) growth •Resemble normal follicular center B cell (centrocytes and centroblasts) •Neoplastic nodules of the same shape and size •Loss of germinal center polarization ûHematopoiesis û ûMyeloid neoplasms •Lymphoid neoplasms ðNHL ðHL •Reactive lymphadenopathy j0305257 Follicular lymphoma lymphocyte centrocyte centroblast j0305257 CENTROCYTE •Small cell with cleaved nuclear outlines Follicular lymphoma kávové zrno ûHematopoiesis û ûMyeloid neoplasms •Lymphoid neoplasms ðNHL ðHL •Reactive lymphadenopathy IMAGE_~1 copy j0305257 CENTROBLAST •Larger cell with nucleoli at nuclear membrane Follicular lymphoma ûHematopoiesis û ûMyeloid neoplasms •Lymphoid neoplasms ðNHL ðHL •Reactive lymphadenopathy Giemsa j0305257 Follicular lymphoma centrocyty centroblasty FL9, přehled40x.jpg 1 nodules of neoplastic cells 2 dominantly non-neoplastic lymphocytes among nodules 1 1 1 2 j0305257 FL3, nej400x.jpg Follicular lymphoma centrocytes centroblasts j0305257 001 HE-40xIZa 008 Bcl-2 40x Follicular lymphoma, Bcl-2 j0305257 20050426-54_KanályRGB 20050426-57_KanályRGB Growth pattern: Follicular Growth pattern: Diffuse CD10 FOLLICULAR LYMPHOMA j0305257 53 Marginal zone lymphomas • Splenic marginal zone lymphoma • Nodal marginal zone lymphoma • Extranodal marginal zone lymphoma (MALT lymphoma) j0305257 Extranodal marginal zone lymphoma (MALT lymphoma) •derived from MALT, BALT •chronic stimulation of immune system •e.g.: chronic gastritis assoc. with Helicobacter pylori (HP) infection • •low grade/aggressive lymphoma •some cases treated through eradication of HP û ûHematopoiesis û ûMyeloid neoplasms •Lymphoid neoplasms ðNHL ðHL •Reactive lymphadenopathy j0305257 Diffuse large B-cell lymphoma (DLBCL) ûHematopoiesis û ûMyeloid neoplasms •Lymphoid neoplasms ðNHL ðHL •Reactive lymphadenopathy •older adults, most frequent lymphoma • •highly aggressive • •de novo or high grade transformation of low grade lymphoma (CLL, FL, MALToma…) • •nodal or extranodal (tonsil, adenoid lymphatic tissue, GIT, skin, bones, thyroid, …) •neoplastic immunoblasts and centroblasts j0305257 Diffuse large B-cell lymphoma (DLBCL) ûHematopoiesis û ûMyeloid neoplasms •Lymphoid neoplasms ðNHL ðHL •Reactive lymphadenopathy neoplastic immunoblasts and centroblasts lymphocyte immunoblast copy anaplastic centrocyte centroblast j0305257 DLBCL2, 400x.jpg DLBCL - nodal - detail j0305257 Burkitt lymphoma ûHematopoiesis û ûMyeloid neoplasms •Lymphoid neoplasms ðNHL ðHL •Reactive lymphadenopathy •extremely highly aggressive NHL • •variants: •endemic (in Africa – children, assoc. with EBV) •sporadic (in other areas, including Europe, USA,..) •Assoc. with immunodeficiency • •t(8;14) → fusion c-myc/IgH → → → dysregulation, overexpression of c-myc → → → → brisk proliferation • •Extranodal bulks: •head – jaws (endemic variant) •abdominal tumors (sporadic variant) Copy according to Blyth M., 2002 j0305257 Burkitt lymphoma ûHematopoiesis û ûMyeloid neoplasms •Lymphoid neoplasms ðNHL ðHL •Reactive lymphadenopathy •morphology: •Tumor cells uniform, intermediate in size, nuclei round or oval, 2-5 prominent nucleoli, basophilic or amphophilic cytoplasm •High mitotic rate •„Starry sky“ pattern •therapy: - very aggressive chemotherapy regimens, majority of patients cured • • • • j0305257 Burkitt lymphoma lymphocyte copy lymphoblast macrophage (starry sky cell) j0305257 Burkitt lymphoma Burkitt - reprint Macrophages with ingested nuclear debris j0305257 DLBCL-detail_burkitt Burkitt lymphoma j0305257 Plasma cell dyskrasias û multiple myeloma û localizes plasmacytoma (=solitary myeloma) û heavy chain disease û primary amyloidosis û monoclonal gammapathy of unknown significance (MGUS) û (MGUS patients develop a defined plasma cell dyskrasia at a rate of 1 % per year) û û û j0305257 Multiple myeloma, plasmacytoma ûHematopoiesis û ûMyeloid neoplasms •Lymphoid neoplasms ðNHL ðHL •Reactive lymphadenopathy •older adults • •1 lesion = plasmacytoma •>1 lesion = multiple myeloma •Lytic lesions throughout the skeletal system → pathological fractures, radiograph of the skull with punch-out bone defects •Also BM infiltration → anemia, leucopenia,… •Myeloma nephrosis (Bence-Jones proteins) •AL amyloidosis • j0305257 Multiple myeloma, plasmacytoma ûHematopoiesis û ûMyeloid neoplasms •Lymphoid neoplasms ðNHL ðHL •Reactive lymphadenopathy Micro: •plasma cells with variable differentiation •low mitotic acitivity • lymphocyte copy plasma cells j0305257 Multiple myeloma prostřílená kalva j0305257 Multiple myeloma – osteolytic lesion myelom -kost Neoplastic plasma cells j0305257 Myeloma: – IHC proof of monoclonality of neoplastic plasma cells myelom kappa Kappa light chains Ig Kappa+ myelom lambda Lambda light chains Ig Lambda + j0305257 f8-04_c.jpg 69 T LYMPHOID NEOPLASMS – CELLS OF ORIGIN TdTCD7 TdT CD7 CD2/CD5 CD3cy CD7 CD2/CD5 CD3mem CD7 CD2/CD5 CD3mem CD4 CD7 CD2/CD5 CD3mem CD8 CD7 CD2/CD5 CD3mem CD4 CD10/bcl6 CD57 CD7/CD2 CD3cy CD56 TdT CD7 CD2/CD5 CD1a CD3cy-mem CD3mem kopie j0305257 T-cell lymphomas (selected entities) •Peripheral T-cell lymphoma, NOS •T-ALL •B-ALL> > >T-ALL •Mycosis fungoides/Sézary syndrome •MF: Primary cutaneous lymphoma •SS: leukemized, erythroderma •Anaplastic Large Cell Lymphoma •Enteropathy-type T-cell lymphoma •Adult T-Cell Leukemia/Lymphoma (HTLV1) • û ûHematopoiesis û ûMyeloid neoplasms •Lymphoid neoplasms ðNHL ðHL •Reactive lymphadenopathy j0305257 Differences between HL and NHL Hodgkin lymphoma Non-Hodgkin Lymphoma Usually localized to a single axial group of LN (cervical, mediastinal, para-aortic) Involvement of multiple peripheral LN Contiguous spreading Non-contiguous spreading Mesenteric LN and Waldeyer ring rarely involved …… commonly involved Extranodal rare Extranodal common Diagnostic (neoplastic) cells admixed with reactive non-malignant inflammatory cells Neoplastic/lymphoma cells dominate B-cell origin B- or T-cell origin j0305257 Hodgkin lymphoma •one of most common malignancies of young adults • •th.: •RT, CHT → excellent prognosis, but risk of secondary malignancies (MDS, AML, lung ca) • û û Hematopoiesis Myeloid neoplasms Lymphoid neoplasms NHL HL Reactive lymphadenopathy û j0305257 Hodgkin lymphoma - classification 1.Classical HL Þdiagnostic cc. CD15+/ CD30+, background ly T- >> B- •Nodular sclerosis (lacunar cc., assoc. EBV) •Lymphocyte-rich •Mixed cellularity •Lymphocyte depletion ð 2.Lymphocyte predominance, nodular ÞL&H („popcorn“) cc.: CD20+/CD15-/ CD30-, ↓T-ly ûHematopoiesis û ûMyeloid neoplasms •Lymphoid neoplasms ûNHL ðHL •Reactive lymphadenopathy j0305257 Hodgkin lymphoma ûdiagnostic tumor cells Reed-Sternberg cells + variants û ûChemokines / cytokines production → chemotaxis of lymphocytes, macrophages, granulocytes incl. eosinophils = reactive non-neoplastic background ûHematopoiesis û ûMyeloid neoplasms •Lymphoid neoplasms ûNHL ðHL •Reactive lymphadenopathy j0305257 Diagnostic cells of HL Sternberg c. copy Reed-Sternberg c. L&H c. Lacunar c. Hodgkin c. j0305257 Diagnostic cells - classical HL Hodgkin Reed-Sternberg Lacunar Sternberg j0305257 L&H c.(popcorn cell) Lymphocyte predominance, nodular: diagnostic cell j0305257 Hodgkin lymphoma, classical, nodular sclerosis NSHD 20x Lacunar cc. j0305257 Hodgkin lymphoma, classical, nodular sclerosis NSHD 100x 1 lacunar cells accumulation 2 mixed reactive background 1 1 2 2 j0305257 HL, classical, mixed cellularity – Hodgkin cc., RS cc. MCHD - high j0305257 Classical HL – cells of the non-neoplastic background NSHD-background Plasma cell Lymphocyte Eosinophils Histiocyte Fibroblast j0305257 Classical HL – lymphocyte depletion Eosinofily lymfodepl temp j0305257 Reactive lymphadenopathy •Reactive hyperplasia: ðFollicular (B) (bacteria, sterile inflammation) ðParacortical (T) ð(viruses, chronic inflammations) û •Sinus histiocytosis Norm_Anatom_Uzlina_Schem_Ioachim1994_1-3_Upr ûHematopoiesis û ûMyeloid neoplasms ûLymphoid neoplasms ûNHL ûHL •Reactive lymphadenopathy j0305257 Reactive lymphadenopathy ûHematopoiesis û ûMyeloid neoplasms ûLymphoid neoplasms ûNHL ûHL •Reacive lymphadenopathy •follicular hyperplasia •Enlarged, irregular (in shape and size), polarized germinal centers, tingible macrophages, mitotic activity in GC •Bacterial infections, RA, toxoplasmosis, … •paracortical hyperplasia •Reactive changes in T-cell regions of LN •Parafollicular T-cell transformation into large proliferating blasts •Viral infections, vaccinations, drugs (phenytoin) •sinus histiocytosis •Distention and prominence of lymphatic sinusoids: hypertrophy of lining endothelial cells and infiltrate of macrophages •Usually non-specific reaction, also in LN draining cancers • •granulomatous inflammation (see General Pathology III) •necrotizing (TBC, cat scratch disease) •Non-necrotizing (sarcoidosis) û j0305257 Follicular hyperplasia - reactive LU1, 100x.jpg j0305257 Sarcoidosis - mediastinal lymph node sarkoidóza2-prehled j0305257 sarkoidóza2-detail Sarcoidosis - mediastinal lymph node