Lymphoid neoplasms lymphoid neoplasms Rasha M. Abd-Rabh lecturer of pathology faculty of medicine...

lymphoid neoplasmslymphoid neoplasms

Rasha M. Abd-Rabhlecturer of pathology

faculty of medicine –Benha university

HistologyHistology

Bean –shaped structureBean –shaped structure CortexCortex paracortexparacortex MedullaMedulla

Lymph nodes are usually beanLymph nodes are usually bean--shaped, shaped, with an indented region known as the with an indented region known as the hilumhilum. .

They are covered by a collagenous They are covered by a collagenous capsule that extends into the body of the capsule that extends into the body of the node as trabeculaenode as trabeculae. . The body of the The body of the lymph node is divided into an outer lymph node is divided into an outer cortex and an inner medullacortex and an inner medulla. .

The cortex contains a high concentration The cortex contains a high concentration of lymphocytes while the inner medulla of lymphocytes while the inner medulla is less cellularis less cellular..

In the cortex, BIn the cortex, B--lymphocytes are lymphocytes are localized in lymphoid follicles just localized in lymphoid follicles just beneath the capsulebeneath the capsule. . In absence of an In absence of an active immune response, these follicles active immune response, these follicles are known as are known as primary lymphoid follicles. .

When an immune response is underway, When an immune response is underway, focal points of intense Bfocal points of intense B--cell proliferation cell proliferation known as germinal centers can be found known as germinal centers can be found in some folliclesin some follicles. . These follicles then These follicles then become known as become known as secondary lymphoid secondary lymphoid folliclesfollicles. .

The TThe T--lymphocytes are located deeper lymphocytes are located deeper within the cortex and are diffusely within the cortex and are diffusely distributed in the paracortical areadistributed in the paracortical area..

In the medulla, parts of the cortical cell In the medulla, parts of the cortical cell mass extends as the medullary cordsmass extends as the medullary cords. . This region contains macrophages and This region contains macrophages and antibodyantibody--secreting plasma cellssecreting plasma cells..

DefinitionDefinition include a diverse group of tumors of include a diverse group of tumors of

B-cell, B-cell, T-cell, and NK-cell origin. T-cell, and NK-cell origin.

In many instances the phenotype of In many instances the phenotype of the the

neoplastic cell closely resembles that neoplastic cell closely resembles that of of

a particular stage of normal a particular stage of normal lymphocyte lymphocyte

differentiation, a feature that is used differentiation, a feature that is used in the in the

diagnosis and classification of these diagnosis and classification of these disorders.disorders.

The vast majority (85% to 90%) of The vast majority (85% to 90%) of lymphoid neoplasms are of B-cell lymphoid neoplasms are of B-cell origin, with most of the origin, with most of the remainder being T-cell tumors; remainder being T-cell tumors; only rarely are tumors of NK cell only rarely are tumors of NK cell origin encountered.origin encountered.

Origin of lymphoid Origin of lymphoid neoplasmsneoplasms

WHO ClassificationsWHO Classifications The WHO 2008 classifications uses morphologic, The WHO 2008 classifications uses morphologic, immunophenotypic, genotypic, and clinical features to immunophenotypic, genotypic, and clinical features to sort the lymphoid neoplasms into five broad sort the lymphoid neoplasms into five broad categories,which are separated according to the cell of categories,which are separated according to the cell of

originorigin  :  :  11..        Precursor B-cell neoplasms (neoplasms of immature B Precursor B-cell neoplasms (neoplasms of immature B

cells)cells)    22..        Peripheral B-cell neoplasms (neoplasms of mature B Peripheral B-cell neoplasms (neoplasms of mature B

cells)cells)     33..        Precursor T-cell neoplasms (neoplasms of immature T Precursor T-cell neoplasms (neoplasms of immature T

cells)cells)    44..        Peripheral T-cell and NK-cell neoplasms (neoplasms of Peripheral T-cell and NK-cell neoplasms (neoplasms of

mature T cells and NK cells)mature T cells and NK cells)    55..        Hodgkin lymphoma (neoplasms of Reed-Sternberg Hodgkin lymphoma (neoplasms of Reed-Sternberg

cells and variants)cells and variants)

PathogenesisPathogenesis Chromosomal translocations and Chromosomal translocations and

other acquired mutations.other acquired mutations. Viruses.Viruses. Chronic Immune Stimulation.Chronic Immune Stimulation. Iatrogenic Factors.Iatrogenic Factors.

To diagnose

Clinical data Gross examination

Microscopic pictureImmunophenotyping

& cytogenetic

Clinical data: Age , Sex , Site and Clinical data: Age , Sex , Site and pattern of involvement , Blood picture.pattern of involvement , Blood picture.

Gross examination: size of lymph node, Gross examination: size of lymph node, homogenous, nodular . homogenous, nodular .

Microscpoic examination:Microscpoic examination:

-L.N architecture.-L.N architecture.

-Pattern of growth; diffuse, nodular, sinusal.-Pattern of growth; diffuse, nodular, sinusal.

-monomorphic or pleomorphic cellular -monomorphic or pleomorphic cellular infiltrate.infiltrate.

-Cellular feature-Cellular feature

-cell size-cell size

-cytoplasm-cytoplasm

- Nucleus &chromatin- Nucleus &chromatin

-Nucleoli-Nucleoli

- mitosis- mitosis

- characteristic feature- characteristic feature

Immunophenotping :Immunophenotping :

-Monoclonal or polyconal.-Monoclonal or polyconal.

Clonal rearrangement of IG gene → B-Clonal rearrangement of IG gene → B-cell lymphomacell lymphoma

Clonal rearrangement of T –cell Clonal rearrangement of T –cell receptors→T –cell lymphomareceptors→T –cell lymphoma

PRIMARILY TPRIMARILY T--CELL ASSOCIATEDCELL ASSOCIATED CD1 :Thymocytes and Langerhans cellsCD1 :Thymocytes and Langerhans cells CD3 :Thymocytes, mature T cellsCD3 :Thymocytes, mature T cells CD4 :Helper T cells, subset of thymocytesCD4 :Helper T cells, subset of thymocytes CD5 :T cells and a small subset of B cellsCD5 :T cells and a small subset of B cells CD8 :Cytotoxic T cells, subset of thymocytes, and CD8 :Cytotoxic T cells, subset of thymocytes, and

some NK cellssome NK cellsPRIMARILY BPRIMARILY B--CELL ASSOCIATEDCELL ASSOCIATED CD10: PreCD10: Pre--B cells and germinalB cells and germinal--center B cellscenter B cells CD19: PreCD19: Pre--B cells and mature B cells but not B cells and mature B cells but not

plasma cellsplasma cells CD20 :PreCD20 :Pre--B cells after CD19 and mature B cells B cells after CD19 and mature B cells

but not plasma cellsbut not plasma cells CD21:EBV receptor; mature B cells and follicular CD21:EBV receptor; mature B cells and follicular

dendritic cellsdendritic cells CD23:Activated mature B cellsCD23:Activated mature B cells CD79aMarrow preCD79aMarrow pre--B cells and mature B cellsB cells and mature B cells

11--Acute Lymphoblastic Acute Lymphoblastic LeukemiaLeukemia//LymphomaLymphoma

((ALLsALLs) ) are neoplasms composed of are neoplasms composed of immature B immature B ((prepre--BB) ) or T or T ((prepre--T) cells T) cells which are referred to as which are referred to as lymphoblastslymphoblasts

children and adolescents, but it also children and adolescents, but it also occurs in adults (About 50% of the occurs in adults (About 50% of the cases present as a mediastinal cases present as a mediastinal mass)mass)..

MorphologyMorphology Diffuse &paracortical region. Diffuse &paracortical region. Scant basophilic cytoplasm.Scant basophilic cytoplasm. nuclei somewhat larger than those of small nuclei somewhat larger than those of small

lymphocytes The nuclear chromatin is delicate lymphocytes The nuclear chromatin is delicate and finely stippled. In many cases the nuclear and finely stippled. In many cases the nuclear membrane is deeply subdivided, imparting a membrane is deeply subdivided, imparting a convoluted appearanceconvoluted appearance. .

nucleoli are either absent or inconspicuousnucleoli are either absent or inconspicuous. . the mitotic rate is highthe mitotic rate is high. . As with other rapidly growing lymphoid tumors, As with other rapidly growing lymphoid tumors,

interspersed macrophages ingesting apoptotic interspersed macrophages ingesting apoptotic tumor cells may impart a “starry sky” tumor cells may impart a “starry sky” appearanceappearance

Differential diagnosisDifferential diagnosis

1- Burkitt lymphoma1- Burkitt lymphoma

2- blastoid variant of mantle cell 2- blastoid variant of mantle cell lymphoma lymphoma

ImmunophenotypingImmunophenotyping

All express TDT ( am marker of All express TDT ( am marker of thymocytes)thymocytes)

80-85%80-85% show T –cell markers (CD1, show T –cell markers (CD1, CD2, CD7)CD2, CD7)..

15-20%15-20% show B-cell markers (CD19, show B-cell markers (CD19, CD20,)CD20,)..

CD99+veCD99+ve

CD34 +veCD34 +ve

22--Small lymphocytic Small lymphocytic lymphomalymphoma

Low grade –B cell lymphomaLow grade –B cell lymphoma..

Affects middle aged and elderly Affects middle aged and elderly individualsindividuals..

It is the most common of the B –cell It is the most common of the B –cell neoplasms to involve the spleenneoplasms to involve the spleen . .

- - Diffuse effacement of the nodal architecureDiffuse effacement of the nodal architecure . .

- - monotonous populationmonotonous population. . -- - small round mature –appearing lymphocytessmall round mature –appearing lymphocytes

- - clumped chromatinclumped chromatin..

- - inconspicuousinconspicuous nucleoli nucleoli..

- - barely visible cytoplasmbarely visible cytoplasm . .

- - SScantycanty mitotic activity mitotic activity. .

as well as scatteredas well as scattered

pro-lymphocytes/paraimmunoblasts(large cell with pro-lymphocytes/paraimmunoblasts(large cell with vesicular nuclei and distinct nucleoli, singly or in vesicular nuclei and distinct nucleoli, singly or in small aggregates that simulate germinal centerssmall aggregates that simulate germinal centers.. These formations (known as proliferative These formations (known as proliferative centers, growth centers, or pseudofollicles) have centers, growth centers, or pseudofollicles) have an increased number of Ki-67-positivean increased number of Ki-67-positive

Diffuse Diffuse Small sizedSmall sized Scanty cytoplasmScanty cytoplasm Clumped chromatinClumped chromatin Inconspicious Inconspicious

nucleolinucleoli Low mitosisLow mitosis Scattered Scattered

prolymphocytesprolymphocytes

ImmunohistochemistryImmunohistochemistry

-Pan –B- cell markers(CD20,CD19, -Pan –B- cell markers(CD20,CD19, Surface Ig) Surface Ig)

-CD23, CD5 +ve.-CD23, CD5 +ve.

Differential diagnosisDifferential diagnosis

1- mantle zone lymphoma.1- mantle zone lymphoma.

33--Follicular lymphomaFollicular lymphoma

It is a low grade neoplasm It is a low grade neoplasm composed of follicle center composed of follicle center (germinal center) B cells (typically (germinal center) B cells (typically both centrocytes and centroblasts)both centrocytes and centroblasts)The disease occurs with a median age of The disease occurs with a median age of

60 years and with a slight female 60 years and with a slight female predominance. Pediatric cases are rare. predominance. Pediatric cases are rare.

MicroscopicallyMicroscopically ::a predominantly nodular or nodular and a predominantly nodular or nodular and diffuse growth patterndiffuse growth pattern . .

Two principal cell types are present in Two principal cell types are present in varying proportionsvarying proportions : :

((11 ) )small cells with irregular or cleaved small cells with irregular or cleaved nuclear contours and scant cytoplasm, nuclear contours and scant cytoplasm, referred to as centrocytes (small cleaved referred to as centrocytes (small cleaved cells)cells) ; ;andand

((22 ) )larger cells with open nuclear chromatin, larger cells with open nuclear chromatin, several nucleoli, and modest amounts of several nucleoli, and modest amounts of cytoplasm, referred to as centroblastscytoplasm, referred to as centroblasts

33 ) )Absent or low mitosisAbsent or low mitosis . .

Depending on the relative proportion of Depending on the relative proportion of small and large cells, follicular small and large cells, follicular lymphomas are subdivided into three lymphomas are subdivided into three categories, respectively designated in the categories, respectively designated in the WHO classification as followsWHO classification as follows ::  

Grade 1: with 0 – 5 centroblasts Grade 1: with 0 – 5 centroblasts ((large large nucleolated cellsnucleolated cells) ) per highper high--power fieldpower field..Grade 2: with 6–15 centroblasts per highGrade 2: with 6–15 centroblasts per high--power fieldpower field.      .     

Grade 3 : with more than 15 centroblasts Grade 3 : with more than 15 centroblasts per highper high--power fieldpower field. . G3a&G3bG3a&G3b

ImmunohistochemistryImmunohistochemistry::

expressing CD19, CD20, and, surface expressing CD19, CD20, and, surface Ig.Ig.

Germinal center B- cell markers: Germinal center B- cell markers: Cd10&Bcl-6 Cd10&Bcl-6

BCL2 is expressed in more than 90% of BCL2 is expressed in more than 90% of cases, in distinction to normal follicular cases, in distinction to normal follicular center B cells, which are BCL2-negative center B cells, which are BCL2-negative

CytogeneticCytogenetic: : The hallmark of follicular lymphoma The hallmark of follicular lymphoma

is a (14;18) translocation that is a (14;18) translocation that juxtaposes the IgH locus on juxtaposes the IgH locus on chromosome 14 and the BCL2 locus chromosome 14 and the BCL2 locus on chromosomeon chromosome 18 18. leads to . leads to overexpression of BCL2 . overexpression of BCL2 .

BCL2 antagonizes apoptosis and BCL2 antagonizes apoptosis and promotes the survival of follicular promotes the survival of follicular lymphoma cells. lymphoma cells.

NodularNodular Closely packed Closely packed

folliclesfollicles Two populations of Two populations of

cellscells Absent mitosisAbsent mitosis

Differential diagnosisDifferential diagnosis

1- reactive follicular hyperplasia1- reactive follicular hyperplasia

44 - -Mantle cell lymphomaMantle cell lymphoma

Mantle cell lymphoma is a low-grade B-Mantle cell lymphoma is a low-grade B-cell neoplasmcell neoplasm . .

Also known as intermediate lymphocytic, Also known as intermediate lymphocytic, mantle zone, centrocytic, and diffuse mantle zone, centrocytic, and diffuse small cleaved cell lymphomasmall cleaved cell lymphoma..

it usually occurs in middle-aged and it usually occurs in middle-aged and elderly individualselderly individuals..

Commonly affects maleCommonly affects male..

MicroscopicallyMicroscopically

1Diffuse effacement by monomorphic small 1Diffuse effacement by monomorphic small lymphocyteslymphocytes

22 - -irregular nuclear contoursirregular nuclear contours

33 - -clumped chromatinclumped chromatin

44 - -inconspicuous nucleoliinconspicuous nucleoli

55 - -minimal cytoplasmminimal cytoplasm

66--no residual germinal centers formationno residual germinal centers formation

77--hyalinized blood vessels & scattered hyalinized blood vessels & scattered epithloid cellsepithloid cells

ImmunophenotypingImmunophenotyping Pan B cell markersPan B cell markers Over expression of cyclin D1Over expression of cyclin D1 +ve for CD5+ve for CD5 _ve for CD23, CD10 and BCL-2._ve for CD23, CD10 and BCL-2.

55 - -marginal zone marginal zone lymphomalymphoma

An uncommon and indolent B-cell An uncommon and indolent B-cell lymphoma.lymphoma.

Affect eldelry patients & slight female Affect eldelry patients & slight female predominance.predominance.

MicroscopicallyMicroscopicallythe nodules are formed of medium -the nodules are formed of medium -sized lymphocytes with irregular sized lymphocytes with irregular nuclear contours, moderate nuclear contours, moderate abundant clear cytoplasm, and abundant clear cytoplasm, and condensed nuclear chromatincondensed nuclear chromatin..

The pattern of involvement is The pattern of involvement is predominantly sinusal and predominantly sinusal and interfollicularinterfollicular..

ImmunophenotypingImmunophenotyping

Pan B-cell markers(CD19, CD20)Pan B-cell markers(CD19, CD20) _ve for CD5, CD23 and cyclin _ve for CD5, CD23 and cyclin

D1,CD10D1,CD10 No Bcl-2 or Bcl-6 genes No Bcl-2 or Bcl-6 genes

rearrangement.rearrangement.

ImmunoImmunoHistochemicHistochemical markersal markers

11--Mantle Mantle cell cell lymphomlymphomaa

22--Follicular Follicular lymphomalymphoma

33--Marginal Marginal zone zone lymphomalymphoma

44 - -small small lymphocytilymphocytic c lymphomalymphoma

Pan-B-cell Pan-B-cell markersmarkers

CD10CD10

CD5CD5

CD23CD23

Cyclin D1Cyclin D1

Bcl-2Bcl-2

++veve

++veve

--veve

++veve

++veve

++veve

--veve

--veve

--veve

++veve

++veve

--veve

--veve

--veve

--veve

++veve

++veve

++veve

--veve

--veve

66--Burkitt lymphomaBurkitt lymphoma

Is a highly aggressive B-cell neoplasm that Is a highly aggressive B-cell neoplasm that

occurs in three major clinical forms: occurs in three major clinical forms:

endemic, sporadic, and immunodeficiency endemic, sporadic, and immunodeficiency

associated. associated.

All three types present primarily All three types present primarily

in extranodal sites, including the GI tract. in extranodal sites, including the GI tract.

There are three variants of BL:There are three variants of BL: the endemic form occurs in Africa, is the endemic form occurs in Africa, is

caused by infection with the Epstein caused by infection with the Epstein Barr virus (EBV), and affects children Barr virus (EBV), and affects children between 4 and 7 years of age.between 4 and 7 years of age.

the sporadic form occurs throughout the sporadic form occurs throughout the word in children and young adults.the word in children and young adults.

immunodeficiency-associated form is immunodeficiency-associated form is

related to HIV infection. related to HIV infection.

Nodal architecture is effaced with a Nodal architecture is effaced with a diffuse or nodular infiltratediffuse or nodular infiltrate

The cells are medium sized and uniform.The cells are medium sized and uniform. Large vesicular nuclei. Large vesicular nuclei. scant cytoplasm, clumpy chromatin, scant cytoplasm, clumpy chromatin, multiple small nucleoli. multiple small nucleoli. numerous mitotic figures.numerous mitotic figures. Many apoptotic bodies and tingible body Many apoptotic bodies and tingible body

macrophages with phagocytosed nuclear macrophages with phagocytosed nuclear debris create a starry-sky pattern.debris create a starry-sky pattern.

Microscopically

Diffuse or nodularDiffuse or nodular Medium –sizedMedium –sized Clumped Clumped

chromatinchromatin Vesicular nulceiVesicular nulcei Multiple prominent Multiple prominent

nucleolinucleoli Increased mitosisIncreased mitosis Starry sky Starry sky

appearanceappearance

ImmunohistochemistryImmunohistochemistry:: B-cell phenotype (positive for CD10, B-cell phenotype (positive for CD10,

CD19, CD20, PAX5, and bcl-6); CD19, CD20, PAX5, and bcl-6); expresses sIg.expresses sIg.

High Ki67High Ki67 Negative for CD23, Cd30, TdTNegative for CD23, Cd30, TdT

CytogeneticCytogenetic: :

--all three forms are linked with Myc all three forms are linked with Myc translocation (t8,14) in about 90% of translocation (t8,14) in about 90% of casescases..

77--Diffuse large B cell Diffuse large B cell lymphomalymphoma

• •Diffuse large B-cell lymphoma Diffuse large B-cell lymphoma (DLBCL) is the most common form of (DLBCL) is the most common form of NHLNHL

Predominantly affects females; peak Predominantly affects females; peak incidence between 20 and 40 years incidence between 20 and 40 years of ageof age

MicroscopicallyMicroscopicallyDiffuse growth pattern composed of large Diffuse growth pattern composed of large atypicalatypical

lymphoid cells with reniform or multilobatedlymphoid cells with reniform or multilobated

nuclei, vesicular chromatin, and distinct nuclei, vesicular chromatin, and distinct nucleolinucleoliLarge amounts of pale or clear cytoplasmLarge amounts of pale or clear cytoplasm

Diffuse Diffuse Large –sizedLarge –sized Vesicular nucleiVesicular nuclei Prominent nucleoliProminent nucleoli

ImmunohistochemistryImmunohistochemistry::

These mature B-cell tumors express These mature B-cell tumors express CD19 and CD20 and show variable CD19 and CD20 and show variable expression of germinal center B-cell expression of germinal center B-cell markers such as CD10 and BCL6. markers such as CD10 and BCL6. Most have surface Ig Most have surface Ig