Blockxiv Neoplasms Lymphoid 2006

8/12/2019 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


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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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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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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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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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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Spleen: typical isolated large mass


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Diffuse large B-cell Lymphoma

Tumor cells show prominent nucleoli


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Tumor cells with large nuclei, open chromatin,and prominent nucleoli


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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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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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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-cell lymphoma

A spectrum of small, intermediate, and large lymphoid cells,many with irregular nuclear contours.


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Anaplastic large cell lymphoma

mitosis


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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

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Blockxiv Neoplasms Lymphoid 2006