Term
ALL
Acute Lymphoblastic leukemia |
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Definition
The most common malignancy of children.
Can present as a mediastinal mass in an adolescent male.
CNS and testicle involvement possible.
Generalized painless lymphadenopathy
Hepatosplenomegaly
Fatigue from anemia
Bleeding from thrombocytopenia
Fever from infection
Labs:
Predominantly lymphoblasts in periphery.
Over 20% blasts in marrow (lymphoblasts!).
CALLA (CD10) positive
TdT positive
Prognosis:
If present, Philadelphia indicates poor prognosis.
If t(12;21) better prognosis
90% 5-year survival.
MRD+ has a worse outcome (post-inducation minimal residual dz)
Treatment:
The leukemia most responsive to therapy.
No Aggressive induction
Consolidation/intensification
Maintenance treatment |
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Term
AML
Acute myeloblastic leukemia |
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Definition
The most common in Adults 40-60
Generalized painless lymphadenopathy
Hepatosplenomegaly
Fatigue from anemia
Fever from infection
Gum infiltration in M5 type (gingival hyperplasia)
DIC and thrombocytopenia --> bruising, petechiae, bleeding
bone pain
hyperviscosity --> vision andmental status changes
Risk factors:
Down Syndrome, Klinefelter syndrome
Fanconi Anemia, Blackfan Diamond syndrome, Shwachman syndrome
Benzene, pesticides, topoisomerase II inhibitors, ionizing radiation
Labs:
Auer rods!
Predominantly myeloblasts in periphery.
Marrow blasts >20%
MPO and NSE
Pathogenesis:
Self-renewal (NPM and Wnt/beta-catenin mutations)
Proliferation (FLT3, c-Kit, Ras/Erk mutation)
Halted differentiation (RARalpha, EML1/ETo mutation)
Avoiding Apoptosis (PI3K/AKT pathway mutation)
Prognosis:
If present, Philadelphia indicates poor prognosis.
20% survival at 5 years.
MRD+ has a worse outcome (post-inducation minimal residual dz)
Treatment:
Aggressive induction
Consolidation/intensification
No Maintenance treatment (bc cell lines may develop resistance to treatment)
Don't treat extramedullary dz bc doesn't help long term survival
** if AML type M3, a retinoic acid receptor alpha mutation, treatment can release Auer rods and cause DIC
AML M3 responds to all-trans retinoic acid |
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Term
CLL
Chronic lymphocytic leukemia |
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Definition
Over 60, esp men.
*most common cause of generalized lymphadenopathy in >60
Insidious onset, few symptoms. Weakness, fatigue, anemia, fever.
Generalized lymphadenopathy, painless.
Moderate hepatosplenomegaly
Hypogammaglobulinemia
Risk factors:
* monoclonal B-cell lymphocytosis
Complications:
Warm (IgG) and cold (IgM) antibody autoimmune hemolytic anemia
Hypogammaglobulinemia --> bacterial infections
associated with autoimmune disorders: Autoimmune hemolytic anemia, immune thrombocytopenic purpura, Evans syndrome (both)
Labs:
Smudge cells
Neoplastic lymphoid cells, usually B cells, resemble normal mature B cells, expressing pan-B-cell markers like CD19 and CD20.
Don't produce antibodies.
CD5 positive, CD 10 negative
Marrow blasts < 10%
Pathogenesis:
B-cell leukemia
Prognosis:
3-7 year mean survival
75% 5 year survival
Treatment:
relieves symptoms
cancer not very responsive to therapy
Fludarabine, opt with cyclophosphamide or rituxan
Chlorambucil, opt with prednisone, for older pts |
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Term
CML
Chronic myelogenous leukemia
(a chronic myeloproliferative disorder) |
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Definition
Adults 40-60 / 35-50 (second most common)
Insidious onset, moderate anemia, fatigue, weakness.
Prominent splenomegaly.
Modest hepatomegaly.
Moderate lymphadenopathy, painless and generalized.
Benzene is a risk factor
Labs:
High WBCs and Platelets, but low RBCs
Philadelphia chromosome (9 and 22 translocated) forming bcr-abl gene
Dif/t from AML by marrow blasts < 10%
Peripheral smear shows mid-late myeloid lineages, few blasts.
Low leukoctye alkaline phosphatase (vs. leukemoid reaction)
Pathogenesis:
A myeloproliferative syndrome.
Clonal proliferation of myeloid stem cells (precursor of RBCs, granulocytes, monocytes, platelets)
Bcr-abl gene (tyrosine kinase) forms from philadelphia chromosome, making a protein with tyrosine kinase activity.
Prognosis:
Blast crisis - increased blasts, transforms into ALL or AML
90% 5 year survival
Treatment:
Imatinib (Gleevec) - blocks activity of the mutatant bcr-abl tyrosine kinase |
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Term
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Definition
Middle-aged men.
*No lymphadenopathy (the only leukemia that does this)
Prominent splenomegaly
Pancytopenia
Some have hepatomegaly
Some have autoimmune vasculitis and arthritis
Labs:
B cells with hair-like filamentous projections
Postive TRAP staining
Pathogenesis:
B-cell
Treatment:
Very responsive to therapy like purine nucleosides
alpha-interferon
2-chlorodeoxyadenosine
deoxycoformycin |
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Term
Polycythemia vera
(a chronic myeloproliferative disorder) |
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Definition
Adults late-middle age.
*Pruritis everywhere after bathing (mast cells release)
*Bleeding: bleeding gums, epistaxis (nose bleeds)
Peptic ulcer disease (Histamine stim's gastric acid production)
Gout (increased nucleated cell brk dwn --> more purines which get broken down into uric acid)
Hepatosplenomegaly
Headache, dizziness, HTN
Ruddy face from vessel congestion
Impaired CNS circulation --> blurred vision, headaches, vertigo, retinal vein engorgement
Erythromelalgia - throbbin hands/feet from occlusion of small arterioles.
Complications:
risk of AML or myelofibrosis
risk of reactive bone marrow fibrosis
risk of thrombotic events from viscous blood -->
transient ischemic attacks and stroke
Labs:
The only polycythemia with low EPO and high Plasma Volume
Serum EPO is best initial test.
Normal SaO2
Increaced RBC mass
leukocytosis, thrombocytosis
high leukocyte alkaline phosphatase
high uric acid
Associations:
RCC, Wilm's tumor, HCC, hydronephrosis
Pathogenesis:
Increased RBCs, WBCs, platelets
An innappropriate absolute polycythemia.
JAK2 mutation in myeloid stem cell.
Very sensitive to growth factors.
Overprodution of RBCs even without hypoxic stimulus for EPO. Overproduction of granulocytes, mast cells, and platelets.
Leads to viscous blood.
Prognosis:
6-18mo Median survival
Treatment:
JAK2 inhibitors
Phlebotomy to decrease viscosity and bring them to an iron deficient state to slow down RBC production.
Hydroxyurea + phlebotomy
Interferon-alpha
Differentiate from:
Chronic hypoxia with high EPO (pulmonary dz, heart dz, high altitudes, heavy smoking)
Inappropriate EPO production (adult polycystic kidney disease, tumors, etc)
Endocrine abnormalities (pheochromocytoma, Cushings) |
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Term
Chronic idiopathic myelofibrosis
aka.
Primary Myelofibrosis
Agnogenic myeloid metaplasia
Myelofibrosis with myeloid metaplasia MMM
(a chronic myeloproliferative disorder) |
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Definition
Over 50-60, most common cause of splenomegaly.
Progressive anemia, splenomegaly, fatigue, weight loss, and night sweats.
Complications:
Infection
Thrombotic events
Bleeding events
Developing into AML
Labs:
* Teardrop-shaped erythrocytes on peripheral smear
Normocytic anemia
Thrombocytosis (high platelets)
Myelofibrosis (fibrous tissue replacing marrow) that spares Megakaryoctes
Marrow is prominently megakaryocytes
high uric acid
Pathogenesis:
A myeloproliferative dz
extensive extramedullar hematopoiesis (liver, spleen usually)
Marrow fills in with fibrosis
JAK 2 mutation common
Treatment:
Kinase inhibitors
Bone marrow transplant |
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Term
Essential thrombocythemia
(a chronic myeloproliferative disorder) |
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Definition
middle aged - elderly
Usually asymptomatic, with only occasional thrombotic / bleeding crises.
splenomegaly
Complications:
Thrombotic events (stroke, DVT, MI, etc)
risk of developing into PMF (myelofibrosis)
Labs:
Tons of platelets (thrombocytosis)
Megakargyocytosis in the marrow.
high uric acid
Pathogenesis:
Only platelets increase.
Jak 2 mutation common.
Megakaryocytes are now hypersensitive to growth factor.
Treatment:
"gentle" chemo to suppress platelets |
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Term
Infectious Mononucleosis
Mono |
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Definition
Young adults.
Generalized lymphadenopathy.
**Spleen is susceptible to traumatic rupture - no sports!
Labs:
anti-EBV antibodies
heterophil antibodies
Pathogenesis:
Epstein-Barr virus (EBV) has an affinity for B cells. |
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Term
Multiple myeloma
aka.
Plasma cell myeloma
Plasmacytoma |
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Definition
Black, 50-60
*Bone pain from "punched out" lytic lesions, esp in axial sk
*Pathologic fractures, esp in ribs
Kidney: Bence Jones proteins casts (Igs), calcifications, multinucleated giant cells, primary amyloidosis, renal failure
Anemia, possible leukopenia/thrombocytopenia
"CRAB" - hyperCalcemia, Renal insufficiency, Anemia, Bone lytic lesions/ Back pain
Risk factors:
Benzene
Radiation
*MGUS
Complications:
Renal failure
Recurrent infections bc Ig produced is nonfunctional
Hyperviscosity --> retinal hemorrhage
Amyloid from monoclonal globulins
Coagulopathy
Labs:
Hyperglobulinemia (because the neoplastic cells produce Ig)
*M protein on electrophoresis
*Bence Jones proteins - excess light chain Ig's in urine
*Rouleaux formation of RBCs - congregated RBCs due to high protein conc of serum (Ig's in this case)
*Hypercalcemia (in some) due to bone destruction without elevated alkaline phosphatase (unlike most cases of hyperCa)
Normocytic anemia
Prolonged bleeding time
Pathogenesis:
Single clone of end-stage B cell (plasma cell), producing a single IgA/IgG called M protein. Usually IgG.
Lytic lesions and pathologic fractures because Myeloma cells inhibit osteoblast differentiation and release interleukin 1 (OC activator)
Prognosis:
3 years = median survival
Treatment:
Autologous transplant
thalidomide
lenalidomide
No good option for a cure |
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Term
Waldenstrom macroglobulinemia
(a type of lymphoplasmacytic lymphoma) |
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Definition
Old men >50
IgM --> hyperviscosity syndrome --> retinal hemorrhages, strokes, CNS changes, etc
No bone lesions, usually no BJ proteinuria
Generalized lymphadenopathy
Mild anemia
Abnormal bleeding
MGUS is a risk factor
Labs:
M protein spike on electrophoresis
Complications:
blind
Pathogenesis:
B cells at a stage somewhere between B cells and plasma cells
These cells produce monoclonal IgM (as the M protein)
Prognosis:
5 yrs = median survival
Slowly progressive course |
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Term
MGUS
Benign monoclonal gammopathy |
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Definition
Older pts
No Bence Jones protein
IgG is produced by the neoplastic B cells
No decrease in normal Igs
Complications:
*-->Multiple myeloma
--> Waldenstrom's macroglobulinemia
Labs:
Very small M protein spike (IgG), not much produced
No Bence Jones proteinuria
Pathogenesis:
Monoclonal neoplastic B cells that can produce IgGs, but not in huge amounts. Aka. similar to multiple myeloma bout without any of the symptoms.
Prognosis:
May be benign - no clinical consequences |
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Term
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Definition
Young white adult men.
Constitutional "B" symptoms: Fever, unexplained weight loss, night sweats
Pruritis
Single group of lymph nodes, esp anterior mediastinal (or cervical, supraclavicular)
Extranodal involvement is rare
Spread is contiguous
Risks:
EBV
Labs:
Reed-Sternberg cells = the neoplastic B or T cells
CD15 and CD30 positive, "owl eyes"
Normocytic anemia
Diagnosis:
Reed-Sternberg cells
Prognosis:
Stage is the most important. (more than type)
5 year survival is 85%
More RS cels --> bad prognosis
More reactive lymphocytes --> good prognosis
Treatment:
Radiotherapy and chemotherapy
Types:
Nodular sclerosing - most common, young women*, anterior mediastinal nodes, Lacunar cells, RS cells rare, good prognosis
Mixed cellularity - older men, EBV in 70%, lots of RS cells
Lymphocyte predominant - asymptomatic young male with cervical or supraclavicular nodal enlargement. Best survival, RS cells rare.
Lymphocte depletion - most aggressive. Old males with disseminated dz. Extensive necrosis and fibrosis. More common in HIV, most have EBV. |
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Term
Small lymphocytic lymphoma
(a type of Non-Hodgkin lymphoma) |
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Definition
Elderly
Indolent course
Generalized lymphadenopathy
Nodes, liver, spleen, bone marrow
Labs:
Pan-B-cell markers. CD 19 and CD 20
CD5 positive
CD10 negative
Pathogenesis:
Neoplasm of small mature B cells
Becomes CLL if not confined to lymph node |
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Term
Follicular (B-cell) lymphoma
(a type of Non-Hodgkin lymphoma) |
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Definition
60-65. The most common form of Non-Hodgkins.
Generalized lymphadenopathy
Bone marrow involvement
Labs:
Proliveration of angulated grooved cells, in a nodular pattern
B-cell markers: CD 19 and CD 20
CD5 negative
CD10 positive
expresses bcl-2, and oncogene (inhibits apoptosis)
Pathogenesis:
Derives from germinal center, B-cell
bcl-2 inhibits apoptosis
t(14;18)
Prognosis:
Indolent course but very difficult to cure
Usually disseminated and incurable at time of diagnosis. |
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Term
Mantle cell lymphoma
(a type of Non-Hodgkin lymphoma) |
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Definition
Older men
Fever, night sweats, unexplained weight loss
Lymphadenopathy
Splenomegaly
Extranodal involvement
Labs:
CD5 +
Pathogenesis:
B cells from mantle zone of lymphoid follicle
Activated cyclin D gene (bcl-1), a cell cycle regulator
t(11;14)
Prognosis:
Disseminated aggressive incurable disease |
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Term
Extranodal marginal zone B-cell lymphoma of MALT type
(a type of Non-Hodgkin lymphoma) |
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Definition
Low grade lymphoma of the stomach
Helicobacter pylori gastritis is a risk factor
Pathogenesis:
Derives from MALT and Arises in sites of chronic inflammation:
Salivary glands in Sjogren syndrome
Thyroid in Hashimoto thyroiditis
Stomach in Helicobacter pylori gastritis |
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Term
Diffuse large B-cell lymphoma
(a type of Non-Hodgkin lymphoma) |
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Definition
60s, though 20% in kids.
large extranodal mass
GI tract, brain, testes, skin
EBV and AIDs are risk factors
Pathogenesis:
Derives from germinal center. Though 20% derive from mature T cells.
Prognosis:
Widespread aggressive dissemination |
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Term
Precursor T lymphoblastic lymphoma/leukemia
(a type of Non-Hodgkin lymphoma) |
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Definition
Common in children.
Anterior mediastinum and cervical nodes - mass.
May present as ALL
Labs:
convoluted nuclei
Pathogenesis:
From thymic lymphocytes
Prognosis:
rapidly disseminates and progresses to ALL |
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Term
Burkitt lymphoma
(a type of Non-Hodgkin lymphoma) |
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Definition
Common in children. Adolescents-young adults.
Para-aortic lymph nodes.
EBV is a risk factor
In American -- GI tract
In African -- Jaw
Bone marrow involvement
leukemic phase
Risks:
EBV
Complications:
tumor lysis syndrome
DIC
Labs:
Starry sky appearance - Reactive histiocytes (macrophages) with phagocytic debris from rapid cell turnover
Pathogenesis:
t(8;14) increased c-myc expression
Derives from B cells.
Prognosis:
Aggressive
May develop into ALL |
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Term
Mycosis fungoides
(a Cutaneous T-cell lymphoma)
(a type of Non-Hodgkin lymphoma) |
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Definition
Adults 40-60
Skin has rash/plaque/nodular masses
(may be erythematous, eczematoid, or psoriasiform)
Pautrier's microabscesses = groups of neoplastic cells in epidermis (cerebriform nucleus)
Spreads to lymph nodes/liver/spleen/lung
Labs:
Dermal infiltrates of atypical CD4 T helper cells
Cerebriform nucleus
Pathogenesis:
Neoplastic peripheral CD4 T helper cells |
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Term
Sezary syndrome
(a Cutaneous T-cell lymphoma)
(a type of Non-Hodgkin lymphoma) |
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Definition
Adults 40-60
Has a leukemic phase, cells with cerebriform nuclei
Skin lesions
Labs:
circulated cells have a nuclear cleft
Pathogenesis:
Neoplastic peripheral CD4 T helper cells |
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Term
Adult T-cell leukemia/lymphoma
(a mature T cell Non-Hodgkin's lymphoma |
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Definition
Japanese, West Africans, Caribbeans
*Skin infiltration (as in all T cell malignancies)
*Lytic bone lesions with hypercalcemia
Hepatosplenomegaly
Generalized lymphadenopathy
Normocytic Anemia
Thrombocytopenia
Etiology:
*HTLV-1 associated (virus)
Labs:
Hypercalcemia
CD4 positive
TdT negative
over 20% lymphoblasts in peripheral smear
Pathogenesis:
This is a monoclonal proliferation of CD4 T helper cells.
Prognosis:
Aggressive. |
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Term
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Definition
Second most common cancer in HIV pt, esp 20-40
Mupltiple peripheral nodes and extranodal involvement:
Most start at lymph node, but may start at stomach, Peyer's patch, or CNS in HIV pt
Peri-aortic lymph nodes commonly involved
Spread is not contiguous
Risk factors:
HIV and immunosuppression
Human T-cell leukemia virus type I --> T cell
Hep C virus --> B cell
Helicobacter pylori --> GI lymphoma
Autoimmune dz (Sjogren's, Hashimoto's thyroiditis)
EBV --> Burkitt's, mostly for Hodgkin's
Pathogenesis:
Can be B or T cell, but usually B cell
Derives at germinal center
Prognosis:
60% 5 year survival
Types:
B-cell
(Burkitt's in kids, Diffuse large B-cell in adults with AIDs and EBV, Extranodal marginal zone lymphoma from Helicobacter pylori gastritis in stomach, Follicular in adults with generalized lymphadenopathy, and Small lymphocytic in over 60)
T-cell
(Precursor T-cel lymphoblastic in kids, Mycosis fungoides, Sezary syndrome)
Specific Types: |
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Term
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Definition
Bartonella henselae causes a reactive lymphadenitis
A mixed B and T cell hyperplasia
Granulomatous microabscesses in regional lymph nodes |
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Term
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Definition
Painful cervical lymphadenopathy
Mononucleosis-like syndrome |
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Term
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Definition
Localized papular lesion at bite, it ulcerates, and causes regional lymphadenitis
Pathogenesis:
Francisella tularensis (gram negative intracellular coccobacillus)
Epidemiology:
Common in hunters and trappers.
Resevoir is deer, rodents, rabbits
Transmission by tick bite or contact with animal hide
Treatment:
Gentamicin |
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Term
Myeloproliferative Dzs
General Features and types. |
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Definition
Middle aged - elderly
Thrombosis and Hemorrhage
Fatigue, bone pain, pruritis
Splenomegaly
Proliferation of one or more of myeloid serious
More Basophils in periphery
More nucleated RBCs in periphery
More uric acid in serum --> gout
Risks:
Developing into AML
Bleeding events
Thrombotic events
Types:
Polycythemia vera (most common)
CML
Chronic idiopathic myelofibrosis
Essential thrombocythemia |
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Term
Nodular sclerosing
vs.
Mixed cellularity
vs.
Lymphocyte predominant
Hodgkins Lymphoma |
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Definition
Nodular sclerosing - most common, young women*, anterior mediastinal nodes, Lacunar cells, RS cells rare, good prognosis
Mixed cellularity - older men, EBV in 70%, lots of RS cells
Lymphocyte predominant - asymptomatic young male with cervical or supraclavicular nodal enlargement. Best survival, RS cells rare. |
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Term
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Definition
High WBC count with left shift (elevated bands).
High leukocyte alkaline phosphatase.
Can see neutrophil precursor in peripheral blood.
Etiology:
Infection
*can be easily confused with leukemia |
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Term
Langerhands cell histiocytosis
LCH |
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Definition
Labs:
S-100 and CD1a positive
Birbeck granules "tennis rackets"
Pathogenesis:
Proliferation of dendritic (Langerhans) cells. |
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Term
Myelodysplastic syndromes
MDS |
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Definition
70 year old man
Often asymptomatic
Anemia, weakness, infection, hemorrhage
refractory anemia
Complications:
>30% progress to AML
bleeding
infections
Labs:
Pancytopenia
hypogranular WBCs - "Pelger-Huet" nucleus
hypolobated megakaryocytes in marrow
hypercellular marrow with ringed sideroblasts
normocytic - macrocytic anemia
Myeloblasts < 20% (once over that it's AML)
Pathogenesis:
acquired clonal disorder of stem cells
The immune response to the mutated clonal proliferation of the stem cells leads to marrow fibrosis, resulting in insufficient hematopoesis and increased apoptosis.
Failure of production of one or more myeloid cell lines.
Accumulated mutations may lead to AML.
Prognosis:
worse if cytopenic in multiple cell lines
high bone marrow blasts (20-30%)
cytogenetics with over 3 abnormalities |
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