GENERAL NOTES:
--myeloid neoplasms incl: leukemias, myelodysplastic syndromes, histiocytoses, plasma cell dz
--malignant neoplasm of blood-forming tissue-->marrow replacement
--decreased apoptosis of cells --> increase in #'s
--ETIO: HTLV-1, oncogenes (p53), envir: EMF, benzene, radiation, x-rays, chemo drugs
--malignancy is found in 50% of pts with unexpected increased platelet counts (esp CML)
--acutes have immatures in PB, esp blasts
--chronics have more mature cells
--over 30% blasts in marrow usu means leukemia
--best way to differentiate btw B-cell and T-cell types: immunophenotyping


MYELODYSPLASIA SYNDROMES = MDS
--MDS considered "pre-leukemic"-->ANLL (acute nonlymphocytic leukemia)/AML (acute myelogenous leukemia)
--A heterogenous group of disorders that result in ineffective hematopoiesis.
--proliferation of abnormal clones of hematopoietic cells in bone marrow-->cytopenias-->extramedullary hematopoiesis-->hepato- & splenomegaly
--BM mb normal or hypercellular
--BM contains < 30% blasts
--S/Sx: fatigue, weakness, anorexia, wt loss, may bleed easily and have increased infx
--LABS: macrocytic anemia with anisocytosis, thrombocytopenia with variations in PLT size
--WBCs mb N/H/L, may see MONOcytosis and up to 5% blasts in PB

ALL = ACUTE LYMPHOCYTIC LEUKEMIA
--80% occurs in children aged 3-5 (ALL my children), the other 20% in adults
--most common malignancy in children (age 4 when pre-B lymphoblasts peak)
--2500 new cases/year
--high rate of mitosis --> aggressive growth, abrupt onset
--2x as common in whites
--thrombocytopenia in 80% (decreased PLTs)
--WBC count varies
--mostly proliferation of B-cell precursors (in children)
--sometimes presents in male adolescent w/ T-cell precursor (pre-T blasts peak when thymus reaches maximal size)
--lymphoblasts common in peripheral blood
--anemia in 90%
--Dx: bone marrow biopsy shows 30%+ leuks
--Prog: best if 3-7 years old with WBC's under 25,000 and no CNS dz
--PROG: 90% of children achieve remission, "partial" = 50% reduction, complete = no cancer detectable on CT scan: 2/3 of that 90% can be considered cured = no return of cancer
--half of pts have CNS dz
--S/Sx that relate to depression of marrow: fatigue, fever, bleeding (petechiae, epistaxis, easy bruising), pallor, infx
--S/Sx: bone pain and tenderness (dt marrow expansion and infiltration of subperiosteum), generalized LAD, spleno/hepatomegaly, testicular involvement
--S/Sx w/ CNS involvement: H/a, vomiting, nerve palsies dt meningeal spread

AML = ACUTE MYELOGENOUS LEUKEMIA
--85-90% occurs in adults
--includes AMML (myelomonocytic)
--may follow myelodysplastic syndrome with macrocytic, normochromic anemia (30%)
--PROGnosis: poor over 50 yo
--myeloblasts common in PB
--90% have anemia and thrombocytopenia
--AUER RODS in blasts: cigar shaped cytoplasmic elements, abn lysosomes?
--increased segmented NEUTS, myelocytes and metamyelocytes in PB
--DX: BM biopsy, over 30% blasts-->leukemia

CLL = CHRONIC LYMPHOCYTIC LEUKEMIA // SLL = Small Lymphocytic Lymphoma
--30% of all leukemia (most common leuk of adults in West, 90%)
--middle age to elderly, average age 60
--2x more in males, rare in Asians
--NOT assoc w/ radiation or drug exposure (only one)
--ETIO: depends on immunodeficiency state
--Dx: sustained absolute LYMPHocyte count over 5,000* (4,500 for pathol class)
--Dx: immunophenotype
--bone marrow always involved, xsome translocations rare
--mid-age to elderly pts
--average survival 3-7, 4-6 years after Dx
--PLT low in 20-30%
--S/Sx: generalized lymphadenopathy & hepatosplenomegaly (50-60%)
--S/Sx: fatigue, wt loss, anorexia, DOE, sense of abdominal fullness
--S/Sx: GI infiltrates can --> diarrhea, malabsorption, ulceration/bleed-->less folate absorbtion-->megaloblastic anemia
--WBC's 20-150,000
--mature lymphocytes
--SLL, small lymphocytic lymphoma lumped in here, accounts for 4% of NHL, indistinguishable from CLL except for the degree of lymphocytosis (not so many lymphs)
--smudge cells* (disrupted tumor cells) --> infiltrate spleen (red & white pulp) & hepatic portal
--in PB find small lymphs with condensed chromatin and scant cytoplasm
--CLL & SLL both can TRANSFORM to agressive lymphoid neoplasm --> pro-lymphocytic transformation 15-30%, Richter syndrome/diffuse large B cell lymphoma 10% (1 yr survival)

CML = CHRONIC MYELOCYTIC LEUKEMIA
--20% of all leukemias
--age 20-50, rare in children, thought to have slower onset
--genders equally affected
--Dx: Philadelphia chromosome in 95%, (xsome #9 switch part w/ #22)
--presence of this xsome lowers prognosis
--Dx: karyotype test
--ASX when WBC's < 50,000
--SX appear when WBC's 200,000-1,000,000
--PLTs are elevated (thrombocytosis) in 60% and decreased in 10%
--some blast forms in PB
--absolute EOS and BASOs elevated
--absolute LYMPHS and MONOs may be normal
--PROGnosis: poor
--untreated-->death in ~4 years
--same incidence in males and females

HAIRY CELL LEUKEMIA = a CLL variant
--neoplasm of B lymphocytes
--most in caucasian MEN (4:1), age 40-60
--chronic if untx, mean 4 years to death from infx
--usu normocytic normochormic anemia with pancytopenia in 60%
--hairy cells are present in PB of 90% (looks hairy, has big nucleus)
--rare but distinctive, about 2% of all leukemias
--S/sx: dt pancytopenia and increased infx
--*bone marrow is always involved but cannot be aspirated ("dry taps")
--splenic red pulp infiltrated, white pulp obliterated
--hepatic triads commonly involved
--hairy cells have folded or round nuclei and modest amounts of pale-blue, agranular cytoplasm

FROM PATHOLOGY: 12 TYPES OF PERIPHERAL B-CELL NEOPLASMS
1) chronic lymphocytic leukemia/small lymphocytic lymphoma
2) B-cell prolymyphocytic leukemia
3) lymphoplastmacytic lymphoma
4) splenic and nodal marginal zone lymphoma
5) extranodal marginal zone lymphoma
6) mantle cell lymphoma
7) follicular lymphoma
8) marginal zone lymphoma
9) hairy cell lymphoma
10) plasmacytoma/plasma cell myeloma
11) diffuse large B-cell lymphoma
12) Burkitt lymphoma
(Most of these are considered NHL, non-Hodgkins. Plasma cell neoplasms are multiple myeloma, classic. Subclassic is hairy cell.)