Integrated Hematology Exam 11/21/06

Name:_______________________ID#:___________

Integrated Hematology: Pathophysiology/Pharmacology/Pathology (BI350/BI279)

CASE 1: (Questions 1-3) A 65 year-old gentleman presents to your office it! a c!ief complaint of !eadac!e" #e states t!at !e !as !ad intermittent !eadac!es for t!e last mont! or t o" $!e !eadac!es are typically relie%ed &y $ylenol" #e also notices t!at !e de%elops itc!ing' especially after !e ta(es a arm s!o er" #e !as tried ta(ing )enadryl' &ut it! only partial impro%ement" #is ife notices t!at !is comple*ion !as &ecome increasingly ruddy o%er t!e last se%eral mont!s" $!e patient !as for t!e most part en+oyed good !ealt!" #e does not smo(e" #e !as no (no n cardiac or respiratory pro&lems" ,e%ie of systems is positi%e only for some soreness in !is left upper -uadrant" .!ysical e*am: /ital signs are normal" #EE0$ re%eals eryt!ematous con+uncti%a" $!ere is no a&normal adenopat!y" 1ungs clear" #eart: S1' S2 normal3 no murmurs' ru&s or gallops" #is a&domen is soft and non-tender" #e !as a 2-finger&readt! spleen" $!e li%er is not palpa&le" E*amination of !is e*tremities is unremar(a&le" #is !emoglo&in is 14 gm5dl' !ematocrit 56' !ite count 12'777' platelet count 567'777" #is perip!eral smear re%eals an increased num&er of platelets' &ut is ot!er ise unremar(a&le" 1" $!is patient most li(ely !as a: A" )cr5a&l translocation" )" #ig! eryt!ropoietin le%el" C" 8A9-2 mutation" :" .roliferation of clonally-related fi&ro&lasts" E" #ypercellular marro due to an infectious process" 2" ;f t!is patient !ad a splenectomy for anot!er reason (suc! as trauma from a motor %e!icle accident)' t!e !istology of t!e spleen ould most li(ely: A" Appear to &e normal" )" :emonstrate an increased num&er of plasma cells" C" )e infiltrated &y s!eets of myelo&lasts" :" :emonstrate myeloid metaplasia (e*tramedullary !ematopoiesis)" E" 0one of t!e a&o%e" Note that the correct answer is D. Myeloid metaplasia would be the expected finding in the spleen of a patient with P.Vera. However, splenic congestion !. "None of the #bove$% would be an appropriate answer as well for a patient in the early !rythrocytotic Phase of P.Vera% & so we will accept answer !. as well.

Integrated Hematology Exam 11/21/06

Name:_______________________ID#:___________

$!is patient as treated appropriately and did ell for t!e ne*t 6 years" #e no presents to !is p!ysician it! symptoms of s!ortness of &reat! and dyspnea on e*ertion" #e is found to &e anemic it! a #& of 6' #ct 2<" #is &one marro aspirate is s!o n &elo in =igure 1"

=igure 1" ()? &iopsy on left3 reticulin stain on rig!t)"

3" $!is marro demonstrates: A" :isease )" C" :" E" transformation to a :1)C1 (,ic!ter>s syndrome)" :isease progression to myelofi&rosis" ?etastatic carcinoma unrelated to t!e initial diagnosis" $ransformation to Acute 1ymp!o&lastic 1eu(emia" Ade-uate cellularity' suggesting perip!eral red cell destruction as an e*planation for t!e anemia"

CASE 2" (Questions < @ 5) A 55 year-old la yer !o !as en+oyed e*cellent !ealt! presents to your office complaining of easy &ruising" #e !as noted t!at o%er t!e last fe ee(s !e al ays seems to !a%e an ecc!ymotic lesion some !ere on !is e*tremities or !is trun(" $!ere as no (no n trauma" Additionally' !e states t!at !e is fatigued more easily t!an is !is norm" An a%id golfer' !e finds it difficult to al( 16 !oles" #e often notes s!ortness of &reat! it! e*ertion and occasional palpitations" An e*amination' %ital signs are normal" #EE0$: con+uncti%al pallor' e*tensi%e s elling of t!e gums (see =igure 2A &elo ) and palatal petec!iae" 0o a&normal adenopat!y" 1ungs are clear" #eart: S1' S2 normal' ;5/; systolic murmur" A&domen is soft' non-tender' no masses" #is e*tremities are negati%e e*cept for a diffuse petec!ial ras! on &ot! lo er e*tremities &elo t!e (nee" " =igure 2A"

Integrated Hematology Exam 11/21/06

Name:_______________________ID#:___________

=igure 2)"

1a&oratory Studies: C)C: B)C 1C'777 it! 15D polys' 17D lymp!s' 5D monos' C7D &lasts3 #& C"6 gm5dl3 ?C/ 653 platelet count 27'777" .$ and .$$ are normal" $!e perip!eral smear is s!o n in =igure 2)" <" $!e most li(ely diagnosis is: A" =ollicular lymp!oma it! e*tramedullary !ematopoiesis" )" Acute lymp!o&lastic lymp!oma5leu(emia" C" C!ronic ?yelogenous leu(emia" :" Acute ?yelogenous leu(emia' ?< or ?5" E" ?ature )-cell leu(emia5lymp!oma" 5" =urt!er diagnostic studies are re-uired to ma(e a diagnosis" )ased on t!e information presented t!us far' !ic! of t!e follo ing is li(ely in t!is caseE A" 0on-specific esterase staining ould &e negati%e" )" $!e patient needs to undergo &one marro aspiration and &iopsy to confirm t!e diagnosis" C" $!e patient s!ould !a%e a lymp! node &iopsy" :" ,esults of cytogenetics studies may !a%e prognostic significance" E" Analysis of $C, gene rearrangements ould detect clonality"

Integrated Hematology Exam 11/21/06

Name:_______________________ID#:___________

CASE 3" (Questions 6-4) A patient it! a similar presentation to t!e one descri&ed in Case 2 (a&o%e) as found to !a%e t!e follo ing cells on perip!eral smear (=igure 3)"

=igure 3"

6" B!ic! of t!e follo ing molecular defects ould &e most li(ely in t!is disorderE A" C!romosomal translocation in%ol%ing a C)= (Core )inding =actor)" )" A%ere*pression of cyclin :1" C" t(631<) :" t(1<316) E" t(4322) C" ;n an adult patient it! t!is disease' !ic! drug is considered essential to treatment: A" C!loram&ucil (leu(eran) )" /incristine C" Cytara&ine (Ara-C) :" )leomycin E" ?et!otre*ate 6" ;f flo cytometry ere done' !ic! of t!e follo ing ould li(ely &e positi%eE A" C:27 )" C:< C" C:5 :" C:33 E" C:15 and C:37 4" B!ic! of t!e follo ing monoclonal anti&ody targeted-t!erapies could &e used to treat t!is patientE A" ,itu*ima& (,itu*an) )" $ositumoma& ()e**ar) C" AlemtuFuma& (Campat!) :" ;&ritumoma& tiu*etan (Ge%alin) E" HentuFuma& ogoFamicin (?ylotarg) <

Integrated Hematology Exam 11/21/06

Name:_______________________ID#:___________

CASE <: (Questions 17-13) A 67 year-old man presents to your office complaining of a mass in !is left a*illa" #e states t!at !e noticed a golf &all siFed mass under !is arm !ile !e as s!o ering" At first !e t!oug!t it as an inflamed gland' &ut !en it did not disappear o%er t!e ne*t mont!' !e decided to come to you for ad%ice" #e ot!er ise feels entirely ell" #e denies fe%ers' nig!t s eats or eig!t loss" #e !as not &een e*posed to any infections' nor is !e a are of any trauma to !is arm" #e specifically denies &eing scratc!ed &y a cat" E*amination re%eals normal %ital signs" #e !as a 2 cm rig!t supracla%icular node' a 2 cm left a*illary node and a 1 cm rig!t inguinal node" 1ungs clear" #eart: S1' S2 normal3 no murmurs' ru&s or gallops" A&domen soft' non-tender' no masses' no organomegaly" #is e*tremities are negati%e" #is C)C' differential and platelet count are normal" A lymp! node &iopsy as performed from t!e rig!t supracla%icular node3 representati%e sections are s!o n in =igure <" ;mmuno!istoc!emical studies re%ealed t!at t!e nodal cells e*pressed (appa (not lam&da) lig!t c!ain' as ell as C:14' C:27' C:22' and surface ;g" =igure <) (!ig! magnification) 17" diagnosisE A" :iffuse )" C" :" E" B!at is t!e most li(ely 1arge ) Cell 1ymp!oma =ollicular !yperplasia )ur(itt>s 1ymp!oma =ollicular 1ymp!oma 1ymp!o&lastic 1ymp!oma

=igure <A (lo magnification)

11" B!ic! of t!e follo ing ould &e 0A$ &e consistent it! t!e diagnosisE A" A lac( of constitutional symptoms" )" .resentation it! Stage ;;; or ;/ disease" C" )lasts in t!e perip!eral &lood" :" Small clea%ed cells" E" A lo 9i-6C" 12" B!ic! statement most accurately reflects t!e natural !istory of t!is diseaseE A" $!is is an aggressi%e disease' it! an untreated life e*pectancy measured in ee(s to mont!s" )" $!is is an indolent disease' it! median sur%i%al in ad%anced stage disease of &et een C and 17 years" C" $!is disease is complicated &y renal failure due to t!e !ig! cell turno%er (uric acid nep!ropat!y)" :" ,elease of lysoFyme from malignant cells results in renal failure" E" $!is disease transforms to an aggressi%e malignancy it!in a median of 2 years"

Integrated Hematology Exam 11/21/06

Name:_______________________ID#:___________

13" B!ic! of t!e follo ing accurately reflects t!e pat!op!ysiological &asis of t!is diseaseE A" ;t is associated it! t!e t(1<316)' resulting in o%ere*pression of &cl-2" )" ;t is associated it! t!e t(4322) resulting in t!e &cr5a&l fusion protein" C" ;t is associated it! t!e t(631<) resulting in o%ere*pression of c-myc" :" ;t is due to a translocation in%ol%ing core &inding factor (C)=)" E" ;t is due to a mutation in =1$-3' a tyrosine (inase receptor important in signal transduction"

=,EE-S$A0:;0H QIES$;A0S:
1<" A patient it! a 0on-#odg(in>s lymp!oma is treated it! a c!emot!erapy regimen" Si* mont!s after completing !er treatment' s!e de%elops symptoms of s!ortness of &reat! and is found to !a%e rales on lung e*am' and ele%ated 8/: (+ugular %enous distention)" CJ, is consistent it! congesti%e !eart failure" $!is could represent a to*ic effect of: A" :o*oru&icin )" /incristine C" ,itu*ima& :" =ludara&ine E" Cyclop!osp!amide" 15" $!e t!ree most common types of 0on-#odg(in>s lymp!oma in c!ildren (in t!e I"S") are: A" 1ymp!o&lastic lymp!oma' =ollicular lymp!oma' :1)C1 )" 1ymp!o&lastic lymp!oma' :1)C1' )ur(itt>s lymp!oma C" =ollicular lymp!oma' Small Cell 1ymp!ocytic 1ymp!oma' :1)C1 :" )ur(itt>s lymp!oma' .erip!eral $ Cell lymp!omas' ?antle Cell lymp!oma E" =ollicular lymp!oma' ?arginal Gone lymp!omas' )ur(itt>s lymp!omas" 16" $!e t o most common types of 0on-#odg(in>s lymp!oma in adults in t!e I"S" are: A" :1)C1 and Small Cell 1ymp!ocytic 1ymp!oma )" =ollicular lymp!oma and :1)C1 C" ?antle cell lymp!oma and )ur(itt>s lymp!oma :" ?arginal Gone lymp!oma and :1)C1 E" #odg(in>s lymp!oma and :1)C1" 1C" A 3< year old oman it! Acute ?yelogenous 1eu(emia under ent induction c!emot!erapy and is no in remission" Cytogenetic studies re%ealed t!at s!e as at a !ig! ris( of relapse" S!e is no considering consolidation treatment it! #ig! :ose c!emot!erapy @ stem cell transplantation" B!ic! of t!e follo ing descri&es t!e properties of !ematopoietic stem cellsE $!ey: A" Can repopulate t!e marro it! all cell lineages including !ematopoietic and stromal supporting cells" )" Are meta&olically indolent ie not !ig!ly proliferati%e cells" C" E*press C:33" :" E*press )-cell and $-cell specific mar(ers' since t!ey can differentiate into lymp!oid or myeloid cells" E" Are easily identifia&le in &one marro aspirates" 6

Integrated Hematology Exam 11/21/06

Name:_______________________ID#:___________

16" B!ic! of t!e follo ing is 0A$ typically due to a disorder of pluripotential stem cells or multipotential progenitorsE A" Aplastic anemia )" ?yelodysplastic syndromes (?:S) C" C?1 :" ."/era E" ?ultiple ?yeloma 14" A 24 year old oman !o complains of fatigue is found to !a%e a !emoglo&in of 4"4 g5dl (normal 12-16)' a lo ?C/ and a lo ?C#C" B!ic! of t!e follo ing is t!e most appropriate drug t!erapyE A" Cyanoco&alamin )" Epoetin C" =errous gluconate :" =ilgrastin E" =olic acid 0A$E: QIES$;A0S 27 @ 21 A,E ,E1A$E:" 27" A 66 year old man presents it! se%ere t!oracic &ac( pain' fatigue and eig!t loss" 1a&oratory studies: #& 6"7 gm5dl' #ct 2<' &c 6'777 it! normal differential @ platelet count" .erip!eral smear s!o s rouleau* formation" Serum creatinine is 5"7 (normal 1"7)" B!ic! of t!e follo ing tests ould &e most useful in ma(ing a diagnosisE A" )one scan" )" Irine analysis and dip stic( for protein (lig!t c!ains)" C" Serum =e' $;)C' ferritin le%els" :" ?easurement of serum %iscosity" E" Serum and urine protein electrop!oresis" 21" $!e anemia in t!is patient may respond !ic! of t!e follo ing medicationsE A" =errous sulfate )" =ilgrastim C" =errous gluconate :" Cyanoco&alamin E" Epoetin 22" A patient is found to &e anemic' and t!e astute clinician orders a reticulocyte count (in addition to ot!er studies)" B!ic! of t!e follo ing disorders ould typically !a%e a lo reticulocyte countE A" Autoimmune !emolytic anemia )" H; !emorr!age (6 days after t!e e%ent) C" Anemia of c!ronic disease :" )12 deficiency 1 ee( into treatment it! )12 E" 0one of t!e a&o%e" Dropped 23" A patient it! li%er disease is found to !a%e t!e follo ing perip!eral &lood smear (=igure 5)"

Integrated Hematology Exam 11/21/06

Name:_______________________ID#:___________

=igure 5"

B!ic! of t!e follo ing statements regarding t!ese cells is 0A$ correctE A" $!ey are slig!tly larger cells (!ig!er ?C/) t!an normal r&cs" )" $!ey are more resistant to osmotic lysis t!an normal cells" C" $!eir ina&ility to c!ange s!ape leads to splenic trapping" :" $!is type of cell may &e seen in a %ariety of !emoglo&inopat!ies" E" ;t is a manifestation of e*cess mem&rane" 'his smear shows target cells that are typically seen in liver disease and in thalassemias and hemoglobinopathies. 'his rbc shape is due to excess membrane ! is a true statement%. !xcess membrane would result in slightly larger cells # is a true statement% that are less li(ely to undergo osmotic lysis ie there is more room inside the cell to ta(e in water before lysis & so they are more resistant to osmotic lysis% ) is a correct statement%. *ncreased splenic trapping occurs in cells that are less flexible and unable to change shape to navigate the microcirculation. 'he classic example we gave you of this was Hereditary +pherocytosis where there is a decrease in the membrane,hemoglobin ratio, less rbc flexibility, and more splenic trapping with rbc destruction. 2<" A 16 year old &oy it! a (no n !emoglo&inopat!y presents in t!e E, &ecause of se%ere deep' s!arp pain in !is legs unresponsi%e to oral pain medication" #is perip!eral smear is s!o n in =igure 6" Dropped =igure 6" ;n A" )" C" :" E" t!is disorder: .atients are e*pected to !a%e a normal lifespan" $!ere is an im&alance of and c!ains due to a deletion in t!e glo&in gene" $!ere is often an impaired a&ility to concentrate urine" Splenomegaly is a common finding in adults" $!ere is no increase in t!rom&otic ris( &ecause platelets are normal"

'his is a case of a patient with +ic(le -ell disease. Patients with ++ have a shortened life expectancy #nswer # is false%. 'here is a single point mutation in the globin chain ) is false & there is no deletion, and no "imbalance$ as in the thalassemias%. #nswer - is correct. +ic(le cell patients typically have an impaired 6

Integrated Hematology Exam 11/21/06

Name:_______________________ID#:___________

ability to concentrate urine the acidic and hypertonic environment in the renal medulla results in sic(ling with microinfarcts%. +plenomegaly is N.' a common finding in adults with ++ disease because of splenic infarction which reduces the si/e of the spleen by the time of adolescence "autoinfarction$%. 0emember that sic(le patients are at increased ris( of infections with encapsulated organisms because of this complication. 1inally, there is an increased thrombotic ris( but not because of normal platelets2 25" E*amination of perip!eral &lood smears may identify r&c a&normalities t!at may trigger a p!ysician to consider a particular diagnosis" B!ic! association is ;0CA,,EC$E A" Sp!erocytes arm autoanti&odies )" ,ouleau* cold agglutinin disease C" Sc!istocytes :;C :" #o ell-8olly &odies splenectomy E" )asop!ilic stippling lead poisoning 26" A patient presents it! a #& of 6"5' #ct of 26' and a normal &c and platelet count" Kou suspect iron deficiency anemia &ecause s!e reports !ea%y menses" B!ic! of t!e follo ing ould &e consistent it! t!is diagnosisE A" :ecreased =e' decreased $;)C' decreased ferritin" )" :ecreased =e' increased $;)C' increased ferritin" C" :ecreased =e' increased $;)C' decreased ferritin" :" :ecreased =e' ?C/ of 45' and decreased ferritin" E" :ecreased e*pression of :?$-1" 2C" A <7 year old man presents it! symptoms of fatigue and ea(ness" #e !as !ad art!ritis for many years" An e*am' !is s(in is found to !a%e a &ronFe discoloration' and !e !as moderate !epatomegaly" #e !as a large e*tended family' and a second cousin is (no n to !a%e !ereditary !emoc!romatosis" #e is suspected to !a%e t!is disorder and is undergoing furt!er e%aluation" B!ic! of t!e follo ing is true of t!is conditionE A" ;n most cases' it is associated it! a mutation leading to do n-regulation of :?$-1" )" =e deposition in t!e pancreas can lead to dia&etes mellitus" C" $reatment is &est accomplis!ed it! iron c!elating agents" :" =erritin le%el is al ays lo in untreated cases" E" ?utation of #=E results in decreased =e a&sorption from t!e H";" tract" 26" A <7 year old oman is determined to !a%e a !emolytic anemia" B!ic! of t!e follo ing la&oratory tests confirms !emolysis as intra%ascular rat!er t!an e*tra%ascularE A" Ele%ated urinary uro&ilinogen )" :ecreased !aptoglo&in C" ;ncreased 1:# :" .ositi%e serum free !emoglo&in E" .erip!eral smear s!o ing sp!erocytes Many of you answered ). 3hile #)+!N' haptoglobin is consistent with intravascular hemolysis, a modest reduction of haptoglobin can occur in extravascular hemolysis, so a decreased haptoglobin is not diagnostic. 4

Integrated Hematology Exam 11/21/06

Name:_______________________ID#:___________

24" A 54 year old oman !ad an isc!emic stro(e 5 years ago' and is on clopidogrel (.la%i*) to decrease !er ris( of su&se-uent isc!emic e%ents" $!is drug functions as an antiplatelet drug %ia !ic! mec!anismE ;t: A" ;n!i&its cycloo*ygenase" )" ;n!i&its t!e Hp;;&5;;;a reaction" C" ;n!i&its t!e A:. reaction" :" ;n!i&its Hp;&" E" All of t!e a&o%e" 37" A 67 year old ;talian man presents to t!e E, it! profound fatigue and !emoglo&inuria after en+oying Easter dinner ( !ic! included fa%a &eans)" #& 6"7' #ct 163 &c and platelet counts ere normal3 1:# 1277' )ili <"7' :irect )ili 1"7' ,etics 26D3 Coom&s direct and indirect negati%e" #e most li(ely !as: A" Cold autoanti&odies" )" ;ncreased le%els of red cell o*idiFed glutat!ione" C" #einF &odies on Brig!t stain" :" ;neffecti%e eryt!ropoiesis" E" ;ncreased or normal serum !aptoglo&in" 0emember that although Hein/ bodies are present in 4565P5D hemolytic episodes which this case describes%, they are only visuali/ed by staining with +upravital stains they are not seen on routine 3right stains.% 31" ;n a patient it! a megalo&lastic anemia' an a&normal .art ; of t!e Sc!illing $est' associated it! a normal part ;; is consistent it!: A" Strict %egan diet" )" Hastrectomy state" C" )acterial o%ergro t!" :" Cro!n>s disease" E" :ietary folate deficiency"

0A$E: QIES$;A0S 32 and 33 A,E ,E1A$E:" 32" A patient it! ,!eumatoid Art!ritis presents it! #& 6' retic count 12D' normal &c @ platelet count" 1:# 677' indirect &ili 2"<" #er perip!eral smear is s!o n in =igure C"

=igure C"

17

Integrated Hematology Exam 11/21/06

Name:_______________________ID#:___________

S!e most li(ely !as: A" .ositi%e urinary !emosiderin" )" Acrocyanosis" C" .ositi%e #einF &ody prep it! supra%ital stain" :" .ositi%e :irect Coom&s test utiliFing Anti ;gH" E" ;ncreased life span of circulating red &lood cells" 33" $!e initial treatment of c!oice for t!is patient is: A" Steroids" )" .lasmap!eresis" C" A%oidance of cold" :" An immunosuppressi%e drug suc! as aFat!ioprine (;muran) E" ,itu*ima&" 3<" A C2 year old oman presents to t!e E, it! fatigue" #er only ot!er complaint is num&ness and tingling of !er !ands and feet" 1a&oratory studies re%eal #& 5"7' #ct 15' ?C/ 127' &c <'777 it! normal differential' platelet count 1579" S!e most li(ely ill !a%e: A" Ele%ated !omocysteine' normal met!ylmalonyl CoA )" :iminis!ed )? cellularity C" ;ncreased reticulocyte count :" ;ncreased 1:# E" ;ncreased lifespan of circulating r&c" 35" .atients it! !omoFygous -t!alassemia ma+or: A" $ypically !a%e normal or only slig!tly ele%ated !ematocrits" )" #a%e ineffecti%e eryt!ropoiesis secondary to c!ain e*cess" C" Se%ere =e deficiency secondary to c!ronic intra%ascular !emolysis it! resultant iron loss" :" #a%e increased #&= le%els in &lood" E" Are typically symptomatic at &irt!"

Dropped 36" A patient de%elops fe%er and c!ills one !our into administration of pac(ed red &lood cells" $!e patient li(ely !as a(n): A" ;gA deficiency" )" ?a+or !emolytic reaction" C" 1eu(oagglutination reaction" :" ,eaction to plasma proteins" E" ,eaction (no n as $,A1;" 'his case describes a non5hemolytic febrile transfusion reaction. 'hese are thought to be due to antibodies formed against donor wbcs or platelets leu(oagglutination reaction%, as well as cyto(ines formed during blood storage. 11

Integrated Hematology Exam 11/21/06

Name:_______________________ID#:___________

'his is not a ma7or hemolytic reaction, which would present with symptoms occurring after only a small amount of blood has been transfused and almost always before the unit is transfused completely. 'hough the symptoms may include fever and chills and thus may initially be difficult to distinguish from a non5hemolytic transfusion reaction%, there may also be symptoms of nausea, chest tightness, restlessness, apprehension, 7oint pain, bac( pain. 'he patient may develop tachycardia, tachypnea, hypotension, and oliguria. Ma7or transfusion reactions are typically due to #). incompatibility reactions. #gain, these occur more 8uic(ly than do the non5hemolytic febrile reactions. #naphylactic reactions can occur in patients who are *g# deficient and have developed *g# antibodies. 3hen they are exposed to donor *g# in the blood product, they can have an anaphylactic reaction. Proteins in donor plasma can cause minor allergic reactions these would be "anaphylactoid$ and might present with urticaria or s(in manifestations in addition to fever and chills%. '0#9* refers to "transfusion5associated lung in7ury$ and symptoms begin suddenly while the blood product is being transfused or up to 6 hours after transfusion. 'he presenting symptom is D:+PN!#. 3C" .atients it! -t!alassemia !o !a%e a one gene deletion ill !a%e: A" A mild microcytosis it!out anemia" )" Ele%ated le%els of #&# t!roug!out adult life" C" Ele%ated le%els of #& )arts t!roug!out adult life" :" Splenomegaly &ecause of c!ronic lo le%els of !emolysis" E" 0one of t!e a&o%e" !ither # or ) is an acceptable answer. Dropped 36" A p!ysician on t!e ards is trying to decide if it is appropriate to gi%e cryoprecipitate to a patient !o is &leeding" ;n ma(ing t!is decision' it ill &e !elpful to remem&er t!at cryoprecipitate does 0A$ contain !ic! of t!e follo ing factors: A" =i&rinogen )" =actor J;;; C" =actor /;;; :" =actor / E" %onBille&rand factor 'he correct answer is D. -ryoprecipitate contains the high molecular weight factors, fibrinogen, factor ;***, factor V***, and von3illebrand factor, but does not contain factor V. 34" Bit! fi&rinolytic t!erapy' t!e goal is to directly or indirectly en!ance t!e generation of !ic! enFymeE A" =actor /;;a )" $!rom&in C" .lasmin :" =actor Ja E" =i&rinogen

12

Integrated Hematology Exam 11/21/06

Name:_______________________ID#:___________

<7" A 37 year old oman presents it! easy &ruising" S!e is on no medications" #er p!ysical e*am is normal e*cept for petec!iae on !er legs" #&' &c it! differential' .$ @ .$$ are all Dropped normal" .latelet count is 3'777" ,enal function is normal" S!e most li(ely !as: A" :ecreased mega(aryocytes in t!e &one marro " )" .latelet plugs in small &lood %essels" C" 1arge platelets on perip!eral smear" :" A&normal e*pression of Hp;;&5;;;a receptors on t!e platelet surface" E" A normal &leeding time" 'his was a case of *'P, and large platelets can be seen on peripheral smear in *'P. *n *'P there is an increase in mega(aryocytes, not a decrease. Platelet plugs in small vessels would be a description of ''P 'hrombotic 'hrombocytopenic Purpura%. #bnormal expression of 4p**b<***a receptors would not result in thrombocytopenia & 7ust platelet dysfunction. 'he bleeding time in *'P would be abnormal because of the low platelet count. Note that this is N.' a case of D*- & the P' and P'' are normal. *t is not ''P or H=+ & renal function is normal. <1" A 27 year old medical student cuts !imself !ile s!a%ing" #e notes t!at t!e &leeding stops immediately (due to %asoconstriction)" #o e%er' !e ill soon &egin to &leed if !e is not a&le to initiate !emostasis it! ad!esion of platelets to damaged endot!elium" $!is step is facilitated &y t!e presence of: A" H. ;& receptors" )" Hp ;;&5;;;a receptors" C" =i&rinogen" :" $!rom&opoietin" E" 0one of t!e a&o%e" <2" A patient !o !as !ad an aortic %al%e replacement is on t!erapeutic doses of arfarin (coumadin)" S!e ill most li(ely !a%e a normal le%el of !ic! factorE A" =actor /;; )" .rotein C C" =actor / :" =actor J E" .rotein S <3" A 26 year old oman presents it! a deep %enous t!rom&osis after flying to Australia" $!oug! s!e !as a predisposing factor (prolonged immo&iliFation)' you plan to e%aluate !er for t!e presence of a =actor / 1eiden mutation &ecause of !er young age" B!ic! of t!e follo ing is trueE A" =actor / 1eiden is a rare disorder" )" ;t is more li(ely t!at t!e patient ould &e deficient in A$;;;' .rotein C or .rotein S" C" =actor / 1eiden is only associated it! arterial t!rom&oses' not %enous t!rom&oses" :" =actor / 1eiden is associated it! t!e a&normal function of factor /;;;" E" =actor / 1eiden is associated it! resistance of t!e factor / molecule to Acti%ated .rotein C" <<" A 66 year old man it! no !istory of e*cessi%e &leeding (foot&all player' multiple dental e*tractions) presents for electi%e gall&ladder surgery" #e !as a normal C)C' normal platelet 13

Integrated Hematology Exam 11/21/06

Name:_______________________ID#:___________

count' normal .=A and a normal .$' &ut !is .$$ is 67 seconds (normal 37 sec)" #e most li(ely !as: A" =actor J;; deficiency )" =actor /;;; deficiency C" =actor ;J deficiency :" %onBille&rand>s disease E" =actor /;; deficiency <5" A patient in t!e ;CI is &eing treated for !ypotension due to &acterial sepsis' and is suspected to !a%e :;C" B!ic! of t!e follo ing patterns is consistent it! t!is diagnosisE A" Sp!erocytes' decreased platelet count' increased fi&rin degradation products" )" Sc!istocytes' !ypofi&rinogenemia" C" :ecreased platelets' increased fi&rin degradation products' increased fi&rinogen" :" Sp!erocytes' !ypofi&rinogenemia' long .$ and .$$" E" Sc!istocytes' normal platelet count' increased fi&rin degradation products" 0A$E: Questions <6 and <C are related" <6" A 27 year old oman undergoes e*traction of !er impacted isdom teet!" $!e normal !emostatic process s!ould result in t!e formation of a &lood clot and control of &leeding at t!e site of e*traction" $!e final step in t!is normal !emostatic process is t!e con%ersion of solu&le fi&rin to insolu&le fi&rin' !ic! is mediated &y: A" =actor ;; ($!rom&in)" )" =actor J;;;" C" =actor /;;;" :" $issue sta&iliFing factor" E" =actor J;;" <C" ;f a patient !as a deficiency of t!is factor' !at type of &leeding pattern ould you e*pectE A" ;mmediate &leeding during t!e e*traction" )" )leeding se%eral !ours after t!e e*traction" C" :elayed &leeding (3-< days later)" :" 0o &leeding" E" Kou ould not e*pect to see &leeding L you ould e*pect t!rom&osis" <6" A 35 year old man comes into t!e E, it! se%ere crus!ing su&sternal c!est pain" #e is found to !a%e S$ ele%ation across t!e precordial leads and is ta(en to t!e cat! la&' !ere !e ill recei%e an infusion of Alteplase (t.A)" $!ere is a significant ris( of &leeding it! t!is t!erapy' yet it mimics t!e p!ysiological process of fi&rinolysis" B!at are t!e protecti%e mec!anisms in physiological fi&rinolysis t!at limit &leedingE A" t.A or(s &est !en it is &ound to fi&rin" . 2antiplasmin &inds free t.A !en it is no longer &ound to fi&rin" C" Endot!elial cells produce .A;-1" :" Endot!elial cells produce t.A in a localized fas!ion at t!e site of in+ury" E" All of t!e a&o%e"

1<

Integrated Hematology Exam 11/21/06

Name:_______________________ID#:___________

'he vast ma7ority of the class got this answer right based on the intent of the 8uestion #nswer !%. However, it is true that there is an error in ). >antiplasmin binds to P9#+M*N when it is no longer bound to fibrin. +o in reality, it may have been difficult to answer !. +ince #, -, and D were all correct, it is difficult to say which is more correct. #ll answers will be accepted to this 8uestion because of this error. <4" A patient !as &een gi%en an anticoagulant" B!ic! of t!e follo ing suggests t!at s!e !as &een treated it! arfarin and not !eparinE A" Anticoagulation is &eing monitored &y measuring t!e prot!rom&in time (.$)" )" Anticoagulation as ac!ie%ed it!in 1 !our of drug administration" C" $!e anticoagulant>s effects are re%ersed &y administering protamine" :" $!e anticoagulant as administered intra%enously" E" $!e drug acts %ia &inding to antit!rom&in ;;;" A0SBE, $,IE A, =A1SE =A, QIES$;A0S 57-52" ($!ese -uestions are related)" A patient is ne ly diagnosed it! a deficiency of factor /;;;" ;n t!is disorder' 57" $!e most common &leeding site is t!e el&o " A" $rue )" =alse 51" $!e num&er of &leeds per year directly correlates it! se%erity of factor deficiency" A" $rue )" =alse 52" $!e treatment of c!oice for t!is disorder is fres! froFen plasma" A" $rue )" =alse 53" A 15 year old &oy is &roug!t in for e%aluation of recurrent se%ere nose&leeds" #e !as !ad no surgical procedures or dental e*tractions" 1a&oratory analysis re%eals t!at !e !as Classic ($ype ;) %onBille&rand>s disease" B!ic! of t!e follo ing is most li(elyE A" #e ould &e e*pected to !a%e normal factor /;;; le%els' &ut decreased %onBille&rand factor and decreased %onBille&rand antigen" )" #e s!ould !a%e a proportionate decrease in factor /;;;' %onBille&rand factor and %onBille&rand antigen" C" #e ould !a%e impaired platelet Hp;;&5;;;A function" :" #e ould &e e*pected to !a%e little or no response to ::A/." E" #e ould !a%e an ele%ated prot!rom&in time (.$)" 5<" B!ic! of t!e follo ing anti-platelet agents is a Hp;;&5;;;a in!i&itor: A" Aspirin )" Clopidogrel (.la%i*) C" Eptifi&atide (;ntegrilin) :" :ipyridamole (.ersantine) E" 0one of t!e a&o%e" 55" Kou are as(ed to e%aluate an 67 year old oman for multiple ecc!ymoses" S!e !as !ad a +oint infection and !as &een on anti&iotics for 3 ee(s" C)C' platelet count is normal" Dropped .$ 25 sec (normal 11 sec)" .$$ <5 sec (normal 37 sec)" S!e most li(ely !as: A" :;C 15

Integrated Hematology Exam 11/21/06

Name:_______________________ID#:___________

)" =actor / deficiency C" 1o le%el of .rotein C :" =actor J in!i&itor E" 0one of t!e a&o%e" 'he (ey here was recogni/ing that a ma7or source of Vitamin ? is endogenous production by bacteria in the 4.*. tract. !radication of normal gut flora because of prolonged treatment with antibiotics can lead to Vitamin ? deficiency. #s you (now, Vitamin ? is needed for the synthesis of factors **, V**, *;, and ; as well as Protein - and Protein +. 'hus the correct answer is -. Note that the patient cannot have D*- & she has a normal platelet count. 56" A surgeon plans to prop!ylactically treat a patient !o !as undergone (nee replacement surgery it! !eparin to decrease t!e ris( of deep %enous t!rom&osis" B!ic! of t!e follo ing statements concerning !eparin and lo molecular eig!t !eparin is correctE A" )ot! need fre-uent monitoring it! a.$$ to ensure proper t!erapeutic le%el" )" ;n correct t!erapeutic dose' &ot! !a%e e-ual antiJa acti%ity" C" )ot! !a%e comparati%e ris( of patient de%eloping #;$" :" 1?B !eparin !as a longer !alf-life t!an unfractionated !eparin" E" Eno*aparin is t!e trade name for unfractionated !eparin" 5C" B!ic! of t!e follo ing statements regarding arfarin is correct: A" )loc(s gamma-car&o*ylation of factors ;;' /;;' /' and J" )" ;n initial <6 !ours of starting t!e drug' patients can &ecome !ypercoagula&le" C" Inli(e !eparin' it does not cross t!e placenta" :" .atients on anti&iotics ill typically need an increase in t!e dosage of arfarin to maintain t!erapeutic effect" E" ;t !as a &road t!erapeutic indo "

56" A 5 year old &oy it! no pre%ious medical !istory is &roug!t to t!e E, &y !is mot!er &ecause !e accidentally ingested a large dose of arfarin (coumadin)" #e is conscious' &ut appears -uite agitated" An .E' !is ). is 1175C7 mm #g' and pulse is 475min" ;n order to decrease !is ris( of &leeding' !ic! of t!e follo ing is t!e most appropriate p!armacot!erapyE A" Acti%ated .rotein C )" 0-acetylcysteine C" .rotamine :" Atropine E" /itamin 9

16

Integrated Hematology Exam 11/21/06

Name:_______________________ID#:___________

54" A <6 year old smo(er it! a deep %enous t!rom&osis is gi%en !eparin" #eparin ac!ie%es its anticoagulant acti%ity &y &inding to !ic! of t!e follo ing su&stancesE A" 2 antiplasmin )" 2 macroglo&ulin C" Antit!rom&in ;;; :" =actor /;;; E" .rot!rom&in

0A$E: QIES$;A0S 67 and 61 are related" 67" A < year old &oy it! a 3 ee( !istory of fe%ers and lac( of energy is found to !a%e se%ere anemia' moderate t!rom&ocytopenia' and a &c of 12'777 cells5mm3 it! 37D &lasts' <7D lymp!s' 27D polys' 17D monocytes" .!ysical e*am re%eals no lymp!adenopat!y" CJ, is normal" A &one marro &iopsy ould most li(ely re%eal: A" Acute lymp!o&lastic leu(emia (A11)" )" Acute myelo&lastic leu(emia (A?1)" C" C!ronic lymp!ocytic leu(emia" :" C!ronic myeloid leu(emia" E" #airy cell leu(emia" 61" B!ic! of t!e follo ing statements is true a&out t!is diseaseE A" ;t is most often a $-cell malignancy in c!ildren" )" A good prognosis ould &e associated it! t!e t(4322) translocation" C" A good prognosis ould &e associated it! !yperdiploidy" :" $!e C0S is rarely affected in t!is disease" E" Aral al(ylating agent c!emot!erapy is !ig!ly effecti%e in t!is disease" 0A$E Questions 62-6< are related" A 55 year old oman presents to !er p!ysician it! fatigue and dyspnea on e*ertion" An p!ysical e*am' s!e is pale' !as no lymp!adenopat!y or !epatosplenomegaly" C)C re%eals an ele%ated &c of 25'777' !& 4"5' !ct 26"53 platelet count 15 9" #er perip!eral &lood smear is s!o n in =igure 6"

=igure 6"

1C

Integrated Hematology Exam 11/21/06

Name:_______________________ID#:___________

62" B!ic! of t!e follo ing is t!e most li(ely diagnosis in t!is patientE A" Acute 1ymp!o&lastic 1eu(emia )" #odg(in>s disease it! marro in%ol%ement C" Acute ?yelogenous 1eu(emia' ?3 :" ;$. E" C!ronic ?yelogenous 1eu(emia 63" B!ic! of t!e follo ing c!romosomal translocations ould you e*pect to find in t!is patientE A" t(4322) )" t(631<) C" t(1531C) :" t(1131<) E" t(1<316) 6<" B!ic! of t!e follo ing statements is 0A$ true a&out t!is diseaseE A" ;t is associated it! a significant ris( of :;C" )" ;t is responds ell to A$,A (All-trans retinoic acid)" C" $!e molecular defect in t!is disease is at t!e transcriptional le%el" :" $!alidomide is appro%ed for t!e treatment of t!is disease" E" Arsenic !as &een used as a differentiating agent in t!is disease"

0A$E: Questions 65-6C are related" 65" A 25 year old oman presents to !er p!ysician after finding a large lump in t!e rig!t side of !er nec( !ic! !as &een present for t!e past mont!" S!e also complains of fe%ers' fre-uent drenc!ing nig!t s eats' and a 17 pound eig!t loss o%er t!e past < mont!s" An e*am' s!e is found to !a%e an enlarged supracla%icular lymp! node and enlarged nodes in t!e left lo er posterior cer%ical c!ain and a*illary regions" $!ere is no e%idence of !epato or splenomegaly" 1ymp! node &iopsy re%eals t!e presence of ,eed-Stern&erg cells it! lacunae surrounding t!e nuclei of t!ese cells" B!ic! of t!e follo ing %ariants of #odg(in disease is most li(ely presentE A" 1ymp!ocyte-:epleted )" 1ymp!ocyte .redominance C" ?i*ed Cellularity :" 0odular Sclerosis E" 1ymp!ocyte-,ic! 66" $!e remainder of t!is patient>s or(up is negati%e for additional sites of disease' including a &one marro aspiration and &iopsy" B!at is !er disease stageE A" ;A )" ;) 16

Integrated Hematology Exam 11/21/06 C" ;;A :" ;;) E" ;;;)

Name:_______________________ID#:___________

6C" $!is patient completed treatment for #odg(in lymp!oma 1 mont! ago" S!e no presents it! increasing dyspnea and a non-producti%e coug!" .!ysical e*am is remar(a&le for fine rales at t!e lung &ases" Arterial &lood gases s!o !ypo*ia" CJ, s!o s pulmonary fi&rosis" B!ic! of t!e follo ing c!emot!erapeutic agents most li(ely produced t!ese effectsE A" )leomycin )" Cyclop!osp!amide C" :o*oru&icin :" Etoposide E" /incristine 66" B!ic! type of #odg(in>s lymp!oma does 0A$ !a%e MClassicalN C:15O and C:37O ,eed-Stern&erg cellsE A" 1ymp!ocyte-:epleted )" 1ymp!ocyte .redominance C" ?i*ed Cellularity :" 0odular Sclerosis E" 1ymp!ocyte-,ic! Dropped 64" A 63 year old patient is diagnosed it! a myelodysplastic syndrome" An appro%ed drug for treatment of t!is disease is: A" Cyclop!osp!amide )" ?et!otre*ate C" :o*oru&icin :" 5-aFacytidine E" )leomycin D. is the correct answer. 'his was covered by Dr. Mega in the lecture on MD+. However, @5a/acytidine was not listed on the pharmacology drug list.

C7" A 5C year old man presents it! painless s elling in !is nec(" .!ysical e*amination is remar(a&le for a 2 cm cer%ical lymp! node @ splenomegaly" )iopsy of t!e cer%ical node re%eals a neoplasm containing small' clea%ed cells t!at recapitulate t!e normal follicular arc!itecture of lymp! nodes" B!ic! of t!e follo ing mec!anisms is most li(ely in%ol%ed in t!e de%elopment of t!is patient>s neoplasmE A" Amplification of 1-myc )" #omoFygous loss of p53 C" A%ere*pression of &cl-2 :" .oint mutation in ras decreasing its H$.ase acti%ity E" ,eciprocal translocation &et een c!romosome 4 and 22"

14

Integrated Hematology Exam 11/21/06

Name:_______________________ID#:___________

C1" A 6C year old man presents it! progressi%e pruritic eryt!roderma' e*foliation' and lymp!adenopat!y" E*amination of t!e perip!eral &lood smear re%eals lymp!ocyte-li(e cells it! cere&riform nuclei" $!ese cells are C:<O" B!ic! of t!e follo ing is t!e most li(ely diagnosisE A" )ur(itt lymp!oma )" :iffuse 1arge ) Cell lymp!oma C" 1ymp!o&lastic lymp!oma :" #odg(in>s lymp!oma E" SeFary syndrome C2" A C7 year old man presents to t!e E, it! a fe%er of 171' CJ, re%ealing pneumonia and t!e follo ing C)C: #& 5' #ct 15' platelet count 37'777' &c 15'777 it! 17D polys' 67D &lasts' and 17D lymp!ocytes" #e most li(ely !as: A" A c!romosomal translocation resulting in o%er-e*pression of c-myc" )" ?aturation arrest of myeloid series in t!e &one marro " C" 1eu(emoid reaction secondary to infection" :" )one marro fi&rosis" E" C!ronic 1ymp!ocytic 1eu(emia" C3" A C7 year old man as recently diagnosed it! myelodysplastic syndrome" $!e data !ic! ill &e most !elpful to you in determining !ic! prognostic group a patient it! ?:S falls into ould &e: A" :egree of anemia )" SiFe of spleen C" .resence of .!iladelp!ia c!romosome :" 0um&er of cell lines in%ol%ed" E" :egree of t!rom&ocytopenia" C<" A 67 year old oman is recei%ing c!emot!erapy for 0on-#odg(in>s lymp!oma" Se%eral days after a treatment' s!e notices &lood in !er urine" B!ic! of t!e follo ing c!emot!erapeutic drugs is most li(ely responsi&le for t!is side effectE A" )leomycin )" Cisplatin C" Cyclop!osp!amide :" :o*oru&icin E" /incristine 'he correct answer to this was -. -yclophosphamide, which causes hemorrhagic cystitis. However this point was not emphasi/ed by Dr. 9a/o in his antineoplastics pharmacology lecture, and it is clear that many of you answered ). -isplatinum because of its associated renal failure. 'hough hematuria is not a typical presentation of cisplatinum renal toxicity, this is not something you might (now. 'herefore we did accept answers ) and - for this 8uestion. 0A$E: QIES$;A0S C5-CC are related"

27

Integrated Hematology Exam 11/21/06

Name:_______________________ID#:___________

A 62 year old man presents to !is p!ysician for !is annual p!ysical e*am" #e is found to !a%e an ele%ated !ite &lood cell count' it! a normal #& and platelet count" #is perip!eral &lood smear is s!o n in =igure 4"

=igure 4"

C5" B!at is t!e most li(ely diagnosis &ased on t!e presentation and perip!eral &lood smearE A" C!ronic 1ymp!ocytic 1eu(emia )" #airy cell leu(emia C" 0on-#odg(in>s lymp!oma :" ,ic!ter>s syndrome E" SeFary syndrome C6" B!ic! of t!e follo ing pattern of mar(ers ould &e most consistent it! t!is diagnosisE A" C:< and C:3 positi%ity )" C:5' C:23' and C:27 positi%ity C" C:33 positi%ity :" $dt positi%ity E" C:14 positi%e' C:27 positi%e' C:5 negati%e CC" B!ic! of t!e follo ing statements a&out t!is disease is trueE A" ;t is staged using t!e ,ai or )inet Staging classifications" )" $!is disorder arises solely from cells t!at !a%e unmutated ;g !ea%y c!ain %aria&le region genes" C" ;t is treated aggressi%ely using com&ination c!emot!erapy and ,itu*ima& it! an aim for cure" :" C!romosomal translocations are not found in t!is disorder" E" .atients it! t!is disease in%aria&ly die from progression to acute leu(emia" C6" :rug MsanctuariesN are potential pro&lems for curati%e treatment it! anticancer drugs" Ane common p!ysiological cause for t!e de%elopment of drug sanctuaries is: A" .rotein &inding" )" #ypot!ermia C" Alopecia :" #ypo*ia E" .ancytopenia

21

Integrated Hematology Exam 11/21/06

Name:_______________________ID#:___________

C4" An 67 year old male !as &een follo ed for t o years it! a !emoglo&in of 17' ?C/ 172' &c 3777 it! <7D polys' <7D lymp!ocytes and 27D monocytes" .latelet count <7'777" ,etic count 1D" An iron stain of !is &one marro aspirate is s!o n in =igure 17" )one marro smear' ;ron stain' 1777*

=igure 17"

#e most li(ely !as: A" )12 deficiency" )" ?yelodysplasia" C" C11" :" Autoimmune !emolytic anemia and t!rom&ocytopenia (E%anPs syndrome)" E" ;ron o%erload due to !emoc!romatosis" 67" A 35 year old man !as &een follo ed for < years it! a diagnosis of ;diopat!ic #ypereosinop!ilic Syndrome" B!ic! of t!e follo ing is 0A$ true of t!is disorderE A" :ramatic responses !a%e &een seen it! imatini& (Hlee%ec)" )" $!is disease may &e due to a c!romosomal alteration t!at results in constituti%e acti%ation of a tyrosine (inase" C" ;t is defined &y a sustained !ig!-grade eosinop!ilia it!out a defina&le secondary cause" :" ;t presents it! clinical and la&oratory similarities to C?1" E" $!ere is no effecti%e treatment for t!is disease" 61" A 6< year old man presents it! progressi%e ea(ness' recurrent fe%er' and nig!t s eats" An p!ysical e*amination' !e is found to !a%e multiple enlarges lymp! nodes in t!e lateral cer%ical region" A lymp! node &iopsy demonstrates diffuse effacement of t!e nodal arc!itecture &y uniform s!eets of large atypical lymp!oid cells it! fre-uent mitoses" B!ic! of t!e follo ing is t!e most li(ely diagnosisE A" :iffuse 1arge ) Cell 1ymp!oma )" #odg(in lymp!oma C" =ollicular lymp!oma :" Small Cell 1ymp!ocytic 1ymp!oma (S115C11) E" ,eacti%e follicular !yperplasia"

22

Integrated Hematology Exam 11/21/06

Name:_______________________ID#:___________

0A$E: Questions 62 and 63 are related" A 57 year old man presents it! fatigue" #e is found to !a%e a palpa&le spleen and a &c of 57'777' #& 4' and a platelet count of <779" #is perip!eral &lood smear is s!o n in =igure 11"

=igure 11"

62" #e most li(ely !as: A" A clonal disorder affecting &c' r&c' platelets' and fi&ro&lasts" )" A clonal proliferation of t!e committed myeloid precursor" C" :ecreased &asop!ils on &one marro " :" An a&normal tyrosine (inase affecting myeloid maturation" E" A leu(emoid reaction" #lthough this 8uestion might have been written more clearly, the (ey point here was that -M9 is a clonal disorder of the P9=0*P.'!N'*#9 stem cell & not the committed myeloid precursor. #nswer ) should be incorrect because the defect lies in the pluripotential stem cell & not in the committed myeloid precursor. However, one could argue that there is a clonal proliferation of the myeloid precursor as a result of the clonal proliferation of the pluripotential stem cell. 1or this reason, we will accept answer ) in addition to answer D. 63" At!er la&oratory findings t!at ould &e consistent it! t!is diagnosis include !ic! of t!e follo ing: A" Ele%ated 1eu(ocyte Al(aline .!op!atase Score (1A.) )" 0ormal cytogenetics" C" An ?:E ratio in t!e &one marro of 1:3" :" An ?:E ratio in t!e &one marro of 27:1" E" .resence of all stages of myeloid de%elopment e*cept t!e myelo&last" 6<" An accepta&le treatment for a patient it! ."/era !o !as a platelet count of 1"2 million is: A" .!le&otomy only )" #ydro*yurea C" Al(ylating agents :" .rednisone E" ,itu*ima&

23

Integrated Hematology Exam 11/21/06

Name:_______________________ID#:___________

65" ?et!otre*ate is one of t!e c!emot!erapeutic agents !ic! is acti%e against Acute 1ymp!ocytic 1eu(emia" B!at is it>s mec!anism of actionE A" $opoisomerase ;; in!i&itor" )" Al(ylating agent" C" )loc(s tu&ulin polymeriFation" :" ;n!i&its ri&onuclotide reductase" E" ;n!i&its di!ydrofolate reductase" 66" A 65 year old man complains of ea(ness' eig!t loss' and &one pain" #e reports !a%ing progressi%e difficulty seeing" .!ysical e*am is significant for !epatosplenomegaly and lymp!adenopat!y" Serum protein electrop!oresis re%eals an ?-protein spi(e' it! an ele%ated serum ;g? le%el" )one marro aspiration s!o s plasmacytoid lymp!ocytes" B!ic! of t!e follo ing is t!e most li(ely diagnosisE A" #ea%y c!ain disease )" ?onoclonal gammopat!y of undetermined significance C" ?ultiple ?yeloma :" .lasmacytoma E" Baldenstrom>s ?acroglo&ulinemia 0A$E QIES$;A0S 6C and 66 are related" 6C" A C7 year old man presents it! left sided a&dominal pain" #e is found to !a%e moderate splenomegaly" C)C: &c 67'777 it! <D &lasts' 12D promyelocytes' 15D myelocytes' 12D metamyelocytes' 4D &ands' 6D polys' 23D lymp!ocytes' 1<D monocytes' 3D &asop!ils" $!e treatment of c!oice in t!is patient ould &e: A" 1eu(op!eresis" )" #ydro*yurea" C" Alp!a ;nterferon" :" ;matini& mesylate (Hlee%ec) E" ,itu*ima& (,itu*an) 66" B!ic! of t!e follo ing statements is true a&out t!is treatment: A" ;t results in t!e !ig!est rate of cytogenic responses ( it! t!e e*ception of &one marro transplantation)" )" ;t is administered intra%enously &ecause it !as a s!ort !alf-life" C" ;t !as a !ig! rate of side effects and MintoleranceN" :" ;t is a relati%ely ine*pensi%e form of t!erapy" E" $!ere is no e%idence of resistance to t!is treatment regimen" Dropped 64" 0o%el t!erapies t!at are &eing used in ?ultiple myeloma include all of t!e follo ing e*cept: A" ?elp!alan and prednisone )" /elcade ()orteFomi&) C" $!alidomide :" ,e%limid (1enolidomide) E" $andem stem cell transplants"

2<

Integrated Hematology Exam 11/21/06

Name:_______________________ID#:___________

Melphalan and prednisone have been in use for ABC years. 'he other treatments are all new therapies for MM. 47" A patient as recently diagnosed it! :iffuse 1arge ) Cell 1ymp!oma" B!ic! of t!e follo ing is 0A$ a significant prognostic factor in t!is diseaseE A" Age )" Serum 1:# C" .erformance Status :" Hene e*pression profiling E" C!romosomal a&normalities 41" Anticancer drugs are fre-uently classified &y t!eir mec!anism of action" Cyclop!osp!amide is an e*ample of a5an: A" Al(ylating agents )" $opoisomerase ;; in!i&itor C" Antimeta&olite :" Antisignaling agent E" ;ntercalating agent 42" B!ic! of t!e follo ing statements is 0A$ true regarding radiation &iologyE A" $!e amount or -uantity of radiation is e*pressed in terms of a&sor&ed dose" )" 1 Hray (Hy) is e-ui%alent to 177 rad" C" =ractionation gi%es normal cells a c!ance to repair during t!e time &et een treatments" :" $!e most c!aracteristic let!al :0A lesion after a dose of ioniFing radiation is t!e single &ase pair deletion" E" Hreater doses of radiation are re-uired under !ypo*ic conditions t!an in o*ic conditions to pro%ide e-ui%alent cell (illing" 43" ;rradiation of ater can produce !armful products suc! as !ydro*ide radicals" Af t!e total cell eig!t' ater represents: A" 5-CD )" 22-2CD C" 37-35D :" 57-55D E" 67-65D 4<" $!e M<,>sN of radiation &iology include all of t!e follo ing' EJCE.$: A" ,epair )" ,e%asculariFation C" ,epopulation :" ,eo*ygenation E" ,edistri&ution 45" B!ic! tissues are affected most &y eac! of t!e M<,sNE A" 0ormal early responding tissues" )" 0ormal late responding tissues" C" $umor cells" :" #ypo*ic cells"

25

Integrated Hematology Exam 11/21/06

Name:_______________________ID#:___________

46" A 6C year old patient it! an 1< lytic lesion due to multiple myeloma is undergoing radiation t!erapy" B!ic! of t!e follo ing statements are trueE A" =i&rosis may &e an acute to*icity t!at ill limit deli%ery of full doses of radiation" )" Effects are most e%ident in rapidly di%iding tissues suc! as lung" C" $o*icities do not resol%e' and are dose-limiting" :" A smaller dose per fraction causes more damage to normal tissue relati%e to tumor" E" :ifferent dose fractionation sc!emes can result in a ider t!erapeutic indo " 4C" A 55 year old man presents it! left upper -uadrant a&dominal discomfort and fatigue" An e*am !e !as moderate splenomegaly and scattered petec!iae on t!e lo er e*tremities" 1a&oratory studies re%eal pancytopenia" An attempt at a &one marro aspirate as unsuccessful" ;f you are a&le o&tain cells for analysis' t!e follo ing ould confirm t!e diagnosis you suspect: A" $!e presence of $-cell mar(ers" )" $!e presence of C:33 and C:13" C" Cytoc!emical staining re%ealing resistance to $artrate Acid .!osp!atase" :" .resence of C:37 and C:15O" E" .resence of Hp;;&5;;;a" Dropped 46" B!ic! of t!e follo ing lymp!omas is t!e only one to &e MgradedN !istopat!ologicallyE A" :iffuse 1arge ) Cell lymp!oma )" ?antle cell lymp!oma C" ?arginal Fone lymp!oma :" =ollicular lymp!oma E" #odg(in>s disease" 'his was covered by Dr. 4riffithDs lecture. 1ollicular lymphoma is the only type of lymphoma that is graded histologically. *Dm guessing that many of you confused +taging and 4radingE 4rading is typically used to describe the degree of differentiation of a tumor by histologic microscopic% examination. # 4rade * tumor is typically well5differentiated. *n many tumor grading schemes, 4rades *V5V are undifferentiated or anaplastic. *n follicular lymphoma, grading is an indication of large cell component remember that follicular lymphomas can transform into D9)-9 & a poor prognosis event%. 1ollicular lymphomas are graded into three groups, *, ** and ***. +tage *** has the highest large cell component and the highest li(elihood of transformation. F#s a reminder, +'#4*N4 refers to extent of spread of the primary tumorG. Ans er $rue or =alse to t!e follo ing -uestions (44-172): 44" ?antle cell lymp!oma is associated it! o%ere*pression of Cyclin :1" A" $rue )" =alse" 177" #;/-associated lymp!omas typically include follicular lymp!oma and S11" A" $rue )" =alse 171" Adult $ Cell 1eu(emia51ymp!oma is associated it! E)/" A" $rue )" =alse 26

Integrated Hematology Exam 11/21/06

Name:_______________________ID#:___________

172" ?arginal Gone lymp!omas !a%e an o%erall poor prognosis" A" $rue )" =alse 173" B!ic! of t!e follo ing is 0A$ an accurate statement a&out treatment of =ollicular 1ymp!omaE A" )ecause it is an indolent disease' M atc!ing and aitingN is an option" )" ;t is typically cured it! standard c!emot!erapy agents" C" =irst line treatment of pre%iously untreated patients may &e com&ination c!emot!erapy (cyclop!osp!amide' %incristine' and prednisone) O ,itu*an" :" ,adioimmunot!erapy it! tositumoma& ()e**ar) and i&ritumoma& tiu*etan (Ge%alin) are undergoing currently undergoing e%aluation for initial treatment of t!is disease" E" .rogression to a more aggressi%e disease occurs at a rate of Q5D per year depending on degree of large cell component present" 17<" .atients !o undergo syngeneic &one marro transplantation !a%e: A" ;ncreased ris( of graft %s" !ost disease !en compared it! allogeneic transplant" )" #ig!er relapse rates !en compared it! allogeneic transplant" C" #a%e increased graft %s" leu(emia effect !en compared it! allogeneic transplant" :" $o remain on immunosuppressi%e t!erapy for life" E" 0one of t!e a&o%e" Ans er $rue or =alse for Questions 175-176: 175" $!e possi&ility of long term sur%i%al after allogeneic &one marro transplant is &etter in #1A-matc!ed si&lings t!an in matc!ed unrelated donors (?I:)" A" $rue )" =alse 176" $-cell depletion in allogeneic transplant decreases graft-%s-!ost disease and t!erefore increases sur%i%al" A" $rue )" =alse 17C" B!ic! of t!e follo ing is not consistent it! acute graft-%s-!ost diseaseE A" ,as! Dropped )" :iarr!ea C" ;ncreased &iliru&in :" =eatures of scleroderma E" :es-uamation +cleroderma is a feature of -H0.N*- graft5versus5host disease. Des8uamation may be one of the s(in manifestations of severe #-='! graft5versus5host disease. 0A$E: Questions 176 and 174 are related"

2C

Integrated Hematology Exam 11/21/06

Name:_______________________ID#:___________

A 6 year old c!ild presents it! a rapidly enlarging a&dominal mass and %isi&le ascites" ?om says t!e c!ild only &ecame really sic( in t!e last 3 ee(s" $!e &one marro &iopsy aspirate is s!o n in =igure 12"

=igure 12"

176" $!is c!ild>s presentation and &one marro aspirate are most consistent it! a diagnosis of: A" Acute ?yelogenous 1eu(emia (A?1) )" )ur(itt>s lymp!oma C" :iffuse 1arge ) cell lymp!oma :" Bilm>s tumor E" 0euro&lastoma 174" B!ic! of t!e follo ing is true of t!is diseaseE A" $!is clinical picture of a rapidly gro ing a&dominal mass in a c!ild is t!e most common presentation of t!is disease orld- ide" )" $!is is an indolent' or slo -gro ing disease" C" $ingi&le-&ody macrop!ages are a prominent feature of t!e !istopat!ology" :" $!is disease is not cura&le" E" $!is disease is a mature' perip!eral $ cell malignancy" 117" $!e t!erapeutic action of imatini& (Hlee%ec) in%ol%es in!i&ition of: A" ?icrotu&ule association )" $yrosine (inase acti%ity C" $etra!ydrofolate upta(e :" :0A polymerase acti%ity E" ,0A polymerase acti%ity 111" A common side effect resulting from treatment it! eit!er cyclop!osp!amide or do*oru&icin ould &e: A" 1oss of taste sensation )" Atoto*icity (ear to*icity) C" ?yelosuppression :" ;ncreased appetite E" 0ig!t &lindness #DD!ND=M, N.0M#9 9#).0#'.0: V#9=!+ B&c (cells5l) #emoglo&in (g5dl) <'577-17'777 13"5-1C"5 (male) 26

Integrated Hematology Exam 11/21/06

Name:_______________________ID#:___________

11"5-15"5 (female) #ematocrit (D) <7-52 (male) 36-<6 (female) ?C/ (fl) 67-177 ?C# (pg) 2C-3< ?C#C (g5dl) 27-35 (mean corpuscular #& concentration) .latelet count 157'777 to <77'7775mm3 .$ 17-12 sec a.$$ 25-36 sec Creatinine (mg5dl) 7"5-1"< $otal )iliru&in (mg5dl) 7"1-1"2 :irect )iliru&in (mg5dl) 7-7"3 1:# (;I51) 56-14< ;ron (=e) (mcg5dl) 65-157 $;)C (mcg5dl) 257-<27 =erritin (g51) 15-277 (male) 12-157 (female)

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