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44 Cards in this Set
- Front
- Back
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-Infxn
-Sterile inflammation w/ necrosis -Drugs (corticosteroids) LOTS of PMNs - BM production or release of PMNs (IL-1, TNF) - Activation of PMN adhesion molecules - LTB4, C5a, IL8 (less PMNs adhere to endothelial cells d/t corticosteroids) absolute PMN count is > 7000uL |
PMN luekocytosis
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-Aplastic or Myelophthistic anemia
- Immune destruction (SLE) -septic shock -Splenic sequestration -Chemotherapy lack of PMNs BM may have more or less cellularity - decreaseProduction- marrow failure - increase Destruction (d/t macs or complement) - Activation of PMN adhesion molecules (ex: endotoxins) -Malaise, weakness, fatigue -Necrotizing lesions (massive growth of organism d/t poor leukocyte response) PB- low/lack PMNs BM: more or less cellular G-CSF may help |
Neutropenia
< 2000 uL |
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- Type 1 hypersensitivity rxn (asthma)
- Invasive helminthiic infxn -Polyarteritis Nodosa -Addison’s dz (cortisol def) -Release of eosinophil chemotactic factor from mast cells (IL5) -no sequestration of eosinophils in LNs (hypocortisol) |
Eosinophilia
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-Hypercortisolism
-Corticosteroids -Corticosteroids sequester eosinophils in LNs |
Eosinopenia
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absolute basophil count > 110/uL - chronic myeloproliferative disorders
(ex: polycythemia vera) |
Basophilia
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>4000/uL in adults
>8000/uL in kids -viral -bacterial -drugs (phenytoin) -Graves dz - increase Production - decrease Entry into LNs |
Lymphocytosis
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-Infxn:
(Mono, viral Hep, CMV, toxoplasmosis) -Drugs: phenytoin -Antigenically stim lymphocytes -Prominent nucleoli and abundant blue cytoplasm |
Atypical lymphocytosis
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EBV (HSV-4)
**Kissing dz** B cells have CD21 receptor sites for EBV -PB: lymphocytosis: (60%, 7-10,000/ µL) [Atypically big, big nucleus, fine chromatin, lots cytoplasm-T cells] -LN enlarged generalized: post cervical, axillary, groin Paracortical expansion- where T cells reside -Spleen enlarged (300-500g) -Liver (atypical lymphs in portal tracts & sinusoids, focal necrosis) -EBV infects B lymphocytes; 2 forms (lytic or latent-polyclonal proliferation) -Cells spread in circulation & secrete Ab-heterophil -Ab vs. Viral Capsid Ag early: IgM late: IgG- for life -increase # of Cytotoxic T-cells/NK cells (Atypical lymphocytes in PB) -LN, spleen, liver infiltrated by atypical lymphocytes Classic Malaise, fatigue, fever, sore throat, lymphadenitis, resolves in 4-6 wks Atypical Malaise, fatigue, (+/-) fever or lymphadenopathy -Hepatitis, -Febrile rash, -Splenic rupture, B-cell proliferation (polyclonal or B-cell lymphoma) -Atypical lymphocytosis (> 20% of WBC count) - + Heterophil Ab test (detects IgM Ab against horse, sheep, bovine RBCs) - + Antiviral Capsid Ag test - increase Serum transaminases from hepatitis |
EBV
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Absolute lymphocyte count
<1500/uL is adults <3000/uL in kids -HIV (lysis of CD4 T cells) -Immunodef: Digeorge-T cells Severe combined- B and T cells -Immune destruction -Corticosteroids -Radiation (lymphocytes most sensitive cells) -Malnutrition - increase Destruction: lysis, apoptosis, immune destruction -decrease Production (radiation) - decrease Release from LNs (Corticosteroids) |
lymphopenia
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- Chronic Infxn
-Autoimmune dz - Malignancy - Response to chronic inflammation or malignancy |
Monocytosis
Absolute monocyte count > 800/uL |
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-Bacterial or viral infections
-Local or general -Large germinal centers -(+/-) PMNs & necrosis (abscess) -Scars on healing Swollen, grey/red, engorged LN (Tender, fluctuant, +/- draining sinus) |
Acute
Non Specific Lymphadenitis |
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-Follicular Hyperplasia:
RA Toxoplasmosis Early HIV -Paracortical Hyperplasia: Viruses Drugs (Dilantin) SLE -Sinus Histiocytosis: cancer 3 Patterns: -Follicular Hyperplasia: B-cell stim large germinal centers -Paracortical Hyperplasia: T-Cell stim. (Virus, drugs) -Sinus Histiocytosis: endothelial cells & histiocytes, Non-tender LN |
Chornic non specific lymphadenitis
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Bartonella Henselae
-Gram – 2 wks post scratch, 90% < 18yrs., Granuloma w/ Stellate microabscesses in germinal ctrs Axillary or cervical adenopathy Resolves in 2-3mon Skin test + for B. Henselae Ag |
Cat scratch
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calssification for lymphoid neoplasm
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morphology
cell origin clinical features genotype tumors of B cells Tumors of T cells/NK cells Hodgkins |
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Cells usually arrested in 1 stage of differentiation
- Normal LN architecture effaced Follicular /nodular -B-cells -Indolent but not curable Diffuse -B or T cells -Aggressive but curable Clonal proliferations of cells: B-Cells: (80%)- may be follicular pattern or diffuse T-Cells: (20%)- Always diffuse Histiocytes: rare, Always diffuse Practical classification of NHLs: -SLL -Follicular Lymphoma -Diffuse Lg cell Lymphoma -Sm Non-cleaved (Burkitt’s) Lymphoma -Lymphoblastic Lymphoma Classification: -- R.E.A.L.— -based on cell of origin: -B-cell (precursor/ immature, peripheral cell/mature) -T-cell (precursor/ immature, peripheral cell/mature) -Hodgkin’s Dz |
Non Hodgkins lymphoma
Non-Hodgkin’s Lymphoma (NHL) -Incidence is ↑ (d/t AIDS) -Death rate ↓ 2/3 nodal 1/3 parenchymal |
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older than 60, B cell neoplasia
most common leukemia in western world foci of mitotically active cell -> proliferaton centers scant cytoplasm LN, BM, spleen, liver infolved absolute lymphocytosis smudge cells CD5 trisomy 12 , deletion of chrome 11/12 is common hypogammaglobulinema transformation to DLBC, or pro lymphocytyc leukemia |
SLL. CLL
if lymphocytes > 4000 -- CLL |
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Nodular appearance, LN effaced
Centrocyte - small cleaved cells - nuclear chromatin course, nucleoli indistinct mixed with LARGE (centroblast) with vesicular chromatin, several nucleoli, modest cytoplasm (no apoptosis/mitosis - unlike reactive follicles) CD19, CD20, CD10, BCL6, BCL2 t(14,18) BCL2 <--> IgH locus (BCL2 prevents apoptosis ) OLDER BM has lymphoma progression to DLBC lymphoma |
follicular lymphoma
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Older Men
Cyclin D1 dysreg t (11.14) no proliferation centers Naive B cell, cleaved cell LN - dffuse/nodular pattern BM involved, also GI tract w submucosal nodules resembling polyps CD5 no CD10 |
Mantel Cell
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most impt in adults 50% of lymphomas
t(14,18) EBV< HIVm HHV8 localized mass w extranodal involvement, GIT, Brain, agressive and fatal if untreated chemo - remission 60-80% neoplastic B cell nuclei very large, forms: round, irreg cleaved nucler contours, dispersed chormatin, serveral distinct nucleoli, modest pale cytoplasm (centroblast) or large round multlobulated vesicular nucleus,2 prominant nucleoli, abundant cytoplasm (immunoblast) |
Diffuse Large B cell Lymphoma
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2-5 prominent nucleoli
t(8,14) high mitotic rate of B cells - starry sky appearance - Mac - are stars 30% child lymphoma extranodule |
Burkitts
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h pylori
extranodal chronic inflammation - sjogren, hashimoto, MALT - salivary, GIT thyroid gland malig lymphoma and stomach |
Marginal Zone Lymphoma
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mutation in NOTCH1, thymic involvement
childhood pre B cell, adolescents pre T cell lymphblasts w irreg nuclear contour, condensed chromatin, small nucleoli, scant cytoplasm Tdt+ (immature) hyperdiploidy (B cell) t(12,21) - good outcome CD19, CD2,7 (t) mediastinal mass male < 20 |
non hodgkins Lymphoblastic Leukemia
can be ALL |
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mycosis fungoides
sezary syndrome - more agressive cutaneous lymphoid malignancy mature t cell CD$ itchy cooked lobster skin |
Cutaneous T Cell lymphoma
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HTLV-1 - Japan, Caribbean, SE US
CD4, TdT - >20% lymphoblasts nomocytic anemia and thrombocytopenia - BM replaced with lymphoblasts CD4 hyperlobulated 4 leaf clover lympho in PB skin lesion , hepatosplenomegaly agressive |
Adult T Cell Leukemia/ Lymphoma
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Reed Sternberg cells with infiltrate of lympho, eosino, plasma, benign histo
RS cells release IL-5 eosin, TNF, and IL13 - mucus and inflamm resp most common, M>F defects in cellular immunity transformed germinal center B cell multinucleated nucleus, prominant nucleoli CD15, CD30 |
Hodgkins, Classical
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Reed Sternberg, L&H variants - Ig pale staining, multilobed
popcorn cell, CD20 young male localized, cervical/supraclavicular LN enlarged stage 1/2 |
Hodgkin - Lymphocyte predominant
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Men > 50, EBV
RS cells numerous increase in eosin, plasma, lympho, histoio CD15, CD30 disseminated Stage 1/2 |
Hodgkins, mixed cellularity
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young females, most common
lacunar cells - pale cell w multilobed nucleus w many small nucleoli CD15, CD30 Ant mediastinal LN, cervical, supraclavicular, collagen bands of fibrosis separating nodules |
Hodgkins Nodular Sclerosing
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RS cells, T lymphs, CD 30, CD15
some w EBV |
hodgkins lymphocyte rich
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uncommon
most have EBC Rs cells , few lymphos CD30, CD15 dissimenated most are stage 3 |
Hodgkinds, Lymphodepleted
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85% b cell, 15 % t cell
hyperdiploidy > 50/cell t (12,21) peak age 4 yr old (b cell), 15-20 (t cell) high nuclear/cytoplasm ratio, course, clumped chromatin, PAS + 1-2 nucleoli, no cytoplasmic granules TdT+ CD10 CALLA + B-ALL pancytopenia Blasts in PB > 30% suppress normal hematopoiesis abrupt stormy onset, testicular enlargement (B-ALL), thymic enlargement (T-ALL) fatigue (decrease RBC), infections (decreased WBC), bleeding (decreased platelet) CNS manifestations - headache, nausea, palsy (b cell) bone pain |
Acute lymphoblastic lymphoma
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good prognosis vs bad prognosis for ALL
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good - 2-10 years, low wbc, pre b cell, hyperdiploidy; t(12,21)
bad - <2, or adult, high WBC, t (9,22), mature b cell |
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age 15-59, age age 50
risk factor - chrom abnormalities, ionizing radiation,, chemicals, alkylating agents RAR- alpha gene in -- Auer rods, faggot cells delicate nuclear chromatin prominant nucleoli course/numerous azurophilic granules in cytoplasm fatigue - rbc, infection - pmn, bleeding - platelets DIC metastic myeloperoxidase, esterase 30% blasts in BM, hypercellular |
AML
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t(15,17)
DIC auer rods age 24-50 |
AML M3
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t(8,21)
auer rods >20% marrow cells are myeloblasts |
AML M2
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myelocytic and monocytic differentiation
monoblasts pos for nonspecific esterase myeoid cells have a range of maturation variable number of auer rods inv 16 |
AML M4
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dry tap of BM aspirates seen with
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myelofibrosis, aplastic anemia
AML M7, hairy cell due to aplastic nature of the marrow giving a 'dry' cell less tap |
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trisomy 12, deletions of 11 and 12
CD5 CD23 small resting lymphos with dark round nuclei,prolymphocytes in BM proliferation centers in LN Smudge cell - cant differentiate into plasma cell age > 60 neutropenia thromboctyopenia decrease Ig's |
CLL
if in LN - SLL, in blood - CLL |
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25-60 year olds, peak 40-50
risk - ionizing radiation, benzene, t(9.22) Bcr-ABL fusion - protooncogene PB - neutrophil, metamyelocyte, myelocytes some baso and eosino thrombocytosis BM - hypercellular Spleen - enlarged red pulp extramedullary hematopoiesis - increased hematopoietic cells can compromise blood supply - infarct extreme splenomegaly blast crisis 70% meylo, 30% lympho decrease leukocyte alkaline phosphate gleevak inhibits bcr-abl fusion tyrosine kinase |
CML
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men > 59
CDc11, CD103 fine hair like extensions of cytoplasm B cell leukemia TRAP stain no lymphadenopathy, pancytopenia splenomegaly survival 4 years |
Hairy cell
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50-60 ages
t(4,14) plasma cells 'clock like nucleus' bone lesions, bone pain, pathological fractures renal involvement - protein casts on DCT - bence jones amyloidosis - AL Chrom for Cyclin D1, Cyclin D3 increased infections rouleaux BM - fibroblasts and Mac secrete IL6 ->plasma cell proliferation, IgG highest plasma cells secrete TNF, IL6, IL1 - bone resorption production of RANkB lingand --> differentiation and activation of osteoclasts hypercalicemia Bence jones in protein, serum M components |
Mult Myeloma
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50-70 M>F
due to alkylating agents pancytopenia BM normal or hypercellular ineffective hematopoiesis, resistant to therapy, can turn into AML |
myelodysplastic syndromes
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40-60 years
JAK2 mutation congestiong, thrombosis, infarction cells hypersensitive to EPO increased MCV, Hct, hyperviscosity hemorrhage |
polycythemia vera
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myelofibrosis in BM
Megakaryocytes make PDGF, TGFB increase WBC/RBC reaction in RB myeloid metaplasia in spleen extramedullary hematopoiesis masive splenomegaly, portal Hytn splenic infarct w left side pleural effusion JAK2 mutation (valine to phenylalanine at residue 617) fibrosis replaces marrow dry tap anemia and thrombocytopenia leukoerythrocytosis - nucleated RBC, immature white blood cell hyperuricemia and gout - (increase cell turnover) malignant cells are megakaryocytes pancytopenia tear drop cells darcocytes |
Myelofibrosis
myeloid metaplasia with primary myelofibrosis |
