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The indications for and the value of laboratory tests in clinical oral pathology
Oral THE
INDICATIONS TESTS
IN
Medicine
FOR AND CLINICAL
THE VALUE OF LABORATORY ORAL PATHOLOGY
CARL REICH, M.D., NEW YORK, N. Y. N ORDER to illustrate the value of laboratory tests in clinical oral pathologg, I think it best to cite several actual cases and delineate, step by step, the: procedures used in order to arrive at a correct diagnosis.
I
Case 1.-A 58-year-old white woman was referred for diagnosis because of pallor, sore tongue, and difficulty in swallowing. The patient stated that, ill acldition to the above-mentioned symptoms of six months’ duration, she also suffered from arthritis in her hands. Physical examination revealed a well-nourished woman, appearing cstremely pale. Her hair was gray, dry, and had no l.uster, and her fingernails were brittSe, ridged, and spoon shaped. The tongue was red and did not show the normal coating. Her throat appeared inflamed and her hands showed swellFrom the history and physical examination. ing and deformity of the joints. this patient was evidently suffering from a severe anemia and also ~I’rom ;I rheumat.oid arthrit.is. The question now arose as to what t,he cause of the anemia was and wbilt could be done to correct it. The peripheral blood count was taken through venous punct.ure. The advantage of taking blood from the vein rather thiln from the finger is that it is possible t.o perform not only the routine count, hut to do the sedimentation rate, coagulat.ion time, clot ret.ra.ction, fra.gility trsts. blood grouping, and, if necessary, serol.ogy and blood chemistry t.ests on t.his one specimen, thus saving the patient unnecessary repeated punctnrrs nnil discomfort. In this particular case, the hemoglobin was 42 per cent ; red counl . 2.500,OOO; white count, 7,300; neutrophil polys, ‘il per cent (nonfilamentetl polys, 21 per cent) ; lymphocytes, 21 per cent ; monoeyt.es, 5 per cent ; plnt.elets. 250,000; sediment.ation rate, 7 mm. in fifteen minutes. 28 mm. in forty-fivfb Read before the Marc11 29. 1954, monthly Clinical Oral Wthology.
1217
wx~ferencc
of the New
York
Tnstitntf~
of
(!.ZRl, REI(‘II
121.8
t?liIllltf~s.
(coagulation
(‘PIit;
Ili~ilIl
thf’
iIIli1
COt’])\IS~liliil’
vi111wtr;ic$ion \.0111111(’
WilS
w’rt~’ tlt~l’lttill. 70
~tlOt’lllill
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Wt*~~~lS~*lll;it~ liritioglol~iti ~~Oti~‘t~ttl.l’ii.tiOtl iViiS “7 (tlol’lllill ::2 lo :I6 1. I~‘t*otti these findings. wc 1’vli that wt. wvrc clwtlitt p wil tt ;I tttivtvwyf iv, ttypoc*hrotiiic, type of ;itic~ttii;i wliivlt is ustt;tll~ ;tsscwi;ilwl evil tt ill1 irott ~Irfic4eticy. This Was Iwrtie out Ity thr I’;tvt tti;tt ttith valor itttltbs wtis less t 111111 I. The tlt?il.tl w~l’pi~s(.ulit.t~ v(jlLltttr \trtts ICSS 11ttttt ttttt*tttttl itttrl tltth ttt(‘ittt ~*(tt~ItllsCUIttt*htmtgldtitt c*oticcWrstion W;IS ;ilSO lrss tliiitl ttot~ittill. ‘I’lw itlVtT;tst~ itt thtb srtlitttelitit.tictt1 Piit.P indic:ated soiltc ac4ivity 0I’ thr ihcuitintoitl at~tliritis. I:hwtttiit0i~l idlit4is is a1~0 known t.o prodlw it.11;tltcbltliit. 1,1111ttr ;tttc~l~tiaoI’ t*tt(~ltttt;ttoi(l al-1ttrif is is 1101 iIS SeWre as in this cil.stk zttltl it is usrtall;v wtmtwy\‘li~ with it w11tr itttks 01’ 1. t*itt.her thttn nticrocytic itt tyIt(a. I-kc*;lliw or IlIt> st)i’~~1~lil~lJ~~. it \\‘ilS c~ousitltWtl ~~tl\%hl~ to study the g;tstric* cc,tttcbtits to t~JJ1v oltt ;III>. possittility 01’ it ItetC*ious alielnia. The gastric COllfW~S~ (‘v(qt 11tt(l(~r 1Iit* stitttrlIatioil ol’ ltistattiittc~. siloww~ 110 free hydrochloric tt(*i~l. This fittflittg votttl)li(~tt~(~(l tttittt(1t.s. its 1itc.k it’ I’t*(lt’ hytlroc~hloric wicl is vhatxvlc~ristiv or Iwt*tti(Gous ;ttt(ltttitt. illfltOli~ll sometimes it. is fOlllitl in ]WO]tlt~ with ii11 ii.ctii-tlrfic.ictit.~ ilil~~llliil illld c~c~~~iiSiOti~lll~ ilt ILOt’ttliil people. It now ltcc*ritttr itttItet*;tliv(l tct 110 tit(tt’t1 cltafitiitivt. sttulics; IiilIllt~l~. ;I sterttit.1 hone Initt’t’(tw ex;ttttitttltioll tttt(I it spt’t1ttt irtttt tltIf(‘l’tttittilfiott. The strt*ttitI ttOli6? IllMT0W ShOWC?tl il tly]t(lY]tl;isl iv ttiit t’ro\\’ wit It it gtwit ittc*re;tse ol’ rryt.tt rol)lRSts. This finding is cdh;tt*;td (ht*istic*01’ itatttt tlcfi&ttt-y tttttl rttlcs Otto lwtwiclious ‘I’ll 11 tttt(Amiil. in which the t~t~pttloltlitsts I,t+c~tlotttitt;tlt~ itt t ttc’ Itotttb IIIC~~I’(IW. St1I’L1111 iron determhmtion \ViiS ;tlso c~otifit*tti;itoi’~ itt tlt>Ll it \VilS VCYy t0U. ilS wctnlcl lte ex])ect.ed iti iitt irott tlefic*ietic*y. wht*rr:is it) I)f~rtiic+tus :itltlilliil it ~oul~l Itc quite high. A4ll thtl I;~lt~t~;ttot*y fimlittgs. f ttet*rI’ctt*t~.Itoitttd c*ottc*lusively to c~hrotiit! tiii~t*ocytic~ tiyItoc~li rottii( iltit~llliil 0I’ irott-tlefi&ticy origin. Ii is vet.) 01 \vPII ktlo\vll that irot I)lit.~~ tttt itttl)(tt*titttl ~YIIC.tlOl 111tl\: ill tIltI Jliilillt~Jl~LtiCt~ the 1~loocl hetnogloltiti. Itut ttlso it) thr I)t.c’st’t’\‘itticttt ol’ the integrity 01’ Ihr c~pithclial st.t*ll(*tUrt+. tt;tttttbly, t tttb lt;tit*. IlililS. iitl(l tlIII~~Il1S Jllt’itl~Ji”~lJlt~S Or thtb 1 Oti~UC illIt tht’Oiit. This ~IGit*ti~l~lilt* l~iiiit‘tll StiO\VtVl t~vi4letiw 0I iI t~ltit4iil ]‘Iunittict~-8insoll sytidroitie with I~ISICI*~CSS ti;iiJa. sIto(ttl-shtt.])c(l trails (kol>-ttiehiit ). SOW totlguta. a11d s0t.t’ throat with difidty itt s~~;llldttg. ‘l’h~r>~lty it1 this (!it.se c~onsisirtl ot’ ItlrgtL clost*s (tl’ irott t)y ttt0ut.h ittttl ~PITOIIS sl1lfa.t.e. 15 gmins thWr linics tliiily. SllP Wits tIlS0 IllIt 011 il high-protein diet. its it is weI1 kttowtt t,hilt hc~tttoploltiti is !)(i IttAt*(*Pitt Ittdtbitt ttttd 4 IttAt’ ctant irott. She wits also given dilute Itytlt.ctc~hlot~i(. ilC4Cl.20 tli’cB]M iti ;I KliJSS 0F \V:ltOl~ it) 1Jth t.;tketl with JliedS. ;Is \vtb I~IIOW 1 It;tt iron is IwSt iottizwl ittt(I ;II~so~I~P~~ frottl tttt She I~~s~~oII~I~~I quicakly IIJ tttt’ritl)y ttttd t ttta ttloo(l I)t’(‘tlttte ttortttitl ilt4tl ititdiuni. tl.f’ttat* it. three-motlth ~wiwl 01 tt.tAitt tttettl. .\I I)tYW~llt it is llt’~‘PSSilY~ to krttp llf?Y 011 il til~lillt~JlilliW (108;lfY 01’ it*ctft. iilid FOtTCbllS Sllll’iltC. 5 gt.ttitts three timrs il tliiy. She is also IIII~ICI* 1t*eitttttcttt fat* hr~* t*lt(~~ltttittoi(l arthritis. ttttvittg recq:ivctl cortisone alit1 ilt. [JWWllt ~llltil~eolitlill~. The I;tttrt* tltaug is I)otettti;tll~ tosin t’tIt< ii II the blood dc3tfXlt.S. il.S it (‘ill1 t~el)tYSS t,hc IHJJlt! Illil.J’J’OW. tt is rlec~cSS~tJ’y. tht~rcfore. to wateh not only her* retI (*our& but her whit.e eonttt tt nit platdel s iiS Well.
I,AJ3ORA’l!ORY
TESTS
IN
CLISICAJ,
ORAJ.
I’.\THOJAO~:Y
I”19
Case 2.--A white girl, aged 1X years, \vijs referred for tli;lguosis IJWIIIIW The p;ltiellt. Kil\‘e ;I s]J”Hgy ~UI~IS itlIt ulcerntiou OFthta thro;lt. history 01 heiug well ~1) to two wreks I)reviouslyq wheu she (!illllc tlow~ wilh She hil(l il s(a\:(‘l*tl ll<‘iltlil~ht Iwhiiltl IVtlilt il])])t’il~‘t”I to tW il. griI)I)y c:o~itlitioii. ttlC fb\-tltJ?lllS,il milt1 SON’ tlll*Oill.. il I’eeling 0)’ tigtittless iti itIt IlPc*k. illl(l il She Si;ly(‘(] it1 t)etl I’or ;I I’(~H.tlil?S. with 11rr tflltllJ(‘l’iltlIl’(l fvwrisli WllSiltiOll. Ilcr I’;ll~liI~ I)hysic+ll tlii~guclse(l the going iIS high ilS IO:! (ltlgr(lt’S iIt llighl. c*cmtlitioli ilS gi*il)t)c alit1 prcsc4betl ilSl)il411, 1~efiic4llii~.ald 1Wd rest. She I’+ c~veretl l’rom the febrile episode, but the swollen ~onc’lit.ion of the gums an(l the throat ulceration pcrsist.cxl. A dental consultation was requested. On physical cssmin;ltiou, the patient aIq)eared to 1~ in good health and (lid not show au) signs cd’ weight loss or tosicity. The gums were swotleu ;Iutl s1~1lgy nutI the throilt was inflanle~l with seven11 ragged il]W~~~l~iOllS. The Iylnph IIO(]W iii the posterior t*ervi(*aI region wow e~ll;~rgetl i>ltd her sl)lwll was pallwble two fil~~~IdJl*~i1dt tlS 1JCloW t 1lCICfl COStalniargii~. A c.omplvtc Mood work-up scenied tlefinitely iutlic;l.tetl autl the rt!suIts \vctx! its follt~\vs : Iicnioglol~iii, 9.5 ]Jer twit : rcil wiiiit, I.WO,OOO; wliitc wunt 1:~.410; iwutrol)liil polys, 41 lwr wilt (1111sqqieiitotl, 1t per cacbiit); I\-uildioeytcs, ;I0 1x9 cent J niolioeytos, 7 per cent; numq4oitl tymphoc*ytes, 18 l~r cent ; eosinol~hils. 4 1)~ cctlt : se(li~llerlti~tio~l ‘l’he Stt?Mlill hone l%tt! in fift.een niinutcs 7 min.? in forty-five niiniit.cs :L? 111111. marrow showed a h~perl)l;Mi(~ INIITOW with no ahnormal wtls. The hcterophil agglutination test. was strongly lmitivc iii jiigli tlilution. Tl~ese findings inadc the diagnosis of 8 virus idrctiou 01: ilie infectious uiotionncloosis typca ver> likely. The positive cliagnostip Iboints wwc tlic good ~l]~]~~‘tll’illl~V’ of the patieut, the lack of anemia, the presc’ncc ol’ monoc-toid Iymplwcytes, or I:~oww~ crlls, the positive hctcrophil a.gglutination toast,and the 1101’11lil~ l~onc~ narrow. This typo of c*onditiou is frequc?nbIy camI~uwtl with leukemia, but should present. no difficult.ies for the csl)eriencetl heul;ltc)logist? as leukemia, a maligna.nt condit,ion. is reflected in the generd c*ontlition of the pabient, and is almost always nclcomI)anied 1)~ iIll a.nemi:t anal ill)ll(~rmd leukemic cells in the bone marrow. This pa.ticnt wils treiltetl for her virus infect,ion by genera t supportive measures, 10cd t.herill)y to the gums ant1 throat, rest, and moderat,e doses of antibiotics to prevent se~nclary infections. Tt is itnportant in this type of case t.o rcnmtll~er that, the liver is often d’ected, even though ja.undice is not. present. Liver Punt4ion tests IllilClV on this ]Jiltirllt showed an iurrease in the thynlol turbitlity ant1 c*tlI)h;llin fl~~t*eul;ltio~~,iIltht)ugh the serum bilirubin was normi~l. This indit*abetl the I)rcstlnce of it milt1 viral hepatitis, and it. was important, therefore, that. the liver t)c I)r’otec+d IJy s~~it;~hleclirtary Illeil.sllres and rest unt,il the functional tests rcturnctl to rlor~tli11. After a. two-mont.h I~rriotl thr I)ilti(ltlf was comIdetely n0rlm1, showing no abnorma~l cells in the peripheral I~lootl and no tlisturhanw of liver func:tion. (,I’
c~tlrnlatous
Case 3.-The patieut was il white girl. ;1get1 II, who wi1.swell until fonr months previously. when she 11~~1iln attack of acaute appendicitis. l’hc i~I)I.)et~(lis wils removed and she was given large closes of I)cnicillin by in,jt+ tion. ( h1t1 wcrk lil.tpr she!tl~rl~pctl il. pccnliar skin eruption which WIS t hc~~lphi.
1220
CARL
REICH
to be due to the penicillin. lier temperature persisted up to 103 degrees daily Ear the next three weeks ant1 her leukocyte co1111trose to .18,000,with 85 pet. cent polynuclear neutrophils and 15 per cent lymphocytes. A slight anemia developed. She was t,reatrd by blood transfusions and cortisone, with a~)parent recovery. Two ntollths Iiltt!r slut had it recaurrence of t.he skin eruptioll. Tllc t~rupt.ion whic*h was orythernatous in 1.\p~, with many paplllC% illtd hdh. IM’MIHP was over the extremit.iq trunk, and I&~. IiCr tcniperature a.g;liJl rleva.ted and again there was :I rise in the leukocyte count.. The possibility 01’ lupus crythematosus WAS c*onsiderc:dant1 a 1~l00d pJY?lWll’iltiOIl for IAN;. ~11~ was ma.de. ‘l!his was report r(l l)ositi\-t: at; the hospital in which she was a. pat.ient at the time. She was t.ren.ted with vortisonc again, with Sony improvement, and was dischargetl. One n~onth Inter there was another rtlc’urren(*e (11 skin eruption, temperature, and leukocytosis with bleeding, spougy gums. At. this time she was admitt et1 i-o I‘lcno~ Hill Hospital aad t.he dermatologica1 service treated her as a lupus erythematosus case! but requested a hematologica. consultation to make cert.ain of the diagnosis. A complete 1~11wl ilIlt bone marrow work-up was done rind the peripheral blood showed H per cent, myeloblasts, while the bonr IIJ~I’~OW showed iI n early myeloblastic iIlfiltIX~iOJ1 with no L.E. cells. On the strtqth of this finding, the L.E. preparation froJl1 the previous hospital Wils ~~evicwcd illl(l it. \vils I’ollntl that, those ct!lls which had been diagnosed as lupus c~yt.h~lHirtosus cells wcr*e ill rea1it.y myelob1asf.s. This error had been caused by a pale stain ; when the same slide was restainrd with Giemsa stain, the myelohlasts wt’r(h unmist.akable. The diagnosis of myeloblastic leukemia, therefore! was definite. The patient has hwn under observation since that t.ime a.ncl the i)(lrccntagc of myeloblasts hiIs risen i (1 90 per cent. This case is of great educational value in that it shows the diiXcnIties sometimes encountered in diagnosing blood preparations, and illustrat,es t,hp importa.nce of meticulous la.boratory technique. @se 4.-A U-year-old white man was referred because pallor of the gums and a sore tongue. He complained of wea.kncss, shortness of breath, il.Jld tingling in the extremities. The patient was well up 1.0nne year previously, and gradually noticed increasing fatigue illld shortness of breath on escrticm. In addition to the sympt.orns, just mentioned, he ills(j complained of a SOW, burning tongue and loss of mpnlory. llis appetite had been ~)oor ant1 he had lost 15 pounds in weight tlurillg t.he last year. On examination, he WRS])alc with i1 slightly yellowish tint.. The tongue was smooth and red and shqwed an absence of papillae. The heart was rapid, with a systolic murmur. His gait was somewhat unsteady a.nd? on further examination, there was some intquality in the reflexes in the lower extremities and loss of vibratory sense. This patient appeared 60 be suffering from pernicious anemia with neurological involvement. Complete bl.ood and bone marrow work-ups showed the following : hemoglobin, 42 per pent : rrd c*r)mll,,
I,dBORATORT
TESTS IN CI,INICAI,
ORAI, I’A\TIIOIA)BY
121
1,300,OOO ; white count, 3,!MKl; neutrophil polys, 55 per cent ; lymphocytes, 38 lter cent.; monocytes, 7 per cent; color in&s over .I ; platelets, .150,000; ltettiatocrit, 20; tnean corpnsc~ular rol uttte, .I 10. I’:s;ttttittat.iort of the peripheral smear showed irregular red (*ells, with ~itrialtlo size itttd shape, many of t.henr l;rrger than nortttnl itttd apltearing t.o Ite c.otttltletely tilled with hemoglobin. Jhtp ol’ t.he polymorphic nuclear neutrolthils WI*P hypersegmented. The sternal KII~~PIWshowe(l the ~)resc~ttc~e ol’ mauy ttt(~gitloltlitsts. This b100d pic$ure showing ma.crocptic! l~loocl with II lenktrpeni~, relnti\:t~ lyttt~~ltoc.;vt&s, increase in tttonocytes? tlitttirtished ltlitt(~lrts. a~ttl c,\-crtttaturt~ ~)olyttnrlrnt* neutrophils is typical of pernicious uttc~tttia. ‘1’11~~fimlittg 01 tltr~itIoblit.sts in the bone rttarrow ctntfirrtted f,his diagttctsis. Patients with pernicious ancqtti;t. are known to suffer from a lack of free hydrochlorio a.cid in t,htt gastric c*ont.ettt,s. Therefore: a gastric analysis was done with histamine stimulation. The injection oi’ hist.amine, 0.5 C.C.to 1,000. will stimulate the production of free hydrochloric acitl in the fnnctional cases, thereby ruling ant an!- psc~tlo acltylin gastric:>. 1’11~patient sltow~d no free hpdrorhloric! ac+l. Before the di;tgttosis (of l)et.ttic?ious nnetnia is definitely given, it is vital that. a G. J. series be done to mlc out, any malignanq- in the gastroint.est.inal tract which might produce pernicious anemia symptottts. This was dotte and proved negative. The diagnosis of prrnicions anemia was definitely established and therapy with vitamin H,, was inst.it.uaed. Three months later the hemoglobin was up t.o 80 per cent. The neurological symptoms had disappeared and the tongue appeared normal. The hydrochloric acid was still a,bsent.from the gastric contents. as this never ret.nt*tts. Case 5.--4 N-year-old whit.e woman was re-fcrred because of bleedittg from t.he gums. She had been well up to one month previously, when she ltcbgatt to have bleeding gums, purpmic spots OVCI* t.he extremit.ies, and csc*tWive mrn~,trnation. L l’hysiral examination was negative escept for hemorrhagic gums a.ttd ntany bla.ck and blue spots over thr body. Esaminat.ion II~ the blond showed : hemoglobin, 75 per cent.; red count, 3?600.000;whit.e count. !I.200 ; neabrophil polys. 71 pet* cent ; Ipmphncytes. 25 per cent ; monoctytcs. 1 p(‘r cent : plate1et.s. 50,000; clotting time, four minutes : no clot refra.cCon all ; blretling time seven minntes (normal, three mittntes). The sternal hot~c~ tttart’ow WRShyperplastic with many megakaryocytts. most of which wt’t*(’ ittttnatJnre and showed absence of pla.telet budding. The splren could not 1~ felt. A dkgnosis of idiopathic throml)ocyt.openic purpnra secondary t.o ltypc~rsplenism was made. The patient was treat.ed with ACTH and cortisone :~tttl responded well for three months. The platelets rose to 100,000 and t,he herttorrhagic manifestations disappeared. At. the end of this time, howeyet-, tltct platelets dropped and bleeding from the gums started again. Because of the danger of cerebra.1hemorrhage, splenectomy was decided upon and performcil. ilt
122!’
CARl,
REICH
The patient rro~vetwl front thr cqxctticut ant1 is NOW pradi(*ally ttot’tttitl. wiMt 150,000 platelets. ttoi*tni~I clot rettxctiott. itntl IIO hetnorrhltgic tttsttifdtttions. I+orn a. study of t.he ~ils(ls dt!scrilted. it is evident. that laboratory teds ztrv c)f grcJ;tt diagnostic. WIUC itt clittid (tt*itl Ititt.holo~y. It should IW etttph~tsiml. however, that laboratory teds itlone itt’v ttot taltt)llgh ;t.ttd thitt, the ti~1.1 cliagiiosis or a pa.tient ‘s contlitiott clt~peitils up011 the intel ligettt intr~l)ret.;ttiort (11 ~(11the findings, Both the ctlinical esatninat.ion and the lalxtyatory teds ttrg.vrt.her.
INDICATIONS TESTS
IN
Medicine
FOR AND CLINICAL
THE VALUE OF LABORATORY ORAL PATHOLOGY
CARL REICH, M.D., NEW YORK, N. Y. N ORDER to illustrate the value of laboratory tests in clinical oral pathologg, I think it best to cite several actual cases and delineate, step by step, the: procedures used in order to arrive at a correct diagnosis.
I
Case 1.-A 58-year-old white woman was referred for diagnosis because of pallor, sore tongue, and difficulty in swallowing. The patient stated that, ill acldition to the above-mentioned symptoms of six months’ duration, she also suffered from arthritis in her hands. Physical examination revealed a well-nourished woman, appearing cstremely pale. Her hair was gray, dry, and had no l.uster, and her fingernails were brittSe, ridged, and spoon shaped. The tongue was red and did not show the normal coating. Her throat appeared inflamed and her hands showed swellFrom the history and physical examination. ing and deformity of the joints. this patient was evidently suffering from a severe anemia and also ~I’rom ;I rheumat.oid arthrit.is. The question now arose as to what t,he cause of the anemia was and wbilt could be done to correct it. The peripheral blood count was taken through venous punct.ure. The advantage of taking blood from the vein rather thiln from the finger is that it is possible t.o perform not only the routine count, hut to do the sedimentation rate, coagulat.ion time, clot ret.ra.ction, fra.gility trsts. blood grouping, and, if necessary, serol.ogy and blood chemistry t.ests on t.his one specimen, thus saving the patient unnecessary repeated punctnrrs nnil discomfort. In this particular case, the hemoglobin was 42 per cent ; red counl . 2.500,OOO; white count, 7,300; neutrophil polys, ‘il per cent (nonfilamentetl polys, 21 per cent) ; lymphocytes, 21 per cent ; monoeyt.es, 5 per cent ; plnt.elets. 250,000; sediment.ation rate, 7 mm. in fifteen minutes. 28 mm. in forty-fivfb Read before the Marc11 29. 1954, monthly Clinical Oral Wthology.
1217
wx~ferencc
of the New
York
Tnstitntf~
of
(!.ZRl, REI(‘II
121.8
t?liIllltf~s.
(coagulation
(‘PIit;
Ili~ilIl
thf’
iIIli1
COt’])\IS~liliil’
vi111wtr;ic$ion \.0111111(’
WilS
w’rt~’ tlt~l’lttill. 70
~tlOt’lllill
Jlcwatwrit HO t0
!I();) : ilttll
M’tis IX ItPi tlit’
tltl’illl
Wt*~~~lS~*lll;it~ liritioglol~iti ~~Oti~‘t~ttl.l’ii.tiOtl iViiS “7 (tlol’lllill ::2 lo :I6 1. I~‘t*otti these findings. wc 1’vli that wt. wvrc clwtlitt p wil tt ;I tttivtvwyf iv, ttypoc*hrotiiic, type of ;itic~ttii;i wliivlt is ustt;tll~ ;tsscwi;ilwl evil tt ill1 irott ~Irfic4eticy. This Was Iwrtie out Ity thr I’;tvt tti;tt ttith valor itttltbs wtis less t 111111 I. The tlt?il.tl w~l’pi~s(.ulit.t~ v(jlLltttr \trtts ICSS 11ttttt ttttt*tttttl itttrl tltth ttt(‘ittt ~*(tt~ItllsCUIttt*htmtgldtitt c*oticcWrstion W;IS ;ilSO lrss tliiitl ttot~ittill. ‘I’lw itlVtT;tst~ itt thtb srtlitttelitit.tictt1 Piit.P indic:ated soiltc ac4ivity 0I’ thr ihcuitintoitl at~tliritis. I:hwtttiit0i~l idlit4is is a1~0 known t.o prodlw it.11;tltcbltliit. 1,1111ttr ;tttc~l~tiaoI’ t*tt(~ltttt;ttoi(l al-1ttrif is is 1101 iIS SeWre as in this cil.stk zttltl it is usrtall;v wtmtwy\‘li~ with it w11tr itttks 01’ 1. t*itt.her thttn nticrocytic itt tyIt(a. I-kc*;lliw or IlIt> st)i’~~1~lil~lJ~~. it \\‘ilS c~ousitltWtl ~~tl\%hl~ to study the g;tstric* cc,tttcbtits to t~JJ1v oltt ;III>. possittility 01’ it ItetC*ious alielnia. The gastric COllfW~S~ (‘v(qt 11tt(l(~r 1Iit* stitttrlIatioil ol’ ltistattiittc~. siloww~ 110 free hydrochloric tt(*i~l. This fittflittg votttl)li(~tt~(~(l tttittt(1t.s. its 1itc.k it’ I’t*(lt’ hytlroc~hloric wicl is vhatxvlc~ristiv or Iwt*tti(Gous ;ttt(ltttitt. illfltOli~ll sometimes it. is fOlllitl in ]WO]tlt~ with ii11 ii.ctii-tlrfic.ictit.~ ilil~~llliil illld c~c~~~iiSiOti~lll~ ilt ILOt’ttliil people. It now ltcc*ritttr itttItet*;tliv(l tct 110 tit(tt’t1 cltafitiitivt. sttulics; IiilIllt~l~. ;I sterttit.1 hone Initt’t’(tw ex;ttttitttltioll tttt(I it spt’t1ttt irtttt tltIf(‘l’tttittilfiott. The strt*ttitI ttOli6? IllMT0W ShOWC?tl il tly]t(lY]tl;isl iv ttiit t’ro\\’ wit It it gtwit ittc*re;tse ol’ rryt.tt rol)lRSts. This finding is cdh;tt*;td (ht*istic*01’ itatttt tlcfi&ttt-y tttttl rttlcs Otto lwtwiclious ‘I’ll 11 tttt(Amiil. in which the t~t~pttloltlitsts I,t+c~tlotttitt;tlt~ itt t ttc’ Itotttb IIIC~~I’(IW. St1I’L1111 iron determhmtion \ViiS ;tlso c~otifit*tti;itoi’~ itt tlt>Ll it \VilS VCYy t0U. ilS wctnlcl lte ex])ect.ed iti iitt irott tlefic*ietic*y. wht*rr:is it) I)f~rtiic+tus :itltlilliil it ~oul~l Itc quite high. A4ll thtl I;~lt~t~;ttot*y fimlittgs. f ttet*rI’ctt*t~.Itoitttd c*ottc*lusively to c~hrotiit! tiii~t*ocytic~ tiyItoc~li rottii( iltit~llliil 0I’ irott-tlefi&ticy origin. Ii is vet.) 01 \vPII ktlo\vll that irot I)lit.~~ tttt itttl)(tt*titttl ~YIIC.tlOl 111tl\: ill tIltI Jliilillt~Jl~LtiCt~ the 1~loocl hetnogloltiti. Itut ttlso it) thr I)t.c’st’t’\‘itticttt ol’ the integrity 01’ Ihr c~pithclial st.t*ll(*tUrt+. tt;tttttbly, t tttb lt;tit*. IlililS. iitl(l tlIII~~Il1S Jllt’itl~Ji”~lJlt~S Or thtb 1 Oti~UC illIt tht’Oiit. This ~IGit*ti~l~lilt* l~iiiit‘tll StiO\VtVl t~vi4letiw 0I iI t~ltit4iil ]‘Iunittict~-8insoll sytidroitie with I~ISICI*~CSS ti;iiJa. sIto(ttl-shtt.])c(l trails (kol>-ttiehiit ). SOW totlguta. a11d s0t.t’ throat with difidty itt s~~;llldttg. ‘l’h~r>~lty it1 this (!it.se c~onsisirtl ot’ ItlrgtL clost*s (tl’ irott t)y ttt0ut.h ittttl ~PITOIIS sl1lfa.t.e. 15 gmins thWr linics tliiily. SllP Wits tIlS0 IllIt 011 il high-protein diet. its it is weI1 kttowtt t,hilt hc~tttoploltiti is !)(i IttAt*(*Pitt Ittdtbitt ttttd 4 IttAt’ ctant irott. She wits also given dilute Itytlt.ctc~hlot~i(. ilC4Cl.20 tli’cB]M iti ;I KliJSS 0F \V:ltOl~ it) 1Jth t.;tketl with JliedS. ;Is \vtb I~IIOW 1 It;tt iron is IwSt iottizwl ittt(I ;II~so~I~P~~ frottl tttt She I~~s~~oII~I~~I quicakly IIJ tttt’ritl)y ttttd t ttta ttloo(l I)t’(‘tlttte ttortttitl ilt4tl ititdiuni. tl.f’ttat* it. three-motlth ~wiwl 01 tt.tAitt tttettl. .\I I)tYW~llt it is llt’~‘PSSilY~ to krttp llf?Y 011 il til~lillt~JlilliW (108;lfY 01’ it*ctft. iilid FOtTCbllS Sllll’iltC. 5 gt.ttitts three timrs il tliiy. She is also IIII~ICI* 1t*eitttttcttt fat* hr~* t*lt(~~ltttittoi(l arthritis. ttttvittg recq:ivctl cortisone alit1 ilt. [JWWllt ~llltil~eolitlill~. The I;tttrt* tltaug is I)otettti;tll~ tosin t’tIt< ii II the blood dc3tfXlt.S. il.S it (‘ill1 t~el)tYSS t,hc IHJJlt! Illil.J’J’OW. tt is rlec~cSS~tJ’y. tht~rcfore. to wateh not only her* retI (*our& but her whit.e eonttt tt nit platdel s iiS Well.
I,AJ3ORA’l!ORY
TESTS
IN
CLISICAJ,
ORAJ.
I’.\THOJAO~:Y
I”19
Case 2.--A white girl, aged 1X years, \vijs referred for tli;lguosis IJWIIIIW The p;ltiellt. Kil\‘e ;I s]J”Hgy ~UI~IS itlIt ulcerntiou OFthta thro;lt. history 01 heiug well ~1) to two wreks I)reviouslyq wheu she (!illllc tlow~ wilh She hil(l il s(a\:(‘l*tl ll<‘iltlil~ht Iwhiiltl IVtlilt il])])t’il~‘t”I to tW il. griI)I)y c:o~itlitioii. ttlC fb\-tltJ?lllS,il milt1 SON’ tlll*Oill.. il I’eeling 0)’ tigtittless iti itIt IlPc*k. illl(l il She Si;ly(‘(] it1 t)etl I’or ;I I’(~H.tlil?S. with 11rr tflltllJ(‘l’iltlIl’(l fvwrisli WllSiltiOll. Ilcr I’;ll~liI~ I)hysic+ll tlii~guclse(l the going iIS high ilS IO:! (ltlgr(lt’S iIt llighl. c*cmtlitioli ilS gi*il)t)c alit1 prcsc4betl ilSl)il411, 1~efiic4llii~.ald 1Wd rest. She I’+ c~veretl l’rom the febrile episode, but the swollen ~onc’lit.ion of the gums an(l the throat ulceration pcrsist.cxl. A dental consultation was requested. On physical cssmin;ltiou, the patient aIq)eared to 1~ in good health and (lid not show au) signs cd’ weight loss or tosicity. The gums were swotleu ;Iutl s1~1lgy nutI the throilt was inflanle~l with seven11 ragged il]W~~~l~iOllS. The Iylnph IIO(]W iii the posterior t*ervi(*aI region wow e~ll;~rgetl i>ltd her sl)lwll was pallwble two fil~~~IdJl*~i1dt tlS 1JCloW t 1lCICfl COStalniargii~. A c.omplvtc Mood work-up scenied tlefinitely iutlic;l.tetl autl the rt!suIts \vctx! its follt~\vs : Iicnioglol~iii, 9.5 ]Jer twit : rcil wiiiit, I.WO,OOO; wliitc wunt 1:~.410; iwutrol)liil polys, 41 lwr wilt (1111sqqieiitotl, 1t per cacbiit); I\-uildioeytcs, ;I0 1x9 cent J niolioeytos, 7 per cent; numq4oitl tymphoc*ytes, 18 l~r cent ; eosinol~hils. 4 1)~ cctlt : se(li~llerlti~tio~l ‘l’he Stt?Mlill hone l%tt! in fift.een niinutcs 7 min.? in forty-five niiniit.cs :L? 111111. marrow showed a h~perl)l;Mi(~ INIITOW with no ahnormal wtls. The hcterophil agglutination test. was strongly lmitivc iii jiigli tlilution. Tl~ese findings inadc the diagnosis of 8 virus idrctiou 01: ilie infectious uiotionncloosis typca ver> likely. The positive cliagnostip Iboints wwc tlic good ~l]~]~~‘tll’illl~V’ of the patieut, the lack of anemia, the presc’ncc ol’ monoc-toid Iymplwcytes, or I:~oww~ crlls, the positive hctcrophil a.gglutination toast,and the 1101’11lil~ l~onc~ narrow. This typo of c*onditiou is frequc?nbIy camI~uwtl with leukemia, but should present. no difficult.ies for the csl)eriencetl heul;ltc)logist? as leukemia, a maligna.nt condit,ion. is reflected in the generd c*ontlition of the pabient, and is almost always nclcomI)anied 1)~ iIll a.nemi:t anal ill)ll(~rmd leukemic cells in the bone marrow. This pa.ticnt wils treiltetl for her virus infect,ion by genera t supportive measures, 10cd t.herill)y to the gums ant1 throat, rest, and moderat,e doses of antibiotics to prevent se~nclary infections. Tt is itnportant in this type of case t.o rcnmtll~er that, the liver is often d’ected, even though ja.undice is not. present. Liver Punt4ion tests IllilClV on this ]Jiltirllt showed an iurrease in the thynlol turbitlity ant1 c*tlI)h;llin fl~~t*eul;ltio~~,iIltht)ugh the serum bilirubin was normi~l. This indit*abetl the I)rcstlnce of it milt1 viral hepatitis, and it. was important, therefore, that. the liver t)c I)r’otec+d IJy s~~it;~hleclirtary Illeil.sllres and rest unt,il the functional tests rcturnctl to rlor~tli11. After a. two-mont.h I~rriotl thr I)ilti(ltlf was comIdetely n0rlm1, showing no abnorma~l cells in the peripheral I~lootl and no tlisturhanw of liver func:tion. (,I’
c~tlrnlatous
Case 3.-The patieut was il white girl. ;1get1 II, who wi1.swell until fonr months previously. when she 11~~1iln attack of acaute appendicitis. l’hc i~I)I.)et~(lis wils removed and she was given large closes of I)cnicillin by in,jt+ tion. ( h1t1 wcrk lil.tpr she!tl~rl~pctl il. pccnliar skin eruption which WIS t hc~~lphi.
1220
CARL
REICH
to be due to the penicillin. lier temperature persisted up to 103 degrees daily Ear the next three weeks ant1 her leukocyte co1111trose to .18,000,with 85 pet. cent polynuclear neutrophils and 15 per cent lymphocytes. A slight anemia developed. She was t,reatrd by blood transfusions and cortisone, with a~)parent recovery. Two ntollths Iiltt!r slut had it recaurrence of t.he skin eruptioll. Tllc t~rupt.ion whic*h was orythernatous in 1.\p~, with many paplllC% illtd hdh. IM’MIHP was over the extremit.iq trunk, and I&~. IiCr tcniperature a.g;liJl rleva.ted and again there was :I rise in the leukocyte count.. The possibility 01’ lupus crythematosus WAS c*onsiderc:dant1 a 1~l00d pJY?lWll’iltiOIl for IAN;. ~11~ was ma.de. ‘l!his was report r(l l)ositi\-t: at; the hospital in which she was a. pat.ient at the time. She was t.ren.ted with vortisonc again, with Sony improvement, and was dischargetl. One n~onth Inter there was another rtlc’urren(*e (11 skin eruption, temperature, and leukocytosis with bleeding, spougy gums. At. this time she was admitt et1 i-o I‘lcno~ Hill Hospital aad t.he dermatologica1 service treated her as a lupus erythematosus case! but requested a hematologica. consultation to make cert.ain of the diagnosis. A complete 1~11wl ilIlt bone marrow work-up was done rind the peripheral blood showed H per cent, myeloblasts, while the bonr IIJ~I’~OW showed iI n early myeloblastic iIlfiltIX~iOJ1 with no L.E. cells. On the strtqth of this finding, the L.E. preparation froJl1 the previous hospital Wils ~~evicwcd illl(l it. \vils I’ollntl that, those ct!lls which had been diagnosed as lupus c~yt.h~lHirtosus cells wcr*e ill rea1it.y myelob1asf.s. This error had been caused by a pale stain ; when the same slide was restainrd with Giemsa stain, the myelohlasts wt’r(h unmist.akable. The diagnosis of myeloblastic leukemia, therefore! was definite. The patient has hwn under observation since that t.ime a.ncl the i)(lrccntagc of myeloblasts hiIs risen i (1 90 per cent. This case is of great educational value in that it shows the diiXcnIties sometimes encountered in diagnosing blood preparations, and illustrat,es t,hp importa.nce of meticulous la.boratory technique. @se 4.-A U-year-old white man was referred because pallor of the gums and a sore tongue. He complained of wea.kncss, shortness of breath, il.Jld tingling in the extremities. The patient was well up 1.0nne year previously, and gradually noticed increasing fatigue illld shortness of breath on escrticm. In addition to the sympt.orns, just mentioned, he ills(j complained of a SOW, burning tongue and loss of mpnlory. llis appetite had been ~)oor ant1 he had lost 15 pounds in weight tlurillg t.he last year. On examination, he WRS])alc with i1 slightly yellowish tint.. The tongue was smooth and red and shqwed an absence of papillae. The heart was rapid, with a systolic murmur. His gait was somewhat unsteady a.nd? on further examination, there was some intquality in the reflexes in the lower extremities and loss of vibratory sense. This patient appeared 60 be suffering from pernicious anemia with neurological involvement. Complete bl.ood and bone marrow work-ups showed the following : hemoglobin, 42 per pent : rrd c*r)mll,,
I,dBORATORT
TESTS IN CI,INICAI,
ORAI, I’A\TIIOIA)BY
121
1,300,OOO ; white count, 3,!MKl; neutrophil polys, 55 per cent ; lymphocytes, 38 lter cent.; monocytes, 7 per cent; color in&s over .I ; platelets, .150,000; ltettiatocrit, 20; tnean corpnsc~ular rol uttte, .I 10. I’:s;ttttittat.iort of the peripheral smear showed irregular red (*ells, with ~itrialtlo size itttd shape, many of t.henr l;rrger than nortttnl itttd apltearing t.o Ite c.otttltletely tilled with hemoglobin. Jhtp ol’ t.he polymorphic nuclear neutrolthils WI*P hypersegmented. The sternal KII~~PIWshowe(l the ~)resc~ttc~e ol’ mauy ttt(~gitloltlitsts. This b100d pic$ure showing ma.crocptic! l~loocl with II lenktrpeni~, relnti\:t~ lyttt~~ltoc.;vt&s, increase in tttonocytes? tlitttirtished ltlitt(~lrts. a~ttl c,\-crtttaturt~ ~)olyttnrlrnt* neutrophils is typical of pernicious uttc~tttia. ‘1’11~~fimlittg 01 tltr~itIoblit.sts in the bone rttarrow ctntfirrtted f,his diagttctsis. Patients with pernicious ancqtti;t. are known to suffer from a lack of free hydrochlorio a.cid in t,htt gastric c*ont.ettt,s. Therefore: a gastric analysis was done with histamine stimulation. The injection oi’ hist.amine, 0.5 C.C.to 1,000. will stimulate the production of free hydrochloric acitl in the fnnctional cases, thereby ruling ant an!- psc~tlo acltylin gastric:>. 1’11~patient sltow~d no free hpdrorhloric! ac+l. Before the di;tgttosis (of l)et.ttic?ious nnetnia is definitely given, it is vital that. a G. J. series be done to mlc out, any malignanq- in the gastroint.est.inal tract which might produce pernicious anemia symptottts. This was dotte and proved negative. The diagnosis of prrnicions anemia was definitely established and therapy with vitamin H,, was inst.it.uaed. Three months later the hemoglobin was up t.o 80 per cent. The neurological symptoms had disappeared and the tongue appeared normal. The hydrochloric acid was still a,bsent.from the gastric contents. as this never ret.nt*tts. Case 5.--4 N-year-old whit.e woman was re-fcrred because of bleedittg from t.he gums. She had been well up to one month previously, when she ltcbgatt to have bleeding gums, purpmic spots OVCI* t.he extremit.ies, and csc*tWive mrn~,trnation. L l’hysiral examination was negative escept for hemorrhagic gums a.ttd ntany bla.ck and blue spots over thr body. Esaminat.ion II~ the blond showed : hemoglobin, 75 per cent.; red count, 3?600.000;whit.e count. !I.200 ; neabrophil polys. 71 pet* cent ; Ipmphncytes. 25 per cent ; monoctytcs. 1 p(‘r cent : plate1et.s. 50,000; clotting time, four minutes : no clot refra.cCon all ; blretling time seven minntes (normal, three mittntes). The sternal hot~c~ tttart’ow WRShyperplastic with many megakaryocytts. most of which wt’t*(’ ittttnatJnre and showed absence of pla.telet budding. The splren could not 1~ felt. A dkgnosis of idiopathic throml)ocyt.openic purpnra secondary t.o ltypc~rsplenism was made. The patient was treat.ed with ACTH and cortisone :~tttl responded well for three months. The platelets rose to 100,000 and t,he herttorrhagic manifestations disappeared. At. the end of this time, howeyet-, tltct platelets dropped and bleeding from the gums started again. Because of the danger of cerebra.1hemorrhage, splenectomy was decided upon and performcil. ilt
122!’
CARl,
REICH
The patient rro~vetwl front thr cqxctticut ant1 is NOW pradi(*ally ttot’tttitl. wiMt 150,000 platelets. ttoi*tni~I clot rettxctiott. itntl IIO hetnorrhltgic tttsttifdtttions. I+orn a. study of t.he ~ils(ls dt!scrilted. it is evident. that laboratory teds ztrv c)f grcJ;tt diagnostic. WIUC itt clittid (tt*itl Ititt.holo~y. It should IW etttph~tsiml. however, that laboratory teds itlone itt’v ttot taltt)llgh ;t.ttd thitt, the ti~1.1 cliagiiosis or a pa.tient ‘s contlitiott clt~peitils up011 the intel ligettt intr~l)ret.;ttiort (11 ~(11the findings, Both the ctlinical esatninat.ion and the lalxtyatory teds ttrg.vrt.her.