Lymphocytic Neoplasia

Front 1

If lymphoid neoplasia primarily involves blood or bone marrow, it is
generally regarded as what?whereas if it primarily involves lymph node or solid tissue, it is
regarded as what?

Back 1

leukemia, regarded as lymphoma, although there are overlaps.

Front 2

What is an antigenic “fingerprint” of cells determined by the types of molecules
they express.?

Back 2

An
immunophenotype (IP) , The IP is used to infer cell lineage and/or document aberrant expression of
molecules specific to certain neoplasms.

Front 3

Normal B-cell markers include what?

Back 3

CD19, CD20, CD22,
CD79a, Pax-5, and kappa and lambda immunoglobulin (Ig) light chains.

Front 4

Typical T-cell markers
include what?

Back 4

CD1a, CD2, CD3, CD4, CD5, CD7, and CD8.

Front 5

Typical NK Cell markers include what?.

Back 5

CD2,
CD7, CD8, CD16, and CD56

Front 6

Many other markers exist that aid in the diagnosis of lymphoid
neoplasms. Some of these markers, such as CD20, are not only useful in demonstrating cell
lineage but is also important in what?

Back 6

planning treatment regimens that may include immunology based
therapy such as anti-CD20 (e.g., rituxamab). Immunophenotypic features will be discussed in
more detail in the case studies.

Front 7

CD45 (leukocyte common antigen) is seen where?

Back 7

on all normal lymphocyte populations (with possibly
the exception of plasma cells, as subsets of normal plasma cells may lack demonstrable
expression).

Front 8

What are important markers for differentiating classical Hodgkin
lymphoma from nodular lymphocyte predominant Hodgkin lymphoma?

Back 8

CD30, CD15, CD45, CD20, and CD3

Front 9

are markers of immaturity in lymphoid populations and may be seen in immature
lymphoid neoplasms but not in mature ones.?

Back 9

CD34 and Tdt

Front 10

are very useful in subcategorizing B-lineage lymphomas and
leukemias. Certain types of B-cell lymphomas express neither of these two markers, or either of
these markers, but not both?

Back 10

CD10 and the T-cell marker CD5

Front 11

What is a marker of cell proliferation used to determine the percentage of neoplastic
cells that are actively proliferating?

Back 11

Ki-67 (Mib-1)

Front 12

Treatment regimens are tailored to specific neoplasms and may include what?

Back 12

surgical excision,
chemotherapy, radiation, immunologic therapy, bone marrow transplantation or any combination
of these.

Front 13

Neoplasms composed of immature lymphoid cells arise from defects in stem cells that lead to clonal
proliferation of leukemic blasts and secondary suppression of normal hematopoiesis. Two broad types of
acute lymphoblastic leukemia/lymphoblastic lymphoma (ALL/LBL) are recognized, what are they?

Back 13

B-ALL/LBL and TALL/
LBL

Front 14

The lymphoblasts of B-ALL/LBL resemble what?" and the lymphoblasts of the T-ALL/LBL resemble what?"

Back 14

normal immature B-cells known as
"hematogones, normal immature T-cells known as
"thymocytes.

Front 15

B-ALL/LBL typically expresses B-lineage markers, which ones and do they express a rearranged immunoglobluin chain?

Back 15

CD19, CD79a, CD22, and sometimes
CD20; they will typically not express surface Ig light chains, but a large proportion of cases will express
CD10.

Front 16

T-ALL/LBL will variably express the T-lineage markers what?.

Back 16

CD1a, CD2, CD3, CD4, CD5, CD7, and
CD8.

Front 17

Both B- and T- ALL/LBL can express the immaturity markers CD34 and TdT (terminal
deoxynucleotidyl transferase). Do the benign counterparts of these neoplasms express these too?

Back 17

Since the benign counterparts of these neoplasms - hematogones (like Blymphoblasts)
and thymocytes (like T-lymphoblasts) – also express these markers, differentiating normal
from neoplastic populations is based on the intensity and pattern of expression. You should know the
antigens that differentiate B-ALL/LBL from T-ALL/LBL, and those that differentiate ALL/LBL from
mature B-cell lymphomas

Front 18

ALL/LBL has a bimodal age distribution in what 2 populations? .

Back 18

with a large incidence peak in early childhood and a
smaller peak in the elderly (i.e., greater than 65 years of age). I

Front 19

In the United States, approximately 85% of
cases of ALL/LBL are of B or T cell lineage? What are common clinical features?

Back 19

B-lineage. Common clinical features are secondary to cytopenias and include
fatigue, hemorrhage and infections. Other common signs and symptoms include bone or joint pain,
lymphadenopathy, skin lesions, and organomegaly. Anterior mediastinal masses with or without vena
caval syndromes (venous flow abnormalities due to tumor impingement on veins) are common in
precursor T-ALL/LBL. Both B- and T-ALL/LBL are highly aggressive and require intensive
chemotherapy. The cure rate in children is high but requires prolonged continuation therapy (up to 3
years). In the elderly, however, the outlook is grim, with a 3-year survival of less than 10%

Front 20

Lymphoma is a tumor of genetically altered lymphocytes with evidence of cell maturation. The two broad
categories of lymphoma, which remain in use clinically and persist largely for historical reasons, are what?

Back 20

(i)
Non-Hodgkin lymphoma and (ii) Hodgkin lymphoma.

Front 21

Non-Hodgkin lymphoma (NHL) is a heterogeneous group of lymphoid neoplasms that are subclassified
by morphologic, clinical, immunophenotypic, and genetic features. Approximately eighty percent are of what lineage?

Back 21

Blineage
and twenty percent are T-lineage.

Front 22

Although NK cells are a distinct subset of lymphocytes,
lymphomas of NK cell origin are considered within the broad category of T-cell lymphoma and labeled
NK/T-cell lymphoma because?.

Back 22

of their similar clinical behavior

Front 23

Sixty to seventy percent of NHLs
manifest predominantly where?

Back 23

lymph nodes while the remaining cases occur in extra-nodal locations.

Front 24

NHL
may arise in what 3 ways?

Back 24

1)out of a reactive polyclonal lymphoid proliferation with the emergence of a dominant clone,
such as in the development of B-cell lymphoma of mucosa associated lymphoid tissue (MALT) in the
setting of chronic gastritis. 2)NHL may arise secondary to translocation of oncogenes into an antigen
receptor locus (Ig or TCR) leading to subsequent overexpression of the oncogene. 3)Alternatively, genetic
rearrangements can also produce novel hybrid proteins leading to uncontrolled cell growth.

Front 25

What lymphomas are
typically composed of small lymphoid cells, have a low rate of proliferation, and are disseminated at
presentation. On the other hand, what lymphomas are typically composed of larger cells, have a
high rate of proliferation, and are often localized at presentation?

Back 25

indolent, aggressive

Front 26

Depending on the specific type, a small
to moderate percentage of indolent lymphomas will transform into more aggressive forms. Indolent NHLs
of B-lineage include what?. .

Back 26

include follicular lymphoma, B-cell small lymphocytic leukemia/small lymphocytic
lymphoma (CLL/SLL), mantle cell lymphoma, marginal zone lymphoma of mucosa-associated tissue
(MALT), splenic marginal zone lymphoma, nodal marginal zone lymphoma, and lymphoplasmacytic
lymphoma

Front 27

Aggressive NHLs of B-lineage include what?

Back 27

various types of diffuse large B-cell lymphoma
(DLBCL) and Burkitt lymphoma. NHLs of T-lineage known as peripheral T-cell lymphomas (PTCLs)
include various subcategories and are generally clinically aggressive.

Front 28

Follicular lymphoma is the second most common lymphoma in the United States and is a
prototypical indolent lymphoma. It occurs more often in adults or children?.

Back 28

It occurs in the aging population (median age of 60 years) and is
rare in children

Front 29

Patients typically present at advanced stages of disease with progressive, painless
lymphadenopathy. Only twenty percent of patients have "B-symptoms"? What are B symptoms?

Back 29

(i.e., weight loss,
pruritus, intermittent fevers, and occasionally drenching night sweats).

Front 30

Clinical staging often
reveals splenic involvement (40% of cases), liver involvement (50% of cases), and bone marrow
involvement in what percent of cases?
.

Back 30

(60% of cases).

Front 31

As with other indolent B-cell neoplasia one of the major challenges
to diagnosing follicular lymphoma is in its differentiation from what?

Back 31

reactive lymphoid hyperplasia

Front 32

Follicular lymphoma recapitulates many of the histologic and cytologic features of normal
germinal centers seen reactive lymph nodes. It is composed of various proportions of neoplastic
centrocytes (i.e., cells with nuclear grooves, or "cleaved" cells) and centroblasts (i.e., cells
without a nuclear groove, or "round" cells). Similar to normal germinal center cells, the
neoplastic cells of lymphoma typically express what antigen?

Back 32

the CD10 antigen.

Front 33

Currently, follicular lymphoma is graded on a
scale of 1-3 based upon what? .

Back 33

the number of large centroblasts present, with a higher number
corresponding to a higher grade.

Front 34

Follicular Lymphoma Cytogenetic and/or molecular investigation typically reveals
clonally rearranged immunoglobulin genes and what translocation

Back 34

a t(14;18)(q32;q21) involving the
immunoglobulin heavy chain (IGH) and BCL-2 genes, respectively

Front 35

Follicular lymphoma---While the disease follows a
chronic indolent course, it is incurable with what median survival rate?

Back 35

a median survival of 8 to 10 years

Front 36

Associated Lymphoid Tissue
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-Associated Lymphoid Tissue (“MALT”
lymphoma) is the prototypical indolent lymphoma involving extranodal tissue. Common sites of
presentation include what?

Back 36

the stomach, thyroid, lung, salivary glands, orbit, and skin.

Front 37

Malt occurs in what patient population?

Back 37

They occur in the
older population with a median age of 60 years. Symptoms depend on the anatomic location
involved. They are believed to be derived from marginal zone B-cells and are associated with
chronic immune stimulation.

Front 38

Conditions associated with MALT lymphoma include what?.

Back 38

Helicobacter
pylori gastritis, Sjogren syndrome-associated sialadenitis, Hashimoto thyroiditis, and Borrelia
burdorfori infection of the skin

Front 39

These MALT lymphomas are characteristically both CD10 and CD5
negative or positive?.

Back 39

negative

Front 40

Common genetic abnormalities in MALT include t(11;18)(q21;q21) involving what genes?
t(14;18)(q32;q21) involving what genes?

Back 40

the API2 and
MALT1 genes, IGH and MALT1 genes,
please note that this involves a different gene on chromosome
18 than the BCL-2 gene involved in follicular lymphoma), and t(1;14)(p22;q32) involving the
BCL-10 and IGH genes

Front 41

Are MALT lymphomas curable?

Back 41

These lymphomas typically remain localized and, although they are
indolent, they are often curable with local therapy including radiation or surgical excision. H.
pylori-associated lymphoma may respond well to antibiotic therapy

Front 42

De novo diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of aggressive
lymphomas composed of large lymphoid cells arranged in a diffuse architecture (See Table 2). As
a whole, DLBCL is the most common non-Hodgkin lymphoma in the United States. It is
generally a disease of what patient population?.

Back 42

older patients (median age in the 60s), although it can occur in any age
group including children

Front 43

DLBCL--Patients often present with a rapidly growing mass that may involve a
lymph node or extranodal tissue. There are several morphologic variants of DLBCL, but in
general, the lymphoma diffusely infiltrates tissue to create sheets of large atypical cells. DLBCL
is also immunophenotypically and molecularly variable. Twenty-five to 50% of cases express what antigen?. Ki-67 (Mib-1) typically varies between 20-80% but can be as high as 100% in rare
cases. Approximately 20% of cases have a t(14;18)(q32;q21) involving the BCL-2 gene (similar
to follicular lymphoma) and 30% have 3q27 abnormalities involving the BCL-6 gene. Gene
expression profiling through microarray technology has demonstrated genetic subsets that
correspond to germinal center (GC) and activated B-cell (ABC) subtypes.

Back 43

the
CD10 antigen

Front 44

Burkitt lymphoma (BL) is a very aggressive B-cell lymphoma that is associated with what translocation?

Back 44

a c-MYC
translocation as a constant genetic feature.

Front 45

BL---what 3 clinical variants?

Back 45

There are three clinical variants: endemic, sporadic,
and immunodeficiency-related.

Front 46

Endemic BL is seen in equatorial Africa, occurs is children (peak
incidence at 4 to 7 years), and is almost invariably associated with what virus?
.

Back 46

Epstein-Barr virus (EBV)

Front 47

Sporadic BL is seen throughout the world, occurs in children and young adults, and
less than 30% of cases are associated with EBV. Immunodeficiency-related BL is seen most
commonly in what patients?

Back 47

patients with human immunodeficiency virus (HIV), who present at a younger age
with CD4 counts above 200 cells/uL. Between 30-50% of cases are associated with EBV. BL
diffusely infiltrates tissue and from a low objective power on microscopic examination gives a
“starry-sky” appearance (i.e., sheets of blue with scattered clear spaces). The "sheets of blue" are
the lymphoma cells and the "stars" are scattered histiocytes with abundant clear cytoplasm. The
histiocytes are clearing the apoptotic debris created from single cell degeneration in this highly
proliferative lymphoma

Front 48

What does BL look like cytologically---except immunologic BL?

Back 48

With the exception of immunodeficiency-related BL (which may have a
spectrum of cytologic appearances), BL is composed of uniformly medium-sized lymphoma
cells with round nuclei, several peripherally located small nucleoli, and deeply basophilic
cytoplasm that often has lipid-containing vacuoles (i.e., they resemble centroblasts). The very
high proliferation rate is demonstrated by the presence of numerous mitotic bodies and nearly
100% positive staining by Ki-67 (Mib-1).

Front 49

BL is CD10 positive and characteristically
demonstrates a very high intensity of what other CD?

Back 49

CD38 expression (CD 38 is an activation molecule
expressed by various hematolymphoid cells at variable intensities).

Front 50

The c-MYC gene on
chromosome 8 is involved in a translocation with either the heavy chain immunoglobulin gene
on chromosome 14 or one of the light chain immunoglobulin genes on chromosome 2 or 22 {i.e.,
t(8;14), t(2;8), or t(8;22)} ---in what lymhoma
Complete remission is possible with high intensity chemotherapy

Back 50

Burkitt's lymphoma

Front 51

As a whole, Hodgkin lymphoma accounts for 30% of the
lymphomas diagnosed in the United States. There are two basic types of Hodgkin lymphoma, what are they?

Back 51

which are
clinically and biologically distinct: (i) classical Hodgkin Lymphoma and (ii) nodular lymphocytepredominant
Hodgkin Lymphoma.

Front 52

Classical Hodgkin lymphoma is further divided into four
subcategories: what are they?

Back 52

(a) nodular sclerosis, (b) mixed cellularity, (c) lymphocyte-rich, and (d) lymphocytedepletion.
The natural history, epidemiology, and clinical features of classical Hodgkin lymphoma differ
from nodular lymphocyte-predominant Hodgkin lymphoma

Front 53

Classical Hodgkin lymphoma (CHL) shows a bimodal age distribution, with the first peak occurring
between the ages of 15 and 35 and the second peak in the 50’s. The lymphoma typically arises in what lymph nodes?.

Back 53

lymph
nodes of the cervical region or mediastinum

Front 54

Hodgkin lymphoma---Patients may present with localized or disseminated disease.
While patients may be asymptomatic at presentation, approximately half present with B-symptoms. As
these symptoms are commonly associated with various types of infectious disease, and the
lymphadenopathy may not always be readily apparent, Hodgkin lymphoma can easily be overlooked if
not included in the differential diagnosis. CHL spreads in an orderly fashion, disseminating to contiguous
lymph node groups or lymphoid structures (e.g., spleen, thymus, Waldeyer’s ring). Left untreated, what happens?

Back 54

it is an
aggressive disease resulting in death. With current therapeutic strategies, however, the lymphoma is
commonly cured up to 90% of the time.

Front 55

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) shows a unimodal age distribution with
the peak occurring between the ages of 30 and 50; however, it can be seen in children. Typically, how many nodes are involved and are B-symptoms involved?.

Back 55

only a
single lymph node in the cervical, axillary, or inguinal region is involved. Mediastinal involvement is
extremely rare and B-symptoms are uncommon

Front 56

NLPH___Clinically, it is a low grade, indolent disease that is
rarely fatal. Although transformation into a high-grade process can occur, it is only seen in 2-3% of cases.
Treatment of a lower stage disease includes what?

Back 56

surgical excision with or without local radiation and anti-
CD20 treatment.

Front 57

defining morphologic characteristic common to all types of Hodgkin lymphoma is quite unique in the
spectrum of human cancer. Unlike most malignant neoplasms, tissue enlargement is due primarily to
what?

Back 57

infiltration by benign, reactive inflammatory cells amid a paucity of lymphoma cells with characteristic
morphologic and phenotypic characteristics that determine the subclassification.

Front 58

The reactive cells in hodgin lymphoma can include what cells?.

Back 58

B-lymphocytes, T-lymphocytes,
plasma cells, eosinophils, neutrophils, and histiocytes. The pattern of infiltration by the benign
inflammatory cells may be nodular or diffuse, and it may or may not be associated with fibrosis

Front 59

While
the immunophenotype of the neoplastic cells in nodular lymphocyte predominant Hodgkin lymphoma
clearly indicate B-cell lineage, the neoplastic cells in classic Hodgkin lymphoma have what immunophenotype?

Back 59

indeterminate
immunophenotype.Although this indeterminate immunophenotype had caused speculation to the cell of
origin for Classic Hodgkin lymphoma in the past, the advent of tissue microdissection in association with
molecular diagnostics revealed a likely cell of origin: greater than 99% of Hodgkin lymphomas are Blineage
with the remaining cases being T-lineage. Even though Hodgkin lymphoma can typically be
diagnosed based on histologic and cytologic features alone, it has become routine practice to confirm the
diagnosis by immunophenotyping the neoplastic cells through immunohistochemical staining for at least
the following five markers: CD45, CD30, CD15, CD20, and CD3.

Front 60

The typical immunophenotype of
neoplastic cells of lymphocyte predominant Hodgkin lymphoma is what? What about classic hodgkins?

Back 60

CD45(+), CD30(-), CD15(-),
CD20(+), and CD3(-), whereas the typical immunophenotype of the neoplastic cells in classic Hodgkin
lymphoma is CD45(-), CD30(+), CD15(+), CD20(-), and CD3(-). Importantly, the immunophenotype of
these cells may vary within the same case and between individual cases.
each subty

Front 61

Almost any lymphoproliferative disorder that consists of mature cells can be associated with a leukemic
phase. “Pure” leukemias are disease states in which blood and bone marrow are the primary sites of
involvement. Leukemias of mature B-cells include B-cell chronic lymphocytic leukemia (CLL), B-cell
prolymphocytic leukemia, and hairy cell leukemia. Mature T-cell and NK cell neoplasms that tend to
present as leukemia or lymphoma?

Back 61

leukemia rather than lymphoma are a heterogeneous group of disorders with variable clinical
behavior. These disorders include large granular lymphocytic leukemia (either T-cell or NK cell), adult Tcell
leukemia/lymphoma, T-cell prolymphocytic leukemia, and aggressive NK cell leukemia. "

Front 62

Sezary
syndrome" involves the leukemic phase of the peripheral T-cell lymphoma known as mycosis fungoides
along with diffuse dermal erythema and diffuse lymphadenopathy. The circulating T-lymphoma cells are known as what?

Back 62

n
sezary syndrome are termed "sezary cells."

Front 63

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) is the most
common form of leukemia in the United States. The incidence increases or decreases with age?.

Back 63

increases, with age (median age of
65), and the disease is rare under the age of 40 years

Front 64

What is an indolent leukemia composed
predominantly of small, mature neoplastic lymphoid cells that individually are indistinguishable
from normal mature lymphocytes. Patients are often asymptomatic at presentation with the
incidental identification of lymphocytosis (defined as greater than 5.0 X 109/L) on routine blood
studies. Symptomatic patients usually complain of fatigue due to associated anemia, bleeding
secondary to thrombocytopenia, or “swollen glands” secondary to lymphadenopathy. Other
presenting features can include hepatosplenomegaly secondary to tissue infiltration by leukemic
cells. Although effective therapies can induce remission of disease, relapses inevitably occur. The
course of the disease often spans greater than 15 years; however, progression into a higher grade
process such large cell lymphoma (Richter’s syndrome) can occur. Clinical staging systems exist
to stratify patients in hopes of predicting prognosis (Tables 3 and 4). Therapy regimens may
differ based upon this clinical staging

Back 64

CLL/SLL

Front 65

Plasma cells are terminally differentiated B-lineage cells that produce and secrete immunoglobulin. The
spectrum of plasma cell neoplasms are collectively called plasma cell dyscrasias and include what?

Back 65

monoclonal
gammopathy of undetermined significance (MGUS), plasma cell myeloma, solitary plasmacytoma,
primary amyloidosis, and immunoglobulin chain deposition disease.

Front 66

Are CLL/SLL the same disease?

Back 66

As mentioned previously CLL and SLL are really the same disease (CLL/SLL), although
involvement of lymph nodes, blood, and bone marrow is variable. Immunophenotypically, the
cells are remarkable in that they express the T-cell marker CD5 (this feature is also seen in mantle
cell lymphoma, which is likewise of B-cell lineage).