3.26.14* Lymphomas Flashcards
PPT* Lecture Notes* Reading (ch 19 and 20)* Pictures
lymphoma
when malignancy lymphocytes accumulate in lymph nodes and cause lymphadenopathy. If they spill over into the blood, that is the leukemic phase)
lymphoma
a. clinical presentaiton- painless enlarged lymph nodes (mostly cervical), splenomegaly in 50% (maybe hepatomegaly)
b. PBS- normochromic/normocytic anemia. Neutrophilia, lymphopenia. Increased erythrocyte sedimentation rate, CRP, LDH.
c. lymph node- RS cells and mononuclear Hodgkin cells.
Types of Hodgkin lymphoma
i. Nodular sclerosis: collagen band encircle nodules in lymph node
ii. lymphocyte rich- scant R/S cells with multiple small lymphoctes
iii. mixed cellularity- R/S cell numerous with intermediate lymphocytes
iv. lymphocyte depleted- diffuse fibrosis disordered connective tissue
Non-Hodgkin lymphomas
a. clonal lymphoid tumors, 85% B cell and 15% T and NK cell. More irregular, more extranodal.
b. clinical presentation: lymphadenopathy, neutropenia/thrombocytopenia/anemia, infections, constitutional symptoms (fever, weight loss) if disseminated.
Non-Hodgkin lymphomas types
Diffuse large B cell Follicular lymphoma CLL/SLL MALT lymphoma Mantle cell lymphoma Primary mediastinal large B cell lymphoma Burkitt and others...
What distinguishes a reactive and malignant B cell lymphoma lymph node
the expression of either kappa or lambda light chains can confirm clonality and distinguish from a reactive node
t(14,18)
follicular lymphoma
t(11,14)
mantle cell lymphoma
t(8,14)
Burkitt lymphoma
t(2,5)
anaplastic large cell lymphoma
immunoperoxidase show
light chains in the lymph node to reveal monoclonal origin
Stage system for Hodgkin lymphoma
1 one area
2 two areas
3 areas on both sides of diaphragm
4 extranodal
when should treatment be done for lymphomas?
when there is significant organomegaly, anaemia, thrombocytopenia, neuropathy, amyloidosis or hyperviscosity.
What is the broadest effective drug treatment for lymphoma
Rituximab, anti-CD20
Marginal zone lymphomas
low grade, arise from marginal zone of B cell germinal follicles
Follicular lymphoma
a. 25% of NHL, average age 60.
b. genetics t(14,18) leading to constituitive BCL-2 expression (reduced apoptosis).
c. grading I or II depending on amount of centrocytes -> centroblasts). III is severe with marrow involvement. staging same as HL.
centrocytes v. centroblasts
During this process of rapid division and selection, B cells are known as centroblasts, and once they have stopped proliferating they are known as centrocytes.
Mantle cell lymphoma
a.
b. origin: derived from pre-germinal centre cells localized in the primary follicles or in the mantle region of secondary follicles.
c. immunophenotype: CD19, CD5, CD22, CD23A.
d. genetics: t(11,14) IgH-cyclin D1.
Immunophenotype of mantle cell lymphoma
CD19, CD5, CD22, CD23A.
Last two distinguish from CLL
Diffuse large B-cell lymphoma
a. cp: rapid lymphadenpathy, infiltration to marrow, GI, brain, spinal cord, kidneys.
b. genes: BCL-6 gene on chromosome 3, sometimes the BCL-2 translocation(20%).
Most common genetic abnormalities in diffuse large B-cell lymphoma
BCL-6 gene on chromosome 3, sometimes the BCL-2 translocation(20%).
Burkitt lymphoma genetic abnormality
overexpression of MYC t(8,14) in nearly all cases.
Burkitt lymphoma (endemic) clinical presentaiton
cp: massive lymphadenopathy often of jaw in children
Burkitt lymphoma (sporadic) clinical presentaiton
GI cancers
Burkitt lymphoma lymph node histology
“starry sky” due to large clear tingible body macrophages with homogenous background
Angioimmunoblastic lymphadenopathy
usually occurs in elderly patients with lymphadenopathy, hepatosplenomegaly, skin rashes and a polyclonal increase in serum IgG.
Mycosis fungoides
chronic cutaneous T-cell lymphoma that presents with severe pruritus and psoriasis-like lesions. Ultimately, deeper organs are affected, particularly lymph nodes, spleen, liver and bone marrow.
Sézary syndrome
dermatitis, erythroderma, generalized lymphadenopathy and circulating T-lymphoma cells. CD4s have a folded or cerebriform nuclear chromatin.
Anaplastic large cell lymphoma
particularly common in children. The disease is CD30-and usually associated with the t(2; 5) (p23; q35) translocation. This leads to overexpression of anaplastic lymphoma kinase (ALK). It has an aggressive course characterized by systemic symptoms and extranodal involvement.
T cell lymphoma types
mycosis fungoides Sezary (leukemic form of MF) Angioimmunoblastic T cell lymphoma Anaplastic large cell lymphoma Adult T-cell leukemia/lymphoma
What 4 major factors must a doctor consider when he/she decides if cure is possible for a patient with lymphoma?
tumor histology (indolent/aggressive, B or T cell)
tumor stage
condition of patient
available therapies
*Name the most common indolent lymphoma. Aggressive lymphoma?
indolent:
aggressive: diffuse large B cell lymphoma
*Be able to stage a patient with lymphoma
(done usually by CAT scan or PET) I. one node II. two nodes III. nodes on both sides of diaphragm IV. organ involvement
*What are the major treatment decision differences between indolent and aggressive lymphomas?
Aggressive lymphoma: treat with aggressive chemo/radiation immediately. Patients will often be cured. Often low stage.
Indolent lymphoma (low grade): wait to treat until symptomatic. Usually high stage. Less likely to be cured. Slow progression.
*Understand the mechanism and sites of action of rituximab and ibrutinib.
Rituximab: anti-CD20 (complement, NK, and phagocytosis of B cell)
b. ibrutinib: anti-bruton tyrosine kinase (blocks BCR from signaling NFkB signalling)
*What is the name of the most common cutaneous lymphoma and what cell can you find in the blood in some of these patients?
mycosis fungoides
*What is a common complication of radiation therapy in young Hodgkin’s Disease women?
Solid breast tumors
*Name two complications of CLL.
Lymphocytosis Lymphadenopathy Splenomegaly Anemia Autoimmune cytopenias Hypogammaglobulinemia
*Name poor prognostic abnormalities in CLL.
High Stage
Increased rate of lymphocyte doubling time
Beta 2 macroglobulin (higher is worst)
Deletion 17p, TP53 mutations,11q deletion
Unmutated VH genes, ZAP-70, CD 38, (means less differentiated)
*When is BMT used in Lymphomas?
relapse
Clinical presentation of lymphoma
lymphadenopathy
night sweats
weight loss
What virus is commonly associated with lymphoma after transplants?
EBV
Complications of lymphoma
a. Lymphadenopathy obstruction
b. Replacement in bone marrow -> pancytopenia
c. Reduction in functional lymphocytes -> hypogammaglobulinemia
d. tumor productions: uric acid, calcium
e. paraneoplastic (AHA, ITP, neuropathy)
What are the indolent lymphomas
follicular B cell
CLL
MALT lymphoma
Mycosis fungoides
Lymphocytic grading system
by increasing numbers of centroblasts present, meaning that mutation happens earlier
What are the aggressive lymphomas
Diffuse large B cell
Mantle cell
Peripheral T cell lymphomas (NOS, Angioimmunoblastic, anaplastic)
What are the highly aggressive lymphomas
Burkitt’s
T cell lymphoblastic lymphoma
What is included in the international prognostic index for aggressive NHL survival?
A- age >60 P- performance status L- LDH elevated E- extranodal sites S- Stage 3-4
positives increase risk or mortality
Therapy for aggressive lymphoma
a. CHOP (chemo)
b. Antibody therapy (rituximab)
c. radio-immunotherapy
d. short course chemo + radiation
e. BMT for relapse
What infections are associated with lymphoma?
HIV (primary CNS esp.)
HHV8 (leads to primary effusion lymphoma and Castleman’s)
HTLV-1 (T cell lymphoma)
EBV (Posttransplant lymphomas, nasopharyngeal)
H. Pylori (MALT lymphoma)
Clinical manifestation of Mycosis Fungoides:
a. Indolent stage: Eczema
b. Invasive tumor stage: ulceration, Sezary syndrome with large numbers of B cell circulating in the blood causing erythrodermis.
PBS of sezary syndrome in MF patient?
cerebriform large, clefted nuclei in T cells.
Angioimmunoblastic T cell Lymphoma
Highly polymorphic background
Constitutional symptoms
Hypergammaglobulinemia
Autoimmune hemolysis
Anaplastic Large Cell Lymphoma
30% childhood lymphomas
Young Adults
Mediastinal presentations
*Favorable if ALK+; unfavorable if ALK-
Hodgkin’s Disease vs. NHL
Different mode of progression Same staging Same staging tests Early stage: treat with short course chemotherapy and focal radiation to area of disease or radiation alone or chemo alone Late stage: treat with chemotherapy ABVD Good prognosis
How does Hodgkin’s lymphoma usually progress?
Hodgkin usually progresses from one lymph node to surrounding. Makes good for radiation because it doesn’t skip around. These patients do better than NHL. Hodgkins has such a high cure rate, so we are very concerned about later diseases.
Late complications of chemo Rx for Hodgkins
Acute leukemia and myelodysplasia Solid tumors-breast, lung, stomach, bone, soft tissues Coronary artery disease Radiation and chemotherapy pneumonitis Infertility Hypothyroidism
Chronic Lymphocytic Leukemia
a. indolent, low grade B cell malignancy
b. clinical presentation: Usually patients > 50 yo. Often asymptomatic.
c. complications: Lymphocytosis
Lymphadenopathy
Splenomegaly
Anemia
Autoimmune cytopenias
Hypogammaglobulinemia
Staging system of CLL
…
Treatment of CLL
a, Chemo drugs
b. rituximab (CD20), alemtuzumab (CD52)
c. radiation
d. corticosteroids
(not done until CLL is problematic)
Hairy cell leukemia
massive splenomegaly
When do you do autologous transplant?
when the cancer will be responsive to chemo. The goal is to temporarily remove bone marrow so that intense chemo/radiation can be used. And get to a low enough burden where self immune system can do the rest.
When do you do allogenic transplant?
When there is a problem with the patient’s own bone marrow, or you need a donor’s cells to fight the recipient’s leukemia.
