Stáhnout prezentaci
Prezentace se nahrává, počkejte prosím
1
Diagnostika lymfomů Extranodální lymfomy
Doc. MUDr. L. Boudová, Ph. D.
2
Contents WHO Classification 2008
3
Lymphomas Clonal disorders of lymphoid cells at various stages of differentiation
HODGKIN L. NON-HODGKIN L. immature cells (precursors) mature cells B T Distinction clinical histological Note: Hodgkin lymphoma is also a (mature)B-cell lymphoma.
4
Lymphoid malignancies Epidemiology
90%: B; FL+ DLBCL – 60% 4% of all new cancers each year Incidence increasing per : 34 lymphoid neoplasms
5
Lymphoma diagnosis Sample Lymph node Bone marrow
Spleen, extranodal tissue Cerebrospinal fluid
6
Lymphoma diagnosis Histology, cytology Immunohistochemistry
Ag detected in tissue slides Molecular biology Clonality, lineage – gene rearrangements Translocation detection, mutations Flow cytometry Clinicopathological correlation, esp. T-cell lymphomas difficult to diagnose
7
Lymphoma diagnosis molecular biology
Gene rearrangement (PCR, Southern blot) Clonality and lineage B-cells: IgH T-cells: T-cell antigen receptor Characteristic translocations Mantle cell lymphoma t(11;14) Follicular lymphoma, diffuse large B-cell l. t(14;18) Anaplastic large cell lymphoma t(2;5) Burkitt lymphoma t(8;14)
8
B-cell lymphoma Clonal disorders of B-cells at various stages
of differentiation of immature cells - lymphoblasts B-acute lymphoblastic leukaemia - frequent, children B-lymphoblastic lymphoma - rare of mature B-cells most common: diffuse large B-cell lymphoma, follicular; plasma cell myeloma
9
Mature B-cell lymphomas
Chronic lymphocytic leukemia/small lymphocytic lymphoma; B-cell prolymphocytic leukemia Lymphoplasmacytic lymphoma Hairy cell leukemia Plasma cell myeloma Monoclonal gammopathy of unknown significance Solitary plasmacytoma of bone Extraosseous plasmacytoma Extranodal marginal zone B-cell lymphoma= MALT Nodal marginal zone B-cell lymphoma Splenic marginal zone lymphoma
10
Mature B-cell lymphomas
Follicular lymphoma Mantle cell lymphoma Diffuse large B-cell lymphoma Mediastinal (thymic) large B-cell lymphoma Intravascular large B-cell lymphoma Primary effusion lymphoma Burkitt lymphoma/leukaemia
11
T-cell lymphoma Precursor T-cell lymphomas
T-acute lymphoblastic leukaemia T-lymphoblastic lymphoma Mature T-and NK cell neoplasms uncommon –10% of all NHL Most frequent : peripheral T-cell lymphoma, unspecified large cell anaplastic lymphoma often difficult to diagnose
12
Most common T-cell lymphomas
1. Leukaemic/disseminated adult T-cell leukaemia - HTLV 1 2. cutaneous - mycosis fungoides, Sezary syndrome, primary cut. anaplast. lymphoma 3. other extranodal - extranod. NK/T - nasal, enteropathy assoc. 4. nodal - peripheral T-cell lymphoma, NOS, anaplastic large cell lymphoma
13
NK/T-cell lymphoma of nasal type
EBV, angiocentric, destructive South America, Asia Lethal midline granuloma NK/T-cell l. Wegener granulomatosis Cocaine abuse
15
Diffuse large B-cell lymphoma
16
Diffuse large B-cell lymphoma
aggresive, potentially curable COMMON! 1/3 of all lymphomas of adults (med. 64 ys) nodal OR extranodal (1/3) GIT, skin, CNS, testis bone, soft tissue, salivary glands, Waldeyer ring, lung, kidney, liver, spleen, female genital tract
17
Diffuse large B-cell lymphoma
Primary OR secondary Chronic lymphocytic leukemia Follicular lymphoma Marginal zone B-cell lymphoma Nodular lymphocyte predom. Hodgkin l. Risk factor: immunodeficiency (often EBV+)
18
Diffuse large B-cell lymphoma
Morphologic variants Centroblastic Immunoblastic Plasmablastic DLBCL subtypes T-cell/histiocyte rich CNS Skin- leg type EBV positive - elderly
19
Special lymphomas of large B-cells
Mediastinal (thymic) Intravascular Chronic inflammation Lymphomatoid granulomatosis ALK positive plasmablastic Arising in HHV8 Castleman dis. Primary effusion
20
Diffuse large B-cell lymphoma, Giemsa
21
Diffuse large B-cell lymphoma Differential diagnosis
Tumors Haematological: lymphomas – peripheral - B, T precursors - B, T myeloid neoplasm Non-haematological: carcinoma, sarcoma, GIST, melanoma, seminoma, glial tumors Reactive disorders: infectious mononucleosis, Kikuchi
22
T-cell /histiocyte rich B-cell lymphoma
CD20 Diffuse/ vaguely nodular diffuse large B-cell lymphoma neoplastic B-cells scarce majority reactive T-cells, histiocytes Small B-cells rare BUT areas with increased numbers of small B-cells associated NLPHL ?
23
T-cell /histiocyte rich B-cell lymphoma
Differential diagnosis 1. Hodgkin lymphoma - classical - NLPHL (nodular paragranuloma) 2. T-cell lymphoma 3. Reactive disorders – T/HRBCL interfollicular
24
Diffuse large B-cell lymphoma clinicopathological subtypes
mediastinal
25
Mediastinal DLBCL Thymus Female, 30 ys Anterior mediastinal mass
Superior vena cava syndrome Clinicopathological differential diagnosis?
27
Mediastinal DLBCL Compartmentalising fibrosis
Polymorphic large cells, abundant pale cytoplasm CD20, CD23, CD30, CD45
28
Mediastinal DLBCL – differential diagnosis
Problems 1. small biopsies, crushed cells, small areas for IH 2. background: small ly, eosinophils; RS cells 3. clinicopathological features – med. mass, young woman Traverse-Glehen : Mediastinal Gray Zone Lymphoma. The Missing Link Between Classic Hodgkin Lymphoma And Mediastinal Large B-Cell Lymphoma. Am J Surg Pathol, Nov. 2005, 29, GRAY ZONE
29
Classical Hodgkin lymphoma
Nodular sclerosis
30
Borderline cases
31
BCLUWFIBDLBCLACHL
32
BCLUWFIBDLBCLACHL DLBCL vs. CHL morphology, IHC
Garcia, Histopathology 2005
33
BCLUWFIBDLBCLACHL DLBCL vs. CHL morphology, IHC
Traverse-Glehen AJSP 2005
34
Differential diagnosis versus
DLBCL Differential diagnosis versus Burkitt lymphoma
35
Burkitt lymphoma 1. endemic (Africa) 2. sporadic (young, rare)
3. immune deficiency-associated - HIV! t(8;14) starry sky
36
BCLUWFIBDLBCLABL
37
BCLUWFIBDLBCLABL DLBCL versus Burkitt morphology, IHC, genetics
Chuang AJCP
39
Extranodal lymphomas the primary tumor is extranodal (not nodal)
The biggest mass is extranodal at the time of the diagnosis Diagnosis may be nmore difficult than in the LN – other tumours may be more common in extranodal localizations (carcinomas..) – think of the possibility of a lymphoma Most common: GIT, skin, Waldeyer,CNS, testis, bone soft tissue, salivary glands, lung, kidney, liver, spleen, female genital tract Histological types: DLBCL, MALT l.
40
Gastrointestinal lymphomas
most common extranodal lymphomas 50%
41
Klinické symptomy často necharakteristické!
pokročilé: tumor v břiše, srůsty kliček, perforace lymfadenopatie hepatosplenomegalie KO: lymfocytóza, LDH endoskopický nález
42
GI lymphomas Site Type B DLBCL, MALT MCL, FL T EATL Stomach Intestines
(ileocaec., jejunum, duodenum)
43
Diffuse large B-cell lymphoma of the stomach
44
DLBCL HE CD20
45
MALT lymphoma versus DLBCL
Gastric DLBCL de novo transformation of a low-grade lymphoma clonal progression in time Independent coexistence of 2 clones: low /high grade component DO NOT USE “HIGH-GRADE MALT LYMPHOMA“
46
MALT lymphoma chronic antigenic stimulation - Helicobacter pylori
stomach, intestine (IPSID) chronic antigenic stimulation - Helicobacter pylori Regulation: specific activated T-cells Slow progression- 90%: stage IE, IIE (bone marrow involvement: rare, 10%)
47
Helicobacter pylori Chronic gastritis
48
Diseases associated with Helicobacter pylori infection
Chronic gastritis Peptic ulcer Gastric carcinoma Gastric MALT lymphoma Disease Association Chronic gastritis Strong causal association Peptic ulcer disease Gastric carcinoma Gastric MALT lymphoma* Definitive etiologic role
49
MALT lymphoma of the stomach
50
MALT lymphoma Different sites common features Architecture Cytology
Immunophenotype extrafolik. infiltráty folikulární kolonizace lymfoepiteliální léze monocytoidní, plazmat. buňky
51
Macroscopy: often noncharacteristic
Microscopy: Wotherspoon criteria - spectrum 0 normal mucosa 1 chronic active gastritis 2 chronic active gastritis with lymphoid follicles 3 suspicious lymphoid infiltrate, probably reactive 4 suspicious lymphoid infiltrate, probably lymphoma 5 MALT lymphoma
52
MALT lymphoma Immunohistochemistry No specific MALT lymphoma marker
Positivity: CD20, CD79a; Ig light chains; Ig heavy chains: IgM; CD43 Negativity: CD5, CD10, bcl6, IgD, cyclin D1 CD21, CD10, Ki-67: residual lymphoid follicles
53
Differential diagnosis of MALT lymphoma
HP gastritis Wotherspoon criteria spectrum 0-5 other lymphomas: DLBCL, MCL, FL… Integrated approach favoring MALT lymphoma: dense lymphoid infiltrate prominent LEL Dutcher bodies infiltration of muscularis mucosae atypia of lymphoid cells B - cell monoclonality
54
B-cell monoclonality detection
Imunohistochemistry - Ig light chains Molecular biology - PCR - IgH rearrangement Polyclonal IgH rearrangement Monoclonal IgH rearrangement
55
repeat the biopsy; sampling
It is often not possible to establish a clear diagnosis in a single biopsy. repeat the biopsy; sampling ? MALT lymphoma/gastritis? Large cell component? Correct diagnosis and treatment Interdisciplinary communication Repeated biopsies, specialized methods
56
MALT lymphoma after therapy
Response: regression of lymphoid infiltrate and LEL Gastric mucosa: atrophy, intestinal metaplasia, empty, fibrotic, basal lymphoid aggregates Always assess Helicobacter pylori B-cell clonality assessment by PCR: not clear
57
Průkaz monoklonality Imunohistochemie lehké řetězy Ig
Molekulární genetika PCR přestavba genu IgH CDR III
58
Gastric MALT lymphoma Recurrent genetic abnormalities
t(11;18)(q21;q21)/ API2-MALT1 usually the sole genetic abnormality, 25% of g. MALT l., H. p. neg., no response to ATB t(14;18)(q32;q21)/ IgH-MALT1 non-gastric t(1;14)(p22;q32)/ IgH-BCL10; t(1;2)(p22;p12) Different strains of Helicobacter pylori
59
MALT l. in other sites than the stomach
Eye – Chlamydia psittaci Skin – Borrelia burgdorferi IPSID – Campylobacter jejuni Salivary, thyroid, lung, orbit, breast, skin Localized; disseminated (30%, after a long period) 5 y OAS: 90%
60
Multiple lymphomatous polyposis
Mantle cell lymphoma Follicular lymphoma MALT lymphoma
61
Mantle cell lymphoma Multiple lymphomatous polyposis M60
bad prognosis imunohistochemistry genetics WHO
62
Mantle cell lymphoma - localisation
Lymph nodes, Waldeyer; bone marrow Extranodal sites: GIT, skin, others GIT: multiple lymphomatous polyposis (MCL, FL, MALT l.)
63
Mantle cell lymphoma CD5 Cyclin D1
64
MALT? MCL? FISH t(11;14)(q13;q32)
65
Enteropathy-associated T-cell lymphoma
Proximal jejunum Very rare x most common GI T-cell lymphoma Acute abdomen (40%) – emergency surgery Obstruction/perforation, peritonitis, sepsis, death Non-acute: pain, weight loss, malabsorption Age 60, M=F
66
Enteropathy-associated T-cell lymphoma
Striking association with celiac disease Histology and immunomorphology Anaplastic/pleomorphic (80%) Celiac dis.+, enteropathy +, CD56- Monomorphic (20%) Celiac dis.-, enteropathy+/-, CD56+ Half of the patients die soon after the manifestation
67
Enteropathy-associated T-cell lymphoma
CD3 T-cells, plasma cells, eosinophils Anaplastic
68
TCR gamma - PCR ABI PRISM TGGE
69
Testicular lymphomas
70
Lymfomy varlete Primární x sekundární 1% všech NHL 2% nádorů varlete
! nejčastější nádor varlete u mužů 50 let !
71
I. Dospělí: DLBCL MALT lymfom, folikulární lymfom T-lymfomy T/NK – lymfomy, nosní typ plasmocytom
II. Děti: před pubertou Sek. (5% systém.): Burkitt, DLBCL, lymfoblastické nádory Primární: folikulární lymfom
72
Infiltrace varlete parciální celková
Zvětšení unilaterální bilat. současné
73
DLBCL Intertubulární růst
74
Destrukce tubulů, difúzní růst
75
Stadium IE Cytologické rysy Nejčastěji: dif. velkobuněčný B-lymfom
- CB, IB - CD20+, CD79a+
76
Lymfom varlete (DLBCL)
! nejčastější nádor varlete u mužů 50 let ! primární diagnózy: 10% chybné („seminom“)
77
Většinou diagnostikován v KLIN. ST. IEA
Prognóza nemocných není tak dobrá, jako u odpovídající rizikové skupiny nodálního DLBCL Pozdních relapsy: CNS, druhostranné varle, zejména u nemocných nedostatečně léčených v úvodu
78
The mysterious link between the brain and the testis
79
CNS lymphomas
80
Primární lymfomy CNS pouze v CNS mozek
1% intrakraniálních nádorů – 1% NHL imunodeficientní x imunokompetentní
81
Multifokální, periventrikulární or unifocal mass
MR Multifokální, periventrikulární or unifocal mass
82
Perivask. manžety CD20 RETIKULIN
83
Predispozice imunitní deficity AIDS EBV-LMP
84
Vzácné prezentace lymfomů v NS
Lokalizace Oko Dura mater Mícha, extradurální expanze Lymphomatosis cerebri Kraniální a periferní nervy Typ lymfomu T-lymfom, ALCL intravask. lymfom SLL, MgZL, FL, PTLD
85
Závěr: primární lymfom CNS
svébytná nádorová jednotka histopatologická diagnóza stereotaktická biopsie
86
Intravaskulární B-lymfom
87
Intravaskulární B-lymfom
88
Lymfoproliferace u imunodeficitů
89
immunodeficiencies Associated tumors Skin, urogenital tract, lymphomas
90
Stavy se sníženou imunitou
1. iatrogenic immunosuppression after transplantation (posttransplantation lymphoproliferative disease, PTLD) 2. autoimmune diseases (RA, SLE) 3. HIV 4. primary immune deficiencies 5. senile EBV-related B-cell lymphomas
91
PTLD Posttransplantation lymphoproliferative disease
Clinicopathological spectrum 1. Histol. Iniciální - časné 2. Polymorfní 3. Monomorfní 4. Hodgkinův lymfom, PTLD podobná Hodgkinově lymfomu
92
Etiopatogeneze imunosuprese infekce EBV
chronická antigenní stimulace štěpem další infekční agens?
93
Klesající imunitní odpověď
Vliv EBV Reaktivní T-buňky „IM“ Polymorfní PTLD Monomorfní PTLD HL Polyklonální lymfoidní proliferace Klonální populace Sekundární genetické změny EBV Plazmocytární hyperplazie Klesající imunitní odpověď
94
PTLD – potransplantační lymfoproliferace
Early – up to 1 year – EBV - strong role Late – after 1 year
95
Frekvence PTLD: 1-10% - typ a stupeň imunosuprese, - EBV status
Lokalizace: často extranodální Nejvíce: 1. rok po transplantaci PTLD časná x pozdní Mortalita: Tx solidních orgánů: 60% kostní dřeně: 80% Reverzibilita: u některých PTLD Původ: příjemce (solidní) x dárce (BMT)
96
EBV Infectious mononucleosis Burkitt lymphoma Hodgkin lymphoma
B-cell lymphomas in immunosuppressed patients (HIV, transplantation) Nasopharyngeal carcinoma
97
HIV and lymphomas 1 st most frequent tumor: Kaposi sarcoma
Lymphoma - AIDS defining illness 3% of patients with AIDS
98
Lymfomy u HIV pozitivních lidí
agresívní B-lymfomy, často extranodální; heterogenní (GIT, CNS) patogenetické faktory: herpesviry: EBV (v 50%), Kaposi Sarcoma Human Virus/HHV 8 (primary effusion lymphoma) chronická antigenní stimulace genetické abnormality poruchy cytokinové regulace prognóza závisí na tíži imunodeficience
99
Lymphomas associated with HIV
Incidence increased: x (versus noninfected population) Incidence decreases with HAART, ↑CD4 Hodgkin lymphoma: AIDS: risk 10 x higher
100
Lymfomy u HIV+ 1. lymfomy postihující také imunokompetentní pacienty časté: Burkittův (klasický, plazmacytoidní, atypický), DLBCL (často v CNS!) vzácnější: extranodální B-lymfom z marginální zóny, periferní T-lymfom, klasický Hodgkinův lymfom 2. lymfomy specifické pro HIV+ pacienty primary effusion lymphoma, plazmoblastický lymfom ústní dutiny 3. léze vyskytující se i u jiných imunodeficiencí - polymorfní "PTLD"
101
Lymfoproliferativní choroby u primárních imunodeficiencí
rare More than 60 PID Heterogenous Manifestattion highly variable Ataxia teleangiectasia Wiskott Aldrich sy CVID SCID XLP…
102
Lymfoproliferativní choroby u primárních imunodeficiencí
hlavně u dětí, častěji u chlapců; (x common variable immunodeficiency: dospělí) většinou extranodální (GIT, CNS) většinou B-lymfoproliferace: fatální infekční mononukleóza, DLBCL, lymfomatoidní granulomatóza, Hodgkinův lymfom; T-lymfomy /leukémie
103
Senile EBV+ lymphoproliferations no other overt ID, only the age…
Oyama AJSP 2003
104
EBV + senile lymphoproliferations
Rare Asia over 50 Various histological appearance
Podobné prezentace
© 2024 SlidePlayer.cz Inc.
All rights reserved.