Lymphoma Flashcards
What are lymphomas?
Lymphomas are a group of diseases caused by malignant lymphocytes that accumulate in lymph nodes and cause characteristic clinical features of lymphadenopathy.
What are the two major subdivisions of lymphomas?
Hodgkin and non-Hodgkin lymphoma.
How is this characterization done?
Based on the appearance of Reed-Sternberg cells in Hodgkin lymphoma.
What is the purpose of the cells seen in Hodgkin lymphoma?
The RS and associated mononuclear cells are neoplastic whereas the infiltrating inflammatory cells are reactive
What is the lineage of the RS cells?
Studies have suggested that the RS cells are of B-lymphoid lineage.
What virus has been detected in over 50% of Hodgkin tissue?
EBV
At what age is Hodgkin most likely to present?
Can present at any age but is rare in children and has a peak incidence in young adults.
Is Hodgkin most likely to present in a specific gender?
2:1 predominance in males
What are the most common symptoms of Hodgkin lymphoma?
- Painless non-tender, asymmetrical, firm, discrete and rubbery enlargement of superficial lymph nodes. 60-70% cervical lymph nodes 10-15% axillary nodes 6-12 inguinal nodes.
- Modest splenomegaly in 50% of patients
- Weight loss, profuse night sweats, weakness, fatigue, anorexia
What are common findings?
- Normochromic mormocytic anemia is most common
- 1/3 of patients have neutrophilia; eosinophilia is frequent
- Advanced disease is associated with lymphopenia and loss of cell mediated immunity
- Platelet count normal or increased in erly disease reduced in later stages
- Serum lactate dehydrogenase is raised initially in 30-40% of cases
How is diagnosis made?
By histological examination of an excised lymph node (polyploid multinucleate RS cell is central to diagnosis four classic types.
What is the immunophenotype present in Hodgkin Lymphoma?
1.CD30 & CD15 RS cells
2.
The presence of infiltrating of what infiltrating cell is a negative prognosis?
Macrophages
What are the four classic types of Classical Hodgkins?
- Nodular lymphocyte predominant (BEST PROGNOSIS)
- Nodular sclerosing (women>men)
- Mixed cellularity (most associated with EBV)
- Leukocyte depleted (worst prognosis)
What features give the best prognosis?
Lymphocyte rich histology
How is clinical staging performed?
Through X-Ray, MRI, and CT
What is absent from Nodular lymphocyte predominant?
Reed-Sternberg cells are absent, PAX-5 positive
How is stage I characterized?
Stage I indicates involvement in 1 lymph node are.
What does stage II involve?
Stage II indicates disease involves 2 or more lymph nodal areas confined to one side of the diaphragm.
What does stage III involve?
Disease involves lymph nodes above and below the diaphragm
What is Stage IV?
Stage IV indicates movement outside the lymph node areas and refers to diffuse or disseminated disease in the bone marrow, liver and other extra nodal sites.
What is the treatment for HL?
Radiotherapy, chemotherapy or a combination of both.
In what stages is Radiotherapy curative by itself?
Stage I and IIA
What therapy is used for Stage III and IV?
Chemotherapy ABVD Adriamycin, Bleomycin, vinblastine, and Dacarbazine
What are some of the modalities used in mordern lymphoma diagnosis?
- Clinical features
- Imprint cytomorphology
- Routine H&E
- Immunophenotyping
- Flow cytometry
- Immunochemistry - Routine Karyotyping
- Molecular genetics
- DNA
- FISH
- PCR - RNA
- CISH
- RTPCR
What are the immunochemical markers in Follicle center Lymphoma?
- Surface Ig
- CD10
- CD19,CD20,CD22,CD79a
What is the abhorrent protein over-expressed.
BCL-2 causing increased cell survival due to reduced apoptosis
What is the translocation in Follicular lymphoma?
t(14;18)
What is the translocation in Diffuse large B Cell Lymphoma?
T (V;3) sometimest(14;18)
What is the over expressed protein?
BCL-6 in most but also BCL-2-IgH
What is significant about Diffuse Large B-Cell Lymphoma?
It is the most common Non Hodgkins Lymphoma.
How can you differentiate between Follicular and Diffuse Large B cell Lymphoma?
Diffuse Large B cell Lymphoma has extranodal involvement and RAPID DIVISION where as FOLLICULAR LYMPHOMA has slow mitosis and few tingible body macrophages..
What is the immunophenotype of affected cells in Diffuse Large B-Cell Lymphoma?
- CD10
- CD20
- CD19
What is the treatment for Diffuse Large B-Cell Lymphoma?
CHOP + R-CHOP
What is the characteristic Morphological presentation of Burkitt’s lymphoma?
Medium sized cells, basophilic cytoplasm with starry sky appearance.
What are the translocations present in Burkitts’?
t(8:22), t(8:14) the most common, t(2;8)
What is the over expressed in Burkitt’s lymphoma?
c-MYC oncogene translocated to the IgH heavy chain gene on chromosome 14 turning it on also the IgL and IgK gene can be invvolved based on the translocation
What viral infection is associated with Burkitt’s?
EBV in the African
Is there a viral component to sopradic Burkitt’s?
No
What is the classic presentation of the two forms of Burkitt’s?
- African form involves the jaw
2. Sporadic form involves abdomen and pelvic lesions
What are the immunophenotypes present in cells of Burkitt’s lymphoma?
1.CD19, CD20, CD22, CD79 AND Ki-67
What are the indolent lymphomas?
- Follicular
- Small lymphocytic/Cll
- MALT lymphomas
- Mycosis fungoides
What are the Aggressive lymphomas?
- Diffuse-except small lymphocytic
- Large cell
- Mantle Cell
- Peripheral T-Cell
What are the Highly aggressive lymphoma?
- Burkitt’s and non-Burkitt’s small cleaved
- T-Cell lymphoblastic
- Primary Nervous system lymphoma
What are the characteristics of indolent lymphomas?
1Higher stage
- Slower progression
- Response to simple therapies
- Incurable except stage I-II
- Survival independent of early treatment
- Treat when symptomatic
- Treat when symptomatic
What are the characteristics of Aggressive Lymphomas.
- Often Lower stage
- Rapid progression
- Require more complex therapies
- Potentially curable
- Early therapy required
What viral infection is commonly associated with lymphoma after transplant?
EBV
What lymphomas are associated with HIV infection?
Primary CNS, Karposi’s sarcoma
What lymphomas are associated with HHV-8 infection?
Karposi’s sarcoma, and primary pleural effusion lymphoma
What lymphomas are associated with HTLV-1?
Peripheral T-Cell lymphoma
What lymphomas are associated with EBV infection?
Post transplant, and primary CNS lymphoma
What lymphomas are associated with H. Pylori infection?
MALT lymphoma
WHat are Sezary cells?
Sézary cells are medium to large T-lymphocytes with ceribriform nuclei and scant cytoplasm. The nucleus has been said to resemble a monocyte nucleus.
What is Mycosis Fungoides?
The most common cutaneous lymphoma. Progresses to Sezary syndrome.
What is Sezary syndrome?
Presents as a disseminated disease with widespread skin involvement erythroderma, lymphadenopathy, and circulating lymphoma cells (Sezary cells)
What is the worst prognostic indicator in CLL?
Del 17q with P53 involvement and Beta 2 microglobulin
*What 4 major factors must a doctor consider when he/she decides if cure is possible for a patient with lymphoma?
- Tumor Histology
- Tumor Stage
- Condition of patient
- Available therapies
Name the most common indolent lymphoma.
Folicular lymphoma
What are the major treatment decision differences between indolent and aggressive lymphomas?
Indolent lymphomas usually have good long term prognosis the recommended course is to closely monitor the patient unless the lymphoma directly interferes with the daily living of the patient aggressive lymphomas should be treated as soon as discovered.
What is the mechanism of action of rituximab.
A monoclonal antibody against CD20, binds CD20 and recruits immune effector functions (complement) to mediate lysis. Used in NL
What is the mechanism of action of ibrutinib?
A selective inhibitor of BTK and prvents signal transduction and cell proliferation
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, Sezary cells.
What is a common complication of radiation therapy in young Hodgkin’s Disease women?
Breast cancer and sometimes infertility
Name two complications of CLL.
- Lymphocytosis
- Lymphadenopathy
- Splenomegaly
- Anemia
- Autoimmune cytopenias
- Hypogammaglobulinemia
Name two poor prognostic chromosome abnormalities inCLL.
- Del 17p (P53)
- Unmutated VH Ig genes
- Zap 70 expression
- CD38
When is BMT used in Lymphomas?
Relapse patients.