Cause of Misdiagnosis

8/6/2019 Cause of Misdiagnosis

1/9

Am J Ro#{149}ntg .nol 130 :867 -875 , M ay 1 9 7 8 19 78 A m er ica n R o en tge n R ay S o c ie ty

867 0361 -803X/78/0500 -0867 $02.00

Tubercu los is : F requen cy o f U nu sua l R ad iog raph ic F ind ing sW A L L A C E T . M IL L E R 1 A N D R O B R O Y M a c G R E G O R 2

The chang ing patte rn o f th e rad lo log ic p re sen ta t io n o ftubercu lo s is w as no ted in a re v iew o f 10 0 consecut iv e caseso f pu lm ona ry tube rcu lo s is . A c tiv e tubercu lo s is w as no t sug -g es ted as a rad io log lc d iagnos is in 4 3% o f th e patie n ts . O f th e10 0 cases , on ly 6 6 had cha ra c te r is tic s o f rea c tiva tio n tube r-cu lo s is (i.e ., m in im a l upper lo b e in fiftra te o r m o re advancedca vita ry d is ea se ). O f th e o th er 34 pa tie n ts , 18 had le ss usua lp res en ta tio n s , m ak ing th e rad iog raph ic d iagnos is d ifficu ft .T h e rem a in ing 16 patie n ts h ad rad iog raph ic p a f te rn s qu ite un -u sua l fo r tubercu lo s is , in c lud ing m ass lik e dens ities re sem -b lln g carc inom a; ch ron ic in filtra te s in a low e r lobe; m ilia rytubercu lo s is , e ith er supe rim posed on d iffu se in te rs titia l lungd is e ase o r assoc ia ted w ith a d iffu se lung pa tte rn a typ ic a l fo rm ilia ry d is ease ; and no rm a l ches t rad iog raph .

In t roduc t ion

T u b e rc u lo s is is re s p o ns ib le fo r c o n s id e ra b le m o rb id itya n d m o rta lity in a ll a re a s o f th e w o rld . C a re fu l p ub lich e a lth m e a su res a n d th e a d ve n t o f ch e m o th e ra p y h a v ed ra m a tica lly d e c re a s ed th e in c id e n ce o f th is d ise a se inm e d ic a lly a d va n c e d co u n trie s . N o n e th e le s s , tu b e rc u lo -s is s till e x is ts in s u ch c o u n trie s , p artic u la r ly in la rg eu rba n p o p u la tio n s . T h e re se e m s to b e a n in cre a s in gfre q u e n cy o f m isd ia g n o s is o f tu b e rc u lo s is , p o ss ib ly d u eto its d e c re a s in g in c id e n ce in p ro p o rtio n to o th er p u l-m on a ry d is e a se .

In 1 9 5 3 , w h en n a tio n a l d a ta firs t b e ca m e a va ila b le , th en e w a ctive tu b ercu lo s is ra te in th e U n ite d S ta te s w a s5 3 .0 p e r 1 0 0 ,0 0 0 p o p u la tio n . In 1 9 7 5 , th is sa m e n e wa c tive ca s e ra te w a s o n ly 1 5 .9 p e r 1 00 ,0 0 0 p o p u la tio n [1 ].A m o re sens itiv e index to th e dec re as ing p reva len ce o ftu b e rcu lo s is in th e p o p u la tio n is th e tu b e rcu lin sk in te s tre a c tiv ity . In P h ila d e lp h ia , 1 6 .4 % o f te e n a g e rs h ad ap o s itive sk in te s t in 1 9 4 8 , w h ile o n ly 1 .4 % w e re p o s itiv ein 1 9 6 8 [2 ].

O f th e n e w ca se s of tu b e rcu lo s is in P h ila d e lp h ia in1 9 7 1 , 6 5 % w e re d ia g n o se d b y n o n tu b e rc u lo s is h o s p ita ls(5 5.2 % ) o r p r iva te p h ys ic ia n s (9 .8% ) [3 ]. T h is d e m o n -s tra te s th e d ra m a tic sh ift in th e ca re o f th e tu b e rcu lo u sp a tie n t fro m th e tu b e rc u lo s is s a n a to rium to th e c o m m u -n ity h o s p ita l. In th is s e ttin g , m isd ia g n o s is o f th e d ise a seis m u ch m o re like ly to o cc ur [4 ] fo r se v e ra l re a so n s . T h etu b e rc u los is pa tie n t is n o w u su a lly d ia g n o se d a n dtre a te d b y p h y s ic ia n s w h o d o n o t h a ve a p rim a ry in te re s tin th is d ise a se , o r e ve n a sp e c ia l in te re s t in p u lm o n a rym e d ic in e o r in fe c tio u s d ise a se . T h e re ce n t d e c re a se din c id e n ce o f tu b e rc u lo s is h a s cre a te d a g ro up o f p h ys i-c ia n s w ith little e xp e rie n ce in th is d is e a se . T h e y m a y fa ilto re co g n iz e th e u su a l m a n ife s ta tio n s o f th e d ise a se a n d

a re e ve n m o re like ly to o v e rlo o k th e un u s u a l o n e s .T u b e rcu lo s is in th e a d u lt is m o re lik e ly to b e a ss oc ia te dw ith a n u n u su a l ra d io g ra p h ic p a tte rn th an in th e p a s t [4 ],ta k in g the in itia l th ru s t o f th e d ia g n o s is in a d ire c tio no th e r th an tu b e rcu lo s is . T h e c o ntin u in g n e e d fo r th ep ro p e r d ia g no s is o f tu b e rcu lo s is a n d e sp e c ia lly th ech a n g in g p a tte rn o f its ra d io g ra p h ic m a n ife s ta tio n s le dt o t hi s r ev ie w.

Sub jec ts and M e thodsW e re vie we d 10 0 co n s e cu tiv e ca se s o f cu ltu re -p ro ve n p u l-

m o n a r y tu b e rc u lo s is se e n in a 4 ye a r p e rio d (1 9 7 1 -1 9 7 5 ) a t th eH os p ita l o f the U n ive rs ity o f P en ns y lva n ia . C r ite r ia fo r in c lus io nw e re a va ila b ility o f b o th h os p ita l ch a rt a n d ra d io g ra p h s a n d a tle a s t o n e p o s itive cu ltu re fo r M yc o b a c te riu m tu b e rc u !o s is . 5 e v -e ra l c as e s o f n o n p u lm o n a ry tu b e rcu lo s is w ith ne g a tive sp u tu mc u ltu re s fo r M . t ub er cu lo sis w e re n o t inc lu d e d . T w o ca s e s o fscro fu la w ith m e d ia s tin a l a d e n o p ath y , o n e ca s e o f h ip tu b e rc u -lo s is w ith p o s itiv e c h e s t film a n d s p u tu m c u ltu re , a n d o n e ca seo f m en in g itis w ith m ilia ry p u lm o n a ry tu b e rc u lo s is a re in c lu d e d.In th is 4 y e a r p e rio d , th e n o n p u lm o n a ry tu b e rcu lo s is c a se se n c ou n te re d w e re : m e n in g itis , fo u r c a se s ; g e n ito u r in a ry , fiv e(tw o b lad d e r, th re e k id n e y); s c ro fu la , e ig h t; a n d b o n e a n d jo in t,tw o (o n e sp in e , o n e h ip ).

O f th e 10 0 c ase s w ith p rov en p u lm o na ry tu be rcu lo s is , 5 5w e re m e n a n d 4 5 w o m e n ; a g e ra n g e w a s 1 9 -7 8 y e a rs (a v e ra g efo r m e n , 5 9 ; fo r w o m e n , 4 9 .6 ). B la cks con s titu ted 59 % o f thes tu dy g ro up ; in th is h osp ita l p op u la tio n , the y re p res en t 4 2 % o ft he a dm is sio ns .

M o s t o f th e 10 0 p a tien ts in th is s tu dy w e re o ve r 4 0 ye ars o fa g e , c o ns is ten t w ith th e n a tio n a l s h ift in th e inc id en ce o f a c tivep u lm o n a ry tu b e rcu lo s is fro m p re d om in a n tly yo u n g a d u lts too ld e r p e rson s [1 , 5 , 6 ]. A nd vo rd [7 ] an d F ro s t [8 ] su gg es te d th a tth is sh ift in the in c id e n ce o f se c o n da ry tu b e rc u lo s is is a fu nc tio no f th e p re va le n c e o f in fe c tio n d u rin g th e p a tie n ts yo u th . S in cep u b lic h e a lth m ea su re s an d ch e m oth e ra p y h a v e g re a tly re d u ce dth e in c id e n ce o f in fec tio n in ch ild re n in the p a s t 3 5 ye a rs , th eg re a te s t n u m b ers o f d o rm a nt tu b e rcu lo u s fo c i a re in th e o ld e rpopu la t ion .

D ia g n os is in a ll in s ta n c e s w a s m a d e b y po s itiv e c u ltu re o rb io ps y . A ll pa tie n ts w ith p u lm o na ry tu be rcu lo s is a nd tw o o f thep a tie n ts w ith m ilia ry d is e a se h a d p o s itive sp u tu m cu ltu re . D ia g -no s is o f pu lm on ary tu be rcu los is w a s m ad e by su rg ica l re m o va lo f a p u lm o n a ry tu b e rc u lo m a in tw o p a tie n ts : sp u tu m fro m o nesu b se q u e n tly g re w M . tu be rc ulo sis . O ne ca s e of lo w e r lo b etu be rcu lo s is a n d tw o ca se s o f m ilia ry tu b e rcu lo s is w e re d iag -n ose d by lu n g b io p sy . A ll c ase s o f tu be rcu lo s is ad en itis w e red ia g n o se d b y b io ps y . O n e ca s e o f d is se m in a te d tu b e rc u lo s ish ad p os itive cu ltu res fro m th e m e n ing e s an d lun g : a n o th e r ha dp o s itive cu ltu re s from p le u ra , lu n g , a n d a b d o m in a l n o d e s . F ivep a tien ts w ith m a ss le s io n s h a d tu b e rcu lo s is in th e re se c tedsp e c im e n w ith su b se q u e n t p o s itive cu ltu re fro m th e sp e c im en .

R e ce ive d A ug us t 3 , 19 77 ; a cce p te d a fte r rev is io n Ja nu ary 3 0 , 1 978 .P res en ted a t the a nn ua l m e e ting o f th e A m e rica n R o en tge n R a y S oc ie ty , B os to n , S ep tem be r 1 977 . D e par tm en t o f R ad io logy , H o sp ita l o f th e U n ive rs ity o f P e nn sy lv an ia , 34 00 S pruce S tre e t, P h ila de lph ia . P e nn sy lvan ia 1 910 4 . A dd res s re p rin tre qu es ts to W . T . M ille r.a D epa rtm en t o f M ed ic in e , H osp ita l o f th e U nive rs ity o f P en ns y lv an ia , P hila d e lph ia , P en ns y lva n ia 1 91 0 4 .


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T A B L E 2P hy s ic a l F ind ing s o n A dm iss ion

Sign

4 .;!.

No .Recorded

Posi t i ve

T A B L E 3C he st R ad io gra ph y

Fig . 1 .-F a r a dva nc ed tub e rcu los is in 72 -y ea r-o ld b lack m a le w ithfeve r, hem op tys is , and 18 k g w e ig h t lo ss . E x te ns ive c av ita ry d ise as e inle ft lu ng w ith b ro nc ho ge n ic sp rea d to rig h t.

F ig . 2 .-M in im a l tu be rcu los is in 38 -ye a r-o ld fem a le w ith c h ro n icco ugh . P rom in en t in filt ra te in rig h t u pp er lob e . D ia gno s is o f th is typ e o ftube rcu lo s is is genera lly n o p rob lem .

S ym p to m a to lo g y is s h o w n in ta b le 1 . C o u g h a nd w e ig h t lossw e re c om m o n, se e n in m ore th an 75 % o f a ll the pa tie n ts . F e ve rw a s p re se n t in le ss th a n 5 0 % a n d h e m o p tys is in 25 % of th ep a tie n ts . P h y s ica l fin d in g s o n a d m iss io n us u a lly w e re n o t h e lp -fu l (ta b le 2 ). L es s tha n on e -th ird o f th e pa tie n ts ha d ab no rm a l

R ad iog raph ic F ind ingsT h e re su lts o f ch e s t ra d io g ra p h y a re lis te d in ta b le 3 .

F a r A d v a n c e d T u b e rc u lo s isT h ere w e re 3 7 p a tien ts w ith ex te n s iv e ca v ita ry tu be rcu -

lo s is , u n ila te ra l o r b ila te ra l ( fig . 1 ). T h e se ca s e s a re g e n -era lly no t a d ia gn o s tic p ro b le m in a la rg e u rb a n h os p ita l

86 8 M IL LE R A N D M a c G R E G O R

T A B L E 1C lin ica l H is to ry

Posi t i veNo . _______________Sy m p t o m .Quest ioned No . I,C o ug h 7 8 62 79A no re x ia , w e ig h t lo ss 7 6 5 8 7 6Fever 75 34 45S w e a ts , c h ills 7 2 4 3 6 0F a tig u e , m a la is e 6 3 3 5 5 6H em op tys is 6 8 1 7 2 5E xpo se d to tu be rcu los is 6 0 1 3 22A ctiv e tu b e rcu lo s is in pa s t 4 6 7 t 1 5P a st sk in te s t p e rfo rm e d 3 5 4 : 9 2 6

. A ve ra ge w eig ht l o ss . 10 k g.t An add it iona l fou r m ay ha ve had activ e tube rcu los is . S k in tes t had been p erfo rm ed o n 27 o f the 35 qu estioned .

No .F e ve r 1 0 0 1 5 1 5W a stin g 8 3 2 9 3 5P ulm o n a ry ra le s 8 8 2 5 2 8D u lln e ss 8 8 2 4 2 7A d e n o p a th y 1 2 9 7 5H e p a to m e g a ly 8 5 1 7 2 0S ple n o m e g a ly 8 4 5 5 6

. O v er 3 7. 8C c.

F ind ing Pa t ien tsU su al re ac tiv atio n tu be rc ulo sis :

E xte ns ive , o bv io us tu b e rc u los is 37M in im a l t ub er cu lo si s:Described as old 12D escribe d as a c tive 19L es s u su al tu be rc ulo sis :P rim a ry t ub er cu lo sis :P le ur al e ff us io n:

A c u te 3Chron ic 4M ed ia s tin a l o r h ila r a d e n o p a th y 4

M il ia ry in fil tr at es 4N o d u le s 3P n e u mo th o ra x 2U n us ua l t ub er cu lo si s:C om ple te ly c le a r 3M as s like d e n s ity ca lle d ca rc in o m a:

U su a l loc a tio n fo r tub e rcu los is 2U n u su a l lo c a tio n fo r tu b e rcu lo s is 5C hro n ic in f iltra te , unu su a l lo ca tion fo r tub e rc u lo s is 4M ilia ry tu be rcu lo s is su pe rim po se d up o n d iffu se in -te rs titia l lu n g d is e a se 1M i li a ry t u be r cu l os i s, a t yp i ca l p a tt e rn 2

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p u lm o na ry s ig ns an d o n ly 3 5% h a d a te m p era tu re a b ove 3 7 .8 C Ca t an y p o in t du rin g h o sp ita liza tio n .


3/9

F ig . 3 .-C hro n ic p leu ra l tub e rc u los is w ith ra d iog ra ph ica lly s tab le pu lm on ary in fi ltra te in 45 -ye a r -o ld b lac k m a le w ith 2 .3 kg w e igh t lo ss an d n ig h ts w e a ts . N o a pp a ren t cha n ge in ch es t fi lm s 6 ye a rs a pa rt. T h ree sp u tu m cu ltu re s w ere p o s itiv e fo r M . t u b e r c u lo s is . D esp ite unchang ing cha racte r o floc u la te d p leu ra l c o llec t ion , flu id w a s pres en t in p leu ra l spa ce a nd p leu ra l b iop sy w as pos itiv e .

U N U S U A L P A T T E R N S O F T U B E R C U L O S IS 86 9

w h ere tu be rcu lo s is is se e n fre qu en tly . N o ne the less , inseve ra l in s ta n ce s , th e d ia g n o s is o f tu b e rcu lo s is w a s n o tsu g ge s ted . In re tro spe c t, m an y o f th e se ca se s w e rera th e r o b v io us fa r a dv a n ce d tu be rcu lo s is . M isd ia g n o s iso f th is typ e o f d ise ase oc cu rred m o s t co m m on ly inp a tie n ts w h o w e re q u ite ill a nd o fte n ad m itte d to th ein ten s ive ca re un it. Th e ex te ns ive in filtra tio n w as th ou g h tto rep re sen t a sp ira tio n p ne um on ia o r lu ng a b sce ss . T w oo f the se pa tie n ts d ie d from re sp ira to ry fa ilu re , p re su m -ab ly se c on d a ry to the ir fa r a d v an c e d d is e as e .M in im al T ub e rc u lo s is

N ine tee n pa tie n ts w ere co rre c tly d ia gn os ed as ha v in gm in im a l a c tive tu b e rcu lo s is (fig . 2 ). H o w e ve r, 1 2 p a tie n tsw h o w e re th o u g h t to h a ve o ld o r s ta b le tu b e rc u lo s issu b se q u e n tly p rov e d to h a ve a c tive d ise a se . T h e se p a -t ie n ts w ere id en tif ied th rou gh a tub e rcu lin s k in tes t an don e o r m o re s p u tu m s p e c im e n s . T h e se c a se s illu s tra te avery important point in the radiographic reporting ofap ica l sc a rr in g . W ith ou t film s d a tin g b a c k a t le a s t 6m o n th s , a n a c cu ra te s ta te m e n t re g a rd in g th e s ta b ility o fa tu b e rc u lo u s le s io n ca n n o t b e m a d e : a ll o f th e se le s io n ssho u ld b e re p o rte d a s tu b e rcu lo s is , a c tiv ity in d e te rm i-na te . E ve n in p a tie n ts w ith u n c h a n g in g ra d io g ra p h ictub e rcu lou s s ca rs , ac tive tub e rcu lou s in fe c tio n ca n s til lbe p re se n t o n s p u tu m c u ltu re . C o n se q u e n tly , th e se p a -tie n ts sh o u ld b e rep o rte d a s ra d io g ra p h ica lly s tab le ra th e r th a n in a c tive [9 ]. T h re e ca se s in th is se r ie s h a dpo s itive cu ltu re s fo r M . tu b er c u lo s is de sp ite ra d io -gra p h ic a lly s ta b le le s io n s (fig . 3 ).

P rim ary T u b e rc u lo s isA lth ou gh prim a ry tub e rcu los is ha s lo n g be en co n -

s id e re d a d is e a se o f ch ild h o o d , th is is n o lo n g e r a na c cu ra te co n c e p t in th e U n ite d S ta te s [4 , 1 0 -1 2]. O n ly as m a ll p e rc en ta g e o f p a tie n ts h a ve a p o s itive sk in tes t a sad u lts , ind ic a tin g tha t th e y a re s usc ep tib le to the de -v e lo p m e n t o f th e p r im a ry d is e a se p ro ce ss . T h e h a llm a rko f p rim a ry tu b e rcu lo s is is h ila r o r m e d ia s tin a la d e n o p a th y o r p le u ra l e ffu s io n (1 0 pa tie n ts , fig s . 4 -7 ).M a n y o f the c as es o f lo w e r lo be in filtra tion o r m as s liked en s itie s , w h ich a re con s ide re d un u sua l c ha rac te ris ticso f tu b e rcu lo s is , m ay a lso re p res e n t p rim a ry tu b e rcu lo s is .If th e se c as es a re in c lud ed , th en a fu ll 1 9 % o f o u r c ase sre p res en t p rim ary tu b e rc u los is . In a re ce n t re p o rt em -p ha s iz in g th e un u sua l rad io g rap h ic ap pe a ran ce o f th ed ise a se , K ah n e t a l. [4 ] fo u nd tha t 1 3 .5 % o f the ir p a tie n tsh a d p rim ary tu b e rcu lo s is .

A d e n o p a t h y . F o u r c a se s h a d m e d ia s tin a l a n d h ila ra d en o p a th y , tw o b ila te ra l a n d tw o u n ila te ra l. O n e p a tie n ta lso h ad a p u lm o n ary in fi ltra te a n d p le u ra l e ffus io n , an dtu be rcu lo s is w a s s u sp e c te d . T he o th er th re e ca se s w e red ia g n o se d a s s a rc o id o s is . O n e o f th e s e p a tie n ts (fig . 5 )su b seq u en tly de ve lo pe d a p n eu m o n ia like in fi ltra te in th er ig h t lo w e r lo b e w hich d id n o t c le a r o n an tib io tic th e ra p y .D ia g no s is w a s m a d e by m e d ias tina l b iop sy in tw o p a-tien ts a nd by s pu tum sm ea r in the o th e r tw o .

S a rco id os is is a co m m on d is ea se u su a lly as so c ia tedw ith m e d ia s tin a l a d e n o p a th y . H ow e ve r, tub e rcu lo s is m a ys h o w a s im ila r p a tte rn [1 2 ]. T u b e rc u lo s is sh o u ld b e


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F ig . 4 .-M e d ias tin a l ad en o pa thy in 3 8 -ye a r-o ld b lac k m a le w ith 6 .8 kgw e ig h t los s . O rig ina l d ia gn os is w as sa rco id , bu t m e d ia s t ina l n ode b io ps ya nd c u ltu re s w e re po s it ive fo r tub e rc u lo s is .

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87 0 M IL LE R A N D M a cG R E G O R

F ig . 6 .-P leu ra l tube rc u lo s is in 2 6 -y ea r-o ld b la ck m a le he ro in ad d ic tw ith fev e r an d 6 .8 k g w e ig h t lo ss . P leu ra l b io psy an d c u ltu re from le f tp le u ra l e f fus ion w ere po s it ive fo r M . t ub e rc u lo s is .

Fig . 5 .-M ed ias tin a l a de no pa thy a nd rig h t low er lob e in filt ra te in 24 -yea r-o ld b lac k fem a le w ith u ve itis . In itia lly . pa tie n t ha d on ly m e d ia s tina la de no pa thy bu t de ve lop ed righ t low er lob e in f iltra te 3 w e eks la te r.S a rco ido s is w as th ou gh t to be lik e ly d iag no s is . A fte r pu lm on ary in f iltra teapp ea red , s pu tum be ca m e p os itive fo r M . t ub e rc u lo s is .

s usp e c ted w h en th e a de no p a th y in vo lve s on ly on e h ilum .A ll d ia g n o se s o f sa rc o id s h ou ld b e c o n firm e d b y b io p syto s h ow th a t n o n c as e a tin g ra th e r th a n ca se a tin gg ra n u lo m a ta a re p re se n t: cu ltu re o f th e su rg ica l sp e c i-m e n is a lso im p o rta n t, s in ce n o t a ll tu b e rcu lo u s n o d e sw ill sh o w ca se a tio n .

T w o o th e r pa tie n ts h ad c oe x is tin g m e d ias tin a l

_i 1

.

...F ig . 7 . - P le u ra l tub e rc u lo s is w ith b ro nc hop le u ra l fis tu la in 6 2 -y ea r-o ldb lac k m a le . Lo n g-s ta n d ing fib ro th o rax o n le ft w ith ex te ns ive p leu ra l

th icke n in g a nd p leu ra l ca lc ifica tio n . A ir- flu id le ve l ( a r r o w ) de ve loped a tle ft ba se 1 y ea r a fte r h is las t film . P le u ra l b iop sy an d cu ltu re rev ea ledM . t ub e rc u lo s is .

a d e n o p a th y a s w e ll a s ce rv ic a l a d e n itis . S ix a d d itio n a lp a tien ts ha d c e rv ica l a de n itis on ly d ia gn os ed b y ly m phn o d e b io p sy ; sp u tu m c u ltu re s w e re n e g a tiv e fo r M .t u b e r c u lo s is . There fo re , th e se s ix c a se s a re n o t in c lu d e din th is re v ie w , a lth o u gh so m e m a y re p re s e nt p r im a rytubercu los is .

P le u ra l E ffu s io n . S e v e n ca ses in th is s tud y h a d u n ila t-


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F ig . 8 .-M ilia ry tu be rcu los is in 6 4 -y ea r-o ld fe m a lew ith co ug h , lo w g rad e fe ve r , a nd 4 .5 k g w e ig h t los s . A tth is s tag e , m il ia ry tub e rcu los is is re la t ive ly e as y tor ec ogn iz e .

F ig . 9 .-M il ia ry tu be rc u lo s is in 7 2 -y ea r-o ld m a le w ith ca rd iac a ndp u lm ona ry fa ilu re . P a tie n t h a d prio r in te rs tit ia l lu ng d ise ase a n d w as fe ltto ha ve p n eu m o n ia an d /o r pu lm on a ry ed em a. A u to p sy re ve a led m ilia rytube rcu los is .

U N U S U A L P A T T E R N S O F T U B E R C U L O S IS 87 1

e ra l p le u ra l e ffu s io n (fig s . 6 an d 7 ), in c lu d in g five ca sesin w h ich it w a s th e o n ly ra d io g ra p h ic fin d in g . P le u ra le ffu s io n is g e n e ra lly co n s id e re d to b e a m a n ife s ta tio n o fp rim ary tub e rc u los is [4 , 1 0 , 1 3 , 14 ]. H o w e ve r, tw o o f o u rp a tien ts w ith p leu ra l e ffu s io n h ad a lon g -s tan d ing h is to ryo f p le u ra l d ise a s e w ith Io cu la te d e ffu s io n s th a t w e res ta b le fo r ye a rs a n d th o u g h t to re p re se n t o ld p leu ra lth ick e n in g . O n e o f the s e p a tie n ts su b se q u e n tly d e -ve lo pe d pu lm on a ry in fi ltra tio n a nd on e a b ron ch op le u ra lfis tu la . B o th h ad M . t ub er cu lo sis c u ltu re d fro m lo cu la te dp le u ra l co lle c tio n . T h u s , a lth o u g h w e h a ve in c lu d e d a llca se s o f p le u ra l e ffu s io n a s p r im a ry tub e rcu lo s is , it islike ly tha t so m e c ase s , esp e c ia lly if lo cu la te d a n d lon gs ta n d in g, re p re se n t s e co n d a ry d ise a s e.M ilia r y T ub erc u lo s isS e ve n p a tie n ts h a d m ilia ry tu be rcu lo s is (fig s . 8 an d 9 ).O n e p atie n t, a d m itte d w ith th e d ia g n o s is o f sc h izo -p hren ia , w as fo un d to h a ve m e n ing ea l tu be rcu lo s is . T hech e s t film w a s o rig in a lly in te rp re te d a s n o rm a l b u t inre tro sp ec t sh ow ed m u ltip le m ilia ry n od u le s . In tw o o the rca s e s , m ilia ry tu b e rcu lo s is w a s s tro n g ly su sp e c te d . In afou rth c ase , tub e rcu lo s is w a s co ns ide re d b u t tho u gh t tob e le ss like ly tha n h yp ers en s itiv ity lun g d is ea se . T u be r-cu lo s is w a s s ub se qu e n tly p rove n in a ll fou r c ase s a nd a llcases responded to drug therapy.

T hre e p a tie n ts ha d a ra th e r un u sua l rad io lo g ic pa tte rnfo r m ilia ry tu be rcu lo s is . A ll th re e h a d in it ia l re sp ira to ryfa ilu re a n d ex te n s ive d iffus e in te rs tit ia l lu n g d ise as e fo rs e ve ra l w e e ks to se ve ra l m o n th s . T h e s e w e re co m p li-c a ted b y su p e rim p o se d m ilia ry tu b e rcu lo s is w h ich w a s

d iag no se d b y lu ng b iop sy (tw o ca ses ) o r au top sy (on ecas e ). T h e d iag n os is w a s q u ite d iff ic u lt be ca use o f th eu n d e rly in g p re e x is tin g lu n g d ise a se . In e a ch ca s e , th e rew a s a cha n ge in the se q ue n tia l ch es t film to a m ilia ryp a tte rn w h ich c o u ld b e id e n tifie d in re tro s p e c t a s co n S is -te n t w ith m ilia ry tu b e rc u lo s is .

T h e ra d io g ra p h s in o n e o f th e s e p a tie n ts im p ro ve ds o m e w h a t a fte r th e ra p y fo r tu b e rcu lo s is b u t d id n o tre v e rt c o m p le te ly to n o rm a l. T h e o th e r tw o p a tien tse xp ire d fro m m ilia ry tub e rcu los is . T h es e th re e cas ese m p ha s iz e the im po rtan ce o f su sp ec ting m ilia ry tu b e r-cu lo s is in c h ro n ica lly ill p a tie n ts . T h e ra d io g ra p h ic a p -pe a ran ce o f e a rly m ilia ry tub e rcu lo s is m ay b e o ve rlo o kedun le ss se a rch ed fo r ca re fu lly . C o nv e rse ly , the pa tie n tw ith ve ry e x te n s ive m ilia ry tu b e rcu lo s is m a y sh o w s u cha n u n u su a l lu n g p a tte rn (fig . 9 ) th a t m ilia ry tub e rcu lo s isis n o t su sp e c te d . O n e p a tie n t w ith m ilia ry tu b e rcu lo s is inth is s e rie s w a s o n im m u n os u p p re s s iv e d ru g s , a n d th isty p e o f d ise a s e m u st b e su sp e c te d in s u ch p a tie n ts .

P n e u m o th o ra xO n e p a tie n t h a d a p n e u m o th o ra x a n d u n su s p e c te d

tu be rcu lo s is (fig . 10 ). A se con d p a tien t ha d apn e um oth o ra x a sso c ia te d w ith fa r ad va nce d tu be r-cu lo s is . T u b e rcu lo s is is a kn o w n a lb e it u nu s u a l e tio lo g yo f p n e u m o th o ra x . O n film s a fte r re ex p a n s io n o f apn e um oth o ra x , a n a p ica l in filtra te sh ou ld b e s ea rch edfo r ca re fu lly . S u ch a n in filtra te w a s ide n tifie d in th e o neca s e w ith u ns u sp e c te d tu b e rcu lo s is , b u t w a s in co rre c tlyin te rp re ted as an o ld sca r. A g a in th e n e ce ss ity o f


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F ig . 10 .-P ne um otho rax an d a p ica l in filt ra te in 6 9 -y ea r-o ld m a le w ithpneumotho r ax ( A ) . O n ree xpa ns ion , in fi ltra te no ted in rig h t u pp er lob e(B ) w as con s id e red o ld tub e rc u lo us sc a r. P a t ien t su bs eq uen tly ex p ired ;ac tiv e tub e rc u lo s is w as cu ltu red from rig h t a p ic a l le s io n .

87 2 M ILL E R A N D M ac G R E G O R

F ig . 1 1 .-T u bercu lou s no du le in a sym ptom atic 30 -ye a r-o ld fe m a le . N odu le in s up erio r s egm e n t o f rig h tlow er lob e w a s d ia gn os ed a s tu be rcu los is a t su rge ry .

re po rtin g an y ap ica l les ion a s o ne o f in de te rm in a tea c tiv ity is e m ph as ize d .T u b e r c u l o m a

T h re e p a tien ts h ad so lita ry n od u le s , tw o in th e sup e rio rse gm en t o f the lo w e r lo be a n d o n e in th e an te rio r

se g m e n t o f a n u p p e r lo b e . O th e r p a tie n ts h a d n o d u le s inth e u p p e r lo b e , b u t s in ce tub e rcu lo s is w a s a lre a d y co n -s id e re d , th e s e w e re n o t th o u g h t to be d ia g n o s tic p ro b -e m s . O th e r a u th o rs [4 , 1 5 ] h a ve re p o rte d m u ltip le

n o du le s a s d ia gn os tic p rob lem s in tha t the y su g ge s tm e ta s ta tic tu m o r. N o su c h c a se s w e re e n co u n te re d inth is re v ie w , a lth o u g h so m e h a ve b e e n se e n p re v io u s ly a tt his in st it ut io n.

A so lita ry no d u le req u ire s p a th o log ic ide n tif ica tio n ;co n se q u e n tly , d ia g n o s is w a s m a d e in tw o p a tie n ts a fte rsu rg ic a l re m o va l o f th e n o d u le (fig . 1 1 ). In th e th ird ,d ia gn os is w as m a de by a po s itive sm ea r; trea tm e n t w itha n titu be rcu lo u s d rug s re su lted in d isa pp e ara n ce o f th en o d u le .M as s lik e D en s itie s

S e ve n p a tien ts h ad m ass lik e de ns itie s (fig . 1 2 ) w h ichw e re fe lt to m os t like ly re p re se n t ca rc ino m a o f the lu ng .F ive o f th e se w e re in lo ca tion s u n u s ua l fo r tu b e rcu lo s is :o n e ea ch in the a n te rio r seg m e n t o f the up p er lo be ,l in g u la , a n d m id d le lo b e , a n d tw o in th e lo w e r lo b e .T he se five le s io n s m a y rep re se n t a n o th e r m an ife s ta tiono f p rim a ry tu b e rcu lo s is . T w o le s io n s w e re in th e p o s-te n o r se g m e n t o f a n u p p e r lo b e . T u b e rcu lo s is s h o u ld n o tb e s ug g e s te d fo r e ve ry m a ss le s io n o f the ch e s t. H o w -e ve r, th is p o ss ib ility m u s t b e co n s id e re d in p a tie n ts w ithb e n ig n p u lm o n a ry cy to lo g y .

B as ila r In fi ltra te sF o ur p a tie n ts h a d ch ro n ic in filtra te s in a lo w e r lo b e

re p re se n ting ba s ila r tu be rcu lo s is (fig . 13 ). T he se in fil-tra te s w e re g e n e ra lly th o u g h t to rep re se n t ch ro n ic in -fla m m a to ry d ise a se o r a p o o rly re sp o n s ive p n e u m o n ia ;


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- 1it

UNUSUAL PAT TERNS OF TUBERCULOSIS 87 3

repo r t .

tu b e rcu lo s is w a s n o t s u sp e c te d in a n y ca s e . D ia g n o s isw a s m a d e in o n e p a tie n t b y th o ra co to m y a n d in th e o th e rth re e b y p o s itiv e sm e a r a n d cu ltu re . T h e s e p a tien ts m a ya ls o re p re se n t p r im a ry tu b e rc u lo s is , a lth o u g h re a c tiv a -tio n tu b e rc u lo s is m a y o cca s io n a lly in v o lve th e lo w e rlo b e .N o rm a l C h e s t F ilm

Th re e p a tien ts w ith p o s itiv e sp u tu m cu ltu re s fo r M .t u b e r c u lo s is h a d a n orm a l c h e s t film , e ve n in re tro sp e c t.O n e o f th e s e p a tie n ts h ad c o e x is tin g tu b e rc u lo s is in atra nsp la n te d k idn ey a n d w a s o n im m u n o su p p re ss ived rug s . T h e o th e r tw o p a tie n ts h a d u n e xp la in e d fe ve rsan d s pu tum cu ltu re s fo r M . t ub er cu lo si s w h ic h b e c a mep o s itiv e a fte r th e y le ft th e ho s p ita l. T h e s e p a tie n ts c o u ldc o n ce iv a b ly re p re se n t p r im a ry tu b ercu lo s is w ith a ve rym in u te fo cu s o f in fe c tio n , o r th e y m ay re p re se n t re a c tiv a -tio n tu b e rcu lo s is w ith su b ra d io g ra p h ic p u lm o n a ry le -s io n s . M ilia ry tu b ercu lo s is is a ls o a co n s id era tio n , b u tn o n e o f th e p a tie n ts su b s e q u e n tly de v e lo p e d d iffu s ein fi ltra te s o r sys te m ic sym p tom s o f m ilia ry d isea se .T h ese th ree ca se s illu s tra te a p o in t in the co u rse o fp u lm o na ry tu be rcu lo s is w h en a ra d io g ra ph ica lly v is ib leles ion is n o t ye t p re s e n t a n d ye t th e p a tie n t h a s a p o s itiv ecu ltu re [16 ]. T he re ce rta in ly is no w a y tha t tu b e rc u los isc a n b e su sp e c te d in th is in s ta n ce .

R ad iog raph ic R epo rtsIn re v ie w in g the o rig in a l rad io g rap h ic re po rts issu ed

o n th e 1 0 0 pa tie n ts , w e fou nd th a t a p os itive d ia gn os is o fa ctive tub e rcu los is w a s m a d e in 5 0 ca se s . T u b ercu lo s isw a s m e n tion ed a s a p o ss ib il ity bu t n o t a p rim ary d iag -n os is in se ven pa tie n ts . A d ia g no s is o f o ld tu b e rc u los iso r a p ica l tu b e rc u lou s s ca r rin g w a s m a d e in 14 p a tien ts .T u b e rcu lo s is w a s n o t m e n tio n e d a s a d ia g n o s tic p o s s ib il-ity in 2 9 pa tie n ts . O f th e se , th re e h a d a n o rm a l c he s tra d io g ra ph , e ve n in re tro sp ec t. T hu s in 26 % o f the ca se s ,th e d ia g n o s is o f p u lm o n a ry tu b e rcu los is w a s n o tsug g es te d b y th e ra d io lo g is t in th e fac e o f ch es t rad io -g ra p h ic fin d in g s w hich su b se q u e n tly p ro ve d to b e tu b e r-cu los is .

T he fa ilu re o f th e ra d io log is t to a le rt th e c lin ic ia n to th ep o ss ib ility o f p u lm o n a ry tu b e rcu lo s is fre q u e n tly le d tolon g de la ys in the ins titu tio n o f th e rap y in m a n y o f th ep a tie n ts in th is re p o rt. T u b e rcu lo s is w a s n o t su s pe c te din itia lly b y th e c lin ic ia n in 42 % o f o u r ca s e s ; 20 % ac tua l lyw e re d isc h a rg e d fro m th e h o sp ita l w ith o u t a n y a n titu b e r-c u lou s th e ra p y , s in ce th e cu ltu re s d id no t be co m e p os i-tive u n til a fte r d isc h a rg e . O n e p a tie n t w a s to ld th a t h eh ad ino p era b le c a rc in om a o f th e lu ng ; w he n h is c u ltu re sg re w M . tu be rc ul os is se ve ra l w ee ks la te r, h e w a s loca tedin Ita ly w he re he w as m ak in g a las t p ilg r im a g e b e fo reh is im p e n d in g d e a th .

In so m e c as es , th e c au se o f th e de la y co u ld no t b eattributed to the radiol ogist. In several instances. aco rre c t d iag n os is o f a c tive o r p os s ib ly a c tiv e tu be r-cu los is w as s ug ge s te d b y th e rad io lo g is t b u t ign o red byth e re fe rrin g p hy s ic ia n . T o p reve n t th is , a m ech a n ismh a s b ee n in s titu te d in ou r ho sp ita l to fo llo w a ll p a tien ts inw h om tu b e rc u lo s is is s u g g e s te d o n th e ra d io g ra p h ic

F ig . 12 .-M ass lik e d en s ity in a sym ptom at ic 79 -y ea r-o ld m a le . R ig h tlo w er lobe m as s w as d iagnosed as tub e rc u los is a t su rge ry .

F ig . 13 .-Low er lobe in fil tra te in 32 -yea r-o ld fem a le . S m ears andcu ltu res o f c h ron ic righ t low er lobe in filt ra te w e re po s itiv e fo r M .tu b e r c u l o s i s .

Dis cuss ionC o n c e p ts o f th e p a th o g e n es is o f s e co n d a ry tu b e rc u -

lo s is h a v e ch a n g e d d u rin g th e p a s t 1 5 ye a rs . U n tilre cen tly , m an y be lie ved th a t se co nd a ry tub e rcu los is re -su Ite d fro m re in fe c tio n o f a p erso n p rev io u s ly se n s itize dto tub e rc le b a c illu s . T h is im p lied a sec on d con tac t w ith


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8 7 4 M IL L E R A N D M a c G R E G O R

tu be rcu lo s is a s a n a d u lt. C u rre n t co n c e p ts o f th e p a th o -g e n e s is o f tu b ercu lo s is , a s e la b o ra te d b y S tea d a n dc o lle a g u e s [1 7 , 1 8 ], a re a s fo llo w s. T he p rim a ry tu b e rcu -b u s le s io n n e a rly a lw a ys o c cu rs in th e w e ll ve n tila ted( lo w e r) p o rtio n s o f th e lu n g . A fte r im p la n ta tio n , th etu be rc le b a c illu s g ro w s a n d m u ltip lie s w ith little o r noim m e d ia te tiss u e re sp o n s e . E ve n tu a lly , a fe w b a c illire ac h th e c ircu la tio n th ro u g h p u lm o n a ry v e in s a n d lym -p h a tic ch a n n e ls a n d a re w id e ly d is se m in a te d . T h e b a c ill iim p la n t a n d m u ltip ly in o rg a n s w ith a m ilie u fa vo ra b lefo r g ro w th , u sua lly in a n a re a o f h igh o xyg en ten s ion .T h is im p lan ta tio n o c cu rs m o st c o m m o n ly in th e a p ic e so f th e lu n g s , a n d m o re ra re ly in th e k id n e y s , b ra in , o rb o n e . L y m ph a tic d ra in a g e in to th e m e d ia s tin u m a lsore su lts in tu b e rc u lo u s g ro w th in lym p h n o d e s, a n d ru p -tu re o f a s m a ll tu b e rc u lo u s fo cu s in to th e p leu ra m a yre su lt in a p le u ra l e ffu s io n .

T h e 4 -6 w e e k in te rv a l b e tw e e n d e v e lo p m e n t o f th ep rim a ry a n d se c o n d a ry le s io n s res u lts fro m th e tim ere q u ired fo r th e h o s t to d e v e lo p sp e c ific c e ll m e d ia te dim m u n ity (d e la ye d h y p e rse n s itiv ity ) . D u rin g th is p h a s e ,o rg a n ism s d isse m in a te fro m th e p rim a ry fo c u s o f in fe c -tio n to o th e r su sc e p tib le p a rts o f th e bo d y . W h e n ce ll-m e d ia te d im m u n ity d e ve lo p s , th e se s ite s a ttra c t in fia m -m a to ry ce lls ; th is res u lts in g ra n u lo m a to u s le s io n s w h ichinh ib it m u ltip lica tio n o f tu b e rc le b a c illi. T h u s if th e im -m u n e re sp o n se in th e h o s t is e xce lle n t, m e ta s ta tic fo c id o n o t d e v e lo p to a s ig n ifica n t d e gre e , a n d th e p a tie n tre ma in s a sy mp to ma tic .

T h e re a re se v e ra l p o ss ib le c lin ica l o u tco m e s, d e p e n d -in g p rim a rily o n th e h o s t im m u n e d e fe n se m e c h a n ism .

1 . In th e p re se n c e of a n e xce lle n t h o s t d e fe n se , th ep a tie n t m a y h a ve n o re s id u a l p u lm o n a ry fin d in g s a n d n oc lin ica l f in d ing o the r th an a po s itive tu be rcu lin sk in te s t.

2 . In a co m p le te fa ilu re o f h o s t de fe n s e m e ch a n ism ,th e p atie n t m a y d e ve lo p m ilia ry tu b e rc u lo s is .3 . W h e n th e h o s t d e fe n se m e ch a n is m is fa irly a d e -q u a te , th e p a tie n t m a y d e ve lo p sm a ll fo c i o f m e ta s ta tictu b e rc le b a c ill i in the a p e x o f th e lu ng o r p e rh a p s in th ek id n e y o r b o n e. T h e se le s io n s a re w a lle d o ff b y th e h o s td e fe n se m e ch a n is m s a n d m a y lie d orm a n t fo r m o n th s o rye a rs ; th e y m a y re a c tiva te , p o ss ib ly as a re su lt o f co n cu r-re n t in h ib itio n o f th e h os t ce ll-m e d ia te d im m u n e d e fe n se(e .g . , b y s te ro id th e ra p y , d e b ilita tin g illn e ss , m a lig n a n cy ,or old age).

4 . If th e p a tie n t h a s a p o o r in itia l im m u n e re sp o n se ,p r im a ry in fe c tio n m a y d e ve lo p d ire c tly in to so m e m a n i-fe s ta tio n o f se c o n d a ry tu b e rc u lo s is su ch a s a p ica l d is -e a s e , ly m p h a d e n itis , o r b o n e o r re n a l tu b e rc u lo s is .

T h e ra d io g ra p h ic m a n ife s ta tio n s o f th e p u lm o n a ry a s -p e c ts o f th is d ise a se va ry w ith th e s ta g e o f th e illn e ss . Inp r im a ry tu b e rc u lo s is , th e re is a lo ca lize d p u lm o n a ryin fi ltra te , us ua lly in the lo w er lu n g fie ld . T h is m a y b ea cco m p a n ie d b y h ila r or m e d ia s tin a l a d e n op a th y o r b y ap le u ra l e ffu s io n ; fre q u e n tly th e se are th e o n ly ra d io -g ra p h ic m a n ife s ta tio n s o f p r im a ry tu b e rc u lo s is . R e a c ti-va tio n (s e co n d a ry ) tu b e rc u lo s is g e n e ra lly o cc u rs in itia llyin th e ap ica l o r p os te rio r se g m e n t o f on e o f th e u p p e rlob e s o r th e s u p erio r s e g m e n t o f a lo w e r lo b e . W h e n

d ise a se b e c o m e s m o re e x te n s iv e , o th e r pu lm o n a ry se g -m e n ts m a y su b se q u e n tly b e c o m e in v o lve d . T h e e a rlyle s io n o f re a c tiv a tio n tu b e rc u lo s is is u su a lly a flu ffy o rs tra n d like in filtra te in a n a p ica l p o rtio n o f th e lu ng ,p o s s ib ly a c co m p a n ie d by p le u ra l th ic ke n in g .

A s th e d ise a se b e c o m e s m o re e x te n s ive , ca v ita tio nfre q u e n tly de v e lo p s in th e le s io n a n d th e re is e n d o b ro n -ch ia l sp re a d to o th e r a re a s o f th e lu n g , o fte n to th esu p e rio r se g m e n t o f th e co n tra la te ra l lu n g . M o re e x te n -s ive fa r-a d va n ce d tu b e rcu los is is a lm o st in va ria b ly a c-co m p a n ie d b y ca v ita tio n , a lth o u g h to m o g rap h y m a y b en e ce ss ary to d e m o n stra te th is .

W h ile th e se a re th e ac ce p te d ra d io g ra p h ic fin d in g s intu b e rc u lo s is , th is s tu d y su g g e s ts th a t th e re a re o th e r,so m e w h a t u n u su a l, m a n ifes ta tio n s o f tub e rcu lo s is w h ichm u s t b e c o n s id e re d in th e d ia g n o s is o f th is d is e as e . A stu b e rcu lo s is b e c o m e s le ss c o m m o n , th e ra d io lo g is t a n dth e c lin ic ia n m u st re m a in a w a re o f its ex is ten c e , p a rtic -u la r ly in th e u rb a n p op u la tio n . T h e y a lso s h o u ld b ea w a re o f th e in cre a s in g fre q ue n c y o f a ra d io g ra p h ica p p e a ra n ce o f th e d ise a s e n o t g e n e ra lly d e scr ib e d in th etex tbooks .

REFERENCES

1 . 1 9 7 3 T u b e rc u lo s is S ta tis tics , S ta te s a n d C itie s . W ash ing -ton , D .C ., D e p artm e n t o f H ea lth , E du ca tio n & W e lfa re , Ju ly1 9 7 4

2. Stein 5: Tuberculous infection in a city. A m R e v R e s p ir D is9 9 :2 98 -3 03 , 1 9 69

3 . S te in 5 : A n n u a l T B R e p o rt, C ity o f P h ila d e lp h ia , 1 9 7 14 . K ah n M A , K o vna t D M , B ac hu s B , W h itcom b M E , B rod y J S ,

S n id e r G L : C lin ic a l a n d ro e n tg e n o g ra p h ic s p e c tru m o fp u lm o n a ry tu b e rcu los is in th e a d u lt. A m J M e d 6 2 :3 1 -3 8 ,1 9 7 7

5 . M a yo ck A L , M acG reg or A R : D ia gn o s is , p re ve n tion a n de arly the ra py o f tu be rc ulo sis . D M 2 2 :3 -6 0 , 19 7 66 . M a cG re g o r A R : A y ea rs e xp e rie n ce w ith tu b e rcu lo s is in a

p riva te u rb a n te a ch in g h o sp ita l in th e p o s tsa n a to riu m e ra .A m J M e d 58 :2 21 -2 27 , 19 75

7 . A nd vo rd K F : W h a t c an w e le a rn b y s tu dy in g T B b y g en e ra -t ions? N or M ag L a eg e vid es k a be n 9 1 :6 4 2 -6 4 7 , 1 9 3 0

8 . F ro s t W H: T h e a g e se le c tio n o f m o rta lity fro m tu b e rcu lo s isi n s u cc es si ve d ec ad es . A m J H y g ie n e 3 0 :9 1 -9 6 , 1 9 3 9

9. D ia g n o s tic S ta n d a r d s a n d C la s s ific a tio n o f T u b e r c u lo s is .N e w Y o rk , N a tio n a l T u b e rcu lo s is a n d R e sp ira to ry D ise a s eAssociation, 1 9 6 9

1 0 . R o p e r W H , W a rin g JJ : P r im a ry se ro fib r in o u s p le u ra l e ffu -s io n in m ilita ry p e rso n n e l. N a t! T u b e rc A s s o c T ra n s 48:150-1 56 , 19 5 2

11 . F r ie de nb e rg A M , lsa ac s M , E lk in M : T h e ch an g in g ro en t-g e n o lo g ic p ic tu re in p u lm o n a ry tu b e rcu lo s is u n d e r m o d e rnc h e mo th e ra p y . A m J R oe n tg e n o ! 81 : 1 9 6 -2 0 6 , 1 9 5 9

1 2 . K ittre d g e R D , F in b y N : B ila te ra l tu b e rc u lo u s m e d ia s tin a llym ph a d e n o pa th y in th e ad u lt. A m J R oe n tg e n o l 9 6 :1 0 2 2 -1 0 2 6 , 1 9 6 6

1 3 . B a d g e r T L : T u b e rc u lo s is . N E n g I J M e d 2 6 1 :3 0 -3 6 , 1 31 -1 3 9 , 1 9 5 9

1 4 . M ye rs JA , B e a rm a n JE , D ix o n H G : T h e n a tu ra l h is to ry o ftu b e rc u lo s is in th e h u m a n b o d y. A m R e v R e s p ir D is 8 7 : 3 54 -36 9, 19 63


9/9

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1 5 . S o ch o ck y S : T u b e rc u lo m a of th e lu n g . A m R e v T u b e rc 1 7 . S te a d W W: T h e ic e b e rg o f m e d ic in e , tu b e rc u lo s is . R a d i o !78 : 4 0 3 -4 1 0 , 1 9 5 8 C !in N o r th A m 3 : 29 9 -3 0 4 , 1 96 5

1 6 . M a c G reg o r A R , C la rk L W , B a s s F : T h e s ig n ific a n ce of 1 8 . S te a d W W , K e rb y G R , S ch lu ete r D P , Jo rd a h C W : T h eiso la tin g lo w n u m b e rs o f m yc ob a c te riu m tu b e rcu lo s is in c lin ica l s p ec tru m o f p rim a ry tu b e rcu lo s is in ad u lts . A nncu lt ur e of s pu tu m sp ec im en s. C h e s t 6 8 : 518 -5 2 3 , 1 9 7 5 In te r n M ed 6 8 : 7 3 1- 73 5, 1968

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