(From Dr. Coutinho, 28 Sept 2000, by Brian Buschman)
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Nodular lymphomas are almost always B-cell related and have a better prognosis.
Diffuse lymphomas can be either B or T-cell related and since they are disseminated in the circulation they have a worst prognosis. Nodular lymphomas may become diffuse lymphomas.
Acute leukemias are based on problems with immature cells. Problems often include shortage of the mature cell type.
Chronic leukemias are problems with mature cells.
Multiple myeloma is a cancer of the plasma cells in the osseous system. Since it is plasma cell related they produce too much Ig usually IgG or IgA and often with BJP. The BJP production leads to myeloma kidney.
MM is often a disease of other cell types that express plasma cell antigens. Various myeloma cells are dependent on IL-1 for differentiation.
Myeloma cells replace most of the marrow cells and lead to destruction of bone by activating of osteoclasts. This causes the bone to be replaces with red-gelatinous tissue. IT also causes hypercalcemia leading to Metastatic calcification. The bones appear to have “punched-outs” on x-ray.
It is a very systemic disease with a poor prognosis.
Langerhans cell histiocytosis is a problem with Langerhans cells (APCs of the skin). The cells have a tennis racket looking appearance called HX bodies or Birbeck granules. They look like rods with a dilated middle or end.
LCH appears in three forms:
1) Acute disseminated LCH (or Letteret-Siwe disease) is a form with LCH all over the body. It usually hits infants and prognosis is poor as with all disseminated disease. Erosion of tissues may be visible on x-ray.
2) Unifocal LCH has isolated proliferative legions, often in the bone. Being unifocal the prognosis is good.
3) Multifocal LCH has problems in multiple places involving bony erosions. It’s prognosis is better then acute disseminated but worse then unifocal.
Hodgkin’s disease starts at a single node or a single chain of nodes and then it spreads. It is based on a target cell that is not yet identified but HD has a classic Teed-Sternberg cell (RS). HS tends to strike young adults (mostly male except for nodular sclerosis) but it has a very good prognosis if caught early.
The classic RS cell is large with a double nucleus surrounded by a clear perinuclear halo. There are variations on the RS cell such as the lacunar cell of nodular sclerosis that shows a single nucleus with many small nucleoli.
There are four subtypes of HD:
1) Mixed cellularity HS involves infiltration of mixes of all types of cells. This one has the classis RS cell showing off it’s CD15 and CD30.
2) Lymphocyte predominance is an infiltration of small lymphocytes and benign histocytes. It is of B-cell origen so it sort of resembles NHL. It has abnormal RS cells that do not have CD15 or CD30. Rather it shows CD20 and CD45 (CD45 is typical of most malignant B-cells).
3) Nodular sclerosis is the only HD form that is more common in women then men. It has colagenous bands that divide the nodes. This type has an excellent prognosis.
4) Lymphocyte depletion is not important for Dr. Couthino.
HD starts at a specific site (whereas NHL starts all over the place) and spreads systemically to the spleen, then liver and then extranodal sites. EBV is a suspected etiological agent.
HD and NHL progress through four stages based on severity:
I. Involves a single node or site.
II. Involves more then one node or site on the same side of the diaphragm.
III. Involves nodes on both sides of the diaphragm.
IV. Involves nodes and non-nodal sites all over the body.
SLL is indistinguishable from CLL and often one leads to the other. It strikes older patients and has an average survival of 4-6 years.
You will see small lymphocytes in the bone marrow and you will see “smudge cells.” These smudge cells are crushed nucli of lymphocytes. They possess the normal-B cell markers as well as CD 5. Like many other it can transform to diffuse large B-cell lymphoma.
Follicular lymphomas are B-cell proliferations that rarely involve the extranodal sites or peripheral blood. Survival is about 7-9 years but decreases rapidly if the condition changes to DCL.
Follicular lymphoma patients exhibit t(14:18) resulting in our expression of bcl-2 and show CD10.
DCL is usually a B-cell. Some show t(14:18) indicating transformation from follicular lymphoma. They express markers CD19 and CD20. It usually presents at a single site.
BL is a small lymphoma divided into three types. BL shows a “starry-sky” appearance from the view of tightly packed B-cells that have multiple prominent nucleoli.
They often show a t(8:14) and a high mitotic index.
Types of BL include:
1) African (endemic) endemic type.
2) Sporadic type
3) HIV related type.
The African type and some of the HIV type demonstrate the EBV.
Mycosis fungoides is a TH cell disease that originates in the skin and shows a cerebriform nucleus. Sezary syndrome is a type of MF with Sezary cells that have the cerebriform nucleus that sometimes are circulating in the blood. Sezary syndromes has an exfolative erythroderma.
Adult T-cell lymphoma/leukemia is caused by HTLV-1. The rumor cells are TH cells that are multinucleated. It is rapidly fatal causing demyelination of the CNS.
LPL is a B-cell neoplasm of the elderly that secretes monoclonal IgM. Symptoms are those of Waldenstrom’s macroglobulinemia. It has Russell bodies which are red globs of Ig but it does not cause bony erosions.
It eventually effects most all systems and is incurable with a 5 year survival.
ALL is a B or T-cell precursor leukemia in children. It is primarily B-cell which is seen mostly in children. B-cell ALL is see mostly in little kids while T-cell type is seen more in teenagers.
Being immature the cells lack surface Ig. They are also related to either t(9:22) with a bad prognosis (this is a shorter version of the Philly chromosome of CML) or related to t(12:21) which has a better prognosis.
Clinically they show a rapid onset, fatigue, fever, bleeding, lymphadenopathy and bone pain.
First if you want to differentiate ALL from AML you look for TdT or peroxidase-positive granules. ALL has no peroxidase positive granules. AML rarely had TdT (which is a DNA terminating polymerase). AML often has red-staining Auer rods.
Mo – Minimally differentiated AML which shows the rough structure of the myeloblasts and does not have Auer rods.
M1 – AML without differentiation are still immature and do not show many granules but now have Auer rods.
M2 – AML with maturation is a result of t(8;22) and has Auer rods.
M3 – Acute pro myelocyte leukemia which has Auer rods and hypergranular promyelocytes. Young patients develop DIC because of the excessive granules. It often has the t(15;17) which moves the RAR-a gene next to the APL. This causes it to go out of remission with the metabolism of retinoic acid.
M4 – Acute myelomonocyte leukemia. There is some differentiation of monocytes and myelocytes. Myelocytes resemble M2 cells. Monoblasts have nonspecific esterase (NSE).
M5 – Acute monocyte leukemia occurs in older patients with a high incidence of organomegaly. Type M5a is made of monoblasts and M5b of monocytes. Monoblasts lack Auer rods but are NSE positive.
M6 – Acute erythroleukemia is seen in the elderly with predominance of proerythroid cells.
M7 – Acute megakaryocytic leukemia with a megakaryocyte predominance. Often with plenty of specific antibodies against GPIIb/IIIa.
Myelodysplastic syndromes is made of myeloid stem cells that are hypercellular but just don’t work properly. It can be idiopathic in old people or may be seen in anybody after 2-8 years of radiation therapy. The radiation obviously causes the whole system to go haywire. It causes pancytopenia. The hypercellular in the BM is stimulated to try to fix the pancytopenia but the cells just don’t work properly.
Chronic myelogenous leukemia occurs in adults and involves the Philly chromosomes, t(9:22) forming the bcr-abl gene causes extra tyrosine kinase activity. It can be recognized by a high leukocyte count (>100,000) mostly neutrophils and a few metamyelocytes. You see “sea-blue histocytes.”
Clinical presentation includes dragging abdomen, lack of AP. It starts out slowly and then after about three years some people speed up and symptoms get worse over time and in others there is a blast crisis that occurs all of a sudden. The blast crisis is a rise in blasts usually myeloblasts since it is a myelogenous leukemia.
Polycythemia vera has a hypercellular BM with a greatly increased Hct with a low level of EPO. Patients shows signs of increased blood viscosity such as cyanosis from pooling of blood in peripheral places. They may have enlarged liver and spleen that are painful. There is a very high RBC turnover causing hyperuricamia and gout in a few.
After a while there will be a spent phase where they run out of ability to make sufficient RBCs and there is fibrosis of the marrow. The spleen and liver take over hematopoiesis so they will enlarge here. It can also transform to AML.
This is not that important but is a platelet increase over 600,000. It is a disease of exclusion because the condition may be caused by other MPDs.
It looks like the spent phase of things like PCV where there hematopoiesis is transferred to the spleen and liver. It is accompanied by fibrosis of the BM caused by fibroblast mitogens PDGF and TGF-b. There is reduced Hct and a left shift. Some RBCs develop a tear-drop shape.
Again there is a dragging sensation in the abdomen and like with PCV there is hyperuricamia and secondary gout.
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