Lymphomas
Clonal disorders of lymphoid cells at
various stages of differentiation
HODGKIN L.
Distinction
clinical
histological
NON-HODGKIN L.
immature cells (precursors)
mature cells
Note:
B
Hodgkin lymphoma is
also a (mature)B-cell
T
lymphoma.
B-cell lymphoma
Clonal disorders of B-cells at various stages
of differentiation
B-cell lymphomas of immature cells - lymphoblasts
B-acute lymphoblastic leukaemia - frequent,
children
B-lymphoblastic lymphoma - rare
B-cell lymphomas of mature B-cells
most common:follicular, diffuse large B-cell
lymphoma; plasma cell myeloma
Classifications
•
•
•
•
•
Kiel
Rappaport
Working formulation
REAL
WHO – 2001, 2008
Lymphomas - classification
• Practical standpoint
• Low grade - B-CLL, follicular, MALT
lymphoma, lymphoplasmacytic lymphoma
Hairy cell leukemia
• High grade - diffuse large B-cell lymphoma
• Burkitt lymphoma (lymphoblastoma, ALL)
• Inbetween (LG - HG): mantle cell lymphoma
• Plasma cell tumors
Chronic leukemia
•
•
•
•
B or T – cell derived
B:
B-chronic lymphocytic leukemia
Hairy cell leukemia
B-cell lymphomas of mature B-cells
B-cell chronic lymphocytic leukemia (B-CLL/SLL)
most common chronic lymphoid leukaemia
• PB- lymphocytosis, BM; lymph nodes, spleen,
liver, extranodal
• Hist.:dark areas of small B-cells
+ pale pseudofollicles (= proliferation centres)
• median age: 50, survival:5, asympt. OR fatigue,
AIHA, infections, enlargement of organs
• SLL
• Richter - DLBCL; prolymphocytic variant
Hairy cell leukemia
Hairy cell
BM, PB, spleen
older man
pancytopenia + splenomegaly
Follicular lymphoma
Over 60
LN, spleen, later BM
often asympt.
Histology
grades
transformation - DLBCL
t (14;18]
bcl2/JHa
Extranodal marginal zone B-cell
lymphoma of MALT
GIT - stomach
lung, head, neck (thyroid, salivary, eyes), skin
Chronic antigenic stimulation
stomach - Helicobacter pylori
thyroid - Hashimoto
Sjogren
IPSID
localized - good prognosis
RISK: transformation - DLBCL
Lymphoplasmacytic lymphoma
/Waldenstrom macroglobulinemia
Monoclonal IgM paraprotein
- hyperviscosity
Bleeding –interference with clotting factors, plts
Cryoglobulinemia – Raynaud phenomenon, cold
urticaria
Visual acuity impairment - red cell sludging,,
Neurolog. problems – headaches, dizziness,
deafness, cerebrovascular accidents,
Waldenstrom macroglobulinemia
any condition producing large Ig
rare, old (HCV)
BM, LN, spleen, (PB)
Mantle cell lymphoma
Aggressive
t(11; 14]
LN, extranodal
cyclin D1
Advanced
More frequent in men over 50
Diffuse large B-cell lymphoma
aggresive, potentially curable
VERY 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
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+)
Diffuse large B-cell lymphoma
Morphologic variants
Centroblastic
Immunoblastic
T-cell/histiocyte rich
Anaplastic
Plasmablastic
Clinicopathologic subtypes
mediastinal (thymic)
intravascular
primary effusion, pyothorax associat.
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
Mediastinal DLBCL
Thymus
Female, 30 ys
Anterior mediastinal mass
Superior vena cava syndrome
Clinicopathological differential diagnosis?
Mediastinal DLBCL
Compartmentalising fibrosis
Polymorphic large cells, abundant pale cytoplasm
CD20, CD23, CD30, CD45
Intravaskulární
B-lymfom
HE
PCR
FRII–FRIV IgH
Intravascular B-cell lymphoma
CD20
Burkitt lymphoma
• endemic (Africa)
• sporadic (young,
rare)
• immune deficiencyassociated - HIV!
• t(8;14)
• starry sky
Burkitt lymphoma:starry sky
Plasma cell neoplasms
Terminally differentiated B-cells
Clone of Ig secreting plasma cells
Serum: monoclonal Ig or its parts
M protein; paraprotein;
Bence Jones proetin
Plasma cell neoplasms
1. Plasma cell myeloma
2. Solitary plasmacytoma -
bone
extraosseous
3. Precursor lesions - MGUS
4. Other
M-component
!no significant lymphadenopathy!
Plasma cell myeloma
Problems: 1. Infiltration of organs
2. Excessive Ig
3. Immune disorder
Sites of involvement
axial skeleton –
liver, spleen, kidney
hypercalcemia, infections
hyperviscosity,amyloidosis
Myeloma kidney
Proteinuria - in 70% of patients
Bence Jones proteinuria and cast nephropathy
1. direct toxicity of IgL
Combinatiom with Tamm-Horsfall protein – casts
Obstructs tubules; inflammation; giant cells, granulomas
2. Amyloidosis
3. Light-chain nephropathy – deposits in glomeruli,
around tubules
4. Hypercalcaemia, hyperuricemia
5. Vascular disease
6. Infections
renal failure
multifactorial