Blood & Lymph Quick Review Exam 1

If blasts are seen in the periphery then look for it to be Leukemia

MPD & MPS can progress to AML
When looking at bone marrow, the Myeloid to Erythroid ratio is
very indicative of what is going on
o The preferred site of bone marrow biopsy is the iliac crest
Reed-Sternberg Cells indicate that the person has
Hodgkins Lymphoma
Myelodysplastic Syndromes can be de novo or secondary
MDS has cytopenia, where as MPD has elevated blood
count and splenomegaly
If more than 20% blasts are seen in bone marrow then it is
indicative that there is some kind of Leukemia
Autosomal Dominant Diseases DONT SKIP GENEATIONS
Autosomal Recessive Diseases CAN SKIP GENERATIONS & BE
BORN TO AN UNAFFECTED PARENT
In Familial Syndromes look for EARLY APPEARANCE, lots
of affected family members
o If the pedigree shows breast and ovarian cancer then it is
likely a BRCA cancer
Benign White Cell Disorders
o Leukopenia: a decreased number of WBCs that puts a
patient at risk of infections
o Leukocytosis: a WBC count above the normal range that
can be indicative of an inflammatory process, infection,
bone tumor. Is usually accompanied by a left shift
(increased immature cells) due to proliferation of
granulocytes and monocytes.
During this may see Dohle Bodies, which are
ribosomal inclusions in the cytoplasm that form
basophilic granulations in the cytoplasm of
neutrophils (Toxic Neutrophils). Often caused by
increase in granulocyte production by the bone
marrow
o Leukemoid Reaction: an increase in WBC count due to
stress or infection as opposed to a primary blood
malignancy (leukemia). See an increase in immature WBCs
but IS NOT CANCER
o Leukoerythroblastic Reaction: results from a lesion in
the bone marrow and is characterized by an increase in
immature granulocytic cells and nucleated RBCs seen in
the periphery

Can be caused by severe megaloblastic anemia,

Gauchers disease, myelomas & myelofibrosis

CBCs
o RDW: tells you the size distribution of the RBCs in a sample
o The MCH and MCHC tell you weather the RBCs are
normochromic, hypochromic or hyperchromic. MCHC< 32%
and MCH<27% indicate hemoglobin deficiency
o MCV, MCH and MCHC normal: normocytic,
normochromic anemia. most often caused by acute
blood loss
o Decreased MCV, MCH, and MCHC: microcytic,
hypochromic anemia. most often caused by iron
deficiency
o Increased MCV, variable MCH and MCHC: macrocytic
anemia. most often caused by Vitamin B12
deficiency (due to pernicious anemia) and folic acid
deficiency
Anisocytosis is marked variation of RBCs.
Poikilocytosis is variation in RBC shape
o The preferred site of bone marrow biopsy is the
anterior or posterior iliac crest. Should take a core
biopsy with the bone marrow aspirate
Examples of indications for bone marrow examination include:
multilineage abnormalities in the peripheral blood, pancytopenia,
circulating blasts, for staging lymphomas
Lymphomas
o Hodgkins Lymphoma
Localized to single group of nodes, contiguous
spread, prognosis much better than NHL.
Characterized by Reed-Sternberg Cells
20yo & 55yo distribution, more in men; strong
association with EBV. B signs (fever, weight loss,
night sweats) indicate poor prognosis
o Non-Hodgkins Lymphoma
Multiple node sites, non-contiguous spread,
Extranodal involvement common, majority is B cell (T
cell and NK cell exist & are typically more aggressive)
More associated with HIV; B signs are usually present
Burkitt Lymphoma: adolescents/young adults;
t(8:14) of c-MYC; associated with EBV; Jaw in
Africa; Pelvis & Abdomen in sporadic; t(2;8); t(9;22)
treat ASAP with chemo (R-EPOCH), Hyper
CVAD, CODOX), CNS prophylaxis

Diffuse Large B Cell Lymphoma: older adults

(20% in children); t(14:18) to BCL-2; indolent
waxing and waning lymphadenopathy. AGGRESSIVE
Treat local with chemo followed by XRT. Treat
advanced with chemo (R-CHOP). Rituximab,
anti-CD20 antibody, add chemo. Treat relapse
with second line chemo followed by ASCT
Mantle Cell Lymphoma: old men; t(11:14)
involving Cyclin D1; CD5+. AGGRESSIVE. Treat
with 2-CDA, pentostatin, anti-CD20 antibodies
Adult T Cell Lymphoma: adults; HTLV & IV drug
use; cutaneous lesions, lytic bone lesions,
hypercalcemia; Japan, West Africa, Caribbean
Anaplastic Large Cell Lymphoma: t(2;5)
Follicular Lymphoma: t(14;18); INDOLENT; 2nd
most common in the US; grade 3 may behave
like high grade lymphoma; stage 1 or 2 treat with
XRT; stage 3 or 4 treat with BR, CHOP-R, R-CVP if
symptomatic
MALT Lymphoma: initially low grade and
indolent; associated with Helicobacter pylori;
treat by eradicating H. pylori, surgery,
radiotherapy, chemo
Primary CNS Lymphoma: AGGRESSIVE. Rare
and can be associated with HIV; focal
neurological symptoms, personality changes,
increased CSF pressure. Treat with high dose
methotrexate &/or whole brain irradiation. Young
patients get HDC+ ASCT

Leukemias
o Acute leukemias are associated with immature blast cells
where as the mature cells are associated with chronic
Leukemia
o Acute Lymphoblastic Leukemia (ALL): <15yo; T Cell
ALL presents as mediastinal mass; associated with
Down Syndrome; Increased peripheral & marrow
lymphoblasts; TdT+, CD10+; Most responsive to
therapy; may spread to CNS & Testes; t(12:21) is a
better prognosis
o Small Lymphocytic Lymphoma (SLL)/Chronic
Lymphocytic Leukemia (CLL): >60; most common adult
leukemia; CD20+, CD5+ B cell neoplasm; asymptomatic;
autoimmune hemolytic anemia; slow progression. PLL or
Richter transformation. No plasmas - hypoglob. Smudge
cells- very fragile cells

o Hairy Cell Leukemias: adults; Mature B Cell tumor in

elderly. Filamentous projections; sequester cells in
spleen red & white marrow; lacks lymphadenopathy;
marrow fibrosis causes dry tap on aspiration; TRAP+;
treat with cladribine, pentostatin
o Acute Myelogenous Leukemia (AML): 65yo; Auer
Rods; Peroxidase+; increased myeloblasts on peripheral
smear; t(15:17); Risk factors are Down Syndrome,
alkylating agents, radiation; M3 AML responds to Alltrans Retinoic Acid (Vit A) which matures cells; risks
DIC
o Chronic Myelogenous Leukemia (CML): 64yo; t(9:22)
BCR/ABL; myeloid stem cell proliferation; esp. increased
Basophils; splenomegaly; VERY LOW LAP; may
accelerate with a blast crisis to AML or ALL; responds
to Imatinib
o LGL - felty syndrome (Neutropenia, RA, Splenomegaly)
Multiple Myeloma
o Monoclonal plasma cell. Cancer from marrow & makes lots
of IgG or IgA. Most Common primary tumor of bones
in adults
o Increased susceptibility to infection, Primary
Amyloidosis; punched out bone on X-ray
o Clock face plasma cells & Rouleaux formation of RBCs
o HyperCalcemia, Renal involvement, Anemia, Bone lytic
lesions/Back pain
Myelodysplastic Syndromes
o Stem cell disorders involving ineffective hematopathology
causing defects in cell maturation of all non-lymphoid
lineages. Can be de novo or secondary. Risks
transformation into AML. Macro anemia
See Pseudo-Pelger-Huet Anomaly: neutrophils
with bilobed nuclei seen after chemotherapy (look
like dumbbells)
5q deletion is fav female normal platelets (ringed
sideroblast)
Therapy related- 5q,7,q8 after alkylator 11q23 after
topo inh
majority will transform to AML
observe unless symt :treat with allo transplant or
erythro gcsf
Important Translocations
o T(8;14)Burkitt Lymphoma (c-MYC)
o T(9;22)CML (BCR-ABL)

o T(11;14)Mantle Cell Lymphoma (Cyclin D1)

o T(14;18)Follicular Lymphoma (BCL-2)
o T(15;17)M3 type of AML
Chronic Myeloproliferative Disorders: JAK2 is involved in
many of the diseases
o Polycythemia Vera: increased hematocrit; JAK2
mutation; itching after shower due to increased
Basophils; erythromyalgia due to blood clots in
extremities; usually has decreased EPO
Secondary polycythemia usually has increased EPO
o Essential Thrombocytosis: overproduction of
abnormal platelets leading to bleeding, thrombosis;
bone marrow with enlarged megakaryocytes
o Myelofibrosis: increased fibroblast activity
obliterates bone marrow OR collagen; proliferation of
monoclonal cell lines; teardrop RBCs; dry bone marrow
tap; MASSIVE splenomegaly
Hyperplasia: increase in cell number; Dysplasia: abnormal
proliferation with loss of size, morphology, shape & orientation
During invasion, cell-cell contact is lost by inactivation of Ecadherin
Tumor grade us the degree of cellular differentiation, mitotic
activity on histology. 1 is low grade & well differentiated, while 4
is high grade & poor differentiation
Tumors with more stroma are very firm
Tumor stage is the degree of localization/spread based on clinical
and pathological finding
o T= tumor size; N= node involvement; M= metastases
Benign tumors are usually well differentiated, well demarcated
with low mitotic activity and no metastases or necrosis
Malignant tumors have poor differentiation, erratic growth, local
invasion, decreased apoptosis, maybe upregulated telomerase
The brain is the metastasis site for lung, breast, GU,
osteosarcoma, melanoma, GI cancers
The liver is the metastasis site for colon, stomach, and
pancreatic cancers
Bone is the metastasis site for prostate, breast, lung and thyroid
cancers
Metastases spread via body cavities (ovarian), lymphatic
(lung) and hematogenous spread (renal cell, and hepatic
cell)
Dermato & Polymyositis: predisposes to visceral malignancy, esp.
genitourinary

Xeroderma Pigmentosum: predisposes to squamous cell

carcinoma, basal cell carcinoma, melanoma
Li-Fraumeni Syndrome: p53 mutation predisposes to various
cancers at a young age (sarcoma, breast, leukemia, adrenal
gland)
The most common cancers in men are Prostate, Lung,
Colon/rectum. In women it is Breast, Lung, Colon/rectum
The most lethal cancers in men are Lung, Prostate, Colon/rectum.
In women it is Lung, Breast, Colon/rectum
Benign Epithelial Cancers: Adenoma forms glands (thyroid,
bronchial, renal tubular, hepatic cell, adrenal), Papilloma
(bladder, choroid plexus), Cystadenoma/Papillary
Cystadenoma forms cysts (ovary)
Polyps: protrusions above a mucosal surface can be benign or
malignant
Malignant Epithelial Cancers: Adenocarcinoma (colon,
lung, stomach, endometrium); Papillary Carcinoma,
Squamous cell Carcinoma see in lungs/skin/cervix/upper
2/3 of esophagus (pavement epithelium & keratin pearls),
Transitional Cell Carcinoma (urinary bladder)
Benign Tumors of Mesenchyme: Hemangioma (closely
packed blood vessels), Leiomyoma common in uterus &
most common tumor in females, called fibroids (smooth
muscle), Rhabdomyoma heart is common place (striated
muscle), Fibroma (connective tissue, ovary), Osteoma (bone),
Lipoma the most common benign tumor in males, well
circumscribed (fat), Chondroma well circumscribed (hyaline
cartilage), Lymphangioma seen in neck and axilla,
peritoneum, mediastinum called a cystic hygroma (lymph
vessels), Hydatidiform Mole (chorionic villi, looks like grapes),
Melanocytic Nevus (melanocytes), Pleomorphic Adenoma
different pattern but same germ layer (parotid gland)
Malignant Tumors of Mesenchyme: Leukemia/Lymphoma
(blood), Angiosarcoma (blood vessels), Leiomyosarcoma
(smooth muscle), Rhabdomyosarcoma (striated muscle),
Fibrosarcoma (connective tissue), Osteosarcoma seen in
young males (bone), Liposarcoma (fat), Choristoma normal
tissue misplaced in another organ, Hamartoma nonorganized overgrowth that is indigenous,

Category
Growth Factors
PDGF- chain

ProtoOncogene

Mode of
Activation

Associated Human Tumor

SIS

Overexpressio
n

Astrocytomas
Osteosarcoma

Fibroblast growth
factors

HST-1
INT-2

TGF- related to
EGF
HGF
Growth Factor
Receptors
EGF-receptor family

CSF-1 receptor
Receptor for glial
cell line
neurotrophic factors
PDGF receptor
Receptor for stem
cell (steel) factor

Overexpressio
n
Amplification

RAS signal
transduction
WNT signal
transduction

Bladder cancer
Breast cancer
Melanoma
Astrocytomas

RAS

Overexpressio
n

HGF

Overexpressio
n

ERB-B1
(EGFR)
ERB-B2
FMS
RET

Overexpressio
n
Amplification
Point mutation
Point mutation

80% Squamous cell carcinomas of lung,

gliomas(50%) H&N Ca (80-100%)
Breast and ovarian cancers
Leukemia
Multiple endocrine neoplasia 2A and B,
familial medullary thyroid carcinomas

PDGF-R

Overexpressio
n
Point mutation

Gliomas

KIT

Proteins Involved in Signal Transduction

GTP-binding
K-RAS
Point mutation

Nonreceptor
tyrosine kinase

Stomach cancer

H-RAS
N-RAS
ABL

Point mutation
Point mutation
Translocation,
t(9;22)

BRAF

Point mutation

-catenin

Point mutation

Hepatocellular carcinomas
Thyroid cancer, follicular

Gastrointestinal stromal tumors and

other soft tissue tumors (TK inhibitor:
imatinib mesylate targeted therapy)
Colon (50%), lung (30%), and pancreatic
(90%) tumors
Bladder and kidney tumors
Melanomas, hematologic malignancies
Chronic myeloid leukemia
Acute lymphoblastic leukemia
Melanomas
Hepatoblastomas, hepatocellular
carcinoma

Overexpressio
n
Nuclear Regulatory Proteins
Transcriptional
C-MYC
activators
N-MYC

Cell-Cycle
Regulators
Cyclins

L-MYC

Amplification

CYCLIN D

Translocation
Amplification
Overexpressio
n
Amplification
or point
mutation

CYCLIN E
Cyclin-dependent
kinase

Translocation
(8:14)
Amplification

CDK4

Burkitt lymphoma
Neuroblastoma, small cell carcinoma of
lung
Small cell carcinoma of lung

Mantle cell lymphoma

Breast and esophageal cancers
Breast cancer
Glioblastoma, melanoma, sarcoma

Activation of Oncogenes
Point Mutation

ras
c-fms

pancreas, colon, lung

myeloid leukemia

Chromosomal Rearrangement
(translocation)

Gene Amplification
(double minutes or homogenous staining
regions)

abl-bcr
(9;22)
myc
(8;14)
N-myc
c-erb
L-myc
and Nmyc
cyclinD

CML and ALL

Burkitts lymphoma

Neuroblastoma
Breast ca
Small cell ca of lung
Breast ca and SCC

Cll- elderly smuge cell