Diseases of White Blood Cells, Lymph

Nodes, Spleen, and Thymus

Floranne Margaret L. Vergara, MD. FPSP. APCP.

General Pathology
Normal
• Lymphocytes and monocytes
– not only circulate in the blood and lymph
– accumulate in discrete, organized masses
• within lymph nodes, thymus, spleen, tonsils, adenoids, and
Peyer patches

• Lymph nodes
– the most widely distributed and easily accessible
component of the lymphoid tissue
– are frequently examined for diagnosis of
lymphoreticular disorders
 Lymph Node
• Flow of lymph

afferent lymph vessels (convex

side)

subcapsular sinus

cortical sinuses

medullary sinuses

efferent lymph vessel (concave

side / hilus)
 Lymph Node
• Parencyma
– Cortex
– Medulla

• Stroma
– Capsule
– Trabeculae
– Meshwork of reticular
fibers
– NO epithelial reticular
cells
• In the cortex
– primary follicles
• contain numerous immunologically naïve B cells

• between primary follicles

– numerous evenly dispersed small T lymphocytes

• the medulla
– contains variable numbers of plasma cells and
relatively few lymphocytes
• With antigenic stimulation
– primary follicles enlarge  transformed into pale-
staining germinal centers
• B cells acquire the capacity to make high-affinity
antibodies against specific antigens

• Mantle zone
– Surround the normal germinal centers
– dark-staining
– contains mainly small naïve B cells
• marginal zone B cells
– B cells with slightly more cytoplasm
– accumulates outside of the mantle zone
– Seen in some reactive conditions
Pathology
 Disorders of white blood cells
• classified into two broad categories
– Proliferative disorders - expansion of leukocytes
• Reactive
– proliferation in response to an underlying primary
• Neoplastic

– Leukopenias - deficiency of leukocytes

 Leukopenia
• usually results from reduced numbers of
neutrophils

• Lymphopenia is less common

– congenital immunodeficiency diseases
– advanced HIV infection
– following therapy with glucocorticoids or cytotoxic
drugs
– autoimmune disorders
– Malnutrition
– certain acute viral infections
 NEUTROPENIA / AGRANULOCYTOSIS

• Neutropenia
– Reduction in the number of granulocytes in the
peripheral blood

• Agranulocytosis
– marked reduction in neutrophil count
• Reduction in circulating granulocytes will
occur if there is
– reduced or ineffective production of neutrophils
– accelerated removal of neutrophils from the
circulating blood
• Inadequate or ineffective granulopoiesis :
– Suppression of myeloid stem cells
• aplastic anemia
• infiltrative marrow disorders (tumors, granulomatous disease, etc.)
• granulocytopenia is accompanied by anemia and
thrombocytopenia.
– Suppression of committed granulocytic precursors
• due to exposure to certain drugs
– Disease states associated with ineffective granulopoiesis
• megaloblastic anemias due to vitamin B12 or folate deficiency
• myelodysplastic syndromes
– defective precursors are susceptible to death in the marrow.
– Rare inherited conditions (such as Kostmann syndrome)
• genetic defects in specific genes result in impaired granulocytic
differentiation.
• Accelerated removal or destruction of neutrophils :
– Immunologically mediated injury to the neutrophils
• may be idiopathic
• associated with a well-defined immunologic disorder (e.g.,
systemic lupus erythematosus)
• produced by exposure to drugs
– Splenic sequestration
• excessive destruction occurs secondary to enlargement of the
spleen
• usually associated with increased destruction of red cells and
platelets as well.
– Increased peripheral utilization
• in overwhelming bacterial, fungal, or rickettsial infections.
• Drugs are responsible for most of the
significant neutropenias (agranulocytoses)
– alkylating agents and antimetabolites used in
cancer treatment
• produce agranulocytosis in a predictable, dose-related
fashion
• cause a generalized suppression of the bone marrow
– production of erythrocytes and platelets is also affected
• chlorpromazine and related phenothiazines
– toxic effect on granulocytic precursors in the bone
marrow

• aminopyrine, thiouracil, and certain

sulfonamides
– immunologically mediated destruction of mature
neutrophils
• Morphology - vary according to the
underlying cause
– the marrow is usually hypercellular
• excessive destruction of mature neutrophils
– owing to the presence of increased numbers of granulocytic
precursors
• ineffective granulopoiesis
– Hypocellular
• agents that suppress or destroy granulocytic precursors
• consequence of agranulocytosis
– Infections
• Severe life-threatening
• high risk for deep fungal infections
• Sites of infection often show a massive growth of
organisms with little leukocytic response
• Treatment
– broad-spectrum antibiotics are given expeditiously
whenever signs or symptoms appear
– granulocyte colony-stimulating factor (G-CSF)
• a growth factor that stimulates the production of
granulocytes from marrow precursors
 LEUKOCYTOSIS

• refers to an increase in the number of blood

leukocytes

• common reaction to a variety of inflammatory

states
• (sometimes ) the first indication of neoplastic
growth of leukocytes
 In acute infection
 there is a rapid increase in the egress of mature
granulocytes from the bone marrow pool
 roughly 50 times the size of the peripheral blood marginal
pool
 The release of IL-1, TNF, and other inflammatory
cytokines  stimulates bone marrow stromal cells and
T cells  produce increased amounts of colony-
stimulating factors (CSFs)  enhance the proliferation
and differentiation of committed granulocytic
progenitors  cause a sustained increase in neutrophil
production
• IL-5 causes eosinophilia
– enhancing the growth, survival, and
differentiation of eosinophils

• IL-7 plays a central role in lymphopoiesis

 Table 14-1. Causes of Leukocytosis
Neutrophilic leukocytosis Acute bacterial infections, especially those caused
by pyogenic organisms; sterile inflammation caused
by, for example, tissue necrosis (myocardial
infarction, burns)

Eosinophilic leukocytosis (eosinophilia) Allergic disorders such as asthma, hay fever,

allergic skin diseases (e.g., pemphigus, dermatitis
herpetiformis); parasitic infestations; drug reactions;
certain malignancies (e.g., Hodgkin disease and
some non-Hodgkin lymphomas); collagen vascular
disorders and some vasculitides; atheroembolic
disease (transient)

Basophilic leukocytosis (basophilia) Rare, often indicative of a myeloproliferative disease

(e.g., chronic myelogenous leukemia)

Monocytosis Chronic infections (e.g., tuberculosis), bacterial

endocarditis, rickettsiosis and malaria; collagen
vascular diseases (e.g., systemic lupus
erythematosus) and inflammatory bowel diseases
(e.g., ulcerative colitis)

Lymphocytosis Accompanies monocytosis in many disorders

associated with chronic immunologic stimulation
(e.g., tuberculosis, brucellosis); viral infections (e.g.,
hepatitis A, cytomegalovirus, Epstein-Barr virus);
Bordetella pertussis infection
 Morphologic changes in
the neutrophils

 Toxic granules
 coarse and darker than
the normal neutrophilic
granules and
 believed to represent
abnormal azurophilic
(primary) granules

 Döhle bodies
 patches of dilated
endoplasmic reticulum
 appear as sky-blue
cytoplasmic "puddles" in
smears stained with
Wright-Giemsa stain.
• Acute lymphadenitis
– in the cervical region
• due to microbial drainage from infections of the teeth
or tonsils
– in the axillary or inguinal regions
• secondary to infections in the extremities
– in mesenteric lymph nodes
• draining acute appendicitis
• self-limited infections
– induce abdominal symptoms mimicking acute appendicitis
• Gross
– swollen, gray-red, and engorged
• Histo
– prominence of the lymphoid follicles
• with large germinal centers
• containing numerous mitotic figures
– Macrophages
• often contain particulate debris of bacterial origin or derived
from necrotic cells
– Pyogenic infections :
• centers of the follicles may undergo necrosis  converted
into a suppurative mass
• Clinically
– enlarged
• because of the cellular infiltration and edema
– distention of the capsule
• tender to touch
– abscess formation is extensive
• become fluctuant
– Healing
• associated with scarring
 CHRONIC NONSPECIFIC LYMPHADENITIS
• different morphologic patterns depending on
the underlying stiumuli
 Follicular Hyperplasia
Synonym
Stimuli activate humoral immune
responses
Histo large, round or oblong B cell-rich
germinal centers (secondary
follicles) surrounded by a collar of
small, resting naïve B lymphocytes
(the mantle zone)
Within germinal centers, 2 distinct
regions (1) a dark zone containing
proliferating blast-like B cells
(centroblasts) and (2) a light zone
composed of B cells with irregular
or cleaved nuclear contours
(centrocytes)
tingible-body macrophages -
phagocytic macrophages
containing nuclear debris
Paracortical Lymphoid
Hyperplasia
trigger cellular immune responses
reactive changes within the T-cell
regions of the lymph node that
encroach on or efface the B-cell
follicles
activated T cells (immunoblasts)
- Within interfollicular regions
- three to four times the size of
resting lymphocytes and have
round nuclei, open chromatin,
several prominent nucleoli, and
moderate amounts of pale
cytoplasm.
Sinus Histiocytosis
Reticular Hyperplasia
refers to distention and
prominence of the lymphatic
sinusoids
Nonspecific
prominent in lymph nodes draining
cancers (breast CA)
lining lymphatic endothelial cells
are markedly hypertrophied
macrophages are greatly
increased in numbers, resulting in
expansion and distension of
sinuses
 Follicular Hyperplasia Paracortical Lymphoid Sinus Histiocytosis
Hyperplasia

Synonym Reticular Hyperplasia

Specific causes rheumatoid arthritis, immunologic reactions prominent in lymph nodes
toxoplasmosis, and early induced by drugs draining cancers, such as
stages of human (especially Dilantin), in carcinoma of the breast
immunodeficiency virus acute viral infections,
(HIV) infection particularly infectious
mononucleosis, and
following vaccination
against certain viral
diseases
 Follicular Hyperplasia
• preservation of the lymph node architecture
– including interfollicular T-cell zones and the sinusoids
• marked variation in the shape and size of
lymphoid nodules
• the presence of
– frequent mitotic figures
– phagocytic macrophages
– recognizable light and dark zones
– all of which tend to be absent from neoplastic
follicles.
 Follicular Hyperplasia
• large, round or oblong B cell-
rich germinal centers
(secondary follicles)
surrounded by a collar of small,
resting naïve B lymphocytes
(the mantle zone)

• dark zone shows several

mitotic figures and numerous
macrophages containing
phagocytosed apoptotic cells
(tingible bodies)
• Clinically
– not tender
• capsules are not under increased tension
– particularly common in inguinal and axillary nodes
Neoplastic Proliferations of White
Cells
• classified into several categories
– Lymphoid neoplasms
• neoplastic cell closely resembles that of a particular stage of
normal lymphocyte differentiation
– Myeloid neoplasms
• from hematopoietic stem cells that give rise to cells of the myeloid
(i.e., erythroid, granulocytic, and/or thrombocytic) lineage
• Three categories
– acute myelogenous leukemias
» immature progenitor cells accumulate in the bone marrow
– myelodysplastic syndromes
» associated with ineffective hematopoiesis and resultant peripheral
blood cytopenias
– chronic myeloproliferative disorders
» increased production of one or more terminally differentiated
myeloid elements
– Histiocytoses
• uncommon proliferative lesions of macrophages and dendritic
cells
ETIOLOGICAL AND PATHOGENETIC FACTORS IN
WHITE CELL NEOPLASIA: OVERVIEW
• Chromosomal translocations and oncogenes
– Nonrandom chromosomal abnormalities, most commonly
translocations, are present in the majority of white cell
neoplasms

• Inherited genetic factors

– individuals with genetic diseases that promote genomic
instability
• such as Bloom syndrome, Fanconi anemia, and ataxia
telangiectasia
– at increased risk for development of acute leukemia
– Down syndrome (trisomy 21) and neurofibromatosis type I
• associated with an increased incidence of childhood leukemia.
• Viruses
– implicated as causative agents
• human T-cell leukemia virus-1 (HTLV-1)
– associated only with adult T-cell leukemia/lymphoma
• Epstein-Barr virus (EBV)
– subset of Burkitt lymphoma
– 30% to 40% of cases of Hodgkin lymphoma
– many B-cell lymphomas occurring in the setting of T-cell
immunodeficiency
– natural killer cell lymphomas
• Kaposi sarcoma herpesvirus/human herpesvirus-8
(KSHV/HHV-8)
– associated with an unusual type of B-cell lymphoma that
presents as a malignant effusion, often in the pleural cavity
• Environmental agents
– Helicobacter pylori infection
• gastric B-cell lymphoma
– gluten-sensitive enteropathy
• intestinal T-cell lymphoma
– HIV-infected individuals
• high risk for B-cell lymphomas

• Iatrogenic factors
– radiotherapy and certain forms of chemotherapy
• increase the risk of subsequent myeloid and lymphoid
neoplasms
LYMPHOID NEOPLASMS
• Leukemia
– is used for lymphoid neoplasms presenting with
widespread involvement of the bone marrow,
usually accompanied by the presence of large
numbers of tumor cells in the peripheral blood

• Lymphoma
– is used to describe proliferations arising as
discrete tissue masses
• the line between the "lymphocytic leukemias"
and the "lymphomas" often blurs
– "lymphoma" occasionally present with a leukemic
peripheral blood picture accompanied by
extensive marrow involvement
– progression of incurable "lymphomas“ 
evolution to "leukemia"
• Groups of lymphomas
– Hodgkin lymphoma
• clinically and histologically distinct
• treated in a unique fashion

– Non-Hodgkin lymphomas (NHL)

 clinical presentation
• 2/3 of NHLs
• virtually all cases of Hodgkin
lymphoma
– Non-tender nodal
enlargement (often greater
than 2 cm)
– can be localized or
generalized
• plasma cell neoplasms
– involving the skeleton cause
local bony destruction
– often present with pain due
to pathologic fractures
• 1/3 of NHLs
– arise at extranodal sites (e.g.,
skin, stomach, or brain)
• leukemic forms
(lymphocytic leukemia)
– signs and symptoms related
to suppression of normal
hematopoiesis by tumor cells
in the bone marrow
– characteristically infiltrate
and enlarge the spleen and
liver
 Classification of NHL
• Revised European-American Classification of
Lymphoid Neoplasms (REAL)
– 1994
– define distinct clinicopathologic entities
• immunophenotype and genetic aberrations
• morphologic and clinical features
– stratify patients into good and bad prognosis
groups
 Classification of NHL
• WHO classification
– reviewed and updated the REAL classification
– inclusion of a number of additional rare entities
– Sort lymphoid neoplasms into five broad categories,
based on their cell of origin
• Precursor B-cell neoplasms (neoplasms of immature B cells)
• Peripheral B-cell neoplasms (neoplasms of mature B cells)
• Precursor T-cell neoplasms (neoplasms of immature T cells)
• Peripheral T-cell and NK-cell neoplasms (neoplasms of
mature T cells and natural killer cells)
• Hodgkin lymphoma (neoplasms of Reed-Sternberg cells and
variants)
 Table 14-2. The WHO Classification of the Lymphoid Neoplasms

I. Precursor B-Cell Neoplasms

Precursor-B lymphoblastic leukemia/lymphoma
II. Peripheral B-Cell Neoplasms
Chronic lymphocytic leukemia/small lymphocytic lymphoma
B-cell prolymphocytic leukemia
Lymphoplasmacytic lymphoma
Splenic and nodal marginal zone lymphomas
Extranodal marginal zone lymphoma
Mantle cell lymphoma
Follicular lymphoma
Marginal zone lymphoma
Hairy cell leukemia
Plasmacytoma/plasma cell myeloma
Diffuse large B-cell lymphoma
Burkitt lymphoma
 Table 14-2. The WHO Classification of the Lymphoid Neoplasms
III. Precursor T-Cell Neoplasms
Precursor-T lymphoblastic leukemia/lymphoma
IV. Peripheral T-Cell and NK-Cell Neoplasms
T-cell prolymphocytic leukemia
Large granular lymphocytic leukemia
Mycosis fungoides/Sézary 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 γδT-cell lymphoma
Adult T-cell leukemia/lymphoma
NK/T-cell lymphoma, nasal type
NK-cell leukemia
V. Hodgkin Lymphoma
Classical subtypes
Nodular sclerosis
Mixed cellularity
Lymphocyte-rich
Lymphocyte depletion
Lymphocyte predominance
 important principles relevant to the lymphoid neoplasms

• Lymphoid neoplasia
– can be suspected from the clinical features
– histologic examination of lymph nodes or other
involved tissues is required for diagnosis

• analyses of antigen receptor genes and/or

their protein products can be used to
distinguish reactive and malignant lymphoid
proliferations
• vast majority of
lymphoid neoplasms
(80% to 85%) are of
B-cell origin
– most of the remainder
being T-cell tumors
– only rarely are tumors
of NK origin
encountered
Markers recognized by antibodies that are helpful in the characterization of lymphomas and leukemias

Antigen Designation Normal Cellular Distribution

Primarily T-Cell Associated
CD1 Cortical thymocytes and Langerhans histiocytes
CD3 Thymocytes, peripheral T cells
CD4 Helper subset of peripheral T cells, single positive
medullary thymocytes, and CD4/CD8 double positive
thymocytes
CD5 T cells and a small subset of B cells
CD8 Cytotoxic subset of peripheral T cells, single positive
medullary thymocytes, double positive cortical
thymocytes, and some NK cells
Primarily B-Cell Associated
CD10 Marrow pre-B cells and germinal center B cells; also
called CALLA
CD19 Marrow pre-B cells and mature B cells but not plasma
cells
CD20 Marrow pre-B cells after CD19 and mature B cells but not
plasma cells
CD21 EBV receptor; present on mature B cells and follicular
dendritic cells
CD23 Activated mature B cells
CD79a Marrow pre-B cells and mature B cells.
Primarily Monocyte or Macrophage Associated
CD11c Granulocytes, monocytes, and macrophages; also
expressed by hairy cell leukemias
CD13 Immature and mature monocytes and granulocytes
CD14 Monocytes
CD15 Granulocytes; also expressed by Reed-Sternberg cells
and variants in classical Hodgkin lymphoma
CD33 Myeloid progenitors and monocytes
CD64 Mature myeloid cells
Primarily NK-Cell Associated
CD16 NK cells and granulocytes
CD56 NK cells and a subset of T cells
Primarily Stem Cell and Progenitor Cell Associated
CD34 Pluripotent hematopoietic stem cells and progenitor cells
of many lineages
Activation Markers
CD30 Activated B cells, T cells, and monocytes; also expressed
by Reed-Sternberg cells and variants in classical Hodgkin
lymphoma
Present on All Leukocytes
CD45 All leukocytes; also known as leukocyte common antigen
(LCA)
Acute Lymphoblastic Leukemia/Lymphoma
• Composed of immature, precursor B (pre-B) or
T (pre-T) lymphocytes referred to as
lymphoblasts
– precursor B-cell tumors
• majority (∼85%) of ALLs
• typically manifest as childhood acute "leukemias“
– precursor T-cell ALLs
• less common
• tend to present in adolescent males as "lymphomas,"
• often with thymic involvement
• Note :
– there is considerable overlap in the clinical
behavior of precursor B-cell and T-cell ALL
– Malignant pre-B and pre-T lymphoblasts
• morphologically indistinguishable
• subclassification of ALL - dependent on
immunophenotyping
• ALL
– Most cases occur in individuals younger than 15 years
old
– almost twice as common in whites as in nonwhites
– slightly more frequent in boys than in girls
– incidence of pre-B ALL is highest at about the age of 4
• perhaps because the number of normal bone marrow pre-B
lymphoblasts (the cell of origin) peaks in early childhood.
– peak incidence of pre-T ALL is in adolescence
• age when the thymus reaches its maximal size
– Both pre-B and pre-T ALL occur in adults of all ages
• much less frequently than in children.
• Important to distinguish ALL from
AML
– may cause identical signs and
symptoms
– lymphoblasts have condensed
chromatin, inconspicuous
nucleoli, and scant agranular
cytoplasm
• definitive diagnosis relies on
detection of B and T lymphocyte-
specific markers with antibodies
• Histochemical stains
– Peroxidase – negative
– Periodic acid-Schiff (PAS)-positive
• Histologic appearance of ALL is similar
– Normal tissue architecture is completely effaced by
lymphoblasts
• having scant cytoplasm
• nuclei somewhat larger than those of small lymphocytes
• nuclear chromatin is delicate and finely stippled
• nucleoli are either absent or inconspicuous
– high rate of mitosis
• a "starry sky" pattern
– produced by interspersed benign tingible body macrophages
• terminal deoxynucleotidyltransferase (TdT)
– expressed only by pre-B and pre-T lymphoblasts, is positive
in >95% of cases

• Approximately 90% of patients with ALL have

numerical or structural changes in the chromosomes of
the leukemic cells
– Most common is hyperploidy (>50 chromosomes)
– Polyploidy
– t(12;21)
– t(9;22) (Philadelphia chromosome)
– t(4;11) translocations
 ALL vs AML
• immunophenotypically and genotypically
distinct
• present with very similar clinical features
• accumulation of neoplastic "blast" cells in the
bone marrow
– suppresses normal hematopoiesis by physical
crowding
• more characteristic of ALL are :
– Abrupt stormy onset
– Symptoms related to depression of normal
marrow function
• fatigue due mainly to anemia
• Fever - reflecting infections due to absence of mature
leukocytes
• bleeding (petechiae, ecchymoses, epistaxis, gum
bleeding) secondary to thrombocytopenia
• more characteristic of ALL are :
– Bone pain and tenderness
• resulting from marrow expansion and infiltration of the
subperiosteum.
– Generalized lymphadenopathy, splenomegaly, and
hepatomegaly
• caused by neoplastic infiltration
– In pre-T ALL presenting in the thymus
• symptoms related to compression of large mediastinal vessels or
airways
– Testicular involvement
– Central nervous system manifestations
• headache, vomiting, and nerve palsies
• resulting from meningeal spread
Diagnosis Cell of Origin Genotype Salient Clinical
Features
Neoplasms of immature B and T cells
Precursor B-cell Bone marrow Diverse Predominantly
acute precursor B-cell chromosomal children with
lymphoblastic expressing TdT translocations; symptoms
leukemia/lympho and lacking t(12;21) relating to
ma surface Ig involving pancytopenia
CBFαand ETV6 secondary to
most common marrow
rearrangement involvement;
aggressive
Precursor T-cell Precursor T-cell Diverse Predominantly
acute (often of thymic chromosomal adolescent
lymphoblastic origin) translocations, males with
leukemia/lympho expressing TdT many involving thymic masses;
ma T-cell receptor variable splenic,
loci; hepatic, and
rearrangements bone marrow
of TAL1 most involvement;
common aggressive
• Prognosis
– With aggressive chemotherapy
• more than 90% of children with ALL achieve complete remission
• at least two thirds can be considered cured

– Several factors have been consistently associated with a worse

prognosis
• age under 2
– possibly because of the strong association of infantile ALL with translocations
involving the MLL gene on chromosome 11
• presentation in adolescence or adulthood
• peripheral blood blast counts greater than 100,000
– reflect a high tumor burden
• the presence of unfavorable cytogenetic aberrations
– t(9;22) (the Philadelphia chromosome).
• favorable prognostic markers include
– age of 2 to 10 years
– low white count
– an early pre-B phenotype
– hyperploidy or t(12;21)
 Chronic Lymphocytic Leukemia (CLL)/
Small Lymphocytic Lymphoma (SLL)

• morphologically, phenotypically, and

genotypically indistinguishable
• differing only in the degree of peripheral blood
lymphocytosis

• diagnostic requirement for CLL

– absolute lymphocyte count >4000 per mm3
 Chronic Lymphocytic Leukemia (CLL)/
Small Lymphocytic Lymphoma (SLL)
• Morpho:
– Lymph node architecture
is diffusely effaced by a
predominant population
of small lymphocytes
• 6 to 12 μm in diameter
• containing round to slightly
irregular nuclei
• condensed chromatin
• scant cytoplasm
– mixed with variable
numbers of larger cells -
"prolymphocytes”
• In PBS
– increased numbers of
small, round
lymphocytes with
scant cytoplasm
– cells are fragile
• frequently disrupted
in the process of
making smears 
producing so-called
smudge cells
• Involvement of the
bone marrow
– all cases of CLL
– most cases of SLL
• infiltrate the splenic
white and red pulp
and the hepatic
portal tracts
• Immunophenotype - tumor cells express
– CD19 and CD20
• the pan B-cell markers
– CD23
– CD5
• a T-cell marker that is expressed on only a small subset
of normal B cells
• chromosomal translocations are rare in
CLL/SLL
• most common findings
– deletions of 13q12-14
– deletions of 11q
– trisomy 12q
– deletion of 17p
• Clinical Features
– ages over 50 (median age 60)
– male predominance (M:F ratio of 2:1)
– often asymptomatic
• symptoms appear - nonspecific
– easy fatigability, weight loss, and anorexia
– Generalized lymphadenopathy and hepatosplenomegaly
• present in 50% to 60% of the cases
– The total leukocyte count is highly variable
• SLL and marrow involvement can be leukopenic
• CLL and heavy tumor burdens can have leukocyte counts in excess
of 200,000 per mm3
• disrupts normal immune function
– Hypogammaglobulinemia is common 
increased susceptibility to infections
– 10% to 15% of patients develop autoantibodies
directed against
• red blood cells  autoimmune hemolytic anemia
• platelets  autoimmune thrombocytopenia
• Course and Prognosis
– extremely variable
– depend primarily on the clinical stage
– median survival is 4 to 6 years
– patients with minimal initial tumor burdens
• can survive for 10 years or more
– presence of deletions of 11q and 17p correlates
with higher-stage disease and portends a worse
prognosis
• tendency of CLL/SLL to transform to more aggressive
lymphoid neoplasms  most patients surviving less
than 1 year
– prolymphocytic transformation
• marked by
– worsening of cytopenias
– increasing splenomegaly
– the appearance in the peripheral blood of large numbers of
"prolymphocytes

– Richter syndrome
• transformation to diffuse large B-cell lymphoma
• heralded by the appearance of a rapidly enlarging mass within a
lymph node or the spleen
Diagnosis Cell of Origin Genotype Salient Clinical Features

Small lymphocytic Naïve B-cell or Trisomy 12, Older adults with

lymphoma/chronic postgerminal deletions of 11q, bone marrow,
lymphocytic center memory B- 13q, and 17p lymph node,
leukemia cell; expresses spleen and liver
CD5 disease; most
have peripheral
blood involvement;
autoimmune
hemolysis and
thrombocytopenia
in a minority;
indolent