13 lymphoid tissue disorders

8/11/2019 13 Lymphoid Tissue Disorders

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13 Lymphoid Tissue Disorders

Lymphadenopathy

Locations of lymphoid tissue

1. Locations

a. Regional lymph nodesb. Tonsils and adenoids (Waldeyer's ring)c. Peyer's patches and appendixd. White pulp of the spleen

. ! cellsa. "erminal follicles in lymph nodesb. Peripheral areas of spleen #hite pulp

$. T cellsa. Paracortex (parafollicular) in lymph nodesb. Periarteriolar sheath in spleenc. Thymus

%. &istiocytesa. inuses in lymph nodes

b. in (Langerhan's cells)

c. Locations of lymphoid disorders

Lymphadenopathy


1. Locationsa. Regional lymph nodesb. Tonsils and adenoids (Waldeyer's ring)c. Peyer's patches and appendixd. White pulp of the spleen


$. T cellsa. Paracortex (parafollicular) in lymph nodesb. Periarteriolar sheath in spleenc. Thymus

%. &istiocytesa. inuses in lymph nodesb. in (Langerhan's cells)



1. Locationsa. Regional lymph nodesb. Tonsils and adenoids (Waldeyer's ring)


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c. Peyer's patches and appendixd. White pulp of the spleen


$. T cells

a. Paracortex (parafollicular) in lymph nodesb. Periarteriolar sheath in spleenc. Thymus

%. &istiocytesa. inuses in lymph nodesb. in (Langerhan's cells)


Lymphadenopathypage %$

page %%page %%

page %

1. *pidemiologya. +ge

i. Patients younger than $, years old -odal enlargement is usually benign disease (,/ of cases).

ii. Patients older than $, years old -odal enlargement is usually malignant disease (0,/ of cases).

b. ausesi. Reacti2e lymphadenitis

&yperplasia of ! cells3 T cells3 or histiocytes

ii. 4nfiltrati2e disease *xamples5metastasis (most common)3 malignant lymphoma

. linical findingsa. Painful nodes imply inflammation (e.g.3 infection)

i. Locali6ed 7rain sites of infection (e.g.3 tonsillitis)

8ost common sites are the anterior cer2ical nodes and inguinal nodes.

ii. "enerali6ed ystemic disease

*xamples5infectious mononucleosis3 systemic lupus erythematosus

(L*)b. Painless nodes imply a malignancy.

i. Lymph nodes are indurated and often fixed to surrounding tissue.

ii. Locali6ed -odes draining a primary cancer site (e.g.3 axillary nodes in breast

cancer) &odgin's lymphoma

iii. "enerali6ed 8etastasis in leuemia

9ollicular !5cell lymphoma

c. :ey nodal groups in2ol2ed in primary or metastatic canceri. ubmental


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8etastatic s;uamous cell carcinoma in the floor of the mouth

ii. er2ical 8etastatic head and nec tumors (e.g.3 larynx< thyroid3 nasopharynx)

&odgin's lymphoma

iii. Left5sided supracla2icular (=ircho#'s nodes) 8etastatic abdominal cancers (e.g.3 stomach< pancreas)

i2. Right5sided supracla2icular 8etastatic lung and esophageal cancers

&odgin's lymphoma

2. +xillary 8etastatic breast cancer

2i. &ilar 8etastatic lung cancer

2ii. 8ediastinal 8etastatic lung cancer

&odgin's lymphoma (particularly nodular sclerosing type)

T5cell lymphoblastic lymphoma

2iii. Para5aortic

8etastatic testicular cancer Testicles migrate to the scrotum from an abdominal location.

!uritt's lymphoma

ix. 4nguinal

8etastatic 2ul2ar and penis cancers

Types of reacti2e lymphadenitis

1. 9ollicular hyperplasia

a. !5cell antigenic responsei. "erminal follicles are sharply demarcated from the paracortex.ii. ells are in different stages of de2elopment.

b. *xamplesi. *arly stages of human immunodeficiency 2irus (&4=) infectionii. Rheumatoid arthritis and L*

. Paracortical hyperplasiaa. T5cell antigenic responseb. 7ermatopathic lymphadenitis

i. -odes draining chronic dermatitis (e.g.3 psoriasis)ii. -odes contain macrophages #ith phagocytosis of melanin pigment.

imulates metastatic malignant melanoma

c. Phenytoin3 2iral infections

$. 8ixed !5 and T5cell hyperplasia< cat5scratch diseasea. "ranulomatous microabscesses in regional lymph nodes (e.g.3 axillary3 cer2ical)b. 7ue to Bartonella henselae

%. inus histiocytosisa. !enign histiocytic response in lymph nodes draining a tumor.

b. 9a2orable sign in the axillary nodes in breast cancer.


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Non-Hodgkin's Lymphomas (NHL)

*pidemiologypage %

page %0

1. +ccount for

0,/ of adult lymphomaso >2er ,/ are of !5cell origin and deri2e from the germinal follicle.

. hildhood lymphomas

a. -&L accounts for 0,/ of cases.

?sually T5cell lymphoblastic lymphoma or !uritt's lymphoma

b. "enerally more aggressi2e than adult lymphomas

. Ris factors for -&La. =iruses

ii *pstein5!arr 2irus (*!=)

!uritt's lymphoma

7iffuse large !5cell lymphoma

iii &uman T5cell leuemia 2irus type 4

+dult T5cell lymphoma or leuemia

b. Helicobacter pylori

8alignant lymphoma deri2es from mucosa5associated lymphoid tissue in the

stomach.ii +utoimmune disease

ii @Agren's syndrome

Predisposes to sali2ary gland and gastrointestinal lymphomas

iii &ashimoto's thyroiditis

Predisposes to thyroid malignant lymphoma

b. 4mmunodeficiency syndromesii hromosome instability syndromes (e.g.3 !loom syndrome)

iii +c;uired immunodeficiency syndrome (+47)

c. 4mmunosuppressi2e therapy

Recipients of organ or bone marro# transplants

ii &igh5dose radiation

Treatment of &odgin's lymphoma

*pidemiologypage %

page %0

1. +ccount for 0,/ of adult lymphomaso >2er ,/ are of !5cell origin and deri2e from the germinal follicle.

. hildhood lymphomas


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a. -&L accounts for 0,/ of cases.

?sually T5cell lymphoblastic lymphoma or !uritt's lymphoma

b. "enerally more aggressi2e than adult lymphomas

. Ris factors for -&La. =iruses

ii *pstein5!arr 2irus (*!=)

!uritt's lymphoma


iii &uman T5cell leuemia 2irus type 4

+dult T5cell lymphoma or leuemia

b. Helicobacter pylori

8alignant lymphoma deri2es from mucosa5associated lymphoid tissue in the

stomach.ii +utoimmune disease

ii @Agren's syndrome

Predisposes to sali2ary gland and gastrointestinal lymphomas

iii &ashimoto's thyroiditis

Predisposes to thyroid malignant lymphoma

b. 4mmunodeficiency syndromes

ii hromosome instability syndromes (e.g.3 !loom syndrome)

iii +c;uired immunodeficiency syndrome (+47)

c. 4mmunosuppressi2e therapy

Recipients of organ or bone marro# transplants

ii &igh5dose radiation

Treatment of &odgin's lymphoma

Pathogenesis

1. 8utation produces a bloc at a specific stage in de2elopment of ! or T cells.

. *xample5accumulation of small clea2ed ! cells in follicular lymphoma

!5cell lymphomas

Table 13-1. ommon Types o! "-ell Non-Hodgkin's Lymphoma

Type #pidemiology Des$ription%&mmunophenotype lini$al indings

!uritt'slymphoma

$,/ of children #ithnon5&odgin'slymphoma (-&L)

*!= relationship #ith t(


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Leuemic phase common


,/ of adults #ith -&Lccurs in adolescents and young adults

$. linical findings

a. ?nifocal lytic lesions in bone (sull3 ribs3 and femur)

b. !one pain and pathologic fractures are common

+ast ell Disorders

>2er2ie#

1. Presentationa. Locali6ed5urticaria pigmentosum3 solitary mastocytomab. ystemic5systemic mastocytosis

. igns and symptoms relate to mast cell release of histamine

o Pruritus and s#elling of tissue

>2er2ie#

1. Presentationa. Locali6ed5urticaria pigmentosum3 solitary mastocytomab. ystemic5systemic mastocytosis

. igns and symptoms relate to mast cell release of histamine

o Pruritus and s#elling of tissue


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?rticaria pigmentosumpage ,

page 1

1. in lesionsa. 8ultiple o2al3 red5bro#n3 nonscaling macules (flat lesions) or papulesb. cratching results in erythematous s#elling of the lesions and pruritus.

alled 7arier's sign

c. 7ermatographism 7ermal edema occurs #hen apparently normal sin is stroed #ith a pointed

[email protected]. Lesions remain hyperpigmented #hen they regress.e. in biopsy

ii 8ast cells ha2e metachromatic granules.

iii "ranules stain positi2e #ith toluidine blue and "iemsa stain.

. Pruritus and flushing may be triggered by foods3 alcohol3 drugs (e.g.3 codeine)

,lasmas ell Dys$rasias

>2er2ie#

1. 8onoclonal !5cell disordersa. 4ncrease in a single immunoglobulinb. 4ncrease in the corresponding light chain

. 4mmunoglobulin is detected as a monoclonal spie (8 component) on serum proteinelectrophoresis.

$. linical significance of 8 componentsa. 8ost commonly due to an increase in 4g"

>ther plasma cell clones are suppressed.

b. !ence Jones (!J) protein

ii Refers to K or light chains excreted in urine

iii +ssociated #ith a plasma cell malignancy

b. 4mmunoelectrophoresis or immunofixation

Techni;ues that identify the immunoglobulin and light chain in serum and light

chains in urine

>2er2ie#

1. 8onoclonal !5cell disordersa. 4ncrease in a single immunoglobulinb. 4ncrease in the corresponding light chain

. 4mmunoglobulin is detected as a monoclonal spie (8 component) on serum proteinelectrophoresis.


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$. linical significance of 8 componentsa. 8ost commonly due to an increase in 4g"

>ther plasma cell clones are suppressed.

b. !ence Jones (!J) protein

ii Refers to K or light chains excreted in urine

iii +ssociated #ith a plasma cell malignancy

b. 4mmunoelectrophoresis or immunofixation

Techni;ues that identify the immunoglobulin and light chain in serum and light

chains in urine

8ultiple myelomapage page

page $

1. *pidemiologya. 8ore common in blac +mericans than in #hitesb. Rare under %, years of agec. 4ncreased ris #ith radiation exposured. 85spie occurs in ,/ to H,/ of cases

i. ?sually 4g" K follo#ed by 4g+ and pure light chain myelomaii. ?rine !J protein is positi2e in 0,/ to ,/ of cases.

. Pathologic findingsa. heets of malignant plasma cells are present in a bone marro# aspirateb. Plasma cells account for o2er 1,/ of cells in the aspirate.

$. eletal system findingsa. !one pain

i. 7ue to Bpunched outB lytic lesionsii. =ertebra is the most common site.iii. >ther sites include ribs3 sull3 pel2isi2. ommonly presents #ith pathologic fractures

b. &ypercalcemia (/ of cases)%. Renal findings

a. Renal failure ($,5,/ of cases)b. 8yeloma idney has different presentations

i. Proteinaceous tubular casts omposed of !J protein

!J protein damages tubular epithelium

4ntratubular multinucleated giant cell reaction

ii. -ephrocalcinosis 8etastatic calcification of tubular basement membranes in the collecting

ducts 8ost common cause of acute renal failure in multiple myeloma

iii. 8etastatic disease to interstitial tissuei2. Primary amyloidosis

Light chains are con2erted into amyloid

Produces a nephrotic syndrome

. &ematologic findingsa. -ormocytic anemia #ith rouleauxb. 4ncreased erythrocyte sedimentation rate


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c. Prolonged bleeding time

7ue to a defect in platelet aggregationii Radiculopathy from bone compression and 2ertebral fractures

ii Recurrent infections are the most common cause of death.

ii Prognosis

o 8edian sur2i2al is 0 months #ithout treatment.

>ther plasma cell dyscrasias

Table 13-3. dditional ,lasma ell Dys$rasias

Type Dis$ussion

8"? 8ost common monoclonal gammopathy

mall 4g" 8 spie in elderly patientsPlasma cells M $/ in bone marro#-o !J protein

olitary seletal plasmacytoma !one si tesC 2ertebra3 ribs3 pel2islight increase in monoclonal protein-o plasmablasts in bone marro#-o !J proteinG/ de2elop multiple myeloma

*xtramedullary plasmacytoma itesC upper respiratory tract (nasopharynx3 sinuses3 larynx)light increase in monoclonal protein

+bsence of malignant plasma cells in the bone marro#+bsence of !J proteinmall percentage may de2elop multiple myeloma

Lymphoplasmacytic lymphoma(WaldenstrAm's macroglobulinemia)

-eoplastic lymphoplasmacytoid ! cells*lderly male5dominant disease8 spie #ith 4g8

!J protein is present"enerali6ed lymphadenopathy (not present in myeloma)

+nemia and bone marro# (no lytic lesions lie myeloma)3 li2er3 and spleenin2ol2ement&yper2iscosity syndrome due to increased 4g8C retinal hemorrhages3stroes3 platelet aggregation defects8edian sur2i2al years

&ea2y5chain diseases 8 protein hea2y chain withoutlight chains+bsence of !J proteinN5&ea2y5chain diseaseC neoplastic infiltration of the @e@unum3 leading tomalabsorption or locali6ed upper respiratory tract diseaseO5&ea2y5chain diseaseC presents as a lymphoma5&ea2y5chain diseaseC often associated #ith chronic lymphocytic leuemiaor lymphoma

!J3 !ence Jones< 8"?3 monoclonal gammopathy of undetermined significance.

pleen Disorders

linical anatomy and physiology


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1. Red pulpo ontains the cords of !illroth #ith fixed macrophages and sinusoids

. White pulpo ontains ! and T cells

$. 4mportant functions of the spleen

a. !lood filtration< macrophages remo2eCi. &ematopoietic elements (e.g.3 old red blood cells)ii. 4ntraerythrocytic parasites (e.g.3 malaria)iii. *ncapsulated bacteria (e.g.3 Streptococcus pneumoniae)

b. +ntigen trapping and processing in macrophages

c. Reser2oir for one third of the peripheral blood platelet pool

d. ite for extramedullary hematopoiesis

linical anatomy and physiology1. Red pulp

o ontains the cords of !illroth #ith fixed macrophages and sinusoids

. White pulpo ontains ! and T cells

$. 4mportant functions of the spleen

a. !lood filtration< macrophages remo2eC

i. &ematopoietic elements (e.g.3 old red blood cells)ii. 4ntraerythrocytic parasites (e.g.3 malaria)iii. *ncapsulated bacteria (e.g.3 Streptococcus pneumoniae)

b. +ntigen trapping and processing in macrophages

c. Reser2oir for one third of the peripheral blood platelet pool

d. ite for extramedullary hematopoiesis

plenomegalypage

1. auses of splenomegalya. Reacti2e hyperplasia of #hite pulp

i. +utoimmune disorders *xamples5L*3 immune thrombocytopenia and anemia

ii. 4nfectious mononucleosis 7ue to antigenic stimulation of T cells

ii i. Parasitic infections 8alaria is the most common cause of splenomegaly in de2eloping

countries.b. 4nfiltrati2e diseases in #hite pulp

*xamples5metastatic -&L3 primary amyloidosis


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b. 4nfiltrati2e diseases of macrophages in red pulp< lysosomal storage diseasesC

i. "aucher disease 7eficiency of glucocerebrosidase

Lysosomal accumulation of glucocerebrosides

8acrophages ha2e a fibrillary appearance

ii. -iemann5Pic disease 7eficiency of sphingomyelinase

Lysosomal accumulation of sphingomyelin

8acrophages ha2e soap bubble appearance

b. 4nfiltrati2e diseases of the red and #hite pulp

*xamples5acute and chronic myelogenous and lymphoid leuemiasb. Phagocytic hyperplasia in the red pulp

*xample5extra2ascular hemolytic anemia in hereditary spherocytosisc. *xtramedullary hematopoiesis in the sinusoids

*xample5myelofibrosis and myeloid metaplasiad. =ascular congestion in the sinusoids

*xample5portal hypertension in cirrhosisii linical findings

a. Left upper ;uadrant pain 8ay be associated #ith splenic infarctions causing friction rubs and a left5sided

pleural effusion

b. &ypersplenism (see belo#)

Portal hypertension in cirrhosis

1. "ross findingso pleen is often surfaced by a thicened (Bsugar5coatedB) capsule from perisplenitis.

. 8icroscopic findings

o alcium and iron concretions called "amna5"andy bodies are present in collagen.

&ypersplenismpage

page 0

1. 7efinition

a. *xaggeration of normal splenic functionb. Red blood cells (R!s)3 #hite blood cells (W!s)3 and platelets3 either singly or incombination3 are se;uestered and destroyed.

. Portal hypertension associated #ith cirrhosis is the most common cause.$. linical findings

a. plenomegalyb. Peripheral blood cytopenias

+nemia3 thrombocytopenia3 neutropenia alone or in combination

c. ompensatory reacti2e bone marro# hyperplasia


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+ttempt by the marro# to replace lost cells

d. orrection of cytopenias #ith splenectomy

plenic dysfunction and splenectomy

1. plenic dysfunctiona. Presence of &o#ell5Jolly bodies (nuclear remnants) in peripheral blood R!sb. Predisposition to infections

i. 4nfections include septicemia3 peritonitisii. 8echanism

oncentration of 4g8 drops leading to a decrease in complement system

acti2ation Reduction in $b3 an opsoni6ing agent3 leads to infection.

iii. Pathogens commonly in2ol2ed Streptococcus pneumoniae

>ther pathogens include Hemophilus influenzaeand Salmonella

paratyphi. 4mmuni6ation helps pre2ent infectious complications.

. plenectomya. 4ncreases the ris for infectionsb. &ematologic findings

i. -ucleated R!sii. &o#ell5Jolly bodiesiii. Target cells (excess membrane cannot be remo2ed)i2. Thrombocytosis

Platelets normally se;uestered in the spleen are no# circulating.

13 lymphoid tissue disorders

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