Flashcards in Hematologic Malignancies V: B-cell lymphomas/leukemias Deck (71)
What happens to B cells if they react with the host, or fail to react with the pathogen?
they are induced to die – and their corpses litter the field in the form of macrophages containing remnants of their nuclei. The remnants tend to pick up hematoxyin – they are “tingible bodies.”
T or F. In general, malignancies which appear to derive from well differentiated cells are less aggressive.
T. These are termed chronic leukemias while those dealing with bone marrow precursor cells are termed acute leukemias.
But there are many exceptions.
Another general rule: malignancies which appear to derive from well differentiated cells (chronic) can transform into more aggressive forms (acute).
If an evil genius wanted to cause a B-cell malignancy, he (or she) would probably start by finding a way to translocate an oncogene to an Ig promoter. This is a key pathogenetic point and you need to know it.
It is highly likely that B and T cells precursors are predisposed to this type of cancer-causing translocation because somatic DNA recombination is an essential part of their development.
T or F. Most lymphoproliferative diseases manifest themselves in more than one organ system.
T. If the bloodstream is the predominant target, we use the term “leukemia.” If not, we use the term “lymphoma”.
In many cases the two overlap.
What happens in follicular lymphoma?
an oncogene (Bcl-2) translocates to an Ig promoter, leading to overexpression, and subsequent lymphoproliferative disease occurs primarily in lymph nodes
What is another example of a lymphoproliferative disease that involves a translation of an oncogene to an Ig promoter?
What is an example of a lymphoproliferative disease that does NOT involves a translation of an oncogene to an Ig promoter?
Chronic lymphocytic Leukemia (small lymphocytic lymphoma)
CLL derives mainly from what cell?
from the most mature forms of B-cells. Most of those are inactive “memory B-cells”. Some are found in the “marginal zone”, a poorly defined region just outside the mantle zone.
Clinical presentation of CLL?
lymphocytosis in older males. High familial incidence
What are the main sites affected in CLL?
peripheral blood more than bone marrow, lymph nodes
in peripheral blood you will see small lymphocytes with little cytoplasm called "smudge" cells
How is CLL diagnosed?
-confirmed by immunophenotyping (flow cytometry).
Again, the patient’s lymphocytes are small with scant cytoplasm and mature (dense) chromatin.
What is unique about the appearance of lymph nodes in CLL?
- characteristic “pseudofollicular” appearance in lymph nodes.
- The pseudofollicles appear to be collections of slightly larger cells which are undergoing DNA synthesis and mitosis.
What abnormalities are normal in cytogenetic analysis of CLL?
80% show abnormalities by FISH
most common to least:
-del11q22-23, del17p13(p53 region)
Immunophenotype of CLL?
Light chain restricted (kappa or lambda),
ZAP-70, CD38 (presence of bad= bad prognosis)
Does a 17p deletion indicate a good or bad prognosis in CLL? What about 13q?
17p (deletes p53)= BAD
What are some other prognostic markers in CLL?
-presence of >30% smudge cells (good)
-an increasing fraction of immature forms (“prolymphocytes”; bad)
-certain genetic features.
Again: P53 (located on 17p) is a bad player in a number of malignancies and is a part of your genome with which you should become intimately familiar.
CLL is common, and at diagnosis you must distinguish it from a more aggressive lymphoproliferative disease with some similar properties: _______
Mantle cell lymphoma
normal counterpart: mantle cell
What is a key difference between CLL and MCL?
no proliferation centers in the lymph nodes in MCL
Clinical presentation of MCL?
Lymphadenopathy and/or Lymphocytosis in older males.
Can look clinically like CLL at presentation.
What are the main sites affected in MCL?
lymph nodes more than bone marrow, spleen, peripheral blood, and GI tract
Morphology of MCL?
peripheral blood: small lymphocytes with little cytoplasm (aka smudge cells)
Lymph nodes: usually homogeneous effacement , 'starry sky'
Immunophenotype of MCL?
light chain restricted (kappa or lambda)
**CD20 strong, CD23-***
What genetic defect in common in MCL?
t(11;14)(q13;q32) (IgH;Cyclin D1) is ALWAYS seen BY FISH
translocation of an oncogene to the IgH promoter
Overexpression of cyclin D1 (CCND1) pushes the cell through the cell cycle (G1 phase to S-phase)
Is CML more or less aggressive than CLL?
key clinical predictors: Ki-67 immunization (mitotic rate)
What is normal counterpart in Burkitt lymphoma (sporadic)?
memory B cells
same in endemic Burkitt lymphoma
Clinical presentation of Burkitt lymphoma (sporadic)?
abdominal mass in children or young adults. Higher incidence in HIV+ individuals
Primary involved sites in Burkitt lymphoma (sporadic)?
ileo-cecal area/ ovaries/kidneys
Morphology of Burkitt lymphoma (sporadic)?
intermediate sized lymphocytes with very blue (basophilic) cytoplasm, unusual cytoplasmic vacuoles, and more variation in nuclear size and shape than we see in the low grade lymphomas like CLL/SLL. (same in endemic BL)
The cells are growing fast, and they die fast too - with the dead cells being taken up by macrophages scattered around in the tumor (the large cells with clear cytoplasm, which at low power make the tumor look like a ‘starry sky’). You can see dark fragments of dead nuclei in some of the macrophages. usually homogeneous effacement in tissue
Clinical presentation of endemic Burkitt lymphoma?
Jaw/facial bone mass in a child (age 4-7) in a p. falciparum malaria-endemic area (Ghana, Papua New Guinea)