leukemia – pathology II

what are the M0, M1, and M2 phases of AML?
M0: so immature they lack cytochemical markers, but diagnosable do to myeloid markers. M1: very immature, few granules M2:mature, tend to be t(8:21) and have a better prognosis
what is a myeloid sarcoma?
a tissue mass of myeloid blasts
what is the difference between reactive and blasts?
pts with EMV/CMV, they can form downey type II cells that look large and have a lot of cytoplasm – but they lack nucleli
what are features of M3 acute promyelocytic AML?
hypergranular promyeolcytes w/many auer rods are seen; *t(15:17 – classic textbook myeloleukemia
why is acute promyelocytic leukemia treated differently?
the enzymes from the auer rods/granules can cause DIC if not treated with ATRA (all-transretinoic acid – b/c t(15:17) is PML-RARalpha). do not miss this – order fluorescence in situ hybridization (FISH) right away if auer rods are not prominent enough to make diagnosis. *however, t(11:17) are resistant to ATRA tx*
what is the M4 AML?
acute myelomonocytic leukemia with monoblasts that are specific for *non specific esterase. inv(16), this usually has a good prognosis
what are features of acute myelomonocytic leukemia?
M4 acute myelomonocytic leukemia cells have monocytic features such as cytoplasmic prominent vacuoles, convoluted nuclei, and some granules. these monocyte-derived cells will stain positive with *non-specific esterase. there will be more myeloblasts w/M4 than w/M5
what are the 2 subtypes of M5 acute monocytic AML?
5a – mostly monoblasts; which are immature, peroxidase negative, stain with non specific esterase (faint red tint) and promonocytes predominate. 5b is mostly mature monocytes. there is a similar prognosis for both, and they tend to be more monotonous than M4 myelomonocytic.
what is M6 AML?
acute erythroleukemia, (very rare); may have dysplastic erythroid precursors and over 30% myeloblasts. very blue cytoplasm, mainly seen in adults, and poor prognosis (aggressive clinical course)
what is M7 AML?
acute megakaryotic which is a rare leukemia of megakaryocyte blasts. it tends to be associated with down’s syndrome due to transient myeloporiesis which can progress to M7. it consists of giant, hard to miss cells. there is one large nucleus w/cytoplasmic blebs and these cells tend to cluster in M7. they do not express myeloperoxidase or lymphoid markers
can pts with AML have gene mutations without obvious abnormalities in their karyotype?
yes
what is the FLT3 mutation?
chr 13 mutation encoding a tyrosine kinase receptor involved in hematopoetic stem cell differentiation/proliferation -> lack of maturation/unrestrained growth. it is seen w/adverse outcome
what is the KIT mutation?
located on chromosome 4, this can be associated with other kinds of CA, it involved a member of the tyrosine kinase receptor (gain of function mutation) and is associated with a poor prognosis
what is the WT1 mutation?
the wilms tumor gene is located on chr 11 and is associated with a poor prognosis in AML pts with a normal karyotype
what is the NPM1 mutation?
the NPM1 mutation is located on chr 5 and occurs in a third of adult AMLs. usually only one allele is affecte and it is associated with a good prognosis in pts with a normal karyotype
what is the CEBPA?
seen in 15% of AMLs, this is associated with a good prognosis in pts w/a normal karyotype
what can many AMLs be treated with?
bone marrow transplants
what are the steps to performing a bone marrow transplant?
finding a compatible donor, wiping the pt’s bone marrow out, giving donor G-CSF to promote generation/peripheralization of stem cells, remove the donor stem cells using pheresis and transfuse them into the recipient.
what does post-bone marrow transplant therapy consist of? what are engraftment studies?
bone marrow bx, flow cytometery, molecular studies <- to detect minimal residual disease. engraftment studies are done to evaluate the amount of donor vs recipient cells in post-transplant marrow (situation dependent)
what is the cell of origin 85% of the time with ALL? what are some general characteristics?
B-cell precursors. they have less cytoplasm than in AML and *no auer rods. they have dense chromatin, fewer nucleolit and usually lack cytoplasmic granules
how do ALL pts present clinically?
more acute/sick, more common in children, symptoms are of bone marrow suppression. there is bone pain and tenderness, generalized lymphadenopathy, splenomegaly, hepatomegaly and testicular invovlement. CNS manifestations are also seen, this is why kids need cranial radiation
how does ALL present immunologically?
ALL cells are usually *TdT, CD19 and *CD10 (CALLA =ALL) positive – but lack surface Ig (marker of mature B cells)
how does ALL present histologically?
cells are smaller, may have mitotic figures (due to active proliferation). they will stain TdT + which is brown red
what is the prognosis for ALL pts?
about 2/3 cure for kids 2-10, thanks to chemotherapy and prophylactic CNS txs. kids less than 2 and adults are less likely to survive (kids <2 often have a translocation of the MLL gene on chr 11 is also associated with a bad prognosis). hyperdiploidy is bad, hypodiploidy is good. there is also a t(9:22), but in a different spot on the phila chr associated with CML
what are the B cell chronic leukemias?
chronic lymphocytic leukemia (CLL), b cell prolymphocyic leukemia (PLL), and hairy cell leukemia (HCL)
what are the T cell chronic leukemias?
t cell prolymphocytic leukemia (T-PLL), T cell large granular lymphocyte leukemia, and adult T cell leukemia/lymphoma, and sezary syndrome
what are chronic leukemias generally characterized by?
chronic leukemias are mature clonal disorders that may involved blood and bone marrow or infiltrate other organs (ie lymph node/spleen). they have unknown etiology except ATLL, usually affect older adults and are indolent, generally w/better prognosis (but lower cure rate)
what is the most common leukemia of adults?
chronic lymphocytic leukemia/small lymphocytic lymphoma. it show lymphocytosis, is indolent, not curable – often asymptomatic, nonspecific, easy fatigability, weight loss, and anorexia. *this can transform into diffuse large B cell lymphoma (richter transformation – nearly impossible to detect which cells will transform and large B-cell lymphoma is a more aggressive form of CLL
what will CLL show on peripheral blood smears?
profound lymphocytosis (small dark and condensed), and smudge cells (membranes are fragile)
what is an important differential to rule out with CLL?
reactive lymphocytosis; which can occur with EBV, HIV, rubella, rubeola, and varicella (usually seen in younger pts). and mature, non-reactive lymphocytosis which can happen with pertussis (but CLL will not have abundant cytoplasm) or transient stress
how does the lymph node appear in CLL/SLL?
wall to wall small lymphocytes and a lack of normal lymph node architecture
what is the immunophenotype for CLL?
CD20, 23 (mature lymphocytes), CD5 usually in T cells – but on all cells in CLL and surface Ig (from plasma cells, most mature B cells)
what is the richter transformation
progression of CLL/SLL to diffuse, large B cell lymphoma transformation
what is B-cell prolymphocytic leukemia?
this is similar to CLL, but prolymphocytes are the majority of all lymphocytes seen and express CD20. this happens usually in pts >70 and presents with the common symtoms, (weakness, malaise, weight loss). the cells are bigger w/big prominent nucleoli and the count rises rapidly
what is hairy cell leukemia?
a rare B cell leukemia seen in middle aged – elderly adults. tumor cells are seen in the bone and spleen and neoplastic cells have tiny hair-like extensions and a *fried egg appearance. the tartrate resistant acid phosphatase stains specifically for this
what is T cell prolymphocytic leukemia?
this is more rare than the B cell form, it has a higher prevalence in men and presents with splenomegaly, hepatomegaly, lymphadenopathy, and sometimes skin lesions. the CD3 marker is necessary to distinguish this from B cells. in this case: prolymphocytes >90% lymphocytes
what is T cell large granular lymphocyte leukemia?
these have toxic granules b/c large granular lymphocytes are usually 1st responders upon infection. this infection is more indolent, but with severe anemia. the mature T cell phenotype is seen and this is a pretty rare leukemia
what leukemia can be caused by a virus?
adult T cell leukemia/lymphoma which is a neoplasm of CD4+ cells infected by human T-cell leukemia virus 1 (HTLV-1 – endemic in japan/caribbean). it causes skin lesions (classic of leukemia), lymphadenopathy, peripheral blood lymphocytosis, hypercalcemia (not sure why, maybe cytokine effect). *clover leaf and flower cells distinguish it histologically
what is sezary syndrome?
the leukemia form of mycosis fungoides – a mature T cell lymphoma that presents in the skin. it presents as red patches on back/extremities (abscesses of lymphocytes called petriae in epidermis). this becomes a syndrome when it goes systemic, and is marked by mature T cells that express CD3 but not CD4 or CD8 (atypical). also, the lymphocytes upon examination have a cerebriform nuclei (brain-like appearance in EM due to many convolutions)
why do leukemia pts require blood transfusions?
b/c their bone marrow is so damaged, they need the platelet and plasma support
what are some considerations for blood transfusions?
graft-versus host disease, cytomegalovirus, and number of stem cells infused
what are controversial factors in terms of blood transfusions?
prophylatic transfusion, (don’t want to over transfuse – very generally, you want to transfuse at between 5-20,000 platelets or if bleeding), transfusion triggers (20,000 for hematopoietic stem cell transplantation patients), and transfusion dose (speculation that lowering mass of transfused platelets might encourage endogenous thrombopoietin production in patient)
what is platlet refractoriness?
pt antibodies to donor cell antigen, can happen especially someone who has had child already and may have antibodies made to certain HLA types or mult. transfusions
b/c neutropenia and infection are common in leukemia pts, why is the use of granulocyte transfusion controversial?
most studies have shown granulocytes do not work all that well
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