YL6: 04.

12a Diseases of the Spleen, Thymus, and White Blood Cells

10/08/2019 Basic Pathologies 2
07:30-11:30 Jan Dy-Ledesma, MD, DPSP
PATHOLOGY

TABLE OF CONTENTS • Sequence of events:

LEARNING OBJECTIVES ..........................................................................1
I. SPLEEN ....................................................................................................1
A. FUNCTIONS OF THE SPLEEN....................................................1
B. SPLENOMEGALY .........................................................................2
C. OTHER ASSOCIATED CONDITIONS .........................................2
II. THYMUS ..................................................................................................3
A. ANATOMY......................................................................................3
B. THYMIC PATHOLOGIES ..............................................................3
III. DISORDERS OF WHITE BLOOD CELLS ............................................4
A. CATEGORIES OF WBC DISORDERS ........................................4
B. NEUTROPENIA/AGRANULOCYTOSIS ......................................4
C. LEUKOCYTOSIS ...........................................................................5
D. LYMPHADENITIS ..........................................................................5
QUICK REVIEW ..........................................................................................6
SUMMARY OF TERMS .....................................................................6
REVIEW QUESTIONS .......................................................................7
REFERENCES ............................................................................................7
REQUIRED .........................................................................................7
APPENDIX ...................................................................................................7
LEARNING OBJECTIVES
• Enumerate the different conditions associated with the spleen
• Discuss common pathologies seen in the thymus
• Discuss benign diseases/conditions associated with white blood
cells (WBCs) and lymph nodes
• Differentiate the various neoplastic conditions that arise in white
blood cells and lymph nodes: (i.e. Leukemia and Lymphoma)
NOTE
• All information in book bullets came from the 9th edition of
Robbins, Chapter 13: Diseases of WBC, Lymph Nodes, Spleen
and Thymus
I. SPLEEN
• Located in the left side of the body
• Serves as a filter for the blood and particulate matter
→ Acts like a sieve that removes dead blood cells or blood borne
agents
• Site of immune responses
• Morphology of a normal spleen
→ Size of a fist; weighs 100-150g in adults
→ Enclosed within a thin, glistening, slate- gray connective
tissue capsule
→ Cut surface reveals extensive red pulp dotted with gray
specks, which are white pulp follicles
1. From the main artery of the spleen, you have a lot of CD4 T-
lymphocytes, macrophages, and dendritic cells.
2. The Antigen Presenting Cells (APCs) would recognize the
abnormal RBC
3. The antigens in some of the microbes/parasites would be
presented to the T-cells found at the periphery and activate
the germinal centers (white pulp)
4. In germinal centers, you have the B-cells which in turn,
produce the antibodies
• Implications: patients who have gone through a splenectomy or
have sickle cell anemia have compromised immune systems
→ Increased susceptibility to sepsis in auto-infarction or
splenectomy, due to inadequate blood supply
→ Patients usually have a high incidence of infection of bacterial
with a polysaccharide capsule (e.g. Klebsiella, Streptococcus
pneumoniae, etc)
Periarteriolar/Periarterial lymphatic sheaths
 Dendritic cells in the periarterial lymphatic sheath trap antigens and
present them to T lymphocytes
• Eccentric collar of T lymphocytes surrounding an artery
• At intervals, this sheath expands to form lymphoid nodules,
composed mainly of B lymphocytes
→ These B cells, in response to antigenic stimulation, are
capable of developing into germinal centers identical to those
seen in lymph nodes
Extramedullary Hematopoiesis
• The spleen produces RBCs and other cellular elements during:
→ Fetal development, the spleen may be a minor site of
hematopoiesis, but this normally disappears at birth
→ Certain disease states, wherein the bone marrow is affected
(e.g. infiltrative tumor or tuberculosis)
▪ When this happens, normal hematopoietic stem cells do
not have a place where they can develop and mature
o In effect, they go to the spleen or liver so they can
be recruited for compensatory extramedullary
hematopoiesis
▪ Severe chronic anemia (thalassemia)
▪ Myeloproliferative disorders (chronic myelogenous
leukemia and primary myelofibrosis)

A. FUNCTIONS OF THE SPLEEN

Phagocytosis of Blood Cells and Particulate Matter
• Some RBCs contain certain particles that need to be removed by
the macrophages in the spleen
→ As it passes through the sinusoids of the spleen, the
macrophages recognize and remove these particles
→ Old RBCs go there to die while macrophages remove them
from the peripheral blood
→ If the RBC contains unwanted parasites (e.g. malaria), the
macrophages recognize and remove these Figure 1. Normal splenic structures
▪ It can also remove WBCs, platelets, and bacteria
• Splenic macrophages: responsible for “pitting” of RBC (process Sequestration of Formed Blood Elements
by which inclusions are excised) • Sequestration: the harboring of the spleen of RBCs and WBCs
→ Heinz bodies: inclusions of denatured hemoglobin from the peripheral blood.
→ Howell-Jolly bodies: nuclear remnants (mostly RNA) → This happens during diseases states and myelodysplastic
syndromes
Antibody Production • Normally, the spleen contains 30-40 mL of RBCs but it increases
• The spleen is the major organ for the mononuclear lymphatic with splenomegaly
system
→ 90% of platelets can be stored in the spleen → produces
→ Like a huge lymph node that filters blood and other particulate spurious thrombocytopenia
matters and an important site for antibody production → In an enlarged spleen, WBCs can also be stored → induces
→ Recall: spleen is made up of red and white pulps which are leukopenia
made up of B cells and T cells

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 B. SPLENOMEGALY Splenic Infarcts
• Spleen enlargement causes a dragging sensation in the left • The spleen, along with kidneys and brain, ranks as one of the most
upper quadrant and discomfort after eating common locations where emboli form
• Can be caused by hypersplenism → Emboli mostly arise from the heart
→ Characterized by anemia, thrombocytopenia, and ▪ It cannot receive thrombus from brain because of the
leukopenia, or a combination of the three called circulation
pancytopenia (depression of all hematopoietic stem cells) ▪ Prone to rupture
▪ Possibly due to sequestration of formed elements inside → If the embolus is infective or secondary to endocarditis,
the spleen and enhanced phagocytosis by macrophages suppuration may be evident
• Can also be caused by:
→ Infections
→ Immunologic/inflammatory conditions
→ Tumors from the spleen (lymphomas)
→ Lymphohematogenous disorders
→ Storage diseases (Gaucher’s disease)
• Can be either acute or chronic in form

Acute
• Acute congestion of the spleen is non-specific and happens over
the course of a few days
→ Recall: Congestion: accumulation or pooling of blood
• Characteristics: Figure 4. Splenic infarcts
→ Pooling of the blood leading to the enlargement of spleen –
400- 500g (3-4x normal weight) Other Diseases
→ Grossly, the spleen looks very beefy, moist, red and heavier • Lymphohematogenous Disorders
because of congestion → E.g. Leukemias and lymphomas
▪ The white pulp is lost • Storage Disease
→ Thin splenic capsule has several important implications: → E.g. Mucopolysaccharidoses, Niemann-Pick disease
▪ Spleen may rupture or burst due to fast growth and thin
size that may cause a pooling of blood in the C. OTHER ASSOCIATED CONDITIONS
retroperitoneum Rupture
o This is considered a medical emergency • Usually secondary to blunt trauma (e.g. during vehicular
• Happens because of: accidents)
→ Infections such as malaria and infectious mononucleosis • Most common predisposing conditions are infectious
→ Immunologic/inflammatory conditions mononucleosis, malaria, typhoid fever, and lymphoid
neoplasms
→ May cause the spleen to enlarge rapidly, producing a thin,
tense capsule that is susceptible to rupture
• This event often precipitates intraperitoneal hemorrhage, which
must be treated by prompt splenectomy to prevent death from
blood loss

Congenital Anomalies
• Hypoplasia
→ Absence of the spleen is very rare, hypoplasia is a more
Figure 2. Acute congestion
common finding
→ If this is present, look for other congenital abnormalities
Chronic
• Spleniculi (accessory spleens)
• Chronic congestion happens over a long period of time
→ There is generally no pathology, but overlooking an accessory
• Characteristics:
spleen during splenectomy is bad because you want all the
→ Enlargement is much bigger at 1000-2000 g (1000-5000 g
spleen to be removed
based on Kumar et al., 2015) ▪ If you don’t take out the problematic spleen, it would
→ Mainly characterized by fibrosis allowing growth to big size result in the hemolysis and sequestration of RBCs
▪ Does not rupture because it is made from fibrous ▪ Accessory spleen can also enlarge
deposits
→ This is only important in splenectomy with diseases like
▪ Sign of chronic, long-standing disease
leukemias
▪ There is no fibrosis in acute disease
▪ The disease will not be cured if accessory spleen is still
▪ The sluggish flow of blood triggers collagen deposition present
along the venous channels of the spleen causing the
→ Only around 10% of autopsy cases
fibrous appearance and congestion
• Secondary to chronic venous pressure
→ High venous pressure due to portal hypertension or liver
cirrhosis
▪ Something is blocking the blood flow
▪ The high pressure induces collagen deposition in the
blood vessels or sinusoids of the spleen
o The organ can be large because the collagen
depositions are very slow

Figure 5. Spleniculi

Neoplasm
 Neoplastic involvement of the spleen is rare except in myeloid and
lymphoid tumors, which cause splenomegaly
• Benign tumors may arise, with lymphangiomas and hemangiomas
being the most common
• May also involve malignant tumors such as lymphoma and
Figure 3. Chronic congestive splenomegaly leukemia

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Table 1. Disorders Associated with Splenomegaly (Kumar et al., 2015)
Infections
Nonspecific splenitis of various The nonspecific reaction in
blood-borne infections these infections is cause by both
(infectious endocarditis) the microbiologic agents
Infectious mononucleosis themselves and by the
Tuberculosis cytokines that are released as
Typhoid fever part of the immune response
Brucellosis
Cytomegalovirus
Syphilis
Malaria
Histoplasmosis
Figure 6. Thymus
Toxoplasmosis
Kala-azar
Trypanosomiasis
Schistosomiasis
Leishmaniasis
Echinococcosis
Congestive States Related to Portal Hypertension
Cirrhosis of the liver Main cause of massive
congestive splenomegaly
Schistosomiosis
• “Pipe-stem” hepatic
fibrosis
• Severe congestive
splenomegaly
Alcoholic cirrhosis and Figure 7. Hassall’s corpuscles
pigment cirrhosis
• Diffuse fibrous scarring B. THYMIC PATHOLOGIES
Portal or splenic vein Can stem from spontaneous Developmental Disorders
thrombosis portal vein thrombosis, DiGeorge Syndrome
usually associated with some • Thymic hypoplasia is seen in this syndrome
intrahepatic obstructive disease,  Marked by severe defects in cell-mediated immunity and variable
or inflammation of the portal abnormalities of parathyroid development associated with
vein (pylephlebitis) hypoparathyroidism
Infiltrating tumors arising in
neighboring organs (e.g. Thymic Cysts
stomach or pancreatic CA) • Benign
Cardiac failure Cardiac decompensation of the • If thymic cysts are present, patient may have underlying
right side of the heart – neoplasm
tricuspid or pulmonic valvular → Common approach: what is causing the cyst? There must
disease, chronic or be a mass somewhere in that area putting pressure on the
pulmonale, or following left- thymus, causing the cyst
sided heart failure  Isolated thymic cysts are not clinically significant
Lymphohematogenous Disorders
Hodgkin lymphoma Rare, except in myeloid and Thymic Follicular Hyperplasia
Non-Hodgkin lymphomas and lymphoid tumors • Benign
lymphocytic leukemias Lymphangiomas and  Refers to the appearance of reactive B-cell lymphoid follicles within
Multiple Myeloma hemangiomas are most the thymus
Myeloproliferative disorders common and often cavernous in • There are some conditions that would induce the proliferation of
Hemolytic anemias type T cells
Immunologic-Inflammatory Conditions • The thymus can be enlarged in infections, immunologic states, and
Rheumatoid arthritis autoimmune disorders (e.g. myasthenia gravis, systemic lupus
Systemic Lupus Erythematosus erythematosus, rheumatoid disease)
Storage Diseases • Can sometimes be mistaken for a goiter, resulting in unnecessary
Gaucher disease surgery
Niemann-Pick disease
Mucopolysaccharidoses Thymoma
Miscellaneous Disorders • Only tumor that can come from thymus
Amyloidosis • Benign tumor but becomes malignant when it invades the
Primary neoplasms and cysts contagious structures like the lungs, pericardial sac, etc.
Secondary neoplasms → Benign: considered non-descript which means that when
you look at them in the microscope, they look the same,
(polygonal or spindle cells)
II. THYMUS
 Well encapsulated
A. ANATOMY  The neoplastic epithelial cells are arranged in a swirling
• Similar to your appendix, in the sense that they aren’t functional pattern and have bland, oval to elongated nuclei with
before, but becoming more important now inconspicuous nucleoli
• Where T cells develop and originate  Only a few small, reactive lymphoid cells are
• Only palpable in childhood and adolescence interspersed
→ As you grow older, it atrophies → Malignant: rarer, cortical type
• Composed of two well-encapsulated fused lobes: ▪ Remember: for malignant neoplasm, invasion tells you
→ Epithelial component (Hassall’s corpuscles/Thymic when it’s malignant
corpuscles) ▪ Arise in the form of squamous cell carcinoma or
 Whorls of medullary epithelial cells with their keratinized lymphoepithelioma-like carcinoma
cores o Looks like a squamous cell with a lot of reactive T
→ T lymphocytes (lymphoid component) lymphocytes
▪ Surrounds epithelial component ▪ Can only be seen surgically

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  The neoplastic epithelial cells are polygonal and have
round to oval, bland nuclei with inconspicuous nucleoli
 Numerous small, reactive lymphoid cells are
interspersed
Figure 8. A: Benign thymoma (medullary type), B: Malignant thymoma
(type I)
NICE TO KNOW
 Note that WHO staging is different according to Robbins
→ In clinical practice: WHO is used more often
Classification Staging Adapted in Robbins (2015)
• Cytologically benign and noninvasive
→ Most often composed of medullary-type epithelial cells
→ No pleomorphism, hyperchromatism, and abnormal mitotic
figures
→ Neoplasm is confined within the thymus
• Cytologically benign but invasive and metastatic
→ Most commonly of cortical variety with abundant cytoplasm
and rounded vesicular nuclei
→ Neoplasm penetrating through capsule and extending to the
pericardium, lungs, and other structures
→ Cellular features are benign
→ Even if cellular features are benign, it is still classified as
metastatic due to invasion
• Cytologically malignant (thymic carcinoma)
→ Usually appears microscopically as squamous cell carcinoma
 Second most common variant is lymphoepithelioma-like
carcinoma, resembling nasopharyngeal carcinomas
→ Cells appear more polygonal or more round
→ Abundance of lymphocytes
WHO Classification
• Type A: Benign becomes malignant when it invades contiguous
structures (lungs, pleural part of lungs, pericardial sac)
• Type B: Frankly malignant, it could either arise as squamous cell
carcinoma or lymphoepithelial like carcinoma (like squamous cell
carcinoma but with a lot of reactive T-cell lymphocytes)
III. DISORDERS OF WHITE BLOOD CELLS
A. CATEGORIES OF WBC DISORDERS
• Increase in WBC levels can manifest in two ways:
→ Leukocytosis: WBC count is greater than normal; or
→ Lymphocytosis: increase in number of lymphocytes in the
blood
When you have an increase or decrease in WBC, you only think of
two things, is it reactive due to an infection or inflammation, or is
it a tumor? There is nothing in between (Ledesma, 2019)
• WBC disorders that do not concern with neoplasia is categorized
under non-neoplastic disorders of white cells
Figure 9. Categories of WBC Disorders
YL6: 04.12a Basic Pathologies 2: Diseases of the Spleen, Thymus, and White Blood Cells
 Disorders of the WBCs can be classified into two broad categories,
proliferative disorders and leukopenias
Proliferative Disorders (Leukocytosis)
• Increase in white blood cells
• Can be reactive or neoplastic
 Reactive proliferations: common in the setting of infections
or inflammatory processes or when leukocytes are needed for
an effective host response
 Neoplastic disorders: less frequent but much more
important clinically
Leukopenia
• Decrease in white blood cells
• Less frequent but more important clinically
• Can indicate an infection or a tumor
• Sometimes used interchangeably with neutropenia in clinics
because for WBCs in peripheral blood, most are neutrophils
 Associated with rare congenital immunodeficiency diseases,
advanced HIV infection, and treatment with high doses of
corticosteroids
B. NEUTROPENIA/AGRANULOCYTOSIS
• Neutropenia: reduction in the number of neutrophils in the blood
→ Neutropenia and leukopenia are used interchangeably in
the clinics because WBCs in peripheral blood are mostly
neutrophils
▪ Thus, when there’s a decrease in neutrophils, there is
also leukopenia
• Agranulocytosis: a clinically significant reduction in neutrophils
→ Has a serious consequence of making individuals susceptible
to bacterial and fungal infections
▪ Because the number of neutrophils is less than 500
• Common infectious lesions in neutropenia:
→ Herpangina: ulcerative necrotizing lesions
▪ Abscess in the tonsillar area
→ Overwhelming candidiasis
• Treatment for neutropenia: give the patient a granulocyte colony
stimulating factor, which will induce the production of neutrophils
• Common causes of neutropenia:
→ Exposure to drugs (i.e., you don’t give chloramphenicol to
children)
→ Chemotherapeutic drugs that depress WBCs
→ Myelodisplastic syndromes
→ Inadequate or ineffective granulopoiesis
→ Increased destruction or sequestration of neutrophils in the
periphery
NICE TO KNOW: CLASSIFICATION OF CAUSES OF
NEUTROPENIA IN ROBBINS
 Inadequate or Ineffective Granulopoiesis, observed in
 Suppression of Hematopoietic Stem Cells
 Suppression of Committed Granulocytic Precursors
 Ineffective Hematopoiesis (seen in Megaloblastic anemia
and Myelodysplastic Syndromes)
 Rare Congenital Conditions (e.g. Kostmann Syndrome)
 Increased Destruction or Sequestration of Neutrophils in
the Periphery, observed in
 Immunologically mediated injury to neutrophils
 Splenomegaly
 Increased peripheral utilization
Inadequate or Ineffective Granulopoiesis
• Suppression of hematopoietic stem cells
→ There is something in the bone (e.g. metastatic cancer,
granulomatous disease)
 Seen in aplastic anemia and a variety of infiltrative marrow
disorders (e.g. tumors, granulomatous disease)
• Suppression of committed granulocytic precursors due to
drug toxicity
→ Most common cause
→ Exposure to chloramphenicol (common drug that decreases
WBCs), sulfonamides, thiouracil, and alkylating
chemotherapeutic agents, and anti-metabolites
• Infective hematopoiesis
→ As seen in myelodysplastic syndromes
▪ Something wrong with the maturation of WBC
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• Congenital Anomalies • Bacterial endocarditis
→ Rare congenital condition (e.g. Kostmann syndrome, which • Rickettsiosis
is seen in Swedish population) • Malaria
 Inherited defects in specific genes impair granulocyte • Autoimmune disorders
differentiation → Systemic lupus erythematosus
• Inflammatory bowel diseases
Accelerated Removal or Destruction of Neutrophils Ulcerative colitis
• Immunologically mediated injury to neutrophils Lymphocytosis • Rare
→ Increased tissue migration, thus low peripheral blood count • Atypical lymphocytes in infectious
 Can be seen in autoimmune diseases or caused by exposure mononucleosis or other types of
to drugs viral infections can mimic
• Splenomegaly due to sequestration of neutrophils leukemia.
• Increased peripheral utilization due to overwhelming sepsis • They may look similar to your
lymphoblasts
C. LEUKOCYTOSIS • Accompanies monocytosis in many
 An increase in the number of white cells in the blood disorders associated with chronic
 Common reaction to a variety of inflammatory states immunologic stimulation
• The most important and common cause of leukocytosis is → Tuberculosis
infection → Brucellosis
• Viral infections
Table 2. Major Mechanisms of Neutrophilic Leukocytosis → Hepatitis A
Type of Leukocytosis Cause → Cytomegalovirus
Increased Production in the Chronic infection or → Epstein-Barr virus
Marrow inflammation (growth factor-
• Bordetella pertussis infection
dependent)
Paraneoplastic (e.g. Hodgkin
Note on lymphocytes: Sometimes, an increase in WBC could
lymphoma; growth factor-
produce a leukemoid reaction because of high count of WBC in
dependent)
leukemia. There can also be leukemoid reactions in certain cancers
Myeloproliferative disorders
or infections. They have a lot of neutrophils in varying stages of
(e.g., chronic myeloid leukemia;
maturation. So you may see some immature forms of granulocytes.
growth factor-independent)
(Ledesma, 2019)
Increased release from marrow Endotoxemia
stores Infection
Reactive Changes in Neutrophils
Hypoxia
• Toxic granules
Decreased margination Exercise
→ Seen in infections or sepsis.
Catecholamines
→ Granules are bigger, numerous, and coarser
Decreased extravasation into Glucocorticoid
tissues → The body’s way of trying to fight off infection.
• Döhle bodies
In steroids, the number is actually normal in the peripheral blood, → A small bluish dot in the cytoplasm that is not connected to
but the problem is, your WBCs don’t go to the sites of inflammation. the nucleus of your neutrophil
That’s why steroids are a good way to keep the inflammation at the ▪ Small bluish dot: enlargement of the endoplasmic
very low level. (Ledesma, 2019) reticulum
• Leukemoid reaction
Types of Leukocytosis → Increase in the number of WBC with varying forms of
maturity (i.e. from the myeloid lineage: promyelocyte,
NOTE metamyelocytes)
For this section, the highlighted words are those mentioned during the ▪ Different stages of maturity that may mimic your chronic
lecture myeloid leukemia
▪ Important note: You shouldn’t see an increase in
Table 3. Types of leukocytosis basophils here
o If you have an increase of basophils, you think of
Leukocytosis Type Cause
Chronic Myeloid Leukemia (CML)
Neutrophilia • Increase in neutrophils
→ CML is not seen in leukemoid reaction
• Acute bacterial infections
→ E.g. from pyogenic organisms
• Sterile inflammation such as necrosis
→ Myocardial infarction
• Burns
Eosinophilia • Allergic disorders
→ Asthma
→ Hay fever
→ Parasitic infections
• Drug reactions
• Malignancies
→ Hodgkin lymphoma
→ Some Non-Hodgkin lymphoma
• Autoimmune disorders
→ Pemphigus
Figure 10. Neutrophils with purple cytoplasmic granules (toxic
→ Dermatitis herpetiformis
granulations) and blue cytoplasmic patches of dilated endoplasmic
• Vasculitides
reticulum (Döhle bodies, black arrow)
• Atheroembolic disease
Induces transient eosinophilia
D. LYMPHADENITIS
Basophilia • Rare
• Inflammation of lymph nodes
Often indicative of myeloproliferative
• May be acute or chronic
disease (e.g. Chronic myelogenous
leukemia or CML)
Monocytosis • Increase in monocytes
• Chronic infections
→ Tuberculosis

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Table 4. Acute and Chronic Lymphadenitis
Acute Chronic
Expect to see many neutrophils May take some time for
changes to be seen
Tender and large due to Non tender lymph nodes
sudden enlargement of lymph
nodes
Due to infection Due to immunologic stimuli
(have undergone a vaccine or
exposure to certain diseases
 Chronic Lymphadenitis produces 3 different patterns of lymph node
reaction: (1) Follicular Hyperplasia (2) Paracortical Hyperplasia
(3) Sinus Histiocytosis
Follicular Hyperplasia
 Caused by antigenic stimuli that activate humoral immune
response
• You should see these 3 things in the germinal center of Follicular
Hyperplasia, which are absent in Follicular lymphoma: (1) Mantle
Zone (2) Germinal Center: Light and Dark Zones (3) Tingible-
body Macrophage
Mantle zone
• Encompassing your germinal center
• Composed of naïve B cells
→ Recall: Naïve B cells are B cells that have not been exposed
to an antigen
Inside the Germinal Center (Light and Dark zones)
• Light zone: composed of centrocytes
 Centrocytes: B cells with irregular or cleaved nuclear
contours
• Dark zone: composed of centroblasts
→ Centroblasts: B cells that have been presented with antigens
by the APCs within the germinal center
→ As the B cells mature and produce high affinity antibodies,
they undergo somatic hypermutations (change the heavy
chains of the immunoglobulins) in order to find a specific
antibody for these antigens
• Sequence of events:
1. B cells go to the dark zone to develop the antibody
2. Once they developed an antibody, the B cells go to the light
zone where they are presented with the antigen
3. If the antibody that they developed is not specific to that
antigen, they go back again to the dark zone until they find the
specific antibody
Tingible- Body Macrophages
• Found in the middle of germinal centers
• "Tingible-body” because it contains many apoptotic debris
→ Apoptotic debris: remnants of B lymphocytes that did not
produce the correct antibody or are self-reactive
Paracortical Hyperplasia
• “Para” – beside the cortical area
→ Increase in the cells of paracortical area
• Paracortical area: houses T lymphocytes
→ Recall: T lymphocytes produce cytokines to encourage the
proliferation and differentiation of B lymphocytes
• Usually virus induced
→ Vaccines: notorious for producing this benign hyperplasia
→ Stimulation of T lymphocytes found in paracortical region
Sinus Histiocytes
• Old name: Reticular Hyperplasia
• Expansion of sinusoids at the center of the lymph node
• Endothelial cells, lining the sinusoids, proliferate and increase in
the number of macrophages
→ Reason why it looks pale pink (because of cytoplasm of
macrophages)
• Most lymph nodes that drain cancers have this pattern
→ E.g. Axillary lymph nodes of Breast CA patients will have this
pattern
• Benign form of lymphadenitis
YL6: 04.12a Basic Pathologies 2: Diseases of the Spleen, Thymus, and White Blood Cells
Others
• Lymphoid follicle formation in non-lymphoid tissues
→ E.g. Colon/Gastrointestinal Tract (aside from Peyer's Patch),
joint spaces (in Rheumatoid arthritis)
• Due to chronic infection
→ Common denominator for all these things in order for
lymphoid follicle to be formed in these areas
QUICK REVIEW
SUMMARY OF TERMS
• The spleen is a site of immune responses
→ Acts like a sieve to filter the blood and particulate matter
→ The major organ for the mononuclear lymphatic system
• Splenic macrophages: responsible for “pitting” of RBC
→ Heinz bodies: inclusions of denatured hemoglobin
→ Howell-Jolly bodies: nuclear remnants (mostly RNA)
• Extramedullary hematopoiesis: the spleen produces RBCs and
other cellular elements during fetal development and certain
disease states
• Sequestration: the harboring of the spleen of RBCs and WBCs
from the peripheral blood
• Splenomegaly: characterized by anemia, thrombocytopenia,
and leukopenia, or a combination of the three called
pancytopenia
→ Acute congestion: non-specific and happens over the
course of a few days, 400- 500g (3-4x normal weight)
→ Chronic congestion: happens over a long period of time,
1000-2000 g
• Splenic infarct: common infarct caused by occlusion of the major
splenic artery or any of its branches
• Other associated conditions of the spleen
→ Rupture: often precipitates intraperitoneal hemorrhage
→ Congenital anomalies: hypoplasia, spleniculi
→ Neoplasm: may either be benign (lymphangiomas and
hemangiomas) or malignant (lymphoma and leukemia)
• Thymus: only palpable in childhood and adolescence, as you grow
older, it atrophies
• Composed of two well-encapsulated fused lobes:
→ Epithelial component (Hassall’s corpuscles/Thymic
corpuscles)
→ T lymphocytes (lymphoid component): surrounds epithelial
component
• DiGeorge Syndrome: thymic hypoplasia, marked by severe
defects in cell-mediated immunity
• Thymic Cyst: uncommon lesions lined by stratified or columnar
epithelium
• Thymic Follicular Hyperplasia: appearance of reactive B-cell
lymphoid follicles within the thymus
• Thymoma: only tumor that can come from thymus
• Leukocytosis: increase in white blood cells
• Leukopenia: decrease in white blood cells
• Neutropenia: reduction in the number of neutrophils in the blood
→ Neutropenia and leukopenia are used interchangeably in
the clinics because WBCs in peripheral blood are mostly
neutrophils
• Agranulocytosis: a clinically significant reduction in neutrophils
• Common causes of neutropenia:
→ Exposure to drugs (i.e., you don’t give chloramphenicol to
children)
→ Chemotherapeutic drugs that depress WBCs
→ Myelodisplastic syndromes
→ Inadequate or ineffective granulopoiesis
→ Increased destruction or sequestration of neutrophils in the
periphery
• Toxic granules: granules are bigger, numerous, and coarser,
seen in infections or sepsis.
body’s way of trying to fight off infection
• Döhle bodies: small bluish dot in the cytoplasm that is not
connected to the nucleus of your neutrophil
• Small bluish dot: enlargement of endoplasmic reticulum
• Leukemoid reaction: increase in the number of WBC with varying
forms of maturity
→ You shouldn’t see an increase in basophils here
• Lymphadenitis: inflammation of lymph nodes
→ Acute: tender and large lymph nodes due to an infection
→ Chronic: non tender lymph nodes due to immunologic stimuli
• 3 Different Patterns of Chronic Lymphadenitis: (1) Follicular
Hyperplasia (2) Paracortical Hyperplasia (3) Sinus
Histiocytosis
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• Follicular Hyperplasia should have: (1) Mantle Zone (2) Germinal IMPORTANT LINKS
Center: Light and Dark Zones (3) Tingible-body Macrophage
• Mantle Zone: encompassing the germinal center with naïve B cells Trans feedback: https://tinyurl.com/AcadsTransFeedback
• Light zone: composed of centrocytes Errata submission: https://tinyurl.com/ContentErrataSubmission
• Dark zone: composed of centroblasts Errata tracker: https://tinyurl.com/ErrataTracker
• Tingible-Body Macrophages: found in the middle of germinal
centers
• Paracortical hyperplasia: increase in the cells of paracortical
APPENDIX
area, usually virus- induced
• Sinus histiocytes: expansion of sinusoids at the center of the
lymph node due to the proliferation and expansion of
macrophages, producing pale pink color
• Common denominator for lymphoid follicle formation: chronic
inflammation

REVIEW QUESTIONS
1. T/F. The spleen, like a huge lymph node, is the major organ for the
multinuclear lymphatic system.
2. Which of the following is true regarding splenomegaly?
a) Causes a dragging sensation in the left upper quadrant and
discomfort after eating
b) Characterized by anemia, thrombocytopenia, and leukopenia
c) Characterized by pancytopenia
d) Only A & B
e) All of the above
3. Which congenital anomaly has generally no pathology but can be
bad when overlooked during a splenectomy?
a) Hypoplasia
b) Spleniculi
c) Neoplasm
d) Splenomegaly
4. The following are normal components of the thymus EXCEPT for:
a) Hassall's corpuscles
b) T lymphocytes
c) B lymphocytes
d) Thymic corpuscles
5. A developmental disorder which is always benign and may indicate
an underlying neoplasm.
a) DiGeorge Syndrome
b) Thymic Follicular Hyperplasia
c) Thymoma
d) Thymic Cysts
6. Which of the following is INCORRECTLY matched?
a) Leukopenia: increase in white blood cells
b) Leukocytosis: increase in white blood cells
c) Lymphocytosis: increase in lymphocytes
d) None of the above
7. An end result of infection is due to a neutrophil count of
a) <250/mm3
b) <300/mm3
c) <500/mm3
d) >600/mm3
8. Leukocytosis with an increased release from marrow stores is
caused by the following EXCEPT:
a) Endotoxemia
b) Catecholamines
c) Hypoxia
d) Infection
9. One can expect to see many neutrophils in acute lymphadenitis.
The most common cause of chronic lymphadenitis is infection.
a) Statement 1 is true. Statement 2 is false.
b) Statement 1 is false. Statement 2 is true.
c) Both statements are true.
d) Both statements are false.
10. Benign hyperplasia which houses T lymphocytes and is usually
virus induced
a) Follicular Hyperplasia
b) Paracortical Hyperplasia
c) Sinus Histiocytosis

Answers (if self-explanatory)

1F. mononuclear lymphatic system. 2E, 3B, 4C, 5D, 6A, 7C, 8B, 9A.
The most common cause of chronic lymphadenitis is immunologic
stimuli. 10B

REFERENCES
REQUIRED
(1) Ledesma, J.D. October 08, 2019. Diseases of the Spleen, Thymus,
and White Blood Cell [Lecture slides].
(2) Kumar, V., Abbas, A.K., & Aster, J.C. 2015. Robbins and Cotran
Pathological Basis of Disease Ninth Edition.

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