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HEMATOLOGY & ONCOLOGY TiKi TaKa

_________________________________
. ANEMIA presentations:
_______________________
. Mild -> Fatigue - loss of energy - tiredness - malaise.
. Severe -> Shortness of breath - lightheadedness - confusion.
. Diseases with similar presentations (Hypoxia - CO poisoning Methemoglobinemia).
. Pallor - flow murmur - pale conjunctiva.
. MICROCYTIC ANEMIA:
____________________
____________________
(1) IRON DEFECIENCY ANEMIA:
____________________________
. The most common cause is chronic blood loss (Bleeding ulcer).
. ++ platelet count.
. Dx -> Best initial test -> IRON STUDIES:
- ____________________________________________
- | -- iron.
.|
- | -- ferritin.
.|
- | -- iron saturation.
.|
- | ++ TIBC (Total iron binding capacity).
.|
|--------------------------------------.|
- | ++ Red cell distribution of width (++ RDW).|
- ____________________________________________
. Dx -> Most accurate test -> Bone marrow biopsy.
. Tx -> Ferrous sulfate orally (May turn the stool BLACK but Guaiac test
-ve).
. PICA -> Appetite for non-nutritive substances (ice - clay - dirt).
(2) ANEMIA OF CHRONIC DISEASE:
_______________________________
. Rheumatoid arthritis.
. End Stage Kidney Disease (ESKD).
. Any chronic infectious, inflammatory or connective tissue disease.
. . Dx -> Best initial test -> IRON STUDIES:
- _______________________________________
- | -- iron.
.|
- | ++ ferritin.
.|
- | Normal or -- iron saturation.
.|
- | -- TIBC (Total iron binding capacity).|
|--------------------------------------.|
- _______________________________________
* IRON IS LOCKED IN STORAGE OR TRAPPED IN MACROPHAGES OR IN FERRITIN.
. Osteoarthritis doesn't cause anemia of chronic disease !
. Exclude anemia of chronic disease if there is NORMAL ESR !
. The only form of anemia that responds to erythropoietin is ESKD.
. Tx -> tt the underlying cause e.g. (METHOTREXATE or INFLIXIMAB for
RA).
. Although iron concentration is low, Iron supplementation is not
benificial.
. IRON IS LOCKED IN STORAGE OR TRAPPED IN MACROPHAGES OR IN FERRITIN.
(3) THALASSEMIA:
_________________

. Very small MCV with few or no symptoms. (55 - 75 ml).


. TARGET cells.
. Dx -> NORMAL iron studies.
. Most accurate test -> HEMOGLOBIN ELECTROPHORESIS:
- Beta -> ++ Hg A2 & Hg F.
- Alpha -> Normal (Most accurately diagnosed by DNA sequencing).
- Hg H has Beta 4 tetrads with 3 gene deleted Alpha thalassemia.
. B thalassemia major -> Both B hemoglobin are deffective.
. Characterized by severe anemia & transfusion dependence at an early
age).
. B thalassemia minor occurs in people heterozygous for the B hemoglobin
gene.
. The only microcytic anemia with a HIGH reticulocytic count is Hg H.
. Microcytic anemia non responsive to iron supplementation.
. No ttt !
(4) SIDEROBLASTIC ANEMIA:
__________________________
. Defect in heme-synthesis.
. Alcoholic pt.
. Isoniazid intake without Vit. B6 "pryridoxine" supplementation.
. Lead exposure.
. Dx -> Iron studies -> HIGH IRON & -- TIBC.
. Dx -> Bone marrow biopsy -> RINGED SIDEROBLASTs.
. Most accurate test -> PRUSSIAN BLUE STAIN.
. Tx -> Minor -> Pyridoxine replacement.
. Tx -> Major -> Remove the toxin exposure.
. "IRON DEFECIENCY ANEMIA"
- "ALPHA THALASSEMIA MINOR"
- "BETA
THALASSEMIA MINOR":
_________________________________________________________________________
_____________
. Hematocrit < 30 %
- Hematocrit > 30 %
- Hematocrit >
30 %
. RDW ++
- RDW normal
- RDW normal
. RBC count -- RBC count normal
- RBC count
normal to ++
. No target cells
- TARGET cells on smear
- TARGET cells
on smear
. -- serum iron & ferritin
- Nor. to ++ iron & ferritin - Nor. to ++
iron & ferritin
. ++ TIBC
- Normal TIBC
- Normal TIBC
. Responds to iron supplem. - No response to iron supplementation
. Normal Hb Electrophoresis - Normal Hb Electrophoresis
- ++ Hb A2 on
Hb Electrophor.
. N.B. MECHANISMS OF ANEMIA IN MICROCYTIC HYPOCHROMIC DISEASES:
_______________________________________________________________
. -- fe intake & ++ blood loss -> IRON DEFECIENCY ANEMIA.
. Defective utilization of storage iron -> ANEMIA OF CHRONIC DISEASES.
. -- globin production -> THALASSEMIA.
. -- Heme synthesis -> LEAD POISONING & SIDEROBLASTIC ANEMIA.
. MICROCYTIC HYPOCHROMIC DISEASE -> FINDINGS IN IRON STUDIES:
_____________________________________________________________
. IRON DEFECIENCY ANEMIA -> -- fe, -- ferritin & ++ TIBC.
. THALASSEMIA -> Normal to ++ fe & ferritin levels.
. ANEMIA OF CHRONIC DISEASE -> -- TIBC.
. SIDEROBLASTIC ANEMIA -> Normal to ++ fe & ferritin levels.

. MACROCYTIC ANEMIA:
____________________
____________________
. Extravascular hemolysis occurs in spleen & liver so u can't see it on
a smear !
. Caused by Vit. B12 or floate defeciency.
. Vit. B12 def. -> neurological findings (Mostly peripheral neuropathyLeast dementia).
. Folate defeciency is NOT associated with neurological findings.
. Suspect Vit B12 def. in STRICT VEGETERIANS with anemia & neurologic
complications.
. METFORMIN blocks B12 absorption.
. B12 def. -> Smooth tongue (Glossitis) & diarrhea.
. -- B12 -> -- production of INTRINSIC FACTOR by gastric parietal cells,
. -- B12 -> Atrohic gastritis -> DOUBLE RISK of GASTRIC CANCER.
. Dx -> Best initial test -> CBC with peripheral smear -> HYPERSEGMENTED
NEUTROPHILs.
. Dx -> Hypersegmented neutrophils + Large MCV = Megaloblastic anemia.
. Dx -> Anisocytosis - poikilocytosis - basophilic stippling.
. Dx -> ++ Bilirubin & LDH.
. Dx -> -- Reticulocytic count.
. Dx -> Most accurate test -> -- Vit. B12 & Folic acid levels.
. If u suspect B12 defeciency but B12 level is normal -> Order Methyl
Malonic acid (MMA).
. Dx -> HOMOCYSTEINE is ++ in both Vit. B12 & folate defeciency.
. Dx -> Most accurate test -> Anti-parietal cell Abs & anti-intrinsic
factor Abs.
. Tx -> REPLACEMENT of Vit B12 & folate.
. Tx -> Folic acid will correct the hematological problems.
. Tx -> Vit. B12 will correct the neurological problems.
. Watch for low potassium after ttt B12 def. !
. N.B. (1):
___________
. Folate & cobalamine (B12) are involved in the conversion of
homocysteine to methionine.
. -- Vit. B12 or folic acid -> ++ Homocysteine level.
. N.B. (2):
___________
. Folic acid & vit. B12 defeciency can be distinguished by measuring
Methyl Malonic acid!
. Vit B12 (Not folic acid) is involved in the conversion of MMA to
succinyl coA.
. -- Vitamin B12 -> ++ MMA.
. -- Folic acid -> NORMAL MMA.
. N.B. (3):
___________
. Laboratory tests ------------> Prinicious anemia -------------> Folic
acid defeciency
_________________________________________________________________________
_______________
. Serum B12 level ------------->
(--)
------------->
Normal.
. Serum folic acid level ------>
(Normal)
-------------> (--).
. Serum LDH level ------------->
(++)
------------->
Normal.

. Achlorhydria ---------------->
Absent.
. Schilling test -------------->
. Methyl malonyl acid MMA ----->
Absent.
. Neurological signs ---------->
Absent.

present

------------->

+ve
++

-------------> -ve.
------------->

++

------------->

. N.B. (4):
___________
. Alcohol abuse is the most common cause of nutritional folate
defeciency in USA.
. N.B. (5):
___________
. Anemia of chronic kidney disease is due to erythropoietin defeciency.
. One must be careful to ensure adequate iron stores prior to
erthropoietin replacement,
. Bec. the erythropoietin induced surge in RBCs production may consume
much iron,
. precipitating an iron defecient state.
. N.B. (6):
___________
. A case of microcytic hypochromic anemia with -- iron & ferritin,
. The most common cause of iron defeciency anemia is GIT blood loss.
. Dietary iron defeciency & malabsorption of iron are rare causes.
. Iron supplementation helps to restore iron reserves but u must detect
the cause !
. So .. perform test for occult blood in the stool.
. N.B. (7):
___________
. The most common cause of folic acid defeciency is NUTRITIONAL.
. Either due to poor diet or Alcoholism.
. May be caused by some drugs either by impairing its absorption
(PHENYTOIN),
. or antagonizing its physiologic effect (Methotrexate - Trimethoprim).
. N.B. (8):
___________
. PERINICIOUS ANEMIA:
______________________
. Most common cause of vit. B12 defeciency.
. Auto-antibodies against the gastric intrinsic factor required for B12
absorption.
. More in Northern Europeans.
. Associated other auto-immune diseases e.g. Autoimmune thyroiditis &
Vitiligo.
. Shiny tongue due to atrophic glossitis.
. Shuffling broad-based gait ataxia.
. Neurological abnormalities with loss of pain & vibration sense.
. Peripheral blood smear -> Macro-ovalocytes, megaloblasts & hypersegmented neutrophils.
. Dx -> Detection of Anti-intrinsic factor Abs.
. N.B. (9):
___________
. Total body stores of Vit.B12 in humans are 2-5 mg with min. daily
requirement 6-9 micg.

. Animal products (meat & dairy) are the only dietary sources of vit.
B12.
. It would take 4-5 years of a pure vegan diet to cause dietary
defeciency.
. In contrast, Folate stores are smaller, clinical defeciency occur
within 4-5 months.
. N.B. (10):
____________
. SCHILLING TEST:
__________________
. Used to detect the cause of vit. B12 defeciency.
. Used to differentiate dietary defeciency from perinicious anemia &
malabsorption.
. In dietary defeciency,
. Oral radiolabelled Vit B12 is absorbed in the gut & excr. by kidneys
in NORMAL amounts.
. But In Malabsorption,
. Oral radio-labelled Vit B12 is excreted in sub-normal amounts.
. HEMOLYTIC ANEMIA:
___________________
___________________
. SUDDEN ONSET of hematological manifestations.
. Dx -> Hemolysis ->
-> ++ indirect bilirubin.
-> ++ reticulocyte count.
-> ++ LDH level.
-> -- Haptoglobin.
. Dx -> Intravascular hemolysis ->
-> Abnormal peripheral smear (schistocytes - helmet cells - fragmented
cells).
-> Hemoglobinuria.
-> Hemosiderinuria.
(1) SICKLE CELL ANEMIA:
________________________
. Very severe pain in the back, chest & thighs.
. Retinal infarction.
. Flow murmur from anemia.
. Splenomegaly in children & asplenia in adults.
. Rales or consolidation from lung infection or infarction.
. Skin ulcers.
. Aseptic necrosis of hip.
. Neurological strokes.
. Cause of Osteomyelitis in sickle cell anemia is SALMONELLA !
. Cause of BM suppression in sickle cell anemia is PARVO B19 !
. Tx -> OXYGEN - HYDRATION with NORMAL SALINE - Pain relief.
. If there is fever -> (Emergency - No spleen) -> Ceftriaxone levofloxacin.
. Tx -> EXCHANGE TRANSFUSION if ->
-> Eye -> Visual disturbance from retinal infarction.
-> Lungs -> Pulmonary infarction with pleuritic pain.
-> Penis -> Priapism from infarction of prostatic plexus of veins.
-> Brain -> Stroke (weakness & aphasia due to sludging & occlusion of
cerebral vessels).

. N.B. -> SUDDEN DROP IN HEMATOCRIT can be caused by FOLATE DEFECIENCY


or PARVO B19 INF:
. Folate defeciency in SCD due to ++ RBCs turnover & consumption of
folate in the BM.
. Daily folic acid supplementation is recommended in all SCD.
. If the pt is already on Folate replacement -> The cause is PARVO B19
viral infection !
. PARVO B19 may invade the bone marrow & causes aplastic anemia.
. Detect Parvo B19 infection by PCR for DNA of Parvo B19.
. On discharge -> Give folate replacement - Pneumococcal vaccine.
. Hydroxyurea (++ Hb F) is given to prevent further crisis.
(2) HEMOGLOBIN SICKLE CELL DISEASE:
____________________________________
. African American pt.
. Family H/O of blood disrder.
. Mild version of sickle cell anemia.
. Visual distrurbance is frequent.
. No painful crisis.
. RENAL problems are common,
. (Hematuria - Isosthenuria "inablility to dilute urine or concentrate
urine" - UTIs).
. Isosthenuria due to RBCs sickling in the vasa rectae of the inner
renal medulla.
. The pt have to wake to urinate 2 - 3 times per night despite
restricting fluid intake.
. No ttt.
(3) AUTOIMMUNE HEMOLYSIS:
__________________________
. H/O of other autoimmune diseases e.g. SLE (peripheral immune
destruction of all cells).
. H/O of CLL or lymphoma (Enlarged Non tender axillary LNs
bilaterally!).
. H/O of penicillin - alpha methyl dopa - quinine or sulfa drug intake.
. Dx -> ++ LDH - ++ indirect bilirubin - ++ reticulocyte count - -Haptoglobin.
. Dx -> peripheral smear -> spherocytes.
. Dx -> Most accurate test -> Coombs test. (WARM Abs = IgG Abs).
. Tx -> Best initial ttt -> Steroids e.g. prednisone.
. If there is recurrent episodes of hemolysis -> SPLENECTOMY is the most
effective ttt.
. If no response to prednisone or splenectomy -> Give IVIG.
(4) COLD INDUCED HEMOLYSIS = COLD AGGLUTININs:
_______________________________________________
. H/O of mycoplasma or EBV infection.
. Coomb's test -> -ve.
. Complement test-> +ve.
. No response to prednisone, spenectomy or IVIG.
. Tx -> RITUXIMAB.
(5) GLUCOSE - 6 - PHOSPHATE DEFECIENCY (G6PD):
_______________________________________________
. X-linked disorder - Only MALE pt. (African American).
. ENZYME defeciency (Glucose 6-phosphate dehydrogenase).
. Sudden onset of hemolysis.
. INFECTION is the most common predisposing factor.
. H/O of intake of Oxidizing drugs (Sulfa - primaquine - Dapsone).

. H/O of ingestion of FAVA BEANS.


. Mechanism of cell damage -> OXIDATIVE STRESS.
. Dx -> Best initial test -> Heinz body test & BITE CELLs.
. +ve prussian blue is indicative of hemosiderin found in urine during
hemolytic episode.
. Heinz bodies are collections of oxidized precipitated Hb embedded in
the RBC membrane.
. Bite cells appear when pieces of the red cell membrane have been
removed by the spleen.
. Most accurate test -> G6PD level after 2 months of symptoms !
. A normal level of G6PD immediately after an episode of hemolysis
doesn't exclude it !
. Tx -> AVOID OXIDANT STRESS.
. N.B. PYRUVATE KINASE DEFECIENCY:
___________________________________
-> can lead to similar presentation as G6PDD .. BUT:
-> Hemolysis not precipitated by sulfa drugs !
-> No bite cells on peripheral smear !
(6) HERIDITARY SPHEROCYTOSIS:
______________________________
. Northern European descent.
. TRIAD of HEMOLYTIC ANEMIA + JAUNDICE + SPLENOMEGALY.
. Autosomal dominant disorder of spectrin (Ptn that provides scaffolding
for RBCs).
. RBCs are not deformable -> Gets trapped in the fenesterations of the
spleen's red pulp.
. Recurrent episodes of hemolysis.
. Splenomegaly.
. Bilirubin gall stones (pigmented Ca bilirubinate) -> Acute
cholecystitis.
. Dx -> +++ MCHC (Mean cell hemoglobin concentration = RBC membrane loss
& dehydration).
. Dx -> Peripheral smear -> Spherocytes.
. Dx -> -ve Coomb's test (+ve in AIHA = Autoimmune hemolytic anemia).
. Dx -> Most accurate test -> OSMOTIC FRAGILITY test.
. Tx -> SPLENECTOMY will prevent hemolysis as spherocytes are destroyed
in the spleen.
. Folate supplementation is important.
. There is a risk for infection with Parvovirus B19 causing aplastic
anemia.
(7) HEMOLYTIC UREMIC $YNDROME (HU$):
_____________________________________
. H/O of E-coli 0157:H7 infection.
. HUS TRIAD (ART):
-> Autoimmune hemolysis -> intravascular hemolysis (Anemia - indirect
hyperbilirubinemia)
-> Renal failure -> ++ BUN & creatinine.
-> Thrombocytopenia -> -- platelets.
. Dx -> Peripheral smear -> Schistocytes.
. Tx -> Most cases resolve on their own.
. Tx -> Severe cases are ttt with plasmapharesis or plasma exchange.
. Steroids don't help !
. Antibiotics worsen the case !
. Platelet transfusion worsen the case !
(8) THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP):
_______________________________________________

.
.
.
.

H/O of TICLOPIDINE use.


HUS TRIAD + FN (Fever & Neurolgical abnormailities).
Dx -> Peripheral smear -> Schistocytes.
Same ttt as HUS (PLASMAPHARESIS or PLASMA EXCHANGE).

(9) PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH):


_______________________________________________
. Pancytopenia.
. Recurrent attacks of dark urine "Specially in the morning !".
. Most common cause of death -> LARGE VESSEL VENOUS THROMBOSIS "PORTAL
VEIN THROMBOSIS".
. PNH may transform to alpastic anemia or acute myelogenous leukemia
(AML).
. PORTAL VEIN THROMBOSIS may be the key to answer PNH case !
. Dx -> Most accurate test -> Flow cytometry -> Cd 55 & CD 59
antibodies.
. Tx -> Best initial ttt -> Glucocorticoids (prednisone).
. Transfusion dependent pts may be ttt with Eculizomab -> inhibit C5
complement.
. Hemolytic anemia + Venous thrombosis = PNH.
(10) MACROVASCULAR TRAUMATIC HEMOLYSIS:
________________________________________
. ++ reticulocytes - ++ LDH - -- Haptoglobin ("intra-vascular hemolytic
anemia).
. Fragmented RBCs.
. Chronic hemolysis -> iron loss -> Microcytic anemia.
. Due to mechanical trauma from artificial valves or calcified aortic
valves.
. N.B. HERIDITARY SPHEROCYTOSIS & AUTOIMMUNE HEMOLYTIC ANEMIA:
______________________________________________________________
. Peripheral blood smerar in both conditions -> Spherocytes without
central pallor.
. Both cause extravascular hemolytic anemia.
. Heriditary spherocytosis -> Autosomal dominant heriditary condition.
. AIHA -> Acquired condition.
. Spherocytosis -> +ve family H/O & -ve Coomb's test.
. AIHA -> -ve family H/O & +ve Coomb's test.
. N.B. PATHO-PHYSIOLOGIC MECHANISMS of ANEMIA in variable diseases:
___________________________________________________________________
. Impaired DNA & purine synthesis -> Vitamin B12 defeciency.
. RBC membrane instability -> Heriditary spherocytosis.
. Impaired Hb synthesis -> Iron defeciency anemia, sickle cell anemia &
Thalassemia.
. Impaired glutathione synthesis -> G6PDD.
. Mechanical injury to RBCs -> Hemolysis with artificial heart valves.
. MET-HEMOGOLBINEMIA:
_____________________
. Shortness of breath for no clear reason.
. Clear lungs on examination.
. Blood locked up in an oxidized state that can't pick up oxygen.
. H/O of exposure to drugs such as nitroglycerin, amyl nitrate,
nitroprusside & dapsone.
. H/O of exposure to anesthetic drugs e.g lidocaine.
. H/O of brown blood !!
. Tx -> Methylene blue !!

. CARBOXYHEMOGLOBINEMIA = CARBON MONOXIDE (CO) POISONING:


_________________________________________________________
. H/O of environmental risk (Pt working in an enclosed space ->
underground parking lot).
. Present with headache, nausea & dizziness.
. Exposure to CO from automobile exhaust.
. CO binds Hb with an affinity app. 250 times that of oxygen.
. -- in blood carrying oxygen capacity.
. As a compensation -> the body ++ RBCs production (++ HCT).
. OBSTRUCTIVE SLEEP APNEA (OSA) -> ++ ERYTHROPOIETIN PRODUCTION:
________________________________________________________________
. Recurrent transient obstruction of the upper airway due to pharyngeal
collapse.
. Obese or over-weight pts have excessive snoring, day time sleeping &
morning headaches.
. Transient episodes of hypoxia -> sensed by the kidneys -> ++
Erythropoietin production.
. Erythropoietin ++ RBCs -> Polycythemia.
. OSA doesn't cause carboxyhemoglobinemia ! xxxxxxxxxxxxxx
. LEUKEMIA:
___________
___________
(A) ACUTE LEUKEMIA:
____________________
. Pancytopenia (Fatigue - bleeding - infections).
. Excess WBCS but don't work (Functional immunodefeciency).
. Dx -> Peripheral smear -> BLASTS.
. AUER RODS = AML ACUTE MYELOID LEUKEMIA.
. DIC is asscociated with M3 (Acute pro-myelocytic leukemia).
. Cytogenetics is used for prognosis & relapse prediction.
. If the pt is at high risk for relapse after chemotherapy,
. BM transplantation sh'd be performed as chemotherapy induces
remission.
. Tx -> Chemotherapy (idarubicin & daunorubicin) -> Acute myelogenous
leukemia.
. Tx -> Add ATRA (All Trans-Retinoic Acid) for -> M3 Acute promyelocytic leukemia.
. Tx -> Ass intra-thecal Methotrexate for ALL Acute Lymphocytic
leukemia.
. N.B. Acute leukemia can sometimes present with extremely HIGH WBCs
count,
. When the WBCs > 100000 -> sludging of WBCs in the blood vessels of eye
& lungs & brain.
. LEUKOSTASIS is ttt with LEKOPHARESIS (Removing of WBCs via blood
centrifugation).
. Hydroxyurea is used to lower the cell count.
(B) MYELODYSPLASIA:
____________________
. Mild slowly progressive pre-leukemia $.
. May progress to acute leukemia.
. MOST COMMON CAUSE OF DEATH -> INFECTION or BLEEDING.
. Elderly pt.
. Pancytopenia (Fatigue - bleeding - infections).
. ++ MCV (Macro-ovalocytes).
. -- Reticulocyte count.

. Dx -> Special neutrophil with 2 lobes (PELGER-HUET) cells.


. Tx -> Supportive with transfusions as needed & AZAcitadine.
. Those with 5q minus $ are ttt with Lenalidomide.
. MYELO-PROLIFEARTIVE DISORDERS:
________________________________
(A) CHRONIC MYELOGENOUS LEUKEMIA (CML):
________________________________________
. ++ WBCs (NEUTROPHILs predominant).
. SPLENOMEGALY.
. Dx -> Best initial -> -- Leukocyte Alkaline Phosphatase (LAP).
. Dx -> Most accurate -> PHILADELPHIA CHROMOSOME (Cytogenic
study:Abnormal chromosome 22)
. formed by reciprocal translocation of chromosom 9 & 22.
. Reciprocal translocation -> BCR-ABL fusion gene -> ABNORMAL TYROSINE
KINASE ACTIVITY !
. {-- LAP} + {++ WBCs} = CML.
. {++ LAP} + {++ WBCs} = LEUKEMOID REACTION = Reactivity from infection.
. Tx -> Best initial -> IMATINIB (Gleevac) " Tyrosine kinase inhibitor".
. BMT is the only way to cure CML (Never best initial ttt).
(B) CHRONIC LYMPHOCYTIC LEUKEMIA (CLL):
________________________________________
. ++ WBCs (LYMPHOCYTES predominant).
. Pt > 50 ys.
. Asymptomatic - found on routine testing.
. Dx -> Peripheral blood smear -> SMUDGE cells "Ruptured nuclei of
lymphocytes".
.
.
.
.
.

Stage
Stage
Stage
Stage
Stage

0
1
2
3
4

->
->
->
->
->

++ WBCs.
Enlarged LNs.
Enlarged Spleen.
Anemia.
-- platelets.

.THE PRESENCE OF THROMBOCYTOPENIA = STAGE 4 -> POOR PROGNOSIS.


. Tx -> Stage 0 & 1 -> No ttt.
. Other stages -> FLUDARABINE + RITUXIMAB.
(C) HAIRY CELL LEUKEMIA:
_________________________
. Middle aged pt with Pancytopenia & massive splenomegaly.
. Dx -> Tartarate resistant acid phosphatase (TRAP) smear -> HAIRY CELLS
!
. Named so bec. the lymphocytes have fine hair like irregular
projections.
. The bone marrow may be become fibrotic -> Un-successful aspirates
(DRY-TAP).
. Tx -> CLADRIBINE.
(D) MYELOFIBROSIS:
___________________
. Same as hairy cell leukemia -> BUT -> NORMAL TRAP level !
. Dx -> TEAR DROP shaped cells on smear.
. Tx -> LENALIDOMIDE or THALIDOMIDE , BMT.
(E) POLYCYATHEMIA VERA (Pvera):
________________________________

. Plethoric face.
. Headache - Blurring of vision - dizziness - fatigue.
. Pruritis happening after a hot bath or shower.
. pruritis due to release of histamine from basophils.
. Hypertension can be one of the presentations of polycythemia.
. ++ incidence of peptic ulcerations (++ Histamine release from
basophils).
. ++ incidence of gouty arthritis ( ++ cell turnover).
. Dx -> CBC "MARKEDLY HIGH HEMATOCRITE & low MCV" !!!
. Dx -> ABG " Absence of hypoxia".
. Dx -> -- Erythropoietin (Most important).
. ++ WBCs & ++ Platelets.
. ++ B 12 & ++ LAP levels.
. MARKEDLY HIGH HEMATOCRITE may lead to THROMBOSIS.
. Ass. with JAK 2 mutation.
. Tx -> PHLEBOTOMY. (HCT < 45%).
. Tx -> Hydroxyurea to -- cell count.
. Tx -> Give daily Aspirin to prevent Thrombosis.
. High risk of thrombosis -> Due to ++ platelet count.
. High risk of bleeding -> Due to impaired platelet function
. N.B. . HERIDITARY TELANGIECTASIA = OSLER - WEBER - RENDU $YNDROME:
____________________________________________________________________
. Diffuse telangiectasia + Recurrent epistaxis + Wide spread AV
MALFORMATIONs.
. AV malformations in lung -> Blood shunt from Rt to Lt side of the
heart.
. AV shunts -> Chronic hypoxemia -> Reactive polycythemia (++ HCT).
(F) ESSENTIAL THROMBOCYTOPENIA:
________________________________
. ++ PLATELET cell count.
. Headache - visual disturbances - pain in hands (Erythromyelalgia).
. Most common cause of death -> Bleeding & thrombosis.
. Tx -> Hydroxyurea to -- cell count.
. Tx -> Give daily Aspirin to prevent Thrombosis.
. PLASMA CELL DISORDERS:
________________________
. ALL are characterized by ++ serum protein with normal albumin (GAMMA
GAP).
_________________________________________________________________________
____
(A) MULTIPLE MYELOMA:
______________________
. Monoclonal proliferation of plasma cells.
. CRAB -> Calcium ++ & Renal impairment & Anemia & Bones pain, lytic
lesions & #s.
-> Skeletal survey -> Punched out osteolytic lesions (if osteoblastic =
Prostate cancer).
-> Serum immune electrophoresis -> Abnormal M spike.
-> Serum protein electrophoresis (SPEP) -> ++ Mono-clonal Antibodies
(IgG).
-> Urine protein electrophoresis (UPEP) -> BENCE-JONES proteins.
-> Peripheral smear -> ROULEEAUX formation of blood cells.
-> ++ Ca.
-> ++ ESR > 100.
-> B2 micro-globulin (detect prognosis).
-> ++ BUN & Creatinine (RF).

-> Most specific test -> Bone marrow biopsy -> ++ PLASMA cells > 10 % !
. Most common cause of death -> INFECTIONS & RENAL FAILURE.
. susceptible to infections due to -- WBCs & -- ability to produce
effective antibodies,
. due to BM infiltration with malignant plasma cells.
. Tx -> Melphalan & steroids.
. Tx -> Most effective ttt -> Autologous stem cells bone marrow
transplantation.
. Tx -> Hypercalcemia -> Hydration & diuresis.
. Tx -> Bone #s -> Biphosphonates.
. Tx -> RF -> hydration.
. Tx -> Anemia -> Erythropoietin.
. Tx -> Prophylaxis against infections with vaccinations (Pnemovax).
(B) MONO-CLONAL GAMMOPATHY OF UNKNOWN SIGNIFICANCE (MGUS):
___________________________________________________________
. Asymptomatic ++ of IgG on SPEP. (due to ++ ptn in old age).
. Elderly pt > 70 ys.
. MGUS require METASTATIC SKELETAL BONE X-RAY to exclude lytic lesions
sugesting MM !
. No ttt.
(C) WALDENSTROM's MACRO-GLOBULINEMIA:
______________________________________
. ++ Ig M -> Hyperviscosity.
. Blurry vision (Dilated segmented tortuous retinal veins)
. confusion & headache.
. Enlarged Lns & Hepatosplenomegaly.
. Dx -> Serum viscosity level -> ++.
. Dx -> SPEP -> ++ Ig M SPIKE !
. Tx -> PLASMAPHARESIS.
. Same ttt as CLL -> Fludarabaine.
(D) APLASTIC ANEMIA:
_____________________
. PANCYTOPENIA with no identified etiology.
. Tx -> Pt < 50 ys & has a match - > BMT.
. Tx -> Pt > 50 ys & NO match -> Anti-thymocyte globulin & cyclosporine.
. N.B. MONO-CLONAL GAMMOPATHY OF UNKNOWN SIGNIFICANCE Vs MULTIPLE
MYELOMA:
_________________________________________________________________________
_
(MGUS)
(MM)
. Absence of anemia.
. Hypercalcemia.
. Renal insuffeciency.
. Lytic lesions in bones.
bones.
. Serum monoclonal protein < 3 g/dl.
protein > 3 g/dl.
. < 10 % plasma cells in the bone marrow.
the bone marrow.

.
.
.
.

Anemia.
Hypercalcemia.
Renal insuffeciency.
Lytic lesions in

. Serum monoclonal
. > 10 % plasma cells in
. ++ B 2 microglobulin.

. MGUS require METASTATIC SKELETAL BONE X-RAY to exclude lytic lesions


sugesting MM !

. LYMPHOMA:
___________
. ENLARGED LNs (Mostly CERVICAL).
. Anemia due to BONE MARROW INFILTRATION by CANCEROUS CELLS !
. Two types_________________________________
|
____________________________________________________
|
|
.HODGKIN's LYMPHOMA
.NONHODGKIN's LYMPHOMA
.__________________
._______________________
. Best initial test -> EXCISIONAL LN BIOPSY.
. SAME.
. REED STERNBERG CELSS.
. NO !
. STAGING by Contrast CT & CXR & BM biopsy:
. SAME.
-> 1 -> Single LN group.
-> 2 -> 2 LN groups on one side of diaphragm.
-> 3 -> LN invovement on both sides of diaphragm.
-> 4 -> Wide-spread disease = B symptoms (fever - weight loss - Night
sweats).
. 90 % of cases present with Stages 1 & 2.
. 90 % of cases present
with stages 3 & 4.
. Tx -> Stages 1 & 2 with no B symptoms -> radiotherapy.
. Tx -> Stages 3 & 4 with B symptoms ----> chemotherapy.
. "ABVD" ->
. "CHOP" ->
- Adriamycin.
- Cyclophosphamide.
- Bleomycin.
- Hydroxyadriamycin.
- Vinblastine.
- Oncovin.
- Dacarbazine.
- Prednisone.
. TUMOR LYSIS $YNDROME:
_______________________
. Ass. with tumors with high cell turn-over.
. Ex: Poorly differentiated lymphoma "Burkitt's lymphoma" & Leukemias
"ALL".
. HYPER {phosphatemia - kalemia - uricemia}.
. HYPO {Calcemia}.
. Both potassium & phosphate r intra-cellular ions, so cell break down > their release.
. Released phosphate binds calcium leading to hypocalcemia.
. Degradation of cell proteins -> ++ uric acid levels.
. TL$ may lead to fatal arrhythmias, ARF & sudden death.
. Tx -> Allopurinol greatly reduces the possibility of acute urate
nephropathy.
. ASYMPTOMATIC LOCALIZED LYMPHADENOPATHY:
_________________________________________
. Several non-tender rubbery cervical Lymph nodes.
. Most commonly in upper respiratory tract infection.
. Commonly observed in children & youn adults.
. Tx -> OBSERVATION !
. GASTRIC MALT = MUCOSA ASSOCIATED LYMPHOID TISSUE MANAGEMENT:
______________________________________________________________
. ERADICATION OF HELICOBACTER-PYLORI !
. TRIPLE THERAPY (OMEPRAZOLE - CLARITHROMYCIN - AMOXICILLIN).

. INFECTIOUS MONONUCLEOSIS (IM):


________________________________
. Acute, benign, self limiting lymphoproliferative condition.
. Caused by Epstein Barr virus (EBV).
. EBV is transmitted by close contact to infected oro-tracheal
secretions.
. Extreme fatigue - malaise - sore throat - fever - generalized
maculopapular rash.
. Posterior cervical lymphadenopathy & palatal petichae.
. Splenomegaly is common.
. Contact sports sh'd be avoided to prevent splenic rupture.
. Leukocytosis with variant lymphocytes (Atypical lymphocytes).
. Dx -> HETEROPHIL ANTIBODIES (SENSITIVE & SPECIFIC).
. HETEROPHIL ANTIBODIES may be NEGATIVE in EARLY disease.
. -ve HETEROPHIL ANTIBODIES doesn't exclude IM.
. COAGULATION DISORDERS:
________________________
________________________
. 1 . VON WILLEBRAND's DISEASE (VWD):
______________________________________
. NORMAL PALTELET COUNT & ABNORMAL PLATELET FUNCTION.
. -- VWF -> -- platelet activation.
. Superficial bleeding from the skin & mucosal surfaces e.g. gingiva,
gums & vagina.
. Epistaxis is a common presentation & worsens with the use of aspirin.
. -- VWF -> destabilizes factor 8 -> ++ aPTT.
. Dx -> Most accurate -> RISTOCETIN COFACTOR ASSAY & VWF level.
. If the level of VWF is normal -> RISTOCETIN test will tell if it is
working properly.
. Tx -> DESMPORESSIN or DDAVP -> Will release sub-endolthelial stores of
VWF & factor 8.
. If DDAVP failed -> Factor 8 replacement.
. TYPES OF BLEEDING:
____________________
____________________
. A -> PLATELET TYPE BLEEDING:
______________________________
. petichae - epistaxis - purpura - gingiva - gums - vagina.
. B -> FACTOR TYPE BLEEDING:
____________________________
. Hemoarthrosis - Hematoma.
. A -> PLATELET TYPE BLEEDING:
______________________________
. 1 . IDIOPATHIC IMMUNE THROMBOCYTOPENIA (ITP):
________________________________________________
. Immune destruction of platelets.
. Platelets count < 50000.
. Ig G auto-antibodies against the paltelet membrane glycoproteins 2B &
3A receptors.
. Mostly occur in children.
. Pt may be asymptomatic.
. Mucocutaneous bleeding, ecchymosis & or petichiae.
. May follow acute viral infection.

. Dx -> ISOLATED THROMBOCYTOPENIA < 100000/ml.


. Dx -> Peripheral smear sh'd be done to exclude other causes e.g. TTP.
. Dx -> Bone marrow -> ++ Megakaryocytes (platelet precursors).
. Dx -> U/$ -> NORMAL SPLEEN.
. Dx -> Check for hepatitis C & HIV infections.
. Dx -> Diagnosis of exclusion.
. Tx -> Platelets > 30000 , without bleeding -> Observe !
. Tx -> Platelets < 30000 , or bleeding -> Corticosteroids Prednisone
(1st line therapy).
. Tx -> Platelets < 20000 ! with eistaxis, melena & intracranial
hemorrhage -> IVIG.
. IVIG: INTRAVENOUS IMMUNOGLOBULIN -> when platelet < 20000 & life
threatening condition.
. Recurrent episodes -> SPLENECTOMY.
. No response to splenectomy -> Romiplostim.
. N.B. HCV & HIV tests as ITP may be the initial presentation of HIV
infection.
. 2 . UREMIA INDUCED PLATELET DYSFUNCTION:
___________________________________________
. Uremia prevents palatelets from degranulation.
. NORMAL PLATELET COUNT + PLATELET TYPR BLEEDING + RENAL FAILURE PT.
. NORMAL Ristocetin test & VWF level.
. Tx -> Desmopressin - DDAVP.
. B -> FACTOR TYPE BLEEDING = COLTTING FACTOR DEFECIENCIES:
___________________________________________________________
* FACTOR 8 = HEMOPHILIA A:
___________________________
. Joint bleeding (Hemarthrosis) or hematoma on a MALE child.
. Dx -> Mixing study then specific factor level.
. Tx -> Minor defeciency -> DDAVP.
. Tx -> Severe defeciency -> Factor 8 replacement.
* FACTOR 9 = HEMOPHILIA B:
___________________________
. Joint bleeding (Hemarthrosis) or hematoma (less common than factor 8
def.).
. Dx -> SAME.
. Tx -> Factor 9 replacement.
* FACTOR 11:
_____________
. Rare bleeding with trauma or surgery.
. Dx -> Same.
. Tx -> FFP Fresh frozen plasma.
. FACTOR 12:
____________
. No bleeding.
. Dx -> Same.
. Tx -> No ttt necessary.
. SENILE PURPURA:
_________________
. occurs in areas susceptible to traumas in elderly (Dorsum of the hands
& forearms).
. Due to PERIVASCULAR CONNECTIVE TISSUE ATROPHY .
. Lesions rapidly resolve leaving a brownish discolouration from
hemosiderin deposition.

. Requires no ttt.
. HEPARIN INDUCED THROMBOCYTOPENIA (HIT):
___________________________________________
. HEPARIN exposure > 5 days then,
. Platelet count reduction > 50 % from baseline.
. Despite -- platelet count ->HIT is highly thrombogenic -> Arterial &
venous thrombosis.
. Necrotic skin lesions at heparin injection sites.
. Acute systemic anaphylactoid recation after heparin.
. Dx -> SEROTONIN RELEASE ASSAY (GOLD STANDARD).
. TTT is started on clinical suspicion before serotonin assay.
. Tx -> CESSATION OF ALL HEPARIN PRODUCTS !
. Tx -> Start Argatroban (direct thrombin inhibitor).
. WARFARIN INDUCED SKIN NECROSIS:
_________________________________
. More common in females.
. Common sites: breasts , buttocks, thighs & abdomen.
. Initial complaint is PAIN FOLLOWED BY BULLAE FORMATION & SKIN
NECROSIS.
. Occurs within weeks after starting therapy.
. Tx -> Discontinue warfarin - Give heparin to continue anticoagulation
- Give Vit. K.
. Acetaminophen, NSAIDs & Amiodarone may potentiate the anticoagulant
effect of warfarin.
. VITAMIN K DEFECIENCY BLEEDING:
________________________________
. Pt kept NPO NOTHING PER ORAL for a prolonged period of time &
receiving Antibiotics.
. OR Newborn hadn't received prophylactic vit. K (Home-born) for
prevention of hemorrhage
. ++++ PT > ++ PTT.
. THROMBOPHILIA = HYPERCOAGULABLE STATES:
_________________________________________
_________________________________________
(1) LUPUS ANTI-COAGULANT or ANTI-CARDIOLIPINS ANTIBODIES:
__________________________________________________________
. Venous thrombosis.
. ++ aPTT (PROLONGED PARTIAL THROMBOPLASTIN TIME).
. Normal PT, BT, platelet count & VWF.
. Spontaneous abortion. (Due to promotion of arterial & venous
thrombosis).
. False +ve VDRL & True -ve FTA-ABS (Excluding $yphilis as a cause of
recurrent abortions
. Dx -> Mixing study.
. Dx -> Russel Viper venom test (Most accurate).
. Tx -> Heparin (LMWH) followed by warfarin.
(2) PROTEIN C DEFECIENCY:
__________________________
. Skin necrosis with the use of Warfarin.
. Dx -> Ptn C level.
. Tx -> Heparin followed by Warfarin.
(3) FACTOR 5 LEIDEN MUTATION:

______________________________
. Most common cause of thrombophilia.
. Dx -> Factor 5 mutation test.
. Tx -> Heparin followed by Warfarin.
(4) ANTI-THROMBIN DEFECIENCY:
______________________________
. No change in the aPTT with a blous of IV heparin !
. Dx -> Anti-thrombin 3 level.
. Tx -> Large amounts of heparin or direct thrombin inhibitor followed
by warfarin.
. DIC = DISSEMINATED INTRAVASCULAR COAGULATION:
_______________________________________________
. Doesn't occur in healthy pts.
. Ass. with sepsis - burns - snake bites - cancer - Abruptio placenta or
AF Embolism.
. BLEEDING related to CLOTTING FACTORS DEFECIENCY & THROMBOCYTOPENIA !!
. ++ both PT & PTT.
. -- platelet count.
. ++ D-dimer & FDP (fibrin degradation products).
. -- fibrinogen level (consumed).
. Tx -> REPLACEMENT by FFP FRESH FROZEN PLASMA (Contains both palatelets
& clot.factors).
. TRANSFUSION REACTIONS:
________________________
________________________
. 1 . ABO INCOMPATIBILITY:
___________________________
. Acute symptoms of hemolysis WHILE the transfusion is occuring.
. Ex -> DURING a transfusion, the pt becomes hypotensive & tachycardic.
. Back & chest pain & dark urine.
. ++ LDH & bilirubin.
. -- Haptoglobin.
. 2 . TRANSFUSION RELATED ACUTE LUNG INJURY (TRALI) = LEUKOAGGLUTINATION REACTION:
_________________________________________________________________________
___________
. Acute Shortness of breath from antibodies in the donor blood against
the repient WBCs.
. Ex -> 20 mins after a pt. receives a blood transfusion, the pt becomes
short of breath.
. Transient infiltrates on CXR.
. All symptoms resolve spontaneously.
. 3 . IgA DEFECIENCY:
______________________
. presents with anaphylaxis !
. In the future, use blood donations from an IgA defecient donor or
washed RBCs.
. Ex -> As soon as the pt. received transfus., he becomes SOB,
hypotensive & tachycardic.
. NORMAL LDH & BILIRUBIN.
. 4 . MINOR BLOOD GROUP INCOMPATIBILITY:
_________________________________________
. To kell, Duffy, Lewis or Kidd antigens or Rh incompatibility !

. Delayed jaundice.
. No specific therapy.
. Ex -> A few days after transfusion, the pt becomes jaundiced.
. The hematocrit doesn't rise with transfusion & he is generally without
symptoms.
. 5 . FEBRILE NON-HEMOLYTIC REACTION:
______________________________________
. Small rise in temperature.
. No ttt required.
. Reaction against donor WBCs antigens.
. prevented by using filtered blood transfusions in the future to remove
WBCs antigens.
. Ex -> A few hours after transfusion, the pt becomes febrile with rise
1 degree in temp.
. No evidence of hemolysis.
. N.B. HYPOCALCEMIA MANIFESTATIONS (PARESTHESIA) AFTER BLOOD TRANSFUSION:
_________________________________________________________________________
. Occurs in pts who receive more than one blood volume of blood
transfusion or packed RBCs over 24 hours may develop ++ plasma level of
CITRATE (A SUBSTANCE ADDED TO STORED BLOOD) -> CHELATION of Ca & Mg by
citrate -> -- Ca -> Paresthesia.
. MIGRATORY SUPERFICIAL THROMBOPHLEBITIS = TROUSSEAU's $YNDROME:
________________________________________________________________
. Hypercoagulable disorder.
. Un-explained superficial venous thrombosis at un-usual sites e.g. arm
& chest area.
. Associated with OCCULT VISCERAL MALIGNANCY !
. Ex. Cancer involving the pancreas "most common".
. The tumor releases mucin that react with platelets forming platelet
rich micro-thrombi.
. H/O of heavy smoking - abdominal pain - migrattory thrombophlebitis.
. Dx -> CT Abdomen -> searching for an occult tumor (pancreatic
carcinoma).
. GLUCAGONOMA:
______________
. Necrolytic migratory erythema:
---------------------------------> Erythematous papules / plaques on face, perineum & extremities.
-> Enlarge & coalese with central clearing & blistering & crusting &
scaling.
. Diabetes Mellitis:
---------------------> Mild hyperglycemia easily controlled with diet & oral agents.
-> Don't require insulin !
. GIT symptoms:
----------------> Diarrhea - anorexia abdominal pain - occasional constipation.
. Other findings:
------------------> Weight loss.
-> Neuropsychiatric (ataxia - dementia - proximal ms weakness).
-> Associated wih venous thrombosis !
. Dx -> Hyperglycemia with ++ GLUCAGON > 500 mg/dl.
. Dx -> Normocytic Normochromic anemia.
. Dx -> CT or MRI to detect the tumor.

. SMOKER + HORNER's $ = LUNG CANCER:


____________________________________
. Horner's $ -> Miosis, ptosis & anhydrosis.
. Simple CXR is the best next step to detect lung cancer.
. SMALL CELL (OAT) LUNG CARCINOMA:
__________________________________
. associated with $yndrome of inappropriate ADH secretion & ACTH
production.
. SIADH (Hyponatremia & -- serum osmolality & ++ urine osmolality).
. Metastasis is already present at the time of diagnosis !
. Tx of SIADH -> Mild (Fluid restriction) or Severe (Hypertonic saline).
. ++ ACTH -> Hypertension - Hypokalemia - Metabolic alkalosis Hyperpigmentation.
. e'out other manifests of Cushing $ (Moon face - Dorsal hump - central
obesity - striae)
. SQUAMOUS CELL CARCINOMA OF THE LUNG:
______________________________________
. Significant smoking H/O.
. HYPERCALCEMIA ++ Ca -> (sCa++mous) !
. Hilar mass.
. ADENOCARCINOMA OF THE LUNG:
_____________________________
. Least association with smoking.
. Located peripherally.
. Consists of columnar cells growing along the septa.
. Presents as a sloitary nodule !
. May be detected incidentally.
. FEBRILE NEUTROPENIA:
______________________
. Single temperature > 38.3c or sustained temp. > 28 c for > 1 hour in a
neutropenic pt.
. Neutropenia = Absolute neutrophil count < 1500 cells/ml.
. Mild (<1500) - Moderate (<1000) - Severe (<500).
. All require antibiotics.
. Moderate & severe neutropenia require hospitalization.
. The most common invading organism is PSEUDOMNAS AERUGINOSA.
. Tx -> HOSPITALIZATION,
. BLOOD CULTURES followed by IV CEFEPIME or PIPERACILLIN TAZOBACTAM.
. SQUAMOUS CELL CARCINOMA OF THE MUCOSA OF THE HEAD & NECK:
___________________________________________________________
. ALCOHOLIC SMOKER.
. HARD UNILATERAL NON-TENDER CERVICAL OR SUBMANDIBULAR lymph node.
. Dx -> Best initial -> PAN-ENDOSCOPY.
. Tx -> Radical neck dissection.
. TESTICULAR TUMOR:
___________________
. Painless hard mass in testicle.
. Suggestive ultrasound.
. Tx -> Orchiectomy (Removal of the testicle & its associated cord).
. FNAC or trans-rectal biopsy are contr'd bec. the risk of spillage of
cancer cells.

. FIBROCYSTIC DISEASE OF THE BREAST:


____________________________________
. Rubbery, firm, mobile & pinful mass in a young pt.
. More pain during menses.
. Aspiration of the cyst -> Clear fluid with diasppearance of the mass.
. Tx -> Observation of the pt 4 - 6 weeks.
. Only send the fluid for cytology if their is blood or foul smelling.
. INVASIVE DUCTAL BREAST CARCINOMA:
___________________________________
. TNM staging is the single most important prognostic tool for breast
cancer.
. Prognosis is best detected using ONCOGENE AMPLIFICATION by FISH !
. FISH = Fluorescent in situ hybridization.
. Over-expression of the oncogene HER2 can be detected by FISH = (Worse
prognosis).
. Positivity predicts a +ve response to TRASTUZUMAB & ANTHRACYCLINE
chemotherapy.
. ER +ve & PR +ve are GOOD prognostic features.
. Tx -> TRASTUZUMAB (Herceptin) is used to ttt breast cancer that is
HER2 +ve.
. Trastuzumab side effect -> CARDIOTOXICITY.
. ECHOCARDIOGRAPHY is recommended before ttt to assess the ejection
fraction.
. INFLAMMATORY CARCINOMA OF THE BREAST:
_______________________________________
. Breast cancer sh'd be considered whenever a pt. without a prior H/O of
skin disease,
. develops a breast rash that is non-responsive to standard ttt !
. When invasive ductal carcinoma is severe, it can infiltrate into the
dermal lymphatics,
. resulting edema - erythema - warmth of the entire breast (inflammatory
carcinoma).
. When the rash is localized to the nipple & has an ulcerating
eczymatous appearance,
. the primary cosideration should be PAGET's DISEASE of the breast.
. 5 % of pts with PAGET's disease have an underlying breast cancer
"ADENO-CARCINOMA".
. Skin biopsy -> Large cells surrounded by clear halos.
. TAMOXIFEN:
____________
. Has mixed agonist & antagonist activity on Estrogen receptors.
. It is used as an adjuvant therapy for early stage breast cancer,
. It reduces the risk of recurrence of the original cancer,, BUT,,
. ++ risk of developing of another cancer in the other breast !
. Estrogenic effects ++ risk of ENDOMETRIAL cancer & Venous thrombosis.
. SQUAMOUS CELL CARCINOMA of the SKIN:
______________________________________
. Any scar that develops into a non-healing, painless, bleeding ulcer.
. Sun-exposed or burned areas are typically involved.
. Rough scaly nodules that can ulcerate & metastasize.
. Tar derivatives (tobacco smoke) & chronic radiation exposure are
predisposing factors.
. Dx -> PUNCH BIOPSY.
. Tx -> Surgical removal with wide excision of the skin around the
tumor.
. BASAL CELL CARCINOMA of the SKIN:

___________________________________
. Most common form of skin cancers in USA.
. Open sore that bleeds, oozes or crusts & remains open for 3 or more
weeks.
. Reddish patch or irritated area, shiny, waxy, scar like with elevated
rolled borders.
. Remains local - Never spreads.
. Tx -> Mohs surgery (Microscopic shaving) -> 1-2 mm of clear margins
are excised.
. Highest cure rate with Mohs surgery.
. Indicated in lesions located at critical areas e.g. perioral region,
nose, lips & ears.
. ESOPHAGEAL CARCINOMA:
_______________________
. Heart burn - significant weight loss - Regurgitation of food - fatigue
- smoking H/O.
. Age > 50 ys.
. Histological types -> Squamous cell carcinoma & Adenocarcinoma.
. SCC -> Ass. with smoking & alcohol consumption.
. Adenocarcinoma -> Barret's esophagus (GERD complication).
. Dx -> BARIUM SWALLOW followed by ENDOSCOPY.
. MYASTHENIA GRAVIS:
____________________
. Ptosis & double vision by the end of the day.
. Dx -> EMG -> Decremental response in compound action potential.
. Dx -> Acetyl choline receptor antibody test +ve.
. Dx -> CT scan chest sh'd be done in all newly diagnosed MG pts
searching for a THYMOMA.
. COLON CANCER SCREENING:
_________________________
* ROUTINE:
___________
-> Colonoscopy at 50 ys then every 10 ys.
* SINGLE FAMILY MEMBER WITH COLON CANCER:
__________________________________________
-> Colonoscopy at 40 ys,
-> or .. 10 ys earlier than the age at which the family member had
cancer,
-> whichever is earlier then every 10 ys.
* HNPCC 3 family members & 2 generations & 1 premature (<50ys):
________________________________________________________________
. Colonoscopy at 25 then every 1-2 ys.
. HNPCC is ass. with high risk of extra-colonic tumors (ENDOMETRIAL
CARCINOMA).
. It is a part of LYNCH $ type 2.
* FAMILIAL ADENOMATOUS POLYPOSIS:
__________________________________
. Sigmoidoscoy at 12 then every 1-2 ys.
. 100 % risk of cancer.
. ELECTIVE PROCTO-COLECTOMY sh'd be done.
* JUVENILE POLYPOSIS - PEUTZ JEHGERs - TURCOT's $ - GARDNER's $:
_________________________________________________________________

. No additional screening.
. ULCERATIVE COLITIS:
_____________________
. Colonoscopy once the diagnosis is established for 8 ys then repeated
every 1 - 2 ys.
. MEN 1 = MULTIPLE ENDOCRINE NEOPLASIA 1:
_________________________________________
. Paratyhroid (>90%) -> parathyroid hyperplasia -> primary
hyperparathyroidism -> ++ Ca.
. Pituitary -> prolactinoma.
. Pancreas / GIT -> Gastrinoma "ZE $" - insulinoma - VIPoma Glucagonoma.
. KEY WORDS-> INTRACTABLE ULCERATION + HYPERCALCEMIA -> ZE$ &
Hyperparathyroidism = MEN1.
. POST-SPLENECTOMY SEPSIS:
__________________________
. Asplenic pt have defective PHAGOCYTOSIS !
. impaired antibody mediated opsonization in phagocytosis.
. High risk of overwhelming infection by encapsulated organisms,
. e.g. Strept. pneumoniae, N. menengitidis & H. influenzae.
. DEEP VENOUS THROMBOSIS = DVT MANAGEMENT:
__________________________________________
. Presents with pain, swelling & discoloration.
. D.D. -> Ruptured Baker's cyst - venous insuffeciency - post-thrombotic
$ & cellulitis.
. Failure to anti-coagulate the pt may lead to pulmanary embolism.
. Modified Wells criteria is a pretest propability of DVT:
-> Previous DVT.
-> Active cancer.
-> Recent immobilization.
-> Localized tendrness along vein distribution.
-> Swollen leg.
-> Pitting edema.
.
. Pre-test propability of DVT using WELLs criteria
.__________________________________________________
.|
._________________________________________
.|
.|
. Not likely
. Likely
.____________
.________
|
.|
. D-Dimer test (+)--------------->. Compression
Ultrasonography
.______________
._____________________________
.|
.|
.|
._________________________________
.|
.|
.|
(-)
(+)
(-)
.|
.|
.|
. Un-likely to have DVT ! (TTT with Heparin & Warfarin)
(Contrast Venography)

. Clinical features of METASTATIC BRAIN CANCER:


_______________________________________________
. Incidence -> Lung > Breast > Un-known primary > Melanoma > Colon.
. Primary solitary brain metastases -> BREAST - COLON - RENAL CELL
CARCINOMA.
. Multiple brain metastasis -> LUNG - MALIGNANT MELANOMA.
. Brain metastasis are the most common intracranial tumors.
. Headache - nausea&vomiting - seizures & focal neurological symptoms
(weakness-aphasia).
. TYPES OF THERAPIES !
______________________
. ADJUVANT -> TTT given in addition to standard therapy.
. INDUCTION -> Initial dose of ttt to rapidly kill tumor cells.
. CONSOLIDATION -> TTT given after induction therapy to -- the tumor
burden.
. MAINTENANCE -> Given after induction & consolidation ttt to kill
residual tumor cells.
. NEO-ADJUVANT -> Given before the standard therapy for a particular
disease.
. SALVAGE -> TTT for a disease when the standard ttt fails.
. MECHANISM OF ACTION of IMP. DRUGS:
____________________________________
. HEPARIN -> "Anti-coagulant" -> ++ ANTI-THROMBIN 3 -> -- Thrombin, 9 &
10.
. WARFARIN -> "Anti-coagulant" -> -- synthesis of Vit. K dep. factors
1972, ptn C & S.
. ASPIRIN -> "Anti-platelet" -> -- cyclo-oxygenase 1 -> -- TXA 2
synthesis.
. CLOPIDOGREL ->"Anti-platelet" -> block platelet sufrace receptors -> - platelet activ.
. ANDROGEN ABUSE:
_________________
. Atheletes commonly abuse androgen to enhance performance in
competetive sports.
. Ex: testosterone & synthetic androgen.
. ++ Muscle mass & strength & ++ physical exercise intolerance.
. Men SEs -> -- testicular function - -- sperm production - testicular
atrophy.
. Men SEs -> Gynecomastia - mood distaurbance - agrressive behavior.
. Women SEs -> ++ Acne - Hirsutism - deepening of voice - menstrual
irregularities.
. Labs -> Erythrocytosis & ++ HCT - Hepatotoxicity - Dyslipidemia ( -HDL & ++ LDL).
. SOLITARY PULMONARY NODULE APPROACH:
_____________________________________
. 3 cm or less coin-shaped lesion,
. in the middle to lateral one third of the lung.
. Surrounded by normal parenchyma.
. Most of them are benign !
. Calcifications of the nodule favors a benign lesion !
. POP CORN calcification -> Hamartoma.
. BULLS EYE -> Granuloma.
. Low risk pts (< 40 ys & non smokers) -> Not a sign of immediate alarm.
. Best approach -> ASKING FOR AN OLD X-RAY !

.
.
or
.

If no change in it for the last 12 months -> Benign.


Followed by CXR every 3 months for the next 12 months -> If no growth
syms -> Leave!
High risk pts (> 40 ys & smokers) -> Full investigation work up !

. GIANT CELL TUMOR OF BONE:


___________________________
. Dx -> X-ray -> Expansile & eccentric lytic area with SOAP & BUBBLE
APPEARANCE.
. Benign but locally aggressive skeletal neoplasm.
. Young adults.
. pain, swelling & -- range of motion at the involved site.
. Pathologic #s are common due to thinning of the bone cortex in weight
bearing areas.
. Affect the epiphysis of the long bones (distal femur & proximal
tibia).
. MRI -> Tumor containing both cystic & hemorrhagic regions.
. Tx -> Surgery.
. COMPRESSION OF THE THECAL SAC or SPINAL CORD by a TUMOR:
__________________________________________________________
. Ex -> H/O of prostatic cancer + Acute onset back pain.
. Rapid recognition is crucial to avoid paralysis.
. Point tenderness over the spine process L5 & S1.
. Imbalance, ms weakness & week rectal sphincter tone.
. Dx -> MRI spine BUTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT
. Initial management with glucocorticoids (dexamethasone) is crucial to
-- swelling,
. as an attempt to preserve neurological function while awaiting the
results of imaging.
. POST-SPLENECTOMY RECOMMENDATIONS:
___________________________________
. Risk for sepsis after splenectomy is present UP TO 30 years & more !
. Anti-pneumococcal, Haemophilus & meningococcal vaccine sh'd be given,
. several weeks before splenectomy.
. Daily oral penicillin prophylaxis for 3 - 5ys following splenectomy.
. CANCER OVARY:
_______________
. NO screening tests !
. Serum CA 125 & pelvic U/$ may help in diagnosis.
. ++ HOMOCYSTEINE levels -> HYPERCOAGULABILITY:
_______________________________________________
. Vit. B6, Folate & Vit. B12 are involved in the metabolism of
homocysteine.
. Vit. B6 lowers homocysteine levels by acting as a cofactor for
cystathionine B-synthase
. which metabolizes homocysteine to cystathionine.
. PAIN CONTROL IN CANCER PATIENTS:
__________________________________
. Give the appropriate pain medication to cancer pts e.g. Ibuprofen.
. If no response .. Use a narcotic drug if it is the most appropriate.
. Use SHORT ACING IV MORPHINE.
. MANAGEMENT OF CHEMOTHERAPY INDUCED NAUSEA & VOMITING:
_______________________________________________________
. Volume repletion + SEROTONIN ANTAGONIST (Block 5HT3 recptors).

. MANAGEMENT OF CANCER RELATED ANOREXIA & CACHEXIA:


___________________________________________________
. PROGESTERONE ANALOG -> ++ Appetite & ++ weight gain.
. PROSTATE CANCER with BONE METASTASIS:
_______________________________________
. Tx -> FOCAL EXTERNAL BEAM RADIATION (If the pt under-went orchiectomy
!).
. BRAIN METASTASIS:
___________________
. SOLITARY -> SURGICAL RESECTION followed by whole brain radiation.
. Multiple -> Palliative whole brain radiation.
. MANAGEMENT OF HYPERCALCEMIA DUE TO UNDERLYING MALIGNANCY:
___________________________________________________________
. Asymptomatic or mild -> Ca < 12 mg/dl:
_________________________________________
. Just avoid thiazides, lithium use, volume depletion or prolonged bed
rest.
. Severe -> Ca > 14 mg/dl:
___________________________
. Immediate ttt -> Normal saline hydration + Calcitonin.
. Long term ttt -> Biphosphonate (Zoledronic acid).
. D.D. of ANTERIOR MEDIASTINAL MASS (4 Ts):
___________________________________________
. Thymoma - Teratoma - Thyroid neoplasm - Terrible lymphoma.
. Germ cell tumors are classified into seminomatous & non-seminomatous.
. Non-seminomatous (Yolk sac tumor - choriocarcinoma - embryonal
carcinoma).
. A mixture of all types of non seminomatous germ cell tumors = MIXED
GERM CELL TUMOR.
. Seminoma -> ++ B-HCG & Normal AFP.
. Non seminoma (MIXED) -> ++ B-HCG & ++ AFP.
. HEMOCHROMATOSIS:
__________________
. NEW-ONSET DIABETES MELLITUS + ARTHROPATHY + HEPATOMEGALY.
. Due to abnormal ++ intestinal absorption of iron -> ++ iron deposition
in tissues.
. Damage to organs ex. liver, pancreas , heart & pituitary.
. Liver -> Hepatomegaly -> Liver cirrhosis -> Hepatocellular carcinoma.
. Pancreas -> Bronze D.M.
. Pituitary -> Hypogonadism.
. Heart -> Restrictive heart failure.
. Joints -> Arthropathy.
. Skin -> Hyperpigmentation.
. Dx -> Iron studies -> ++ fe, ++ ferritin, ++ transferrin saturation.
. Dx -> Liver biopsy -> confirm the diagnosis.
. LEAD POISONING:
_________________
. Lead bind to erythrocytes & disrupts hemoglobin synthesis ->
Microcytic anemia.
. Due to chronic lead exposure & toxicity.
. Acute exposure -> Abdominal pain & constipation.
. Chronic exposure -> Fatigue, iiritability & insomnia.

. Hypertension - Sensori-motor neuropathies - Neuropsychiatric


disturbances - Nephropathy
. OCCUPATIONAL HISTORY IS VERY IMPORTANT !
. BATTERY MANUFACTURING - PLUMBING - MINING - PAINTING - PAPER HANGING &
AUTO-REPAIR.
. Dx -> Blood Lead level.
. Dx -> Peripheral smear -> BASOPHILIC STIPPLING.
. Tx -> CHELATION THERAPY.

Dr. Wael Tawfic Mohamed


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