Hodgkin and Non-Hodgkin Lymphoma

Question 1

Lymphoma and corresponding developmental stage.

Answer 1

Acute lymphoblastic leukemia – immature B-cell Mantle cell lymphoma – mantle cell
Follicular lymphoma – germinal center B-cell Hodgkin lymphoma – germinal center B-cell Burkitt lymphoma – germinal center B-cell CLL/SLL – mature B-cells of pre- or post-GC stage Plasma cell myeloma – plasma cell

Question 2

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) Definitions

Answer 2

CLL = lymphocytosis of ≥5 × 109/L for at least 3 months, Monoclonal B cell with mature immunophenotype positive for CD5, weak CD20, weak surface immunoglobulin, CD23, weak CD22, and weak CD11c Typically negative for CD10, FMC7, and CD79b
SLL = Extramedullary sites of disease predominate,
Diffuse infiltrate of small lymphocytes,
and Monoclonal B cell with mature phenotype similar to CLL

Question 3

CLL/SLL Clinicla features

Answer 3

CLL is the most common leukemia in the Western world and accounts for ~ 30% of all leukemia
 SLL accounts for ~7% of Non-Hodgkin lymphoma (NHL)
 Median 65 years, male predominance, M:F=2:1
 Most elderly patients with CLL are either asymptomatic (70% of cases) or only
mildly symptomatic, whereas some patients may present with fatigue, infection, autoimmune hemolytic anemia, hepatosplenomegaly, lymphadenopathy, or extranodal involvement.

Question 4

CLL/SLL Morphologic features

Answer 4

SEE HANDOUT.

Lymphocytosis!!!

Question 5

CLL/SLL immunophenotype

Answer 5

Positive: CD5, CD23, CD19

Weak: CD20, surface immunoglobulin, CD22, CD11c

Negative: CD10, FMC7

Question 6

CLL/SLL common genetic findings

Answer 6

Deletion of 13q14 (50% of cases and favorable diagnosis)

Trisomy 12 in <20% of cases.

Question 7

Follicular Lymphoma (FL) Definitions

Answer 7

A lymphoma of germinal center B cells (centrocytes and centroblasts) with typically at least a partially follicular pattern

Question 8

FL clinical features

Answer 8

requency: 40% of adult lymphomas in US, 20% worldwide
 Age: mostly adults, median 60 years
 Gender: male = female
 Locations: mostly lymph nodes, also spleen, bone marrow, Waldeyer’s ring, GI tract,
skin and soft tissue
 Clinical presentations: more than 80% cases have widespread stage III or IV disease
at diagnosis, 40% have bone marrow involvement; however, patients often
asymptomatic except for lymphadenopathy

Question 9

FL morphologic features

Answer 9

Closely packed follices, extranodal or intramedullary involvement, Follicals with scant or absence mantle of zone.
Centrocytes and Centroblasts are the tumor cells.

Question 10

FL immunophenotype

Answer 10

B-cell markets positive: CD_19, CD20+, BCL2+ psitive, Germinal center B-cell marker positive CD10 and BCL6.

Question 11

FL cytogenetic findings

Answer 11

75-90% of cases have translocations of t(14:18)(q32:q21)

Question 12

Mantel Cell Lymphoma Definition

Answer 12

A B-cell neoplasm composed of monomorphic small to medium-sized lymphocytes with irregular nuclei that morphologically resemble centrocytes but often have slightly less irregular nuclear contours. The tumor cells typically express B-cell markers (CD19 and CD20) and CD5, and do not express CD23. This neoplasm is genetically characterized by BCL1 gene rearrangement at 11q13, leading to a constant overexpression of cyclin D1, which plays an important pathogenetic role in tumor development.

Question 13

MCL clinical features

Answer 13

MCL comprise approximately 3-10% of NHL
 Age: middle to older age, median age 60 years; M:F=2:1
 Location: mostly lymph nodes, also spleen and bone marrow; most common
extranodal sites, gastrointestinal tract and Waldeyer’s ring
 Clinical presentations: most patients present with stage III or IV with
lymphadenopathy, hepatosplenomegaly; >50% of cases with massive splenomegaly and marrow involvement; >25% cases with peripheral blood involvement that can mimic prolymphocytic leukemia

Question 14

MCL Immunophenotype

Answer 14

B-cell markers positive: CD19+, CD20+

Question 15

MCL Cytopgenetic finding

Answer 15

t(11:14)(q13;q32) involving BCL1 gene

Question 16

MCL clinical behavior

Answer 16

in contrast to other small b-cell lymphoma that are mostly indolent, MCL is usually moderatly aggressive.

Question 17

Burkitts Lymphoma (BL) definition

Answer 17

A highly aggressive B-cell lymphoma, often presenting at extranodal sites or as a leukemic form. The tumor is typically composed of monomorphic, medium-sized B cells with basophilic cytoplasm and a high mitotic rate. Translocations involving the MYC oncogene on chromosome 8 at band 8q24 are a constant feature

Question 18

BL clinical features

Answer 18

 Epidemiology:
o Endemic BL: typically in the malaria belt of equatorial Africa, as the most
common childhood malignancy in this region, peak 4-7 years of age, involves
jaw or abdomen, 95% EBV positive.
o Sporadic BL: mostly in children or young adults. 30% of childhood
lymphomas
o Immunodeficiency-associated BL: primarily in HIV patients
 Locations:
o Endemic: jaw and other facial bones in 50% cases, also distal ileum, cecum
and omentum
o Sporadic: mostly in ileocecal area o Immunodeficiency-associated: HIV
 May present in blood and diffuse marrow involvement at diagnosis

Question 19

BL cytogenetic findinds

Answer 19

Most cases have a characteristic translocation, t(8;14)(q24;q32), which juxtaposes the MYC gene at 8q24 next to IGH@ at 14q32

Question 20

BL clinical behavior

Answer 20

Highly aggressive but potentially curable. Curable with aggressive therapy in ~60% cases.

Question 21

Plasma Cell Neoplasms Definition

Answer 21

A clonal proliferation of immunoglobulin-producing plasma cells that ecrete a single class of immunoglobulin or a polypeptide subunit of a single immunoglobulin, which is usually detectable as a monoclonal protein (M protein) on serum or urine protein electrophoresis. Most plasma cell neoplasms originate as bone marrow tumors, but they occasionally present in extramedullary sites.

Question 22

Plasma Cell myeloma

Answer 22

Definition: a bone marrow–based, multifocal plasma cell neoplasm associated with an M protein in serum or urine. PCM originates from the marrow with disseminated marrow involvement in most cases. Other organs may be secondarily involved. The diagnosis of myeloma is made by a combination of clinical, morphologic, immunologic, and radiographic information. The disease spans a clinical spectrum from asymptomatic to highly aggressive disease.

Question 23

Hodgkin Lymphoma (HL)

Answer 23

Classification: the WHO classification has recognized two major types of Hodgkin lymphoma, the nodular lymphocyte-predominant subtype of Hodgkin’s lymphoma (NLPHL) and the classical Hodgkin’s lymphomas (CHLs), which is further classified into four subtypes.
 Nodular lymphocyte-predominant Hodgkin’s lymphoma  Classical Hodgkin’s lymphoma
o Nodular sclerosis classical Hodgkin’s lymphoma
o Lymphocyte-rich classical Hodgkin’s lymphoma
o Mixed cellularity classical Hodgkin’s lymphoma
o Lymphocyte-depleted classical Hodgkin’s lymphoma