Blockxiv Neoplasms Lymphoid 2006
Transcript of Blockxiv Neoplasms Lymphoid 2006
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neoplasms of the
Lymphoid System
T. Utoro
Department of Pathology GMUSM
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Structure of Normal Lymphnode
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Lymphoid Neoplasms
Certain relevant principles must beemphasized
Can be suspected from the clinical features, but
histological examination of lymph nodes andother involved tissue is required for diagnosis
The vast majority of lymphoid neoplasm (80% -85%) are of B-cell origin; most of the remainderbeing T-cell tumors; only rarely are tumors of NKorigin encountered
Two basic forms of B-cell lymphoma: follicular &
diffuse type
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Lymphoid Neoplasmsclose to immune regulatory system
Lymphoid neoplasm are tumors of the immunesystem disrupt normal immune regulatorymechanisms (evidences: susceptibility toinfection, autoimmune diseases)
Patients with inherited or acquired immunodefi-ciency are at high risk of developing certainlymphoid neoplasm, particularly these associatedwith EBV infection
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Lymphoid Neoplasms
All lymphoid neoplasms are derived from singletransformed cell monoclonal
Divided into 2 big groups: NHLs and HLs
NHLs often present as involvement of a particular tissuesite, but sensitive molecular assay usually show that thetumor is widely disseminated at the time of diagnosis only systemic therapy are curative
HLs are often presents at a single site spreadsmethodically to contiguous lymph nodes groupearlycourse tumors may be cured with local therapy alone
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Lymphoid Neoplasms
HL spreads in orderly fashion, and as a result
staging is of importance in determining therapy
In contrast, the spread of NHL is less predictable
most patients are assumed to have systemic
disease at the time of diagnosisstaging in
particular NHL provides useful prognosis
information, but generally not important in guidingtherapy
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E T I O L O G Y
Chromosomal translocation:CML, Burkitt lymphoma
Inherited genetic factors:Bloom syndrome, Fanconi
anemia, ataxia telangiectasia, Down syndrome
Viruses:HTLV-1, EBV, KSHV, HHV-8
Environmental agents:Helicobacter pylorii (gastric B-cell
lymphoma), gluten-sensitive enteropathy (T-cell lymphoma),
HIV (B-cell lymphoma) Iatrogenic factors:radiotherapy & chemotherapy
mutagenic effect
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The WHO Classification of the
Lymphoid NeoplasmsI. Precursor B-cell Neoplasms:neoplasms of
immature B-cells
II. Peripheral B-cell Neoplasms:neoplasms ofmature B-cells
III. Precursor T-cell Neoplasms:neoplasms ofimmature T-cells
IV. Peripheral T-cell and NK-cell Neoplasms:neoplasms of mature T-cell and NK-cell
V. Hodgkin Lymphoma:neoplasms of Reed-Sternberg cells and variants
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Origin of Lymphoid Neoplasms
CLP:common lymphoid precursor; BLB:pre-B lymphoblast;NBC:naive B-cell; MC:mantle B-cell; GC:germinal center B-cell;
MZ:marginal zone B-cell; DN:CD4/CD8 double negative pre-T cell;
DP:CD4/CD8 double positive pre-T cell; PTC:peripheral T-cell
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The WHO Classification of theLymphoid Neoplasms
I. Precursor B-cell Neoplasms
ALL
The WHO Classification of theLymphoid Neoplasms
III. Precursor T-cell Neoplasms
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Acute lymphoblastic leukemia / lymphoma
-Originate from B-cell or T-cell, mostly from T-cell
-Can be differed by B-cell marker CD22
-The nuclear chromatin is delicate and finely stippled,
and nucleoli are either absent or inconspicuous
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The WHO Classification of theLymphoid Neoplasms
II. Peripheral B-cell Neoplasms
CLL / small lymphocytic lymphoma B-cell prolymphocytic leukemia
Lymphoplasmacytic lymphoma
Splenic and nodal marginal zone lymphoma
Extranodal marginal zone lymphoma Mantel cell lymphoma
Follicular lymphoma
Marginal zone lymphoma
Hairy cell leukemia
Plasmacytoma / plasma cell myeloma
Diffuse large B-cell lymphoma
Burkitt lymphoma
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II. Peripheral B-cell NeoplasmsSmall Lymphocytic Leukemia
Small Lymphocytic Lymphoma
The two indistinguishable disorders: morphologically,
phenotypically, and genotypically; differing only in the
degree of peripheral blood lymphocytosis Proliferation center: loose aggregates of pro-lymphocyte
pathognomonic
Tumor cells usually infiltrate the splenic white and red
pulp, and the hepatic portal tract, although the extent ofinvolvement varies widely.
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II. Peripheral B-cell NeoplasmsSmall Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Diffuse effacement of nodal architecture The majority of the tumor cells are
small round lymphocytes.
Arrow: pro-lymphocyte
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II. Peripheral B-cell Neoplasms
Follicular Lymphoma The most common form of NHL in the USA
(45% of adult lymphomas)
Usually present in the middle age and afflictsmales and females equally
Less common in Europe, and rare in Asian
population
The tumor cells closely resemble normal
germinal center B-cells
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II. Peripheral B-cell Neoplasms
Follicular Lymphoma In most cases,at low magnification, a predominantly
nodular or nodular and diffuse growth pattern isobserved
Two principle cells are observed in varying proportion:(1) small cell with irregular or cleaved nuclear contourand scant cytoplasmcentrocyte
(2) larger cells with open nuclear chromatin, severalnucleoli, and modest amount of cytoplasm centroblast
Involvement: bone marrow (85%), spleen, liver
Te overall median survival is 7 to 9 years, is notimproved by aggressive therapy
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Follicular Lymphoma (spleen)
Prominent nodules represent white pulp follicles expanded byfollicular lymphoma cells
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Follicular Lymphoma
Malignant lymph follicles are marked by Bcl-2 positive
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Follicular Lymphoma
Small lymphoid cells with condensed chromatin and irregular orcleaved nuclear outline (centrocyte), mixed with a population of
larger cells with nucleoli (centroblast)
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Mantle cell lymphoma
Neoplastic lymphoid cells surround a small, atrophicgerminal center exhibiting mantle zone pattern of growth
Homogenous population of small lymphoid cells with somewhat irregular
nuclear outlines, condensed chromatin, and scant cytoplasm.
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II. Peripheral B-cell Neoplasms
Diffuse large B-cell lymphoma(DLBCL)
Slight male predominance
Age about 60 years
5% of childhood lymphoma
Clinically present with a rapidly enlarging,
often symptomatic mass, at a single nodalor extranodal site
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Diffuse large B-cell lymphoma
Spleen: typical isolated large mass
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Diffuse large B-cell Lymphoma
Tumor cells show prominent nucleoli
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Diffuse large B-cell lymphoma
Tumor cells with large nuclei, open chromatin,and prominent nucleoli
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II. Peripheral B-cell Neoplasms
Burkitt lymphoma Categories: (1) African (endemic) Burkitt lymphoma,
(2) sporadic (non-endemic), (3) a subset of aggressive
lymphoma occuring in individual with HIV infection Responds well to short-term, high dose chemotherapy
(children & young adults)
Clinical feature
Both endemic & non-endemic are found largely inchildren and young adults (30%)
Most tumor manifests at extra-nodal sites
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Burkitt lymphoma
Low power: many tingible body
macrophages Starry sky appearance
Monotonous appearance, tumor cells
with multiple small nucleoli and high
mitotic index (typical)
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Burkitt Lymphoma
Several starry sky macrophages was shown (arrows)
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II. Peripheral B-cell Neoplasms
Multiple myeloma of the skull
The sharply punched-out bone lesions aremost obvious in the calvarium
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Multiple myeloma (bone aspirate)
Normal marrow cells are replaced by plasma cells
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Lymphoplasmacytic lymphoma
Bone marrow biopsy:
various degrees of plasma cell differentiationMast cell
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The WHO Classification of theLymphoid Neoplasms
IV. Peripheral T&NK-cell Neoplasms
T-cell prolymhocytic leukemia
Large granular lymhocytic leukemia
Mycosis fungoides/ Sezary 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 T-cell lymphoma Adult T-cell leukemia/Lymphoma
NK/T-cell lymphoma, nasal type
NK-cell leukemia
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Peripheral T&NK-cell Lymphoma
Peripheral T-cell lymphoma
T-cell lymphoma without specific defining features fallcollectively into the category of unspecified
Account for approximately half of all T-cell lymphoma inthe western world
As a group they are aggressive malignant with low 5-yrs
They may be nodal or extra nodal
Variable expressionmost nodal expressing CD4+ They may be associated with eosinophilia
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Peripheral T&NK-cell Lymphoma
Peripheral T-cell lymphoma
A spectrum of small, intermediate, and large lymphoid cells,many with irregular nuclear contours.
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Peripheral T&NK-cell Lymphoma
Anaplastic large cell lymphoma
mitosis
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The WHO Classification of theLymphoid Neoplasms
V. Hodgkin Lymphoma
Classical subtype
Nodular sclerosis
Mixed cellularity
Lymphocyte-rich
Lymphocyte depletion
Lymphocyte pre-dominance
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V. HodgkinLymphoma
Lymphocyte predo-
minant.
Mixed cellularity
Lymphocyte rich
Lymphocyte depleted
Nodular sclerosis
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V. Hodgkin Lymphoma
Reed-Sternberg cell, positive for CD30
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V. Hodgkin Lymphoma
Reed-Sternberg cell
Mirror-image nuclei contain large eosinophilic nucleoli
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Reed-Sternberg cells and variants
A. Diagnostic RS-cellswith 2 nuclear lobes, large inclusion-
like nucleoli, and abundant cytoplasm
B. Mononuclear variant.
C. Lacunar variant,characteristic of the nodular sclerosissubtype. It has a folded or multilobated nucleus lying
within a clear space created by disruption of its
cytoplasm during processing
D. Lymphohistiocytic (L&H) variant, complex nuclear
irregularities, small nucleoli, fine chromatin, and abundant
pale cytoplasm.
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Hodgkin lymphoma(Reed-Sternberg cells and variants)
A B
C D
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Hodgkin lymphoma:nodular sclerosis type
Well-defined bands of pink, acellular collagen that subdivided
the tumor cells and associated reactive infiltrate into nodules
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Hodgkin lymphoma:mixed cellularity type
Numerous mature-looking lymphocytes surround scattered,
large pale-staining L&H variants (popcorn cells)
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Hodgkin lymphomalymphocytic predominance type
Reed-Sternberg cells is surrounded by reactive cells, including eosinophils
Ann Arbor Staging System
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Ann Arbor Staging System
Stage I
A/BaI
IE
Involvement of a single lymph node region
or
A single extra lymphatic organ or site
Stage II
A/B
II
IIE
Involvement of 2 or more lymph node regions on the same
side of the diaphragm, or
With localized contiguous involvement of an extra
lymphatic organ or site
Stage III
A/B
III
IIIE
IIIS
IIIES
Involvement of lymph node regions of both sites of the
diaphragm
Or, with localized contiguous involvement of an extra
lymphatic organ or site, or
With involvement of spleen, orboth extra lymphatic organ or site and spleen involvement
Stage IV
A/B
IV Diffuse or disseminated involvement of one or more extra
lymphatic organs with or without associated lymph node
involvement
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References
Rubins Pathology. Clinical Foundations of
Medicine, 2005. Emanuel Rubin cs; Lippincott
Williams & Wilkins.
Robbins Pathologic Bases of Medicine, 2005.
Cotran, Kumar, Collins. Saunders
Pathology, 2nded. 2002. Arthur S. Schneider,
Philip A. Szanto; Lippinctt Williams & Wilkins
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Mycosis Fungoides
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MycosisFungoides
A mature T-cell lymphoma presenting
in the skin with patches/plaques, and
characterized by epidermal and
dermal infiltration of small to medium
T-cells with cerebriform nuclei.
Mycosis Fungoides
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Mycosis Fungoides
Plaques lesion with infiltrates of
atypical, cerebriform lymphocytes
in the upper dermis
The epidermis is involved, mainly with
single cells
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Mycosis Fungoides
Neoplastic cells with cerebriform nuclei form Pautrier microabscess within epidermis.
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MycosisFungoides
Tumor lesion with more massive
infiltrates involving both the
upper and deep dermis
Mycosis Fungoides
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Mycosis Fungoides
B. In the epidermis Pautrier abscess can be seen.C. The neoplastic cells show an