Term
| what cytochemical stains are characteristic of AML? |
|
Definition
| myeloperoxidase (myeloid cells); nonspecific esterase (monocytes) |
|
|
Term
| which cell surface markers are characteristic of AML? |
|
Definition
|
|
Term
| what is TdT and with which leukemia or lymphoma do we associate it with? |
|
Definition
| enzyme involved in rearranging DNA for TCR or BCR (nuclear antigen). it's expressed by lymphocytes and therefore associated with ALL |
|
|
Term
| what cell surface markers are associated with early B cells (ALL)? |
|
Definition
|
|
Term
| what cell surface markers are associated with early T cells? |
|
Definition
|
|
Term
| what are the normal counterparts of B-ALL? what surface markers do we see? |
|
Definition
| pro/pre-pre B cell (have rearranged Ig heavy chain gene, but no surface Ig yet and no CD20 yet) express TdT and CD19, cells look like small blasts, the size of lymphocytes; pre-B cell (have cytoplasmic Ig heavy chain, but no surface Ig yet) express TdT, CD19, CD20, cells are larger blasts |
|
|
Term
| in what disease do cells hide out in CNS and testes? (privileged sites) |
|
Definition
| B-ALL (usually a blood and bone marrow involvement, but there can be neoplastic infiltration of other organs and lymphoblasts may hide out in CNS and testes) |
|
|
Term
| there are 2 normal cell counterparts in B-ALL. which one is associated with a better prognosis? |
|
Definition
|
|
Term
| what age is associated with a good prognosis in B-ALL? |
|
Definition
| 2-10 years of age. less than 2 and more than 10 is associated with poorer prognosis |
|
|
Term
| in B-ALL, t(12:21) TEL-AML1 translocation associated with? |
|
Definition
|
|
Term
| in B-ALL, BCR-ABL translocation (philidelphia chromosome) associated with? |
|
Definition
|
|
Term
| in B-ALL, t(4:11) translocation (MLL gene) is associated with? |
|
Definition
|
|
Term
| what is the normal cell counterpart in T-ALL/L? |
|
Definition
| thymocyte (rearranging TCR genes) |
|
|
Term
| what cell surface markers are associated with T-ALL/L? |
|
Definition
| TdT, CD7, CD2, CD5, CD3 -/+, some CD4/CD8 (double positive) |
|
|
Term
| B-ALL is most likely to present as? |
|
Definition
| leukemia. infrequently as a lymphoma |
|
|
Term
| T-ALL/L most frequent presentation? |
|
Definition
| mass of the mediastinum or lymph nodes (breathing problem at clinical presentation); can also present as leukemia, same treatment. |
|
|
Term
| who is most at risk for T-ALL/L? |
|
Definition
| slightly older children (adolescence) - corresponds loosely to age of peak thymus development |
|
|
Term
| T-ALL/L is associated with which mutation? |
|
Definition
|
|
Term
| what is the cure rate for childhood ALL? |
|
Definition
| 85% cure rate (ph+ 10% cure rate) |
|
|
Term
| what is the normal counterpart cell in burkitt lymphoma/leukemia? |
|
Definition
| early mature B cell or germinal center B cell |
|
|
Term
| what are the surface markers for burkitt lymphoma/leuk? |
|
Definition
| CD19, CD20, surface IgM, Bcl-6 (NO TdT bc finished rearranging DNA for BCR) |
|
|
Term
| what are the 3 main clinical presentations of burkitt lymphoma/leuk? |
|
Definition
| (leukemic presentation uncommon) 1. endemic burkitt: africa, EBV assoc, children, jaw presentation. 2. non-endemic burkitt: outside of africa, few EBV assoc, children, intestinal involvment. 3. burkitt in immunosuppressed patients: extranodal, 25-35% EBV assoc. |
|
|
Term
| morphology of burkitt lymphoma |
|
Definition
| medium sized cells, very high mitotic rate and single cell necrosis (apoptosis) aggressive cancer; ingestion of single dead cells by macrophage "starry sky" appearance |
|
|
Term
| morphology of cells in burkitt leukemia |
|
Definition
| huge cells, high N/C ratio, small rim of basophilic cytoplasm and vacuoles |
|
|
Term
| what chromosomal translocations are associated with burkitt lymphoma/leuk? |
|
Definition
| c-MYC (chr 8) translocated to chr 14 (C-mu heavy chain), chr 2 (kappa light chain), chr 22 (lambda light chain). translocation of c-MYC is a diagnostic criteria |
|
|
Term
| what is required for malignant transformation in burkitt? |
|
Definition
| EBV sets the stage for the acquisition of mutations (uses CD21 as receptor to get into B cells --> blatantly infects cell or promotes proliferation and acts as a mitogen) --> c-myc translocation and overexpression of MYC protein --> further mutations necessary (p53, p14ARF/MDM2/p53) --> burkitt! |
|
|
Term
| normal cell counterpart for follicular lymphoma? |
|
Definition
| follicular center B cells |
|
|
Term
| cell surface markers for normal follicular center B cells? |
|
Definition
| surface Ig, CD19, CD20, CD10, bcl-6, NO bcl-2 |
|
|
Term
| morphology of follicular lymphoma cells? |
|
Definition
| centrocytes and centroblasts |
|
|
Term
| normal function of follicular B cells? |
|
Definition
| site of proliferation. B cells respond to Ag, undergo somatic hypermutation and isotype switching. if it has a low affinity for its Ag --> dies via apoptosis (normal GC has lots of cell death) |
|
|
Term
| what is the translocation associated with follicular lymphoma? |
|
Definition
| t(14:18). BCL2 (chr18) translocated to Ig gene (chr14)--> BCL2 overexpressed --> prevents apoptosis of follicular B cells which should die. BCL2 is "on" in interfollicular zone because long-lived memory T cells live there and we don't want them to die. |
|
|
Term
| what are 2 ways we can differentiate between regular/hyperplastic follicle and lymphoma? |
|
Definition
| stain for light chains. if regular/hyperplastic will be a mix of lambda and kappa, if neoplastic will be ALL lambda or ALL kappa. also stain for bcl-2 (normal: all bcl2 is in interfollicular zone and none in GC. neoplastic: bcl2 will stain in GC) |
|
|
Term
| clinical features of follicular lymphoma? |
|
Definition
| generalized lymphadenopathy. transformation to more aggressive form after years. |
|
|
Term
| how do we treat follicular lymphoma? |
|
Definition
| it's an indolent lymphoma, cells just sit there and accumulate (not actively dividing and no increase in metabolic activity bc theyre not really functional cells) --> resistance to chemotherapy --> patients live for a long time. |
|
|
Term
| what are the normal cell surface markers for mantle zone B cells? |
|
Definition
| CD19, CD20, CD5, usually sIgM, BCL2 |
|
|
Term
| what is the translocation associated with mantle zone lymphoma? |
|
Definition
| t(11:14); BCL1 (cyclin D1) (chr 11) translocated to Ig gene (chr 14) --> allows progression thru cell cycle (g1->s) and division. OVEREXPRESS cyclin D1 (bcl-1)! lack Ig somatic hypermutation. (in 1/3 of patients its not a translocation, its a mutation) |
|
|
Term
| clinical features of mantle zone B cells? |
|
Definition
| generalized lymphadenopathy, frequently involves intestinal tract, marrow, blood, spleen, and liver |
|
|
Term
| how does clinical course of mantle cell lymphoma compare to follicular cell lymphoma? |
|
Definition
| mantle cell is more aggressive than follicular lymphoma. have to treat patients differently - earlier and more aggressively |
|
|
Term
| normal counterpart for marginal zone lymphoma? |
|
Definition
| marginal zone B cells, postgerminal center, memory B cell |
|
|
Term
| normal cell surface markers for marginal zone B cells? |
|
Definition
| CD19, CD20, surface Ig, NO CD5 |
|
|
Term
| where are marginal zone B cells best developed? |
|
Definition
| MALT (GI tract, salivary glands, breast tissue, lung, UG tract) and spleen |
|
|
Term
| translocations associated with marginal zone lymphoma? |
|
Definition
| MALT or BCL10 upregulation: t(11:18), t(14:18), t(1:14). activate NF-kB to promote B cell survival |
|
|
Term
| what increases an individual's risk of developing a marginal zone lymphoma? |
|
Definition
| (MALT lymphoma) - associated with chronic antigenic stimulation; organ specific autoimmune disease. chronic stimulation of B cells acts as fertile ground for generation of mutations/lymphoma |
|
|
Term
| what are 3 common types of marginal zone lymphomas and the underlying disease causing them? |
|
Definition
| hashimotos thyroiditis (lymphoma in thyroid); sjorgrens (lymphoma in salivary gland); h.pylori infection (lymphoma in stomach) --> stomach tissue only has lymph tissue in inflammatory conditions --> go and treat h.pylori before it acquires mutations that make it ag-stimulation-dependent |
|
|
Term
| what is clinically distinctive about marginal zone lymphomas? |
|
Definition
| remain localized so surgery is possible. indolent. lymphocytes in MALT have unique circulation pattern - only traffic among MALT-associated tissue --> when MALT lymphoma disseminates, it only goes to other MALT tissue --> remains localized and can benefit from surgery |
|
|
Term
| what is the normal cell counterpart in diffuse large B cell lymphoma? |
|
Definition
| mature activated B cell or immunoblast; variable morphology |
|
|
Term
| what are the 3 possible etiologies of diffuse large B cell lymphoma? |
|
Definition
| 1. progression of a low-grade lymphoma (like follicular cell) that has resisted therapy 2. de novo (may be localized and more treatable) 3. immunodeficiency patients (associated with EBV or HHV) |
|
|
Term
| what is the genotype like in diffuse large B cell lymphomas? |
|
Definition
| 1. same translocation as the lymphoma it progressed from. 2. if de novo, may have translocation or mutation of BCL-6 gene --> BCL6 dysregulation |
|
|
Term
| what are the two subgroups in diffuse large b cell lymphoma that respond differently to chemo? |
|
Definition
| 1. GC-like - in GC, BCL6 is turned on and represses transcription of the p53 --> allowing somatic hypermutations to occur w/o being "repaired". BCL6 is mutated and p53 is not --> can use chemo to turn on a cell's p53 and induce apoptosis bc p53 is protected in GC (helps avoid a p53 mutation which would lead to a very aggressive hard to treat neoplasm). 2. activated-B-cell-like - genes turned on similar to activated B cells --> respond poorly to chemo |
|
|
Term
| what is the normal cell counterpart in CLL/SLL? |
|
Definition
|
|
Term
| what cell surface markers are associated with CLL/SLL? |
|
Definition
| CD19, CD20, CD5, BCL2, surface IgM and/or IgD |
|
|
Term
| how do CLL and SLL present clinicially? |
|
Definition
| CLL - predominantly leukemia with blood and bone marrow involvement. SLL - predominantly lymphoma involving LN and spleen in a diffuse pattern. eventually the 2 patterns merge |
|
|
Term
| what is CLL/SLL associated with? |
|
Definition
| autoantibody production against RBC and/or platelets --> autoimmune hemolytic anemia and/or immune thrombocytopenia (ITP); suppression of normal B cell function --> decreased Ig and infections; long-lived tumor cells resistant to therapy may transform into aggressive forms, diffuse large B cell lymphoma |
|
|
Term
| what is the genotype associated with CLL/SLL? |
|
Definition
| frequently karyotypic abnormalities but nothing pathognmonic. translocations are rare. TRISOMY 12 common. deletion of chr 13q12-14; codes for miRNA that normally inhibits translation of bcl-2 mRNA --> overexpression of bcl-2 --> cells live forever |
|
|
Term
| whats the normal cell counterpart for hairy cell leukemia? |
|
Definition
| peripheral B cell, ? stage |
|
|
Term
| what are the cell surface markers assoc with normal peripheral B cell with unknown stage (hairy cell leuk counterpart)? |
|
Definition
| CD19, CD20, surface Ig (usually IgG) |
|
|
Term
| what is the cell morphology of hairy cell leukemia cells? |
|
Definition
| small-medium cells, round/oval nucleus, abundant cytoplasm, "hairy" projections |
|
|
Term
| what are the clinical features of hairy cell leukemia? |
|
Definition
| splenomegaly (infiltration of spleen and bone marrow, also liver), marrow fibrosis, pancytopenia, few cells circulating in peripheral blood |
|
|
Term
| what treatment is used for hairy cell leukemia? |
|
Definition
|
|
Term
| characteristics of T cell neoplasms? |
|
Definition
| extranodal (skin, lung, etc); in LN in the interfollicular zone always diffuse; CD4+ subset; associated with "inflammatory" background |
|
|
Term
| how do we define T-cell neoplasms as monoclonal? i.e. how do we tell it apart from inflammation? |
|
Definition
| no easy marker. sometimes an aberrant phenotype (loss of pan-T markers) OR gene rearrangement studies for the TCR gene (only do this when neoplasm looks aggressive and we cannot distinguish b/w lymphoma and inflammatory rxn) |
|
|
Term
| normal cell counterpart for mycosis fungoides/sezary syndrome? |
|
Definition
| mature CD4+ T cells expressing adhesion molecules for homing to skin |
|
|
Term
| morphology of cells in mycosis fungoides/sezary syndrome? |
|
Definition
| cerebriform nucleus and sezary cells |
|
|
Term
| what are the clinical features of mycosis fungoides/sezary syndrome? |
|
Definition
| neoplastic T cells as single cells or clusters (pautriers abscesses) in epidermis and superficial dermis as a band-like infiltrate --> form plaque --> tumor --> neoplastic cells gain entry into lymph and blood circulation. secondary involvement of LN, blood (sezary syndrome) and other organs in sezary syndrome, skin involvement is generalized and there is an associated leukemia of sezary cells (exfoliative erythroderma) |
|
|
Term
| are there cell surface markers for mycosis fungoides/sezary syndrome? |
|
Definition
| not usually for t-cell leukemias. but there is sometimes an aberrant phenotype, loss of pan T cell marker (usually CD7) |
|
|
Term
| what is the normal cell counterpart in adult T-cell leukemia/lymphoma? |
|
Definition
|
|
Term
| what is the morphology of adult T cell leukemia/lymphoma? |
|
Definition
| cloverleaf nucleus, large pleiomorphic cell (in leukemia, lots of cloverleaf nucleus cells, in lymphoma only a few) |
|
|
Term
| what is the genotype of adult T cell leukemia/lymphoma? |
|
Definition
| CD4+ T cells with high levels of CD25 (IL2 receptor alpha chain); many with foxp3 expression - may be Treg cells. |
|
|
Term
| what is the etiology of adult T cell leukemia/lymphoma? |
|
Definition
| HTLV-1 retroviral infection of CD4+ T cells with clonal integration. virus endemic in japan (leukemic) and caribbean (lymphomatous); transmission similar to HIV, long incubation period (30-40 yrs), only minor % of infected will develop malignancy, but when it does occur its rapidly fatal |
|
|
Term
| what are the clinical features of adult T cell leukemia/lymphoma? |
|
Definition
| lymphomatous or leukemic, may involve skin; increased Ca levels d/t PTH-like hormone production by malignant cells; autocrine stimulation of cells that produce and respond to IL-2 expressing high levels of IL2 receptor; extremely aggressive disease |
|
|
Term
| what are some forms of treatment for adult T cell leukemia/lymphoma? |
|
Definition
| antibodies to IL2, antibodies to IL2 receptor - to break auto-stimulatory loop |
|
|
Term
| what is the normal cell counterpart in anaplastic large cell lymphoma? |
|
Definition
|
|
Term
| what is the cell morphology of anaplastic large cell lymphoma cells? |
|
Definition
| large, pleiomorphic, multinucleate and/or multilobed nucleus (overlap with hodgkins) |
|
|
Term
| what are the cell surface markers in anaplastic large cell lymphomas? |
|
Definition
| CD30, no lineage specific markers (no T or B cell markers) |
|
|
Term
| clinical features of anaplastic large cell lymphoma? |
|
Definition
| varied - invades LN in sinusoidal pattern (leaving LN architecture intact) or may be primary to skin or have retroperitoneal involvement. can present with mediastinal mass |
|
|
Term
| what genotype is associated with anaplastic large cell lymphoma? |
|
Definition
| t(2:5); places ALK gene (anaplastic lymphoma kinase) from chr2 next to NPM (nucleophosmin) from chr5. fusion protein is a constitutively active tyrosine kinase --> translocates to nucelus and acts as an oncogenic transcription factor |
|
|
Term
| what is a good prognosis factor in anaplastic large cell lymphoma? |
|
Definition
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