Intro to Lymphomas Flashcards
reactive disorders
benign. cells responding appropriately to stimuli via a mixed polyclonal expansion.
neoplasm
malignant clonal expansion of a single cell. autonomous to a stimulus, can’t be controlled and eventually leads to organ replacement, functional compromise, and death.
leukemia
neoplasm that extensively involves the bone marrow and spills into the peripheral blood. Often cells native to the marrow and immature lymphocytes (lymphoblasts)
lymphoma
tumors that form solid masses, typically involving lymph nodes or related sites (spleen, GI, skin). Composed of native cells, i.e. mature lymphocytes.
CLL/SLL (chronic lymphocytic leukemia/small lymphocytic lymphoma)
low grade/indolent B cell neoplasm that always involves lymph nodes but usually has circulating peripheral blood component.
acute
immature stage of differentiation. early undifferentiated state (blast cells)
chronic
mature stage of differentiation. cyte cells.
acute term for lymphoid lineage neoplasms
precursor
chronic term for lymphoid lineage neoplasms
peripheral
components for modern classification system for non hodgkin lymphomas
morphology, immunophenotype, genotype, putative cell of origin, clinical features
where are lymphocytes derived from?
immature pluripotent cells in the bone marrow
where does maturation of lymphoblasts take place?
bone marrow (b cells) and thymus (T cells)
lymphatics in the bone marrow
none! clinically important because if lymphoma cells are found in the marrow, it is indicative of stage 4, widely disseminated disease
difference between primary and secondary follicles
primary: aggregate of naive, unstimulated, mature B cells
secondary: stimulated B cells (develop following antigen exposure). consists of germinal center and mantle. antibodies are refined
lymph node cortex
houses B and T lymphocytes. divided into perifollicular T cell rich zone and the B cell rich follicles
lymph node medulla
location of plasma cells
multiple myeloma
malignant plasma cells home in on bone marrow instead of staying confined to medulla
what occurs within germinal centers?
antibody refinement via class switching and somatic hypermutation. expansion of CD10+BCL6+BCL2- B cells
mantle of secondary follicles
rim of naive b cells surrounding germinal center. not antigen stimulated
tangible body macrophages
histiocytes gobbling up dying cells within the germinal center and laden with cellular debris
why don’t germinal center cells express BCL2?
need apoptosis to occur since so much growth and mitosis occurs within the germinal center
centrocytes
smaller quiescent activated B cells that have modified their Ig loci. migrate from dark to light zone of germinal center to make contact with follicular dendritic cells.
margin in secondary follicles
composed of B cells that have traversed the germinal center, refined their Ig’s and have become quiescent as memory or plasma cells. prominent in the spleen.
vast majority of non hodgkin lymphomas are derived from what type of cell?
mature B cells. they undergo multiple rounds of DNA damage as they refine their antibodies
why is Hodgkin lymphoma a classification of its own?
neoplastic cells don’t look like lymphocytes under the microscope and don’t resemble them immunophenotypically either. but is still of lymphoid origin (mature B cells).
small lymphomas
size is the same as a resting lymphocyte
large lymphoma
size is as big or bigger than nucleus of histiocyte
nodular lymphomas
slower acting, derived mostly from germinal center B cells, low grade lesions
diffuse lymphomas
high grade, less well differentiated
indolent
slowly growing
immunophenotype
the expression pattern of surface and intracellular protein markers in a given cell population
how to assess immunophenotype
flow cytometry and immunohistochemistry
markers of immature B cells
TdT, CD19
markers of mature B cells
CD19, CD20
markers of germinal center B cells
CD10, BCL6 (-BCL2)
markers of immature T cells
TdT, CD1a, cCD3
markers of mature T cells
CD2, sCD3, CD5, CD7
markers of T cell subsets
CD4/8
reason to karyotype lymphoma cells
look for translocations
importance of IgH
tends to dysregulate whatever it is juxtaposed next to, so that a normal gene is massively over expressed after the translocation
translocation of burkitts lymphoma
t(8;14). IgH/Myc. over expression of MYC
translocation of follicular lymphoma
t(14;18). IgH/BCL2. over expression of BCL2
what causes the symptoms of lymphomas (B symptoms)
cytokines released by the neoplasms (typically fevers, night sweats, weight loss)
